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Positive
(news)
|
Late |
Iacoviello et al., upcoming study (News) (not included in the study count) |
INTERVIEW EXCLUSIVE : Efficacité de l'hydroxych loroquine confirmée sur 3451 patients italiens. Réduction de la mortalité de 30% |
Upcoming study of 3,451 hospitalized patients in Italy reports that HC Q results in a 30% reduction in mortality. Treatment started on the first day of admission in most cases. |
|
Positive
(news)
|
Late treatment study |
Iacoviello et al., upcoming study (News) (not included in the study count) |
INTERVIEW EXCLUSIVE : Efficacité de l'hydroxych loroquine confirmée sur 3451 patients italiens. Réduction de la mortalité de 30% |
Upcoming study of 3,451 hospitalized patients in Italy reports that HC Q results in a 30% reduction in mortality. Treatment started on the first day of admission in most cases.
Currently no formal study is available so this is not included in the study count.
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Inconc.
|
Late |
Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint) |
Clearing the fog: Is HC Q effective in reducing COVID-19 progression: A randomized controlled trial |
Study of 349 low-risk hospitalized
patients with 151 non-consenting or ineligible patients used as
controls. SOC included zinc, vitamin C and vitamin D. A statistically
significant improvement in PCR negativity is shown at day 7 with HC
|
|
Inconc.
|
Late treatment study |
Kamran et al., medRxiv, doi:10.1101/2020.07.30.20165365 (Preprint) |
Clearing the fog: Is HC Q effective in reducing COVID-19 progression: A randomized controlled trial |
Study of 349 low-risk hospitalized
patients with 151 non-consenting or ineligible patients used as
controls. SOC included zinc, vitamin C and vitamin D. A statistically
significant improvement in PCR negativity is shown at day 7 with HC Q treatment, 52.1% (HC Q)
versus 35.7% (control), p=0.001, but no statistically significant
difference at day 14, or in progression. Patients were relatively young
and there was no mortality. Only 3% of patients had any disease
progression and all patients recovered, so there is little if any room
for treatment benefit. Progression among higher-risk patients with
comorbidities was lower with treatment (12.9% versus 28.6%, p=0.3, very
few cases).Despite the title, this is not an
RCT since patients self-selected the arm, or were chosen based on
allergies/contraindications. The treatment group had about twice the
number of patients with comorbidities. Treatment delay is unknown - it
was recorded but not reported in the paper.Viral
load was not measured. As with other studies, PCR may detect
non-replicable viral nucleic acid, this is more likely at day 14.
Details on the test accuracy are not provided, authors note that RT-PCR
sensitivity ranges from 34-80%.
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Positive
|
Late |
Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 (Peer Reviewed) |
Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time |
Retrospective of 132 hospitalized patients. HC Q+AZ
significantly reduces death/ICU, HR=0.45, p=0.04. Adjusted for Charlson
Comorbidity Index (including age), obesity, O2, lymphocyte count, and
treatments. Mean delay.. |
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Positive
|
Late treatment study |
Davido et al., Int. J. Antimicrobial Agents, 2020, doi:10.1016/j.ijantimicag.2020.106129 (Peer Reviewed) |
Impact of medical care including anti-infective agents use on the prognosis of COVID-19 hospitalized patients over time |
Retrospective of 132 hospitalized patients. HC Q+AZ
significantly reduces death/ICU, HR=0.45, p=0.04. Adjusted for Charlson
Comorbidity Index (including age), obesity, O2, lymphocyte count, and
treatments. Mean delay from admission to treatment 0.7 days.
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|
In Vitro
|
In Vitro |
Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count) |
A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Ch loroquine Activity |
In vitro study presenting a new theory on SARS-CoV-2 infection and why HC Q/C Q provides benefits, which potentially explains the observed relationships with smoking, diabetes, obesity, age, and.. |
|
In Vitro
|
In Vitro |
Sheaff, R., bioRxiv, doi:10.1101/2020.08.02.232892 (Preprint) (In Vitro) (not included in the study count) |
A New Model of SARS-CoV-2 Infection Based on (Hydroxy)Ch loroquine Activity |
In vitro study presenting a new theory on SARS-CoV-2 infection and why HC Q/C Q
provides benefits, which potentially explains the observed
relationships with smoking, diabetes, obesity, age, and treatment delay,
and confirms the importance of accurate dosing. Metabolic analysis
revealed HC Q/C Q
inhibit oxidative phosphorylation in mitochondria (likely by
sequestering protons needed to drive ATP synthase), inhibiting infection
and/or slowing replication.
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Positive
|
Late |
D'Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter) |
Effectiveness of Hydroxych loroquine in COVID-19 disease: A done and dusted situation? |
HC Q+AZ
adjusted death HR 0.44, p=0.009. Propensity scores include baseline
COVID-19 disease severity, age, gender, number of comorbidities,
cardio-vascular disease, duration of symptoms, date of admission,
baseline .. |
|
Positive
|
Late treatment study |
D'Arminio Monforte et al., Int. J. Infectious Diseases, doi:10.1016/j.ijid.2020.07.056 (Letter) |
Effectiveness of Hydroxych loroquine in COVID-19 disease: A done and dusted situation? |
HC Q+AZ
adjusted death HR 0.44, p=0.009. Propensity scores include baseline
COVID-19 disease severity, age, gender, number of comorbidities,
cardio-vascular disease, duration of symptoms, date of admission,
baseline plasma CRP. IPW censoring. Retrospective study of 539 COVID-19
hospitalized patients in Milan, with treatment a median of 1 day after
admission. HC Q 197 patients, HC Q+AZ
94, control 92. Control group received various other treatments.
Authors excluded people receiving other drugs which could have biased
the effect of HC Q when used in combination.
Residual confounding is possible (e.g., people with CVD were more
frequent in control), however people in the control group were more
likely to require mechanical ventilation.
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|
Inconc.
|
PEP |
Mitjà et al., medRxiv, doi:10.1101/2020.07.20.20157651 (Preprint) |
A Cluster-Randomized Trial of Hydroxych loroquine as Prevention of Covid-19 Transmission and Disease |
Death rate reduced from 0.6% to
0.4%, RR 0.68, not statistically significant due to low incidence (8
control cases, 5 treatment cases).
For positive symptomatic cases, a greater effect is seen for nursing
home residents, RR=0.49 [0.21 - .. |
|
Inconc.
|
Post Exposure Prophylaxis study |
Mitjà et al., medRxiv, doi:10.1101/2020.07.20.20157651 (Preprint) |
A Cluster-Randomized Trial of Hydroxych loroquine as Prevention of Covid-19 Transmission and Disease |
Death rate reduced from 0.6% to
0.4%, RR 0.68, not statistically significant due to low incidence (8
control cases, 5 treatment cases).For positive
symptomatic cases, a greater effect is seen for nursing home residents,
RR=0.49 [0.21 - 1.17], vs. overall 0.89, possibly because the exposure
events are identified faster in this context, versus home exposure where
testing of the source may be more delayed. The trial is too small for
significance here. If the trend continued this result would be
significant at p<0.05 after about 25% more patients were added.Enrollment
was up to 7 days after exposure, median 4 days. Treatment delay is
unclear. The exposure event timing is not detailed. It appears to be
based on the date of a positive test for a contact, which is likely to
be much later than the actual exposure time. 13.1% were already positive
at baseline, which is consistent with the actual exposure time being
significantly earlier. PCR testing has a very high false-negative rate
in early stages (e.g., 100% on day 1, 67% on day 4, and 20% on day 8
[1]), hence it is likely that a much higher percentage were infected at
an unknown time before enrollment. Medication administration is not
detailed. Sensitivity and specificity of the tests is not provided.Given
the delay identifying index cases, PCR test delay, and PCR false
negative rate at early stages, the treatment delay in general was very
long and could be over 2 weeks.The RR for
non-PCR positive at baseline is 0.74. Including the PCR-positive at
baseline patients reduced this to 0.89. This is also consistent with
earlier treatment being more effective.The
paper does not mention zinc. Zinc deficiency in Spain has been reported
at 83% [2], this may significantly reduce effectiveness. HC Q
is a zinc ionophore which increases cellular uptake, facilitating
significant intracellular concentrations of zinc, and zinc is known to
inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely
thought to be important for effectiveness with SARS-CoV-2 [3].This
study focuses on the existence of symptoms or PCR-positive results,
however severity of symptoms is more important. Research has shown HC Q
concentrations can be much higher in the lung compared to plasma [4],
which may help minimize the occurrence of severe cases and death.There
is a treatment-delay response relationship consistent with an effective
treatment, however the authors only provide 3 ranges and do not break
down the earliest treatment delay times.The
definition of COVID-19 symptoms is very broad - just existence of a
headache alone or muscle pain alone was considered COVID-19. There was
an overall very low incidence of confirmed COVID-19 (138 cases across
both arms). There were no serious adverse events that were adjudicated
as being treatment related. Authors exclude those with symptoms in the
previous two weeks, however, those with symptoms up to several months
before may still test PCR-positive even though there may be no viable
virus.There appears to be incorrect data.
Table 2, secondary outcomes, control, hospital/vital records shows that 8
of 1042 is 9.7% (we get 0.8%).Nasopharyngeal viral load analysis issues include test unreliability and temporo-spatial differences in viral shedding [5].In
summary, this study appears positive in the context of very delayed
treatment and very small sample sizes, however we have classified it as
inconclusive for now pending further analysis and feedback. Preliminary
analysis. Supplementary Appendix is not currently available. Please
submit any corrections or comments.
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Positive
|
PrEP |
Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint) |
Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital |
Study of hospital health care workers showing HC Q
prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94
positive health care workers with a matched sample of 87 testing
negative. Full course prophylaxis wa.. |
|
Positive
|
Pre-Exposure Prophylaxis study |
Khurana et al., medRxiv, doi:10.1101/2020.07.21.20159301 (Preprint) |
Prevalence and clinical correlates of COVID-19 outbreak among healthcare workers in a tertiary level hospital |
Study of hospital health care workers showing HC Q
prophylaxis reduces COVID-19 significantly, OR 0.30, p=0.02. 94
positive health care workers with a matched sample of 87 testing
negative. Full course prophylaxis was important in this study which used
a low dose of 400mg/week HC Q (800mg for week 1), so it may take longer to reach therapeutic levels. Actual benefit of HC Q may be larger because severity of symptoms are not considered here but HC Q may also reduce severity.
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Negative
|
Late |
Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa201901 (Peer Reviewed) |
Hydroxych loroquine with or without Azithromycin in Mild-to-Moderate Covid-19 |
Late stage RCT of 667 hospitalized
patients with up to 14 days of symptoms at enrollment and receiving up
to 4 liters per minute supplemental oxygen, not finding a significant
effect after 15 days.
Authors note: "the trial cannot de.. |
|
Negative
|
Late treatment study |
Cavalcanti et al., NEJM, July 23, 2020, doi:10.1056/NEJMoa201901 (Peer Reviewed) |
Hydroxych loroquine with or without Azithromycin in Mild-to-Moderate Covid-19 |
Late stage RCT of 667 hospitalized
patients with up to 14 days of symptoms at enrollment and receiving up
to 4 liters per minute supplemental oxygen, not finding a significant
effect after 15 days.Authors note: "the trial
cannot definitively rule out either a substantial benefit of the trial
drugs or a substantial harm", sample sizes are too small.The
paper uses the terms mild and moderate, however all patients had
serious enough disease to be hospitalized, and 14% were actually
randomized in the ICU.The trial had
significant protocol deviations and unusually low medication adherence.
Randomization resulted in 64.3% male patients (HC Q) vs. 54.2% (control) which may significantly affect results due to the much higher risk for male patients.Authors
note: "our aim was to exclude patients already receiving longer and
potentially therapeutic doses of the study treatments" in explanation
for why the study protocol was changed to exclude patients with previous
use of the medications >24hrs. Analyzing these patients rather than
excluding them may have revealed effectiveness with early use as shown
in other studies.The trial initially required
enrollment within 48 hours of admission and was changed to remove this
requirement, this change is likely to reduce effectiveness because
enrollment was moved later, compared to the time the disease became
serious enough for hospitalization.
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In Vitro
|
In Vitro |
Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count) |
Ch loroquine does not inhibit infection of human lung cells with SARS-CoV-2 |
The title of this paper does not appear to match the results. Fig. 1b @100uM shows C Q
results in a ~4.5 fold decrease (on a linear scale) in extracellular
virus, p=0.05, after 24 hours (we do not see the supplementa.. |
|
In Vitro
|
In Vitro |
Hoffmann et al., Nature, (2020), doi:10.1038/s41586-020-2575-3 (Peer Reviewed) (In Vitro) (not included in the study count) |
Ch loroquine does not inhibit infection of human lung cells with SARS-CoV-2 |
The title of this paper does not appear to match the results. Fig. 1b @100uM shows C Q
results in a ~4.5 fold decrease (on a linear scale) in extracellular
virus, p=0.05, after 24 hours (we do not see the supplementary data at
this time so this is estimated from the graph). This decrease may
continue if examined over longer time periods. Fig. 1a shows a ~45-50%
entry inhibition @100uM for HC Q/C Q (p=0.0005/0.0045), ~10-30% @10uM (p=0.13/0.99). Inhibition is significantly better with Vero cells.In vitro study of C Q and HC Q inhibition of SARS-CoV-2 into Vero (kidney), Vero-TMPRSS2, and Calu-3 (derived from human lung carcinoma) cells.Although there are several theories on how HC Q may help with COVID-19, authors do not consider the most common theory where HC Q
functions as a zinc ionophore, facilitating significant intracellular
concentrations of zinc. Zinc is known to inhibit SARS-CoV RNA-dependent
RNA polymerase activity, and is widely thought to be important for
effectiveness with SARS-CoV-2 [1].Calu-3 is
one of many cell lines derived from human lung carcinomas [2]. Calu-3
cells resemble serous gland cells. They do not express 15-lipoxygenase,
an enzyme specifically localized to the surface epithelium, but they do
express secretory component, secretory leukocyte protease inhibitor,
lysozyme, and lactoferrin, all markers of serous gland cells. [3] note
that the absence of systemic inflammation, circulatory factors, and
other paracrine systemic influences is a potential limitation of the
isolated cell system.RT-PCR is used, we note that nucleic acid may persist even after the virus is no longer viable [4].It is unclear how the authors conclude "C Q
does not block SARS-CoV-2 infection of Calu-3" cells, when the results
show statistically significant inhibition at higher concentrations.Further,
it is unclear how the authors go from these results in one specific
type of pulmonary adenocarcinoma cells that resemble serous gland cells,
in vitro, into the title of the paper which claims no inhibition in lung cells.Further, it is unclear how another leap is made to "will not be effective against COVID-19" given the multiple theories of HC Q/C Q effectiveness.
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Positive
|
Late |
Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960 (Preprint) |
Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid |
HC Q HR
0.83 [0.77-0.89] based on propensity score matched retrospective
analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88],
14 other medications showed either no signicant benefit or a negative
.. |
|
Positive
|
Late treatment study |
Bernaola et al., medRxiv, doi:10.1101/2020.07.17.20155960 (Preprint) |
Observational Study of the Efficiency of Treatments in Patients Hospitalized with Covid-19 in Madrid |
HC Q HR
0.83 [0.77-0.89] based on propensity score matched retrospective
analysis of 1,645 hospitalized patients. Prednisone HR 0.85 [0.82-0.88],
14 other medications showed either no signicant benefit or a negative
effect.
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|
Meta
(positive)
|
Early |
Risch, H., American
Journal of Epidemiology, July 20, 2020, doi:10.1093/aje/kwaa152 (Peer
Reviewed) (meta analysis - not included in the study count) |
Response to: “Early Outpatient Treatment of
Symptomatic, High-Risk Covid-19 Patients” and “Re: Early Outpatient
Treatment of Symptomatic, High-Risk Covid-19 Patients that Should be
Ramped-Up Immediately as Key to the Pandemic Crisis” |
Updated meta analysis including 7
new studies of high-risk outpatients, for a total of 12 studies, all
showing significant benefit. |
|
Meta
(positive)
|
Early treatment study |
Risch, H.,
American Journal of Epidemiology, July 20, 2020,
doi:10.1093/aje/kwaa152 (Peer Reviewed) (meta analysis - not included in
the study count) |
Response to: “Early Outpatient
Treatment of Symptomatic, High-Risk Covid-19 Patients” and “Re: Early
Outpatient Treatment of Symptomatic, High-Risk Covid-19 Patients that
Should be Ramped-Up Immediately as Key to the Pandemic Crisis” |
Updated meta analysis including 7
new studies of high-risk outpatients, for a total of 12 studies, all
showing significant benefit.
Meta studies are not included in the percentages or study count.
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Meta
(positive)
|
PEP |
Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in the study count) |
Efficacy of Hydroxych loroquine as Prophylaxis for Covid-19 |
Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HC Q is effective when used early, p<0.01.
The effectiveness found is especially notable considering the limitatio.. |
|
Meta
(positive)
|
Post Exposure Prophylaxis study |
Watanabe, M., arXiv.org, arXiv:2007.09477 (Preprint) (meta analysis - not included in the study count) |
Efficacy of Hydroxych loroquine as Prophylaxis for Covid-19 |
Secondary analysis of Boulware et al.'s PEP trial and treatment delay-response data, confirming that HC Q is effective when used early, p<0.01.The
effectiveness found is especially notable considering the limitations
of the study. Treatment was relatively late, with enrollment up to
4 days after exposure, and an unspecified shipping delay. While the
paper does not provide shipping details, the study protocol gives some
detail allowing us to estimate the treatment delay as ~70 to 140 hours
after exposure on average for the 1-4 days since enrollment specified in
the paper (we will update this when authors respond to our request for
details). There was only 75% medication adherence, including 16% who did
not take the medication at all. The study relies on Internet surveys.
Meta studies are not included in the percentages or study count.
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Positive
|
Early |
Hong et al., Infect. Chemother., 2020, 52:e43 (Peer Reviewed) |
Early Hydroxych loroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication |
HC Q 1-4
days from diagnosis was the only protective factor against prolonged
viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4
days delay vs. 22.9% for 5+ days delayed treatment. Authors report.. |
|
Positive
|
Early treatment study |
Hong et al., Infect. Chemother., 2020, 52:e43 (Peer Reviewed) |
Early Hydroxych loroquine Administration for Rapid Severe Acute Respiratory Syndrome Coronavirus 2 Eradication |
HC Q 1-4
days from diagnosis was the only protective factor against prolonged
viral shedding found, OR 0.111, p=0.001. 57.1% viral clearance with 1-4
days delay vs. 22.9% for 5+ days delayed treatment. Authors report that
early administration of HC Q significantly ameliorates inflammatory cytokine secretion and that COVID-19 patients should be administrated HC Q as soon as possible. 42 patients with HC Q 1-4 days from diagnosis, 48 with HC Q 5+ days from diagnosis.
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|
Inconc.
|
Early |
Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed) |
Hydroxych loroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial |
~70 to 140 hour (inc. shipping) delayed outpatient treatment with HC Q reduced combined hospitalization/death by 50%, p=0.29 (5 HC Q cases, 10 control cases), and reduced hospitalization by 60%,.. |
|
Inconc.
|
Early treatment study |
Skipper et al., Annals of Internal Medicine, doi:10.7326/M20-4207 (Peer Reviewed) |
Hydroxych loroquine in Nonhospitalized Adults With Early COVID-19: A Randomized Trial |
~70 to 140 hour (inc. shipping) delayed outpatient treatment with HC Q reduced combined hospitalization/death by 50%, p=0.29 (5 HC Q
cases, 10 control cases), and reduced hospitalization by 60%, p=0.17.
There was one hospitalized control death and one non-hospitalized HC Q
death. It is unclear why there was a non-hospitalized death, external
factors such as lack of standard care may be involved. Excluding that
case results in one control death and zero HC Q
deaths (not statistically significant but noted as reducing mortality is
the most important outcome). Details for the hospitalizations and
deaths such as medication adherence and treatment delay may be
informative but are not provided.The paper
states the end point was changed from hospitalization/death to symptom
severity because they would have required 6,000 participants. However,
if the observed trend continued, they would hit 95% significance on the
reduction in hospitalization at ~725 patients, and 95% on the reduction
in combined hospitalization/death at ~1,145 patients, which is a lot
less than 6,000, and also less than the original plan of 1,242 patients.
We hope the trial can be continued for statistical significance.Treatment
is relatively late, ~70 to 140 hours after symptoms, including the
shipping delay. The paper does not mention the shipping delay but
partial details are provided in the study protocol. They are not clear
but indicate no shipping on the weekends and a possible 12pm cutoff for
same day dispensing and mailing. Assuming that enrollments were evenly
distributed between 6am and 12am each day, we get an average of ~46
hours shipping delay. We have asked for shipping details and will update
with more accurate values when available. In any case the treatment
delay is quite long and there is no overlap with the more typical delays
used such as 0 - 36 hours for oseltamivir.The paper compares 0 - 36 hour delayed treatment with oseltamivir (influenza) and ~70 to 140 hour delayed treatment with HC Q
(COVID-19), noting that oseltamivir seemed more effective. However, a
more comparable study is McLean (2015) who showed that 48 - 119 hour
delayed treatment with oseltamivir has no effect. This suggests that HC Q is more effective than oseltamivir, and that HC Q may still have significant effect for some amount of delay beyond the delay where oseltamivir is effective.6
people were included that enrolled with >4d symptoms, although they
do not match the study inclusion criteria. This reduces observed
effectiveness. The paper says 56% (236) were enrolled within 1 day of
symptoms, but results show only 40% for "<1d", 56% is possibly for
<48hrs, we have asked for clarification.Patients
in this study are relatively young and most of them recover without
assistance. This reduces the room for a treatment to make improvements.
The maximum improvement of an effective treatment would be expected
before all patients approach recovery, as shown in the figure below.
Authors focus on the end result where most have recovered, but it is
more informative to examine the curve and the point of maximum
effectiveness. Authors did not collect data for every day but they do
have interim results for days 3, 5, 10. The results are consistent with
an effective treatment and show a statistically significant improvement,
p = 0.05, at day 10 (other unreported days might show increased
effectiveness).Results also show a larger
treatment effect for those >50, not statistically significant due to
the small sample, but noted as COVID-19 risk dramatically increases with
age. The effect may be more visible here because younger patients may
on average have more mild cases with less room for improvement. In
general patients in this study have relatively mild symptoms on average,
limiting the chance to observe improvement.The
study relies on Internet surveys. Known fake surveys were submitted to
the similar PEP trial and there could be an unknown number of undetected
fake surveys in both trials. The study shows a high incidence of side
effects in the placebo arm, which could be in part due to fake entries
[1].The granularity change in the histograms
of Figure S4 raise concerns [2]. Data on increasing severity, less
affected by the lower bound where everyone has recovered, also supports
effectiveness [3].Research shows the placebo used in the US may be protective for COVID-19 [4] so the true effectiveness of HC Q could be higher than observed.Treatment
delay reporting has changed from the companion PEP trial which reported
results for enrollment delays 1, 2, 3, and 4 separately (and from which
we can confirm a statistically significant delay-response
relationship), while this trial combines 1-2 and 3-4, and adds <1.
Since the two trials share reporting (some patients were moved between
trials) it's not clear how the new category was added.RCT
of 423 patients with Internet surveys. Medication adherence was only
77% so the true effect of treatment is likely higher. Analysis of
primarily low risk patients, authors note the results are not
generalizable to the COVID high-risk population. We will update when
hearing back on questions asked.In summary, we believe the results of this study are positive for HC Q
being an effective treatment, however we have classified this study as
inconclusive for now pending feedback and further analysis.
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Inconc.
|
Early |
Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed) |
Hydroxych loroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial |
This paper has inconsistent data -
some of the values reported in Table 2 and the abstract correspond to 12
control hospitalizations, while others correspond to 11 control
hospitalizations.
There was a 25% reduction in hospitalization an.. |
|
Inconc.
|
Early treatment study |
Mitjà et al., Clinical Infectious Diseases, ciaa1009, doi:10.1093/cid/ciaa1009 (Peer Reviewed) |
Hydroxych loroquine for Early Treatment of Adults with Mild Covid-19: A Randomized-Controlled Trial |
This paper has inconsistent data -
some of the values reported in Table 2 and the abstract correspond to
12 control hospitalizations, while others correspond to 11 control
hospitalizations.There was a 25% reduction in hospitalization and 16% reduction in the median time to symptom resolution for HC Q, without statistical significance due to small samples.Treatment
delay is unknown at this time. They report a delay of up to 120 hours
after symptoms plus an additional unspecified delay where medication was
provided to patients at the first home visit. We have asked for details
of the treatment delay and will update when hearing back. They do not
break down results by treatment delay.The
paper does not mention zinc. Zinc deficiency in Spain has been reported
at 83% [1], this may significantly reduce effectiveness. HC Q
is a zinc ionophore which increases cellular uptake, facilitating
significant intracellular concentrations of zinc, and zinc is known to
inhibit SARS-CoV RNA-dependent RNA polymerase activity, and is widely
thought to be important for effectiveness with SARS-CoV-2 [2].Undetectable
viral load was changed to 3 log10 copies/mL potentially masking
effectiveness. For viral load authors use nasopharyngeal swabs, we note
that viral activity in the lung may be especially important for
COVID-19, and that research has shown HC Q
concentrations can be much higher in the lung compared to plasma [3]. We
also note that viral detection by PCR does not equate to viable virus
[4]. Accuracy of the tests is not provided.Nasopharyngeal viral load analysis issues include test unreliability and temporo-spatial differences in viral shedding [5].293
low-risk patients with no deaths. No serious adverse events. We have
asked for more details on the treatment delay and viral load change and
will update when hearing back.
|
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|
Meta
(positive)
|
Early, Late |
Raoult et al., Preprint (Preprint) (meta analysis - not included in the study count) |
Hydroxych loroquine and
Azithromycin as a Treatment of COVID-19: Results of an Open-Label
Non-Randomized Clinical Trial: Response to David Spencer (Elsevier) |
Updated meta analysis showing
significant reductions in mortality and viral shedding. Mortality OR
0.53 [0.4-0.71] for clinical studies, 0.92 big data studies, 18,211
patients. Persistent viral shedding OR 0.47 [0.28-0.79], 4,540 patients. |
|
Meta
(positive)
|
Early, Late |
Raoult et al., Preprint (Preprint) (meta analysis - not included in the study count) |
Hydroxych loroquine
and Azithromycin as a Treatment of COVID-19: Results of an Open-Label
Non-Randomized Clinical Trial: Response to David Spencer (Elsevier) |
Updated meta analysis showing
significant reductions in mortality and viral shedding. Mortality OR
0.53 [0.4-0.71] for clinical studies, 0.92 big data studies, 18,211
patients. Persistent viral shedding OR 0.47 [0.28-0.79], 4,540 patients.
Meta studies are not included in the percentages or study count.
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|
Negative
|
Late |
An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint) |
Treatment Response to Hydroxych loroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea |
Retrospective of hospitalized patients with 31 HC Q
patients and 195 standard treatment patients, not showing a significant
difference in terms of viral clearance or recovery. There was no
mortality in either group.
.. |
|
Negative
|
Late treatment study |
An et al., medRxiv, doi:10.1101/2020.07.04.20146548 (Preprint) |
Treatment Response to Hydroxych loroquine and Antibiotics for mild to moderate COVID-19: a retrospective cohort study from South Korea |
Retrospective of hospitalized patients with 31 HC Q
patients and 195 standard treatment patients, not showing a significant
difference in terms of viral clearance or recovery. There was no
mortality in either group."It is notable that
HQ plus antibiotics group had worse baseline clinical profiles (i.e.
higher percentage of moderate severity patients, more patients with
fever >=37.5C, higher average body temperature) and prognostic
indicators such as age, LDH, lymphocyte count, and CRP". We
note that propensity score matching removed almost all of the male
patients in the control group (40% -> 5%) but increased the
percentage of male patients in the treatment group. This provides a
large advantage to the control group because there is a very large
difference in severity and mortality based on gender [1].In
terms of viral RNA clearance we note that other research has found that
"active viral replication drops quickly after the first week, and
viable virus was not found after the second week of illness despite the
persistence of PCR detection of RNA” [2].
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|
Positive
|
PrEP |
Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7 (Peer Reviewed) |
COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study |
Rheumatic disease patients on HC Q
had a lower risk of COVID-19 than those on other disease-modifying
anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for
age, sex, smoking, systemic lupus erythemat.. |
|
Positive
|
Pre-Exposure Prophylaxis study |
Zhong et al., Lancent Rheumatology, 10.1016/S2665-9913(20)30227-7 (Peer Reviewed) |
COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study |
Rheumatic disease patients on HC Q
had a lower risk of COVID-19 than those on other disease-modifying
anti-rheumatic drugs, OR 0.09 (0.01–0.94), p=0.044 after adjusting for
age, sex, smoking, systemic lupus erythematosus, infection in other
family members, and comorbidities. 43 patients with rheumatic disease
and COVID-19 exposure.
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|
Positive
|
Early |
Scholz et al., Preprints 2020, 2020070025, doi:10.20944/preprints202007.0025.v1 (Preprint) |
COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxych loroquine and Azithromycin: A Retrospective Case Series Study |
Early treatment with HC Q+AZ+Z
results in 84% lower hospitalization and 80% lower death -
hospitalization OR 0.16 (p<0.001), death OR 0.2 (p=0.16). No cardiac
side effects. Retrospective 518 patients (141 treated, 37.. |
|
Positive
|
Early treatment study |
Scholz et al., Preprints 2020, 2020070025, doi:10.20944/preprints202007.0025.v1 (Preprint) |
COVID-19 Outpatients – Early Risk-Stratified Treatment with Zinc Plus Low Dose Hydroxych loroquine and Azithromycin: A Retrospective Case Series Study |
Early treatment with HC Q+AZ+Z
results in 84% lower hospitalization and 80% lower death -
hospitalization OR 0.16 (p<0.001), death OR 0.2 (p=0.16). No cardiac
side effects. Retrospective 518 patients (141 treated, 377 control).
|
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|
Positive
|
Late |
Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed) |
Treatment with Hydroxych loroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19 |
HC Q decreases mortality from 26.4% to 13.5% (HC Q) or 20.1% (HC Q+AZ). Propensity matched HC Q HR 0.487, p=0.009. Michigan 2,541 patients retrospecti.. |
|
Positive
|
Late treatment study |
Arshad et al., Int. J. Infect. Dis., July 1 2020, doi:10.1016/j.ijid.2020.06.099 (Peer Reviewed) |
Treatment with Hydroxych loroquine, Azithromycin, and Combination in Patients Hospitalized with COVID-19 |
HC Q decreases mortality from 26.4% to 13.5% (HC Q) or 20.1% (HC Q+AZ). Propensity matched HC Q HR 0.487, p=0.009. Michigan 2,541 patients retrospective. Before propensity matching the HC Q
group average age is 5 years younger and the percentage of male
patients is 4% higher which is likely to favor the treatment and the
control respectively in the before-propensity matching results.Some
reported limtiations of this study are inaccurate [1]. Corticosteroids
were controlled for in the multivariate and propensity analyses as were
age and comorbidities including cardiac disease and severity of illness.
Age was an independent risk factor associated with mortality. HC Q
was independently associated with decreased mortality, distinct from
the steroid effect. 91% of all patients began treatment within two days
of admission. HC Q was used throughout the study period, limiting time bias. Patients assigned to HC Q group had moderate and severe illness at presentation, which would favor worse outcome with HC Q.
|
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|
Safety
|
N/A |
Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count) |
Incidence of arrhythmias and electrocardiographic
abnormalities in symptomatic pediatric patients with PCR positive
SARS-CoV-2 infection including drug induced changes in the corrected QT
interval (QTc) |
In pediatric patients with PCR
positive active COVID-19 infection, significant arrhythmias are
infrequent, but occur at an incidence higher than expected in a general
pediatric population. Comorbidities are not more common in patients
wit.. |
|
Safety
|
N/A |
Samuel et al., Heart Rhythm, doi:10.1016/j.hrthm.2020.06.033 (Peer Reviewed) (not included in the study count) |
Incidence of arrhythmias and
electrocardiographic abnormalities in symptomatic pediatric patients
with PCR positive SARS-CoV-2 infection including drug induced changes in
the corrected QT interval (QTc) |
In pediatric patients with PCR
positive active COVID-19 infection, significant arrhythmias are
infrequent, but occur at an incidence higher than expected in a general
pediatric population. Comorbidities are not more common in patients with
arrhythmias than in patients without arrhythmias. However, providers
still need to be vigilant for comorbidities that may independently place
patients at risk for arrhythmias. COVID-19 treatment using HC Q
leads to significant QTc prolongation, but was not associated with
arrhythmias in pediatric patients. The long term sequelae of arrhythmia
development in this population and their impact on outcome needs to be
studied.
|
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|
Positive
|
Late |
Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z (Peer Reviewed) |
Risk Factors for Mortality in Patients with COVID-19 in New York City |
HC Q
decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not
significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients
in New York City. |
|
Positive
|
Late treatment study |
Mikami et al., J. Gen. Intern. Med., doi:10.1007/s11606-020-05983-z (Peer Reviewed) |
Risk Factors for Mortality in Patients with COVID-19 in New York City |
HC Q
decreases mortality, HR 0.53 (CI 0.41–0.67). IPTW adjustment does not
significantly change HR 0.53 (0.41-0.68). Retrospective 6,000 patients
in New York City.
|
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|
Positive
|
PrEP |
Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed) |
Chronic treatment with hydroxych loroquine and SARS-CoV-2 infection |
Chronic treatment with HC Q
provides protection against COVID, odds ratio 0.51 (0.37-0.70). Note
that patients with SLE, RA, and other autoimmune conditions have a
significantly increased susceptibility to and incide.. |
|
Positive
|
Pre-Exposure Prophylaxis study |
Ferreira et al., J. Medical Virology, July 9, 2020, doi:10.1002/jmv.26286 (preprint 6/29) (Peer Reviewed) |
Chronic treatment with hydroxych loroquine and SARS-CoV-2 infection |
Chronic treatment with HC Q
provides protection against COVID, odds ratio 0.51 (0.37-0.70). Note
that patients with SLE, RA, and other autoimmune conditions have a
significantly increased susceptibility to and incidence of infections,
so the actual benefit may be significantly higher [1, 2, 3, 4, 5, 6, 7].
|
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|
Safety
|
N/A |
Mfeukeu-Kuate et al. (Preprint) (not included in the study count) |
Electrocardiographic safety of daily Hydroxych loroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon |
No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HC Q+AZ. 51 relatively young patients 39 +/- 11. |
|
Safety
|
N/A |
Mfeukeu-Kuate et al. (Preprint) (not included in the study count) |
Electrocardiographic safety of daily Hydroxych loroquine 400mg plus Azithromycin 250mg as an ambulatory treatment for COVID-19 patients in Cameroon |
No life-threatening modifications of the QT interval was observed in non-severe COVID-19 patients treated ambulatory with HC Q+AZ. 51 relatively young patients 39 +/- 11.
|
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|
Positive
|
Early |
Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed) |
Outcomes of 3,737 COVID-19 patients treated with hydroxych loroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis |
Early treatment leads to
significantly better clinical outcome and faster viral load reduction.
Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737
patients. |
|
Positive
|
Early treatment study |
Lagier et al., Travel Med. Infect. Dis. 101791, Jun 25, 2020, doi:10.1016/j.tmaid.2020.101791 (Peer Reviewed) |
Outcomes of 3,737 COVID-19 patients treated with hydroxych loroquine/azithromycin and other regimens in Marseille, France: A retrospective analysis |
Early treatment leads to
significantly better clinical outcome and faster viral load reduction.
Matched sample mortality HR 0.41 p-value 0.048. Retrospective 3,737
patients.
|
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|
|
In Vitro
|
In Vitro |
Wang et al., bioRxiv, doi:10.1101/2020.06.22.164665 (Preprint) (In Vitro) (not included in the study count) |
Ch loroquine and hydroxych loroquine as ACE2 blockers to inhibit viropexis of COVID-19 Spike pseudotype virus |
In vitro study, not included in the study count or percentages. C Q and HC Q inhibit the entry of COVID-19 spike pseudotype virus using ACE2 high expressed HEK293T cells. |
|
In Vitro
|
In Vitro |
Wang et al., bioRxiv, doi:10.1101/2020.06.22.164665 (Preprint) (In Vitro) (not included in the study count) |
Ch loroquine and hydroxych loroquine as ACE2 blockers to inhibit viropexis of COVID-19 Spike pseudotype virus |
In vitro study, not included in the study count or percentages. C Q and HC Q inhibit the entry of COVID-19 spike pseudotype virus using ACE2 high expressed HEK293T cells.
|
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|
|
Positive
|
Early |
Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint) |
Efficacy and safety of ch loroquine or hydroxych loroquine in moderate type of COVID-19: a prospective open-label randomized controlled study |
Significantly faster clinical recovery and shorter time to RNA negative (from 7.0 days to 2.0 days (HC Q), p=0.01. 67 patients with mild/moderate cases. |
|
Positive
|
Early treatment study |
Chen et al., medRxiv, doi:10.1101/2020.06.19.20136093 (Preprint) |
Efficacy and safety of ch loroquine or hydroxych loroquine in moderate type of COVID-19: a prospective open-label randomized controlled study |
Significantly faster clinical recovery and shorter time to RNA negative (from 7.0 days to 2.0 days (HC Q), p=0.01. 67 patients with mild/moderate cases.
|
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|
Positive
(news)
|
PrEP |
SMSH Sawai Man Singh Hospital, India (News) (not included in the study count) |
HC Q beneficial as preventive drug: SMS doctors told ICMR |
PrEP with 4,300 very high risk
healthcare workers in a hospital with up to 500+ COVID patients at a
time, only 1% cases, all recovered. |
|
Positive
(news)
|
Pre-Exposure Prophylaxis study |
SMSH Sawai Man Singh Hospital, India (News) (not included in the study count) |
HC Q beneficial as preventive drug: SMS doctors told ICMR |
PrEP with 4,300 very high risk
healthcare workers in a hospital with up to 500+ COVID patients at a
time, only 1% cases, all recovered.
Currently no formal study is available so this is not included in the
study count.
|
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|
Negative
(news)
|
Late |
NIH, study not available yet (News) (not included in the study count) |
NIH halts clinical trial of hydroxych loroquine |
NIH halts late stage trial reporting no harm and no benefit. 470 patients. |
|
Negative
(news)
|
Late treatment study |
NIH, study not available yet (News) (not included in the study count) |
NIH halts clinical trial of hydroxych loroquine |
NIH halts late stage trial reporting no harm and no benefit. 470 patients.
Currently no formal study is available so this is not included in the study count.
|
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|
|
Positive
|
Late |
Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint) |
Hydroxych loroquine with
or without azithromycin and in-hospital mortality or discharge in
patients hospitalized for COVID-19 infection: a cohort study of 4,642
in-patients in France |
Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HC Q and HC Q+AZ. No significant effect is seen on 28-day mortality, however many more control .. |
|
Positive
|
Late treatment study |
Sbidian et al., medRxiv, doi:10.1101/2020.06.16.20132597 (Preprint) |
Hydroxych loroquine
with or without azithromycin and in-hospital mortality or discharge in
patients hospitalized for COVID-19 infection: a cohort study of 4,642
in-patients in France |
Retrospective of 4,642 hospitalized patients in France showing significantly faster discharge with HC Q and HC Q+AZ.
No significant effect is seen on 28-day mortality, however many more
control patients are still in hospital at 28 days suggesting there will
be a significant improvement when extending past 28 days. Note that the
median age is higher in the group not treated with HC Q
or AZ. For other issues with the adjustments see [1]. Also see the
analysis here [2]. We received feedback from one person that thinks the
trial should be considered negative because the control patients still
in hospital should be disregarded. However, based on other studies, it
seems very likely that a significant number of deaths in the control
group occurred past 28 days whereas no treated patients remained in
hospital. This should be simple for the authors to resolve by extending
the analysis. Even if we ignore this, it still shows significantly
faster discharge for treatment, so we do not see how we can consider it
negative. We note that the substantial reduction in hospital time is a
very large cost reduction and may lower mortality in general by reducing
the chance of exceeding maximum capacity. Additional feedback is
welcome.
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|
|
Inconc.
|
Late |
Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed) |
Compassionate use of hydroxych loroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital |
Retrospective of 89 hospitalized
patients, survival HR 0.89 [0.23-3.47], not statistically significant.
Authors note that unmeasured confounders may have persisted and the
study may be underpowered. |
|
Inconc.
|
Late treatment study |
Paccoud et al., Clinical Infectious Diseases, doi:10.1093/cid/ciaa791 (Peer Reviewed) |
Compassionate use of hydroxych loroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital |
Retrospective of 89 hospitalized
patients, survival HR 0.89 [0.23-3.47], not statistically significant.
Authors note that unmeasured confounders may have persisted and the
study may be underpowered.
|
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|
Positive
|
Late |
Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 (Peer Reviewed) |
Hydroxych loroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China |
30 hospitalized patients. Early use of HC Q
is more effective, 43% reduction in progression from moderate to
severe. "Early" is relative here, within 7 days of hospitalization. |
|
Positive
|
Late treatment study |
Xue et al., J. Med. Virology, June 17, 2020, doi:10.1002/jmv.26193 (Peer Reviewed) |
Hydroxych loroquine treatment in COVID-19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China |
30 hospitalized patients. Early use of HC Q
is more effective, 43% reduction in progression from moderate to
severe. "Early" is relative here, within 7 days of hospitalization.
|
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|
|
Negative
(news)
|
Late |
World Health Organization, study not available yet (News) (not included in the study count) |
“Solidarity” clinical trial for COVID-19 treatments |
WHO stopped the Solidarity late stage trial of HC Q
reporting no benefit. Later news reported "little or no reduction in
mortality" [1]. The study has not been released yet and few details are
available. Th.. |
|
Negative
(news)
|
Late treatment study |
World Health Organization, study not available yet (News) (not included in the study count) |
“Solidarity” clinical trial for COVID-19 treatments |
WHO stopped the Solidarity late stage trial of HC Q
reporting no benefit. Later news reported "little or no reduction in
mortality" [1]. The study has not been released yet and few details are
available. This trial used an extremely high dose which may be related
to the relatively poor results [2].
Currently no formal study is available so this is not included in the
study count.
|
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|
|
Positive
(news)
|
PrEP |
WHIP COVID-19 (News) (not included in the study count) |
Henry Ford Health System still moving forward with hydroxych loroquine study |
Ongoing WHIP COVID-19 HC Q
PrEP study reports analyzing their data and seeing a significantly
improved outcome in a group of COVID-19 patients who received HC Q. For more details on the study se.. |
|
Positive
(news)
|
Pre-Exposure Prophylaxis study |
WHIP COVID-19 (News) (not included in the study count) |
Henry Ford Health System still moving forward with hydroxych loroquine study |
Ongoing WHIP COVID-19 HC Q
PrEP study reports analyzing their data and seeing a significantly
improved outcome in a group of COVID-19 patients who received HC Q. For more details on the study see [1].
Currently no formal study is available so this is not included in the study count.
|
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|
Theory
|
Theory |
Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count) |
Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxych loroquine-Azithromycin Combination in COVID-19 Therapy |
Theory paper, not included in the
study count or percentages. Proposes a new mechanism supporting the
synergistic interaction between HC Q+AZ. |
|
Theory
|
Theory |
Scherrmann, AAPS J 22, 86 (2020), doi:10.1208/s12248-020-00465-w (Peer Reviewed) (Theory) (not included in the study count) |
Intracellular ABCB1 as a Possible Mechanism to Explain the Synergistic Effect of Hydroxych loroquine-Azithromycin Combination in COVID-19 Therapy |
Theory paper, not included in the
study count or percentages. Proposes a new mechanism supporting the
synergistic interaction between HC Q+AZ.
|
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|
|
Negative
|
Late |
Giacomelli et al., medRxiv, doi:10.1101/2020.06.05.20123299 (Preprint) |
Early administration of lopinavir/ritonavir plus hydroxych loroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study |
Late stage study of hospitalized
patients comparing treatment starting within 5 days versus later. Note
that "early" here is only relative - all patients are hospitalized so
this is "late" and "very late". Th.. |
|
Negative
|
Late treatment study |
Giacomelli et al., medRxiv, doi:10.1101/2020.06.05.20123299 (Preprint) |
Early administration of lopinavir/ritonavir plus hydroxych loroquine does not alter the clinical course of SARS-CoV-2 infection: a retrospective cohort study |
Late stage study of hospitalized
patients comparing treatment starting within 5 days versus later. Note
that "early" here is only relative - all patients are hospitalized so
this is "late" and "very late". The "early" treatment group is
significantly older. Severe adverse events attributed by authors to
concurrent administration of LPV, making it difficult to make
conclusions about HC Q.
|
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|
|
Positive
|
Early |
Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint) |
A short therapeutic regimen based on hydroxych loroquine
plus azithromycin for the treatment of COVID-19 in patients with
non-severe disease. A strategy associated with a reduction in hospital
admissions and complications. |
80 moderate cases, HC Q+AZ
appears to reduce serious complications and death. Moderate treated
cases resulted in hospitalization at the same rate as mild untreated
cases suggesting efficacy. |
|
Positive
|
Early treatment study |
Otea et al., medRxiv, doi:10.1101/2020.06.10.20101105 (Preprint) |
A short therapeutic regimen based on hydroxych loroquine
plus azithromycin for the treatment of COVID-19 in patients with
non-severe disease. A strategy associated with a reduction in hospital
admissions and complications. |
80 moderate cases, HC Q+AZ
appears to reduce serious complications and death. Moderate treated
cases resulted in hospitalization at the same rate as mild untreated
cases suggesting efficacy.
|
Source
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|
|
Positive
|
Late |
Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed) |
Beneficial effect of Hydroxych loroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an observational study |
68 very high risk nursing home residents, median age 86, HC Q+AZ
early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7
died, significantly less than other nursing homes in France and the same
as the med.. |
|
Positive
|
Late treatment study |
Pirnay et al., Hosp. Pharm. and Clinician, doi:10.1016/j.phclin.2020.06.001 (Peer Reviewed) |
Beneficial effect of Hydroxych loroquine-Azithromycin combination in the treatment of elderly patients with Covid-19: results of an observational study |
68 very high risk nursing home residents, median age 86, HC Q+AZ
early treatment within 2.5 days onset, 2 stopped due to QTc. Only 7
died, significantly less than other nursing homes in France and the same
as the median death for the same period in 2019/2018.
|
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|
Positive
|
PrEP |
Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint) |
Pre exposure Hydroxych loroquine use is associated with reduced COVID19 risk in healthcare workers |
HC Q reduced cases from 38% to 7%. 106 people. No serious adverse effects. |
|
Positive
|
Pre-Exposure Prophylaxis study |
Bhattacharya et al., medRxix, doi:10.1101/2020.06.09.20116806 (Preprint) |
Pre exposure Hydroxych loroquine use is associated with reduced COVID19 risk in healthcare workers |
HC Q reduced cases from 38% to 7%. 106 people. No serious adverse effects.
|
Source
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|
|
Meta
(positive)
|
Early, Late |
Million et al., New
Microbes and New Infections, doi:10.1016/j.nmni.2020.100709 (Peer
Reviewed) (meta analysis - not included in the study count) |
Clinical Efficacy of Ch loroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world |
[H]C Q effective and reduces mortality by a factor 3. Meta analysis of 20 studies. |
|
Meta
(positive)
|
Early, Late |
Million et
al., New Microbes and New Infections, doi:10.1016/j.nmni.2020.100709
(Peer Reviewed) (meta analysis - not included in the study count) |
Clinical Efficacy of Ch loroquine derivatives in COVID-19 Infection: Comparative metaanalysis between the Big data and the real world |
[H]C Q effective and reduces mortality by a factor 3. Meta analysis of 20 studies.
Meta studies are not included in the percentages or study count.
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Negative
|
Late |
Horby et al., medRxiv, 7/15/2020, doi:10.1101/2020.07.15.20151852 (press release 6/5) (Preprint) |
Effect of Hydroxych loroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial |
RECOVERY trial reports no
significant benefit seen for very late stage very sick patients. Results
may be due to the unusually high dosage used [1, 2]. Patients were
extremely sick (average of 9 days post symptoms, 60% requiring oxygen
an.. |
|
Negative
|
Late treatment study |
Horby et al., medRxiv, 7/15/2020, doi:10.1101/2020.07.15.20151852 (press release 6/5) (Preprint) |
Effect of Hydroxych loroquine in Hospitalized Patients with COVID-19: Preliminary results from a multi-centre, randomized, controlled trial |
RECOVERY trial reports no
significant benefit seen for very late stage very sick patients. Results
may be due to the unusually high dosage used [1, 2]. Patients were
extremely sick (average of 9 days post symptoms, 60% requiring oxygen
and an additional 17% requiring ventilation/ECMO), and unusually high
death rate was seen in both arms. 1,561 HC Q patients, 3,155 SOC.A
secondary analysis has found several inconsistencies in the data [3],
and found evidence of excess mortaliy within the first few days that
could be due to overdose.
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|
Positive
(see notes)
|
PEP |
Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed) |
A Randomized Trial of Hydroxych loroquine as Postexposure Prophylaxis for Covid-19 |
COVID-19 cases are reduced by [49%,
29%, 16%] respectively when taken within ~[70, 94, 118] hours of
exposure (including shipping delay). The treatment delay-response
relationship is significant at p=0.002. PEP delayed treatment RCT.
Cur.. |
|
Positive
(see notes)
|
Post Exposure Prophylaxis study |
Boulware et al., NEJM, June 3 2020, doi:10.1056/NEJMoa2016638 (Peer Reviewed) |
A Randomized Trial of Hydroxych loroquine as Postexposure Prophylaxis for Covid-19 |
COVID-19 cases are reduced by
[49%, 29%, 16%] respectively when taken within ~[70, 94, 118] hours of
exposure (including shipping delay). The treatment delay-response
relationship is significant at p=0.002. PEP delayed treatment RCT.Currently
this is the only study where we have evaluated the result as positive
while the authors indicate it is negative. We provide a detailed explanation of why the results presented here are positive [1]. Note that author comments also differ from the published conclusion.
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Positive
|
Early |
Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed) |
Azithromycin and Hydroxych loroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19 |
Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HC Q+AZ)
or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective
study of 88 patients with case control analysis with matched pa.. |
|
Positive
|
Early treatment study |
Guérin et al., Asian J. Medicine and Health, July 15, 2020, doi:10.9734/ajmah/2020/v18i730224 (preprint 5/31) (Peer Reviewed) |
Azithromycin and Hydroxych loroquine Accelerate Recovery of Outpatients with Mild/Moderate COVID-19 |
Mean clinical recovery time reduced from 26 days (SOC) to 9 days, p<0.0001 (HC Q+AZ)
or 13 days, p<0.0001 (AZ). No cardiac toxicity. Small retrospective
study of 88 patients with case control analysis with matched patients.
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Positive
|
Late |
Ayerbe et al., Journal of Thrombosis and Thrombolysis, doi: 10.1007/s11239-020-02162-z (Peer Reviewed) |
The association between treatment with heparin and survival in patients with Covid-19 |
2075 hospital patients in Spain. HC Q reduces mortality from 30% to 13%. Not adjusted for age and gender. HC Q group 10% more males and 6 years younger. Study primarily interested in Heparin. |
|
Positive
|
Late treatment study |
Ayerbe et al., Journal of Thrombosis and Thrombolysis, doi: 10.1007/s11239-020-02162-z (Peer Reviewed) |
The association between treatment with heparin and survival in patients with Covid-19 |
2075 hospital patients in Spain. HC Q reduces mortality from 30% to 13%. Not adjusted for age and gender. HC Q group 10% more males and 6 years younger. Study primarily interested in Heparin.
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|
Positive
|
Late |
Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint) |
Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxych loroquine and azithromycin in Lebanon |
HC Q+AZ potentially explains 94.7% success in treating a fairly complex cohort. |
|
Positive
|
Late treatment study |
Chamieh et al., medRxiv 2020.05.28.20114835, doi:10.1101/2020.05.28.20114835 (Preprint) |
Viral Dynamics Matter in COVID-19 Pneumonia: the success of early treatment with hydroxych loroquine and azithromycin in Lebanon |
HC Q+AZ potentially explains 94.7% success in treating a fairly complex cohort.
|
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|
Positive
|
PrEP |
Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed) |
Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19 |
4+ doses of HC Q associated with a significant decline in the odds of getting infected, dose-response relationship exists. |
|
Positive
|
Pre-Exposure Prophylaxis study |
Chatterjee et al., Indian J. Med. Res., June 20, 2020, doi:10.4103/ijmr.IJMR_2234_20 (Peer Reviewed) |
Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19 |
4+ doses of HC Q associated with a significant decline in the odds of getting infected, dose-response relationship exists.
|
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|
Positive
|
Late |
Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed) |
Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of ch loroquine for the treatment of COVID-19 |
197 C Q
patients, 176 control. Mean time to undetectable viral RNA and duration
of fever significantly reduced. No serious adverse events. |
|
Positive
|
Late treatment study |
Huang et al., National Science Review, nwaa113, doi:10.1093/nsr/nwaa113 (Peer Reviewed) |
Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of ch loroquine for the treatment of COVID-19 |
197 C Q
patients, 176 control. Mean time to undetectable viral RNA and duration
of fever significantly reduced. No serious adverse events.
|
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|
Meta
|
Early |
Risch, American Journal
of Epidemiology, kwaa093, 27 May 2020, doi:10.1093/aje/kwaa093 (Peer
Reviewed) (meta analysis - not included in the study count) |
Early Outpatient Treatment of Symptomatic,
High-Risk Covid-19 Patients that Should be Ramped-Up Immediately as Key
to the Pandemic Crisis |
Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy. |
|
Meta
|
Early treatment study |
Risch,
American Journal of Epidemiology, kwaa093, 27 May 2020,
doi:10.1093/aje/kwaa093 (Peer Reviewed) (meta analysis - not included in
the study count) |
Early Outpatient Treatment of
Symptomatic, High-Risk Covid-19 Patients that Should be Ramped-Up
Immediately as Key to the Pandemic Crisis |
Five studies, including two controlled clinical trials, have demonstrated significant outpatient treatment efficacy.
Meta studies are not included in the percentages or study count.
|
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|
Negative
|
Late |
Ip et al., medRxiv, doi:10.1101/2020.05.21.20109207 (Preprint) |
Hydroxych loroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study |
Retrospective study of late stage
use on 2,512 hospitalized patients showing no significant differences in
associated mortality for patients receiving any HC Q during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22].. |
|
Negative
|
Late treatment study |
Ip et al., medRxiv, doi:10.1101/2020.05.21.20109207 (Preprint) |
Hydroxych loroquine and Tocilizumab Therapy in COVID-19 Patients - An Observational Study |
Retrospective study of late stage
use on 2,512 hospitalized patients showing no significant differences in
associated mortality for patients receiving any HC Q during the hospitalization (HR, 0.99 [95% CI, 0.80-1.22]), HC Q alone (HR, 1.02 [95% CI, 0.83-1.27]), or HC Q+AZ
(HR, 0.98 [95% CI, 0.75-1.28]). Misclassification is possible due to
manual abstraction of EHR data. They observed a change in the
prescribing patterns of HC Q during the study timeframe. Confounding by indication.
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|
Positive
(advisory)
|
PEP, PrEP |
ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) |
Revised advisory on the use of Hydroxych loroquine (HC Q) as prophylaxis for SARS-CoV-2 infection |
Healthcare workers on HC Q prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HC Q prophylaxis to asymptomatic household contacts of cases and fron.. |
|
Positive
(advisory)
|
PEP, PrEP |
ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) |
Revised advisory on the use of Hydroxych loroquine (HC Q) as prophylaxis for SARS-CoV-2 infection |
Healthcare workers on HC Q prophylaxis less likely to get COVID. Significant dose-response relationship. Extends recommended HC Q prophylaxis to asymptomatic household contacts of cases and frontline workers. Degree of benefit not quantified.
Currently no formal study is available so this is not included in the study count.
|
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|
|
Retracted
|
Late |
Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed) |
Hydroxych loroquine or ch loroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis |
Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted. |
|
Retracted
|
Late treatment study |
Mehra et al., The Lancet, May 22, 2020, doi: 10.1016/S0140-6736(20)31180-6 (Peer Reviewed) |
Hydroxych loroquine or ch loroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis |
Incorrect at first read (implausible death, ventilation, and population numbers). This paper was retracted.
|
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|
|
Meta
(negative)
|
Late |
Chacko et al., medRxiv, doi:10.1101/2020.05.14.20101774 (Preprint) (meta analysis - not included in the study count) |
Hydroxych loroquine in COVID-19: A systematic review and meta-analysis |
Meta analysis not seeing a
significant effect other than time to resolution of chest CT. Limited by
heterogeneous nature of studies, baseline severity varied, most studies
have a small sample size, endpoints reported at varying times, dos.. |
|
Meta
(negative)
|
Late treatment study |
Chacko et al., medRxiv, doi:10.1101/2020.05.14.20101774 (Preprint) (meta analysis - not included in the study count) |
Hydroxych loroquine in COVID-19: A systematic review and meta-analysis |
Meta analysis not seeing a
significant effect other than time to resolution of chest CT. Limited by
heterogeneous nature of studies, baseline severity varied, most studies
have a small sample size, endpoints reported at varying times, dosage
varied, and AZ, Zinc are not considered.
Meta studies are not included in the percentages or study count.
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|
Negative
|
Late |
Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint) |
Outcomes of Hydroxych loroquine
Treatment Among Hospitalized COVID-19 Patients in the United States-
Real-World Evidence From a Federated Electronic Medical Record Network |
EHR analysis of 3,372 hospitalized
COVID-19 patients not showing a significant difference for mortality or
the risk of mechanical ventilation. Subject to the limitations of EHR
analysis. Misclassification is possible. Confounding by indic.. |
|
Negative
|
Late treatment study |
Singh et al., medRxiv, doi:10.1101/2020.05.12.20099028 (Preprint) |
Outcomes of Hydroxych loroquine
Treatment Among Hospitalized COVID-19 Patients in the United States-
Real-World Evidence From a Federated Electronic Medical Record Network |
EHR analysis of 3,372 hospitalized
COVID-19 patients not showing a significant difference for mortality or
the risk of mechanical ventilation. Subject to the limitations of EHR
analysis. Misclassification is possible. Confounding by indication.
|
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|
Positive
|
Late |
Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint) |
Treatment Response to Hydroxych loroquine,
Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First
Report on the Pharmacological Outcomes from South Korea |
Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HC Q+antibiotic. Preprint withdrawn pending peer review. |
|
Positive
|
Late treatment study |
Kim et al., medRxiv, doi:10.1101/2020.05.13.20094193 (Preprint) |
Treatment Response to Hydroxych loroquine,
Lopinavir/Ritonavir, and Antibiotics for Moderate COVID 19: A First
Report on the Pharmacological Outcomes from South Korea |
Retrospective of 97 moderate cases. Time to viral clearance significantly shorter for HC Q+antibiotic. Preprint withdrawn pending peer review.
|
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|
|
Positive
|
Early |
Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint) |
Doxycycline and Hydroxych loroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities |
54 patients in long term care facilities. 6% death with HC Q+AZ compared to 22% using a naive indirect comparison. |
|
Positive
|
Early treatment study |
Ahmad et al., doi:10.1101/2020.05.18.20066902 (Preprint) |
Doxycycline and Hydroxych loroquine as Treatment for High-Risk COVID-19 Patients: Experience from Case Series of 54 Patients in Long-Term Care Facilities |
54 patients in long term care facilities. 6% death with HC Q+AZ compared to 22% using a naive indirect comparison.
|
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|
|
Inconc.
|
PrEP |
Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint) |
Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxych loroquine therapy |
Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HC Q 0.5-4.0%, no-HC Q 0.4-2.7%). Confirmed cases were 1 HC
|
|
Inconc.
|
Pre-Exposure Prophylaxis study |
Macias et al., medRxiv, 10.1101/2020.05.16.20104141 (Preprint) |
Similar incidence of Coronavirus Disease 2019 (COVID-19) in patients with rheumatic diseases with and without hydroxych loroquine therapy |
Very small retrospective study of rheumatic disease patients, sample size is too small for statistical significance (HC Q 0.5-4.0%, no-HC Q 0.4-2.7%). Confirmed cases were 1 HC Q and 2 no-HC Q, confimed+likely cases were 1 HC Q and 3 no-HC Q. 1 HC Q and 2 no-HC Q
patients were admitted to hospital. We do not think a conclusion can be
drawn based on these sample sizes. Further, there are very significant
differences between the groups, for example 30% of the HC Q group have SLE vs. 2.5% of the no-HC Q
group. SLE patients have a 5.7 times relative risk of pneumonia
according to [1], whereas the relative risk with glucocorticoids and
TNF-α inhibitors is significantly lower [2]. Two more recent studies
with rheumatic disease/autoimmune condition patients provide higher
confidence.
|
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|
|
Positive
|
Late |
Yu et al., Sci China Life Sci., 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed) |
Low Dose of Hydroxych loroquine Reduces Fatality of Critically Ill Patients With COVID-19 |
Retrospective, 550 critically ill patients. 19% fatality for HC Q versus 47% for non-HC Q. |
|
Positive
|
Late treatment study |
Yu et al., Sci China Life Sci., 2020 May 15, 1-7, doi:10.1007/s11427-020-1732-2 (Peer Reviewed) |
Low Dose of Hydroxych loroquine Reduces Fatality of Critically Ill Patients With COVID-19 |
Retrospective, 550 critically ill patients. 19% fatality for HC Q versus 47% for non-HC Q.
|
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|
|
Negative
|
Late |
Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed) |
Clinical efficacy of hydroxych loroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data |
Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions [1]. None of the 15 patients receiving HC <.. |
|
Negative
|
Late treatment study |
Mahévas et al., BMJ 2020, 369, doi: https://doi.org/10.1136/bmj.m1844 (Peer Reviewed) |
Clinical efficacy of hydroxych loroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data |
Observational study of 181 patients with advanced disease requiring oxygen showing no benefit for HC Q. Power of study appears too low to support conclusions [1]. None of the 15 patients receiving HC Q+AZ were transferred to intensive care or died compared to 23% overall.
|
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|
|
Negative
|
Late |
Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed) |
Association of Treatment With Hydroxych loroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State |
Restrospective observational late stage study showing no significant differences but calling for clinical trials.
Zervos et al. [1] point out serious limitations that they say should be corrected on the record: patients receiving HC
|
|
Negative
|
Late treatment study |
Rosenberg et al., JAMA, May 11, 2020, doi:10.1001/jama.2020.8630 (Peer Reviewed) |
Association of Treatment With Hydroxych loroquine or Azithromycin With In-Hospital Mortality in Patients With COVID-19 in New York State |
Restrospective observational late stage study showing no significant differences but calling for clinical trials.Zervos et al. [1] point out serious limitations that they say should be corrected on the record: patients receiving HC Q
with or without AZ were overall sicker on presentation and had multiple
other risk factors including much higher risk based on ethnicity;
patients receiving HC Q were more likely to be
obese, diabetic, have chronic lung disease, and cardiovascular
conditions; yet these sicker patients had approximately the same
mortality rates compared to patients with a milder course of the disease
and less risk factors. However, the authors conclude that "there are no
significant benefits." It is noteworthy that HC Q
was associated with a significant survival benefit in a larger cohort
of patients from New York City as reported by Mikami et al [2].
|
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|
|
Positive
|
Late |
Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed) |
A report from the Brescia Renal COVID Task Force
on the clinical characteristics and short-term outcome of hemodialysis
patients with SARS-CoV-2 infection |
Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HC Q but p=0.12, OR 0.44 (0.16–1.24). |
|
Positive
|
Late treatment study |
Alberici et al., Kidney Int., 98:1, 20-26, July 1, 2020, doi:10.1016/j.kint.2020.04.030 (preprint 5/10) (Peer Reviewed) |
A report from the Brescia Renal
COVID Task Force on the clinical characteristics and short-term outcome
of hemodialysis patients with SARS-CoV-2 infection |
Analysis of 94 hemodialysis COVID-19 positive patients. Reduction in death seen with HC Q but p=0.12, OR 0.44 (0.16–1.24).
|
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|
|
Inconc.
|
Late |
Carlucci et al., doi:10.1101/2020.05.02.20080036 (Preprint) |
Hydroxych loroquine and azithromycin plus zinc vs hydroxych loroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients |
Observational retrospective. Addition of Zinc to HC Q+AZ reduces mortality. |
|
Inconc.
|
Late treatment study |
Carlucci et al., doi:10.1101/2020.05.02.20080036 (Preprint) |
Hydroxych loroquine and azithromycin plus zinc vs hydroxych loroquine and azithromycin alone: outcomes in hospitalized COVID-19 patients |
Observational retrospective. Addition of Zinc to HC Q+AZ reduces mortality.
|
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|
|
Theory
|
Theory |
Derendorf, H., Int. J.
Antimicrobial Agents, 7 May 2020, doi:10.1016/j.ijantimicag.2020.106007
(Peer Reviewed) (Theory) (not included in the study count) |
Excessive lysosomal ion-trapping of hydroxych loroquine and azithromycin |
Discusses pharmacokinetic properties of HC Q+AZ as a potential underlying mechanism of the observed antiviral effects. |
|
Theory
|
Theory |
Derendorf,
H., Int. J. Antimicrobial Agents, 7 May 2020,
doi:10.1016/j.ijantimicag.2020.106007 (Peer Reviewed) (Theory) (not
included in the study count) |
Excessive lysosomal ion-trapping of hydroxych loroquine and azithromycin |
Discusses pharmacokinetic properties of HC Q+AZ as a potential underlying mechanism of the observed antiviral effects.
|
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|
|
Inconc.
|
Late |
Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer Reviewed) |
Observational Study of Hydroxych loroquine in Hospitalized Patients with Covid-19 |
There appears to be a major error
in this paper. Before propensity matching, 38 control patients had
hypertension. After propensity matching, 146 patients had hypertension
(Table 1). This is not possible. Even if all propensity matched co.. |
|
Inconc.
|
Late treatment study |
Geleris et al., NEJM, May 7, 2020, doi:10.1056/NEJMoa2012410 (Peer Reviewed) |
Observational Study of Hydroxych loroquine in Hospitalized Patients with Covid-19 |
There appears to be a major error
in this paper. Before propensity matching, 38 control patients had
hypertension. After propensity matching, 146 patients had hypertension
(Table 1). This is not possible. Even if all propensity matched control
patients had hypertension, the control prevalence would only be 14%
compared to 49% for treatment. Since patients with hypertension are at
much greater risk of mortality (HR 2.12, see [1]), this appears to
invalidate the results.Observational study of
1,446 hospitalized patients showing no significant effect on a combined
intubation/death outcome for late treatment.However, secondary analysis shows the success of HC Q was hidden by combining intubation and death - death / (combined death/intubation) for HC Q was 60% vs. control 89%, for details see: [2].RCT recommended. No AZ or Zinc. HC Q
group much sicker - patients already in mild/moderate ARDS, most of the
control group not in ARDS. Control cases received other therapeutics.
|
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|
Positive
(news)
|
N/A |
Sermo (News) (not included in the study count) |
Sermo reports: COVID-19 treatment trends over 6
weeks and 33,700 interviews: Usage, efficacy and safety perceptions of
most-used therapies |
HC Q used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians. |
|
Positive
(news)
|
N/A |
Sermo (News) (not included in the study count) |
Sermo reports: COVID-19 treatment
trends over 6 weeks and 33,700 interviews: Usage, efficacy and safety
perceptions of most-used therapies |
HC Q used by 55% of physicians worldwide for COVID. Survey of 6,150 physicians.
Currently no formal study is available so this is not included in the study count.
|
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|
Animal
|
Animal |
Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count) |
Hydroxych loroquine use against SARS-CoV-2 infection in non-human primates |
Monkey study which reports no effect of HC Q or HC Q+AZ.
However, there are actually several signs of effectiveness despite the
very small sample sizes and 100% recovery of all treated and contr.. |
|
Animal
|
Animal study |
Maisonnasse et al., Nature, 2020, doi:10.1038/s41586-020-2558-4 (preprint 5/6) (Peer Reviewed) (not included in the study count) |
Hydroxych loroquine use against SARS-CoV-2 infection in non-human primates |
Monkey study which reports no effect of HC Q or HC Q+AZ.
However, there are actually several signs of effectiveness despite the
very small sample sizes and 100% recovery of all treated and control
monkeys.58% reduction in lung lesions: the
final day lung lesion data shows 63% of control monkeys have lesions,
while 26% of treated monkeys do, p=0.095 (the final day data is missing
for 7 monkeys, these are predicted based on the day 5 results and the
trend of comparable monkeys).97% increase in
viral load recovery after one week: 3 of 8 control monkeys (38%) have
recovered with <= 4 log10 copies/mL viral load, compared to 17 of 23
treated monkeys (74%), p=0.095. 3 of 8 (38%) control monkeys also have a
higher peak viral load than 100% of the 23 treated monkeys
post-treatment. The group with the lowest peak viral load is the PrEP
group.All animals were infected with the same
initial viral load, whereas real-world infections vary in the initial
viral load, and lower inital viral loads allow greater time to mount an
immune response.
|
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|
Positive
|
Late |
Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint) |
Early Hydroxych loroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study |
166 patients hospitalised with COVID-19, HC Q
increased survival 1.4 - 1.8 times when patients admitted in early
stages. Early is relative to hospital admission here - all patients
relatively serious condition. |
|
Positive
|
Late treatment study |
Membrillo de Novales et al., Preprints 2020, 2020050057, doi:10.20944/preprints202005.0057.v1 (Preprint) |
Early Hydroxych loroquine Is Associated with an Increase of Survival in COVID-19 Patients: An Observational Study |
166 patients hospitalised with COVID-19, HC Q
increased survival 1.4 - 1.8 times when patients admitted in early
stages. Early is relative to hospital admission here - all patients
relatively serious condition.
|
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|
Positive
|
Early, Late |
Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 (Peer Reviewed) |
Early Treatment of COVID-19 Patients With Hydroxych loroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille, France |
Retrospective 1061 patients. HC Q+AZ safe and results in a low fatality rate. |
|
Positive
|
Early, Late |
Million et al., Travel Med Infect Dis., 2020 May 5, doi:10.1016/j.tmaid.2020.101738 (Peer Reviewed) |
Early Treatment of COVID-19 Patients With Hydroxych loroquine and Azithromycin: A Retrospective Analysis of 1061 Cases in Marseille, France |
Retrospective 1061 patients. HC Q+AZ safe and results in a low fatality rate.
|
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|
|
Inconc.
|
PrEP |
Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed) |
Continuous Hydroxych loroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis |
Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HC Q patient cases. Only considers people tested at a time when primarily symptomatic cases.. |
|
Inconc.
|
Pre-Exposure Prophylaxis study |
Gendelman et al., Autoimmunity Reviews, 19:7, July 2020, doi:10.1016/j.autrev.2020.102566 (Peer Reviewed) |
Continuous Hydroxych loroquine or Colchicine Therapy Does Not Prevent Infection With SARS-CoV-2: Insights From a Large Healthcare Database Analysis |
Very small study of rheumatic disease/autoimmune disorder patients showing no significant difference but with only 3 chronic HC Q
patient cases. Only considers people tested at a time when primarily
symptomatic cases were tested. Note that patients with SLE, RA, and
other autoimmune conditions have a significantly increased
susceptibility to and incidence of infections [1, 2, 3, 4, 5, 6, 7],
with this context the results suggest HC Q is
effective, but this is still inconclusive with the small sample size.
Two more recent studies with rheumatic disease/autoimmune condition
patients provide higher confidence.
|
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|
Safety
|
N/A |
Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in the study count) |
Risk of QT Interval Prolongation Associated With Use of Hydroxych loroquine
With or Without Concomitant Azithromycin Among Hospitalized Patients
Testing Positive for Coronavirus Disease 2019 (COVID-19) |
Study of 90 hospitalized patients given HC Q, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HC Q, and 442ms for HC Q+AZ. Medi.. |
|
Safety
|
N/A |
Mercuro et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1834 (Peer Reviewed) (not included in the study count) |
Risk of QT Interval Prolongation Associated With Use of Hydroxych loroquine
With or Without Concomitant Azithromycin Among Hospitalized Patients
Testing Positive for Coronavirus Disease 2019 (COVID-19) |
Study of 90 hospitalized patients given HC Q, 53 also receiving AZ, 53% hypertension, 29% diabetes mellitus, baseline median QTc 473ms for HC Q, and 442ms for HC Q+AZ. Median change for HC Q+AZ ΔQTc of 23ms vs. 5.5ms for HC Q.
Other factors such as stress cardiomyopathy or myocarditis could not be
ruled out. Without a control arm, they could not conclude that HC Q and AZ conferred increased cardiotoxic risk; however, compared with HC Q
alone, ΔQTc differences were likely associated with the addition of AZ.
The likelihood of prolonged QTc was greater in those who received
concomitant loop diuretics or had a baseline QTc of 450 milliseconds or
more. HC Q was discontinued in 10 patients due
to adverse events including nausea, hypoglycemia, and 1 case of torsades
de pointes. There were no deaths reported.Appropriate
use and careful analysis of contraindications, risks, and benefits are
important. More recent and much larger studies have not shown
significant safety concerns, including outpatient RCTs showing no
serious adverse events, and even the RECOVERY trial which used an
unusually high dose of HC Q (including 237
patients also receiving AZ) reports they "did not show any excess in
ventricular tachycardia (including torsade de pointes) or ventricular
fibrillation in the hydroxych loroquine arm",
and "serious cardiovascular toxicity has been reported very rarely
despite the high prevalence of cardiovascular disease in hospitalized
patients, the common occurrence of myocarditis in COVID-19, and the
extensive use of hydroxych loroquine and azithromycin together."
|
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|
|
Safety
|
N/A |
Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in the study count) |
Assessment of QT Intervals in a Case Series of
Patients With Coronavirus Disease 2019 (COVID-19) Infection Treated With
Hydroxych loroquine Alone or in Combination With Azithromycin in an Intensive Care Unit |
Study of 40 very serious condition
ICU patients, 75% required invasive mechanical ventilation, 63% received
vasoactive drugs, 50% received other treatments favoring QT
prolongation. HC Q with or w/o AZ was given to 4.. |
|
Safety
|
N/A |
Bessière et al., JAMA Cardiol., May 1, 2020, doi:10.1001/jamacardio.2020.1787 (Peer Reviewed) (not included in the study count) |
Assessment of QT Intervals in a Case
Series of Patients With Coronavirus Disease 2019 (COVID-19) Infection
Treated With Hydroxych loroquine Alone or in Combination With Azithromycin in an Intensive Care Unit |
Study of 40 very serious condition
ICU patients, 75% required invasive mechanical ventilation, 63%
received vasoactive drugs, 50% received other treatments favoring QT
prolongation. HC Q with or w/o AZ was given to
45% and 55% respectively. They showed an increase in QTc, more
significant with the combination of HC Q+AZ
where prolonged QTc was observed in 36% (10 with ΔQTc >60
milliseconds and 7 with QTc ≥500 milliseconds). No ventricular
arrhythmia, including torsades de pointes, was recorded. While these
results may not be generalizable outside the ICU, caution is recommended
in use, especially with the combination.Appropriate
use and careful analysis of contraindications, risks, and benefits are
important. More recent and much larger studies have not shown
significant safety concerns, including outpatient RCTs showing no
serious adverse events, and even the RECOVERY trial which used an
unusually high dose of HC Q (including 237
patients also receiving AZ) reports they "did not show any excess in
ventricular tachycardia (including torsade de pointes) or ventricular
fibrillation in the hydroxych loroquine arm",
and "serious cardiovascular toxicity has been reported very rarely
despite the high prevalence of cardiovascular disease in hospitalized
patients, the common occurrence of myocarditis in COVID-19, and the
extensive use of hydroxych loroquine and azithromycin together."
|
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|
Positive
(news)
|
Late |
Seydi (News) (not included in the study count) |
Coronavirus: a study in Senegal confirms the effectiveness of hydroxych loroquine |
Preliminary results of Senegal trial with 181 patients showing faster recovery with HC Q, and even faster recovery with HC Q+AZ. |
|
Positive
(news)
|
Late treatment study |
Seydi (News) (not included in the study count) |
Coronavirus: a study in Senegal confirms the effectiveness of hydroxych loroquine |
Preliminary results of Senegal trial with 181 patients showing faster recovery with HC Q, and even faster recovery with HC Q+AZ.
Currently no formal study is available so this is not included in the study count.
|
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|
|
Positive
|
Early |
Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed) |
Efficacy of ch loroquine and hydroxych loroquine in the treatment of COVID-19 |
Analysis of COVID-19 and malaria,
finding that COVID-19 is highly pandemic in countries where malaria is
least pandemic, and vice versa, suggesting that C Q/HC Q (widely used for malaria) are pr.. |
|
Positive
|
Early treatment study |
Meo et al., Eur. Rev. Med. Pharmacol. Sci. 2020, 24 (8), 4539-4547, doi:10.26355/eurrev_202004_21038 (Peer Reviewed) |
Efficacy of ch loroquine and hydroxych loroquine in the treatment of COVID-19 |
Analysis of COVID-19 and malaria,
finding that COVID-19 is highly pandemic in countries where malaria is
least pandemic, and vice versa, suggesting that C Q/HC Q
(widely used for malaria) are protective for COVID-19. This paper also
includes a review of 9 articles supporting the efficacy of HC Q and C Q.
|
Source
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|
|
Safety
|
N/A |
Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed) |
The Effect of Ch loroquine, Hydroxych loroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection |
201 hospitalized patients. No serious side effects of HC Q.
No instances of Torsade de pointes, or arrhythmogenic death were
reported. They report that although use of these medications resulted in
QT prolongation, c.. |
|
Safety
|
N/A |
Saleh et al., Circulation: Arrhythmia and Electrophysiology, doi:10.1161/CIRCEP.120.008662 (Peer Reviewed) |
The Effect of Ch loroquine, Hydroxych loroquine and Azithromycin on the Corrected QT Interval in Patients with SARS-CoV-2 Infection |
201 hospitalized patients. No serious side effects of HC Q.
No instances of Torsade de pointes, or arrhythmogenic death were
reported. They report that although use of these medications resulted in
QT prolongation, clinicians seldom need to discontinue therapy.
|
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|
|
In Vitro
|
In Vitro |
Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (Peer Reviewed) (In Vitro) (not included in the study count) |
In vitro testing of combined hydroxych loroquine and azithromycin on SARS-CoV-2 shows synergistic effect |
HC Q and AZ has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung. |
|
In Vitro
|
In Vitro |
Andreani et al., Microbial Pathogenesis, doi:/10.1016/j.micpath.2020.104228 (Peer Reviewed) (In Vitro) (not included in the study count) |
In vitro testing of combined hydroxych loroquine and azithromycin on SARS-CoV-2 shows synergistic effect |
HC Q and AZ has a synergistic effect in vitro on SARS-CoV-2 at concentrations compatible with that obtained in human lung.
|
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|
|
Inconc.
|
Early |
Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint) |
COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes |
Small limited trial with 100 patients concluding that HC Q improved clinical outcome. |
|
Inconc.
|
Early treatment study |
Ashraf et al., medRxiv doi:10.1101/2020.04.20.20072421.t (Preprint) |
COVID-19 in Iran, a comprehensive investigation from exposure to treatment outcomes |
Small limited trial with 100 patients concluding that HC Q improved clinical outcome.
|
Source
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|
|
Positive
|
Early |
Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint) |
Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths |
Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using [H]C Q, showing dramatically lower death in [H]C Q countries. This paper does not at.. |
|
Positive
|
Early treatment study |
Izoulet M., SSRN, doi:10.2139/ssrn.3575899 (Preprint) |
Countries which Primarily Use Antimalarial Drugs As COVID-19 Treatment See Slower Dynamic of Daily Deaths |
Compares the dynamics of daily deaths in the 10 days following the 3rd death in countries using and not using [H]C Q, showing dramatically lower death in [H]C Q
countries. This paper does not attempt to account for population age
and other differences between the countries and recommends further
study.
|
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|
|
Negative
|
Late |
Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed) |
Outcomes of hydroxych loroquine usage in United States veterans hospitalized with Covid-19 |
Retrospective 368 hospitalized patients, no significant reduction in mortality or the need for mechanical ventilation with HC Q or HC Q+AZ. Study notes HC Q was more likely.. |
|
Negative
|
Late treatment study |
Magagnoli et al., Med (2020), doi:10.1016/j.medj.2020.06.001 (preprint 4/21) (Peer Reviewed) |
Outcomes of hydroxych loroquine usage in United States veterans hospitalized with Covid-19 |
Retrospective 368 hospitalized patients, no significant reduction in mortality or the need for mechanical ventilation with HC Q or HC Q+AZ. Study notes HC Q was more likely to be prescribed to patients with more severe disease.
|
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|
|
Positive
|
PEP |
Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 (Peer Reviewed) |
Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals? |
Post exposure prophylaxis of 211
high-risk people after major exposure event in a long term care
hospital, showing no positive cases after 14 days. |
|
Positive
|
Post Exposure Prophylaxis study |
Lee at al., Int. J. Antimicrob. Agents, 2020, Apr 17, doi:10.1016/j.ijantimicag.2020.105988 (Peer Reviewed) |
Can Post-Exposure Prophylaxis for COVID-19 Be Considered as an Outbreak Response Strategy in Long-Term Care Hospitals? |
Post exposure prophylaxis of 211
high-risk people after major exposure event in a long term care
hospital, showing no positive cases after 14 days.
|
Source
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|
|
Negative
|
Late |
Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed) |
Ch loroquine diphosphate
in two different dosages as adjunctive therapy of hospitalized patients
with severe respiratory syndrome in the context of coronavirus
(SARS-CoV-2) infection: Preliminary safety results of a randomized,
double-blinded, phase IIb clinical trial (CloroCovid-19 Study) |
Increased incidence of prolonged QT
and death in high dose treatment arm. Patients >75 only enrolled in
high dose arm, age of high dose arm significantly higher than low dose
arm (p=0.02). Very sick at baseline, 43% in ICU, 88.9% on respi.. |
|
Negative
|
Late treatment study |
Borba et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2020.8857 (Peer Reviewed) |
Ch loroquine
diphosphate in two different dosages as adjunctive therapy of
hospitalized patients with severe respiratory syndrome in the context of
coronavirus (SARS-CoV-2) infection: Preliminary safety results of a
randomized, double-blinded, phase IIb clinical trial (CloroCovid-19
Study) |
Increased incidence of prolonged
QT and death in high dose treatment arm. Patients >75 only enrolled
in high dose arm, age of high dose arm significantly higher than low
dose arm (p=0.02). Very sick at baseline, 43% in ICU, 88.9% on
respiratory therapy prior to treatment.
|
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|
|
Positive
|
Early |
Esper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint) |
Empirical treatment with hydroxych loroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine |
636 patients. HC Q+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized. |
|
Positive
|
Early treatment study |
Esper et al., Prevent Senior Institute, São Paulo, Brazil (Preprint) |
Empirical treatment with hydroxych loroquine and azithromycin for suspected cases of COVID-19 followed-up by telemedicine |
636 patients. HC Q+AZ reduced hospitalization 79% when used within 7 days (65% overall). Non-randomized.
|
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|
|
Theory
|
Theory |
Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Peer Reviewed) (Theory) (not included in the study count) |
Hyperglycemia, hydroxych loroquine, and the COVID‐19 pandemic |
Theory on the effectiveness of HC Q. HC Q
has been shown to block the polarization of macrophages to an M1
inflammatory subtype and is predicted to interfere with glycosylation of
a number of pr.. |
|
Theory
|
Theory |
Brufsky, A., J. Medical Virology, doi:10.1002/jmv.25887 (Peer Reviewed) (Theory) (not included in the study count) |
Hyperglycemia, hydroxych loroquine, and the COVID‐19 pandemic |
Theory on the effectiveness of HC Q. HC Q
has been shown to block the polarization of macrophages to an M1
inflammatory subtype and is predicted to interfere with glycosylation of
a number of proteins involved in the humoral immune response, possibly
including the macrophage FcR gamma IgG receptor and other
immunomodulatory proteins, potentially through inhibition of
UDP‐N‐acetylglucosamine 2‐epimerase. In combination with potential other
immunomodulatory effects, this could possibly blunt the progression of
COVID‐19 pneumonia all to way up to ARDS.
|
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|
|
Negative
|
Late |
Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed) |
Hydroxych loroquine in patients with COVID-19: an open-label, randomized, controlled trial |
150 patients very late stage RCT. No significant difference. More symptomatic relief with HC Q. Treatment very late, average 16.6 days after symptom onset. Data favorable to HC Q was deleted in .. |
|
Negative
|
Late treatment study |
Tang et al., BMJ 2020, 369, doi:10.1136/bmj.m1849 (Peer Reviewed) |
Hydroxych loroquine in patients with COVID-19: an open-label, randomized, controlled trial |
150 patients very late stage RCT. No significant difference. More symptomatic relief with HC Q. Treatment very late, average 16.6 days after symptom onset. Data favorable to HC Q was deleted in the second version, see analysis [1].
|
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|
|
Positive
|
Late |
Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Peer Reviewed) |
Update on Use of Ch loroquine/Hydroxych loroquine to Treat Coronavirus Disease 2019 (COVID-19) |
Increasing evidence from completed clinical studies shows C Q and HC Q effective (HC Q more effective). |
|
Positive
|
Late treatment study |
Gao et al., Biosci Trends, May 21, 2020, 14:2, 156-158, doi:10.5582/bst.2020.03072, Epub Apr 13, 2020 (Peer Reviewed) |
Update on Use of Ch loroquine/Hydroxych loroquine to Treat Coronavirus Disease 2019 (COVID-19) |
Increasing evidence from completed clinical studies shows C Q and HC Q effective (HC Q more effective).
|
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|
Negative
|
Late |
Barbosa et al., Preprint (Preprint) |
Clinical outcomes of hydroxych loroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study |
Small retrospective study with 63 patients (32 treated with HC Q),
showing no effectiveness, however the baseline state of each arm
significantly differs. This preprint was submitted to NEJM but has not
been publishe.. |
|
Negative
|
Late treatment study |
Barbosa et al., Preprint (Preprint) |
Clinical outcomes of hydroxych loroquine in hospitalized patients with COVID-19: a quasi-randomized comparative study |
Small retrospective study with 63 patients (32 treated with HC Q),
showing no effectiveness, however the baseline state of each arm
significantly differs. This preprint was submitted to NEJM but has not
been published several months later.
|
Source
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|
|
Positive
|
Early |
Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed) |
Clinical and microbiological effect of a combination of hydroxych loroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study |
Pilot study suggesting improvement with HC Q+AZ and recommending further study. |
|
Positive
|
Early treatment study |
Gautret et al., Travel Medicine and Infectious Disease, doi:10.1016/j.tmaid.2020.101663 (Peer Reviewed) |
Clinical and microbiological effect of a combination of hydroxych loroquine and azithromycin in 80 COVID-19 patients with at least a six-day follow up: A pilot observational study |
Pilot study suggesting improvement with HC Q+AZ and recommending further study.
|
Source
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|
|
Meta
(negative)
|
Late |
Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in the study count) |
Quantifying treatment effects of hydroxych loroquine
and azithromycin for COVID-19: a secondary analysis of an open label
non-randomized clinical trial (Gautret et al, 2020) |
Secondary analysis of Gautret et al. showing "modest to no impact of HC Q treatment, with more significant effects from [HC Q+AZ]". |
|
Meta
(negative)
|
Late treatment study |
Lover, medRxiv, doi:10.1101/2020.03.22.20040949 (Preprint) (meta analysis - not included in the study count) |
Quantifying treatment effects of hydroxych loroquine
and azithromycin for COVID-19: a secondary analysis of an open label
non-randomized clinical trial (Gautret et al, 2020) |
Secondary analysis of Gautret et al. showing "modest to no impact of HC Q treatment, with more significant effects from [HC Q+AZ]".
Meta studies are not included in the percentages or study count.
|
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|
|
Positive
|
Late |
Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed) |
Treating COVID-19 with Ch loroquine |
22 patients. All C Q patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for C Q vs. 6.5 days for Lopinavir/Rotinavir. |
|
Positive
|
Late treatment study |
Huang et al., Journal of Molecular Cell Biology, Volume 12, Issue 4, April 2020, 322–325, doi:10.1093/jmcb/mjaa014 (Peer Reviewed) |
Treating COVID-19 with Ch loroquine |
22 patients. All C Q patients discharged by day 14 versus 50% of Lopinavir/Rotinavir patients. Symptom onset to treatment 2.5 days for C Q vs. 6.5 days for Lopinavir/Rotinavir.
|
Source
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|
|
Positive
|
Late |
Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint) |
Efficacy of hydroxych loroquine in patients with COVID-19: results of a randomized clinical trial |
62 patients. RCT showing significantly faster recovery with HC Q.
13% progressed to severe cases in the control group, versus 0% for the
treatment group. Significant improvement seen in pneumonia on chest CT
for 61% .. |
|
Positive
|
Late treatment study |
Chen et al., medRxiv doi:10.1101/2020.03.22.20040758 (Preprint) |
Efficacy of hydroxych loroquine in patients with COVID-19: results of a randomized clinical trial |
62 patients. RCT showing significantly faster recovery with HC Q.
13% progressed to severe cases in the control group, versus 0% for the
treatment group. Significant improvement seen in pneumonia on chest CT
for 61% of treated patients and 16% of control patients.
|
Source
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|
|
In Vitro
|
In Vitro |
Clementi et al., Front.
Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704 (preprint 3/31)
(Peer Reviewed) (In Vitro) (not included in the study count) |
Combined Prophylactic and Therapeutic Use Maximizes Hydroxych loroquine Anti-SARS-CoV-2 Effects in vitro |
In vitro study, not included in the
study count or percentages, showing greater inhibition for combined pre
and post-exposure treatment for Vero E6 and Caco-2 cells. |
|
In Vitro
|
In Vitro |
Clementi
et al., Front. Microbiol., 10 July 2020, doi:10.3389/fmicb.2020.01704
(preprint 3/31) (Peer Reviewed) (In Vitro) (not included in the study
count) |
Combined Prophylactic and Therapeutic Use Maximizes Hydroxych loroquine Anti-SARS-CoV-2 Effects in vitro |
In vitro study, not
included in the study count or percentages, showing greater inhibition
for combined pre and post-exposure treatment for Vero E6 and Caco-2
cells.
|
Source
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|
|
Negative
|
Late |
Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter) |
No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxych loroquine and azithromycin in patients with severe COVID-19 infection |
11 patients with severe cases. No evidence of benefit for HC Q. |
|
Negative
|
Late treatment study |
Molina et al., Médecine et Maladies Infectieuses, 50:4, June 2020, 10.1016/j.medmal.2020.03.006 (preprint 3/28) (Letter) |
No evidence of rapid antiviral clearance or clinical benefit with the combination of hydroxych loroquine and azithromycin in patients with severe COVID-19 infection |
11 patients with severe cases. No evidence of benefit for HC Q.
|
Source
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|
Positive
(news)
|
Late |
Zhong Nanshan (钟南山) (News) (not included in the study count) |
Efficacy and safety of ch loroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial |
197 patients. HC Q effective. Viral RNA negative in 95.9% versus 79.6% control. Median time to negative tests 3 days versus 9 days for control. |
|
Positive
(news)
|
Late treatment study |
Zhong Nanshan (钟南山) (News) (not included in the study count) |
Efficacy and safety of ch loroquine for treatment of COVID-19. An open-label, multi-center, non-randomized trial |
197 patients. HC Q effective. Viral RNA negative in 95.9% versus 79.6% control. Median time to negative tests 3 days versus 9 days for control.
Currently no formal study is available so this is not included in the study count.
|
Source
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|
|
Theory
|
Theory |
Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory) |
Is Hydroxych loroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19? |
C Q and HC Q
inhibit replication at early stages of infection, no similar effect
reported for other drugs which are only able to interfere after cell
infection. Large volume of existing data on .. |
|
Theory
|
Theory |
Pagliano et al., Clin. Infect. Dis., 2020 Mar 24, doi:10.1093/cid/ciaa320 (Peer Reviewed) (Theory) |
Is Hydroxych loroquine a Possible Post-Exposure Prophylaxis Drug to Limit the Transmission to Health Care Workers Exposed to COVID19? |
C Q and HC Q
inhibit replication at early stages of infection, no similar effect
reported for other drugs which are only able to interfere after cell
infection. Large volume of existing data on safety.
|
Source
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Theory
|
Theory |
Hu et al., Nature
Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9 (Peer
Reviewed) (Theory) (not included in the study count) |
Insights from nanomedicine into ch loroquine efficacy against COVID-19 |
C Q is
known in nanomedicine research for the investigation of nanoparticle
uptake in cells, and may have potential for the treatment of COVID-19. |
|
Theory
|
Theory |
Hu et al.,
Nature Nanotechnology, 15, 247–249, 2020, doi:10.1038/s41565-020-0674-9
(Peer Reviewed) (Theory) (not included in the study count) |
Insights from nanomedicine into ch loroquine efficacy against COVID-19 |
C Q is
known in nanomedicine research for the investigation of nanoparticle
uptake in cells, and may have potential for the treatment of COVID-19.
|
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|
Positive
(advisory)
|
PrEP |
ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) |
Advisory on the use of hydroxy-ch loroquine as prophylaxis for SARS-CoV-2 infection |
Recommends HC Q for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo. |
|
Positive
(advisory)
|
Pre-Exposure Prophylaxis study |
ICMR, Indian Council of Medical Research (Advisory) (not included in the study count) |
Advisory on the use of hydroxy-ch loroquine as prophylaxis for SARS-CoV-2 infection |
Recommends HC Q for prophylaxis in asymptomatic healthcare workers as found effective in-vitro and in-vivo.
Currently no formal study is available so this is not included in the study count.
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Positive
(news)
|
Late |
Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count) |
Shanghai Experience of COVID-19 Management |
Clinical studies of HC Q with 184 cases and 21 hospitals show HC Q is effective. |
|
Positive
(news)
|
Late treatment study |
Hu et al., Shanghai Combined Task Force on COVID-19 (News) (not included in the study count) |
Shanghai Experience of COVID-19 Management |
Clinical studies of HC Q with 184 cases and 21 hospitals show HC Q is effective.
Currently no formal study is available so this is not included in the study count.
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Source
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In Vitro
|
In Vitro |
Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not included in the study count) |
Hydroxych loroquine, a less toxic derivative of ch loroquine, is effective in inhibiting SARS-CoV-2 infection in vitro |
HC Q effective in vitro and less toxic than C Q. In addition to direct antiviral activity, HC Q is a safe and successful anti-inflammatory agent that has been used extensiv.. |
|
In Vitro
|
In Vitro |
Liu et al., Cell Discovery 6, 16 (2020), doi:10.1038/s41421-020-0156-0 (Peer Reviewed) (In Vitro) (not included in the study count) |
Hydroxych loroquine, a less toxic derivative of ch loroquine, is effective in inhibiting SARS-CoV-2 infection in vitro |
HC Q effective in vitro and less toxic than C Q. In addition to direct antiviral activity, HC Q
is a safe and successful anti-inflammatory agent that has been used
extensively in autoimmune diseases and can significantly decrease the
production of cytokines and, in particular, pro-inflammatory factors.
Therefore, in COVID-19 patients, HC Q may also
contribute to attenuating the inflammatory response. Careful design of
clinical trials is important to achieve efficient and safe control of
the infection.
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Positive
|
Early |
Gautret et al., Int. J. of Antimicrobial Agents, 17 March 2020, doi:10.1016/j.ijantimicag.2020.105949 (Peer Reviewed) |
Hydroxych loroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial |
HC Q
significantly associated with viral load reduction / elimination,
enhanced with AZ. This early and small trial has significant
limitations, larger and more recent trials by the same group confirm the
results. |
|
Positive
|
Early treatment study |
Gautret et al., Int. J. of Antimicrobial Agents, 17 March 2020, doi:10.1016/j.ijantimicag.2020.105949 (Peer Reviewed) |
Hydroxych loroquine and azithromycin as a treatment of COVID-19: results of an openlabel non-randomized clinical trial |
HC Q
significantly associated with viral load reduction / elimination,
enhanced with AZ. This early and small trial has significant
limitations, larger and more recent trials by the same group confirm the
results.
|
Source
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|
Review
|
N/A |
Sahraei et al., Int. J.
Antimicrobial Agents, April 2020, 55:4,
doi:10.1016/j.ijantimicag.2020.105945 (Peer Reviewed) (not included in
the study count) |
Aminoquinolines against coronavirus disease 2019 (COVID-19): ch loroquine or hydroxych loroquine |
Discussion of mechanisms of action, C Q vs. HC Q, early studies, safety. |
|
Review
|
N/A |
Sahraei et
al., Int. J. Antimicrobial Agents, April 2020, 55:4,
doi:10.1016/j.ijantimicag.2020.105945 (Peer Reviewed) (not included in
the study count) |
Aminoquinolines against coronavirus disease 2019 (COVID-19): ch loroquine or hydroxych loroquine |
Discussion of mechanisms of action, C Q vs. HC Q, early studies, safety.
|
Source
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Review
|
N/A |
Todaro and Rigano (Preprint) (not included in the study count) |
An Effective Treatment for Coronavirus (COVID-19) |
Discussion of existing research, treatment guidelines, and mechanisms of action for C Q and HC Q, recommending use. |
|
Review
|
N/A |
Todaro and Rigano (Preprint) (not included in the study count) |
An Effective Treatment for Coronavirus (COVID-19) |
Discussion of existing research, treatment guidelines, and mechanisms of action for C Q and HC Q, recommending use.
|
Source
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|
Theory
|
Theory |
Devaux et al.,
International Journal of Antimicrobial Agents,
doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not
included in the study count) |
New insights on the antiviral effects of ch loroquine against coronavirus: what to expect for COVID-19? |
Discusses mechanisms of C Q interference with the SARS-CoV-2 replication cycle. |
|
Theory
|
Theory |
Devaux et
al., International Journal of Antimicrobial Agents,
doi:10.1016/j.ijantimicag.2020.105938 (Peer Reviewed) (Theory) (not
included in the study count) |
New insights on the antiviral effects of ch loroquine against coronavirus: what to expect for COVID-19? |
Discusses mechanisms of C Q interference with the SARS-CoV-2 replication cycle.
|
Source
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|
Meta
(positive)
|
N/A |
Cortegiani et al., J.
Crit. Care, June 2020, 57:279-283, doi:10.1016/j.jcrc.2020.03.005, Epub
Mar 10, 2020 (Peer Reviewed) (meta analysis - not included in the study
count) |
A Systematic Review on the Efficacy and Safety of Ch loroquine for the Treatment of COVID-19 |
Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI. |
|
Meta
(positive)
|
N/A |
Cortegiani
et al., J. Crit. Care, June 2020, 57:279-283,
doi:10.1016/j.jcrc.2020.03.005, Epub Mar 10, 2020 (Peer Reviewed) (meta
analysis - not included in the study count) |
A Systematic Review on the Efficacy and Safety of Ch loroquine for the Treatment of COVID-19 |
Review of six articles and 23 ongoing clinical trials in China recommending research and clinical use adhering to MEURI.
Meta studies are not included in the percentages or study count.
|
Source
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|
In Vitro
|
N/A |
Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (Peer Reviewed) (not included in the study count) |
In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxych loroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) |
HC Q is more potent than C Q in vitro for inhibiting SARS-CoV-2. Simulates HC Q concentration in lung fluid and provides dosing recommendations. |
|
In Vitro
|
N/A |
Yao et al., Clin. Infect. Dis., 2020 Mar 9, doi:10.1093/cid/ciaa237 (Peer Reviewed) (not included in the study count) |
In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxych loroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) |
HC Q is more potent than C Q in vitro for inhibiting SARS-CoV-2. Simulates HC Q concentration in lung fluid and provides dosing recommendations.
|
Source
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|
Negative
|
Late |
Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed) |
A pilot study of hydroxych loroquine in treatment of patients with common coronavirus disease-19 (COVID-19) |
30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HC Q but not statistically significant. One HC Q patient developed to .. |
|
Negative
|
Late treatment study |
Chen et al., J. Zhejiang University (Med Sci), doi:10.3785/j.issn.1008-9292.2020.03.03 (Peer Reviewed) |
A pilot study of hydroxych loroquine in treatment of patients with common coronavirus disease-19 (COVID-19) |
30 moderate hospitalized cases, all recovered. Time to RNA negative comparable. Less frequent radiological progression with HC Q but not statistically significant. One HC Q patient developed to a severe case. Treatment group 4 years older and with higher incidence of hypertension.
|
Source
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|
Positive
|
Late |
Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Peer Reviewed) |
Ch loroquine and Hydroxych loroquine as Available Weapons to Fight COVID-19 |
Recommending C Q and HC Q for COVID-19 based on 20 clinical studies in China and a strong rationale for use. |
|
Positive
|
Late treatment study |
Colson et al., Int J. Antimicrob Agents, doi: 10.1016/j.ijantimicag.2020.105932. Epub 2020 Mar 4. (Peer Reviewed) |
Ch loroquine and Hydroxych loroquine as Available Weapons to Fight COVID-19 |
Recommending C Q and HC Q for COVID-19 based on 20 clinical studies in China and a strong rationale for use.
|
Source
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|
Positive
|
Late |
Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed) |
Expert Consensus on Ch loroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia |
Early trials in China show C Q results in shorter hospital stays and improved patient outcomes. |
|
Positive
|
Late treatment study |
Jiang et al., Chin. J. Tuberc. Respir. Dis., 2020, 43, doi:10.3760/cma.j.issn.1001-0939.2020.0019 (Peer Reviewed) |
Expert Consensus on Ch loroquine Phosphate for the Treatment of Novel Coronavirus Pneumonia |
Early trials in China show C Q results in shorter hospital stays and improved patient outcomes.
|
Source
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|
|
Positive
|
Late |
Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047 (Peer Reviewed) |
Breakthrough: Ch loroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies |
Results from 15 clinical trials in China showing C Q is effective. |
|
Positive
|
Late treatment study |
Gao et al., BioScience Trends, 2020, doi:10.5582/bst.2020.01047 (Peer Reviewed) |
Breakthrough: Ch loroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies |
Results from 15 clinical trials in China showing C Q is effective.
|
Source
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|
Positive
(news)
|
Late |
Sun Yanrong, deputy head of the China National Center for Biotechnology Development (News) (not included in the study count) |
Antimalarial drug confirmed effective on COVID-19 |
HC Q under clinical trials in >10 hospitals in China and has shown fairly good efficacy. |
|
Positive
(news)
|
Late treatment study |
Sun Yanrong, deputy head of the China National Center for Biotechnology Development (News) (not included in the study count) |
Antimalarial drug confirmed effective on COVID-19 |
HC Q under clinical trials in >10 hospitals in China and has shown fairly good efficacy.
Currently no formal study is available so this is not included in the study count.
|
Source
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|
|
In Vitro
|
In Vitro |
Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (Peer Reviewed) (In Vitro) (not included in the study count) |
Remdesivir and ch loroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro |
In vitro study, not included in the study count or percentages. Remdesivir and C Q potently blocked virus infection in vitro. |
|
In Vitro
|
In Vitro |
Wang et al., Cell Res. 30, 269–271, doi:L10.1038/s41422-020-0282-0 (Peer Reviewed) (In Vitro) (not included in the study count) |
Remdesivir and ch loroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro |
In vitro study, not included in the study count or percentages. Remdesivir and C Q potently blocked virus infection in vitro.
|
Source
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|
|
In Vitro
|
In Vitro |
de Wilde et al.,
Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8, 4875-4884,
doi:10.1128/AAC.03011-14 (Peer Reviewed) (In Vitro) (not included in the
study count) |
Screening of an FDA-Approved Compound Library
Identifies Four Small-Molecule Inhibitors of Middle East Respiratory
Syndrome Coronavirus Replication in Cell Culture |
C Q inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range. |
|
In Vitro
|
In Vitro |
de Wilde
et al., Antimicrobial Agents and Chemotherapy, Jul 2014, 58:8,
4875-4884, doi:10.1128/AAC.03011-14 (Peer Reviewed) (In Vitro) (not
included in the study count) |
Screening of an FDA-Approved
Compound Library Identifies Four Small-Molecule Inhibitors of Middle
East Respiratory Syndrome Coronavirus Replication in Cell Culture |
C Q inhibits SARS-CoV, MERS-CoV, and HCoV-229E-GFP replication in the low-micromolar range.
|
Source
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|
Animal
|
Animal |
Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count) |
Anti-malaria drug ch loroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model |
C Q, a
known autophagy inhibitor that is in clinical use, can efficiently
ameliorate acute lung injury and dramatically improve the survival rate
in mice infected with live avian influenza A H5N1 virus. |
|
Animal
|
Animal study |
Yan et al., Cell Research, 23, 300–302, doi:10.1038/cr.2012.165 (Peer Reviewed) (not included in the study count) |
Anti-malaria drug ch loroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model |
C Q, a
known autophagy inhibitor that is in clinical use, can efficiently
ameliorate acute lung injury and dramatically improve the survival rate
in mice infected with live avian influenza A H5N1 virus.
|
Source
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|
Animal
|
Animal |
Keyaerts et al.,
Antimicrob. Agents Chemother, August 2009, 53(8),
doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the study
count) |
Antiviral Activity of Ch loroquine against Human Coronavirus OC43 Infection in Newborn Mice |
C Q inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with C Q acquired transplacentally or via maternal milk. The highest survi.. |
|
Animal
|
Animal study |
Keyaerts
et al., Antimicrob. Agents Chemother, August 2009, 53(8),
doi:0.1128/AAC.01509-08 (Peer Reviewed) (not included in the study
count) |
Antiviral Activity of Ch loroquine against Human Coronavirus OC43 Infection in Newborn Mice |
C Q inhibits HCoV-OC43 replication in HRT-18 cells. A lethal HCoV-OC43 infection in newborn C57BL/6 mice can be treated with C Q
acquired transplacentally or via maternal milk. The highest survival
rate (98.6%) was found when mother mice were treated daily with a
concentration of 15 mg of C Q per kg of body weight. Survival rates declined in a dose-dependent manner, with 88% survival when treated with 5 mg/kg C Q and 13% survival when treated with 1 mg/kg C Q. C Q can be highly effective against HCoV-OC43 infection in newborn mice and may be considered as a future drug against HCoVs.
|
Source
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|
In Vitro
|
In Vitro |
Kono et al., Antiviral
Research, 77:2, February 2008, 150-152, 10.1016/j.antiviral.2007.10.011
(Peer Reviewed) (In Vitro) (not included in the study count) |
Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by ch loroquine: Involvement of p38 MAPK and ERK |
C Q significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. C Q affects the activation of p38 mitogen-activated protein kinase (MAPK) and extracell.. |
|
In Vitro
|
In Vitro |
Kono et
al., Antiviral Research, 77:2, February 2008, 150-152,
10.1016/j.antiviral.2007.10.011 (Peer Reviewed) (In Vitro) (not included
in the study count) |
Inhibition of human coronavirus 229E infection in human epithelial lung cells (L132) by ch loroquine: Involvement of p38 MAPK and ERK |
C Q significantly decreased viral replication of HCoV-229E at concentrations lower than in clinical usage. C Q
affects the activation of p38 mitogen-activated protein kinase (MAPK)
and extracellular signal-regulated kinase (ERK). p38 MAPK inhibitor,
SB203580, inhibits CPE induced by HCoV-229E infection and viral
replication.
|
Source
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|
In Vitro
|
In Vitro |
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (Peer Reviewed) (In Vitro) (not included in the study count) |
New insights into the antiviral effects of ch loroquine |
Update to 2003 paper, not included in the study count or percentages. Hypothesis of C Q inhibiting SARS replication has been confirmed in two in-vitro studies. C Q affected an early stage of SAR.. |
|
In Vitro
|
In Vitro |
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(06)70361-9 (Peer Reviewed) (In Vitro) (not included in the study count) |
New insights into the antiviral effects of ch loroquine |
Update to 2003 paper, not included in the study count or percentages. Hypothesis of C Q inhibiting SARS replication has been confirmed in two in-vitro studies. C Q affected an early stage of SARS replication.
|
Source
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|
In Vitro
|
In Vitro |
Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count) |
Ch loroquine is a potent inhibitor of SARS coronavirus infection and spread |
In vitro study, SARS-CoV-1, not included in the study count or percentages. C Q
has strong antiviral effects on SARS CoV infection when cells treated
either before or after exposure, suggesting prophylactic and treat.. |
|
In Vitro
|
In Vitro |
Vincent et al., Virol. J. 2:69, 2005, doi:10.1186/1743-422X-2-69 (Peer Reviewed) (In Vitro) (not included in the study count) |
Ch loroquine is a potent inhibitor of SARS coronavirus infection and spread |
In vitro study, SARS-CoV-1, not included in the study count or percentages. C Q
has strong antiviral effects on SARS CoV infection when cells treated
either before or after exposure, suggesting prophylactic and treatment
use. Describes three mechanisms by which the drug might work and
suggests it may have both a prophylactic and therapeutic role in
coronavirus infections.
|
Source
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|
In Vitro
|
In Vitro |
Keyaerts et al.,
Biochem. Biophys. Res. Comm., 323:1, 8 October 2004,
doi:10.1016/j.bbrc.2004.08.085 (Peer Reviewed) (In Vitro) (not included
in the study count) |
In vitro inhibition of severe acute respiratory syndrome coronavirus by ch loroquine |
In vitro study, SARS-CoV-1, not included in the study count or percentages. IC50 of C Q
for antiviral activity (8.8) is significantly lower than cytostatic
activity CC50 (261.3), selectivity index of 30. IC50 for inh.. |
|
In Vitro
|
In Vitro |
Keyaerts
et al., Biochem. Biophys. Res. Comm., 323:1, 8 October 2004,
doi:10.1016/j.bbrc.2004.08.085 (Peer Reviewed) (In Vitro) (not included
in the study count) |
In vitro inhibition of severe acute respiratory syndrome coronavirus by ch loroquine |
In vitro study, SARS-CoV-1, not included in the study count or percentages. IC50 of C Q
for antiviral activity (8.8) is significantly lower than cytostatic
activity CC50 (261.3), selectivity index of 30. IC50 for inhibition of
SARS-CoV in vitro approximates the plasma concentrations of C Q reached during treatment of acute malaria. C Q may be considered for immediate use in the prevention and treatment of SARS-CoV infections.
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Theory
|
Theory |
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count) |
Effects of ch loroquine on viral infections: an old drug against today's diseases |
Not included in the study count or percentages. Discussion/review noting that C Q
exerts antiviral effects, inhibiting the replication of several viruses
including members of the flaviviruses, retroviruses, and coron.. |
|
Theory
|
Theory |
Savarino et al., Lancet Infect. Dis., doi:10.1016/S1473-3099(03)00806-5 (Peer Reviewed) (Theory) (not included in the study count) |
Effects of ch loroquine on viral infections: an old drug against today's diseases |
Not included in the study count or percentages. Discussion/review noting that C Q
exerts antiviral effects, inhibiting the replication of several viruses
including members of the flaviviruses, retroviruses, and coronaviruses.
Notes that C Q has immunomodulatory effects,
suppressing the production/release of tumour necrosis factor α and
interleukin 6, which mediate the inflammatory complications of several
viral diseases.
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|
Inconc.
(news)
|
N/A |
Edwin Wiley Grove (News) (not included in the study count) |
Laxative Bromo Quinine |
Quinine has been used for
respiratory infections since 1889. Not included in the study count or
percentages, just as an interesting observation. |
|
Inconc.
(news)
|
N/A |
Edwin Wiley Grove (News) (not included in the study count) |
Laxative Bromo Quinine |
Quinine has been used for
respiratory infections since 1889. Not included in the study count or
percentages, just as an interesting observation.
|
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