Original document :
CQ / HCQ Research Papers and Reports
to April 20, 2020
Summary Interpretation of the Data In This Report
The HCQ-AZ combination, when started immediately after
diagnosis, appears to be a safe and efficient treatment for COVID-19,
with a mortality rate of 0.5%, in elderly patients. It avoids worsening
and clears virus persistence and contagious infectivity in most cases.
CQ / HCQ Research Papers and Reports
January to April 12 2020
22 August 2005
Special Pathogens Branch
VIncet, E.Bergon, S. Benjannet, BR Erickson, Pierre Rollin, T.G.
Ksiazek, NG Seidah,
is a potent inhibitor of SARS coronavirus infection and spread.
Virology Journal. (2005) 2: 69
has strong antiviral effects on SARS CoV infection of primate cells in
tissue culture. These
inhibitory effects are observed when cells are treated with the drug
either before or after exposure to the virus, suggesting both
prophylactic preventative and treatment use.
The paper describes three mechanisms by which the drug might work and
suggest it may have both a prophylactic and therapeutic role in
28 January 2020
M. Wang, R. Cao, L. Zhang, X. Yang, J. Liu, M. Xu, Z. Shi, Z. Hu, W.
Zhong, G. Xiao
TO THE EDITOR Cell Research Remdesivir
and chloroquine effectively inhibit the recently emerged novel
coronavirus (2019-nCoV) in vitro.
Cell Research (2020) 0:1–3; https://doi.org/10.1038/s41422-020-0282-0
Remdesivir and Chloroquine in addition to five other drugs were tested
in tissue culture against a clinical sample of virus from a COVID-19
and Chloroquine are highly effective in the control of 2019-nCoV
infection in vitro. Since
these compounds have been used in human patients with a safety track
record and shown to be effective against various ailments, we suggest
that they should be assessed in human patients suffering from the novel
February 13, 2020
Physicians work out treatment guidelines for coronavirus,
Biomedical Review http://www.koreabiomed.com/news/articleView.html?idxno=7428
Korean COVID-19 Central Clinical Task Force, held the sixth video
conference and agreed on treatment principles for patients with
- If 10 days have passed since the onset of the illness and the symptoms are
mild, physicians do not have to start an antiviral medication.
- If patients are old or have underlying conditions with serious symptoms,
physicians should consider an antiviral treatment as soon as possible.
lopinavir 400mg/ritonavir 100mg (Kaletra two tablets, twice a day) or
chloroquine 500mg orally per day. Alternate is hydroxychloroquine 400mg
orally per day.
February 18, 2020.
Gao, Zhenxue Tian, Xu Yang Breakthrough:
Chloroquine phosphate has shown apparent efficacy in treatment of
COVID-19 associated pneumonia in clinical studies.
BioScience Trends Advance Publication, DOI: 10.5582/bst.2020.0104
far, results from more than 100 patients have demonstrated that chloroquine phosphate is superior to
the control treatment in inhibiting the exacerbation of pneumonia,
improving lung imaging findings, promoting a virus negative conversion,
and shortening the disease course.
Severe adverse reactions to chloroquine phosphate were not noted in the
aforementioned patients. Given these findings, a conference was held on
February 15, 2020; participants including experts from government and
regulatory authorities and organizers of clinical trials
reached an agreement that chloroquine phosphate has potent activity
27 February 2020
Colson , Jean-Marc Rolain , Jean-Christophe Lagier , Philippe Brouqui ,
Didier Raoult , Chloroquine
and hydroxychloroquine as available weapons to ﬁght COVID-19,
International Journal of Antimicrobial Agents Feb (2020), doi:
following the very recent publication of results showing the in vitro activity of
chloroquine against SARS-CoV-2, data have been reported on the efficacy
of this drug in patients with SARS-CoV-2-related pneumonia (named
COVID-19) at different levels of severity.
Following the in vitro results, 20 clinical studies were launched in several
The first results obtained from more than 100 patients showed
the superiority of chloroquine compared with treatment
of the control group in terms of reduction of exacerbation of
pneumonia, duration of symptoms and delay of viral clearance, all in
the absence of severe side effects.
This has led in China to include chloroquine in the recommendations
regarding the prevention and treatment of COVID-19 pneumonia.
teams showed that Chloroquine
could reduce the length of hospital stay and improve the evolution of
leading to recommend the administration of 500 mg of chloroquine twice
a day in patients with mild, moderate and severe forms of COVID-19
4 March 2020
and hydroxychloroquine as available weapons to fight COVID-19.
J Antimicrob Agents.
2020 Mar 4 : 105932. doi: 10.1016/j.ijantimicag.2020.105932
[Epub ahead of print] PMCID: PMC7135139 IPMID: 32145363
review of the safety and efficiency of CQ and HCQ reviewing more than 20
clinical studies in several Chinese hospitals.
Although only available in letter form, this data caused China to
recommend Chloroquine in the National Guidelines for the Treatment of
9 March 2020
F/ Ye2, M. Zhang, C.Cui, R. Lu, H. Li, W. Tan, D. Liu. In
Vitro Antiviral Activity and Projection of Optimized Dosing Design of
Hydroxychloroquine for the Treatment of Severe Acute Respiratory
Syndrome Coronavirus 2 (SARS-CoV-2).
Infect Dis. 2020
Mar 9. pii: ciaa237. doi: 10.1093/cid/ciaa237.
was found to be more potent than chloroquine at inhibiting SARS-CoV-2
in vitro. Hydroxychloroquine
sulfate 400 mg given twice daily for 1 day, followed by 200 mg twice
daily for 4 more days is recommended to treat SARS-CoV-2 infection.
9 March 2020
Expert Chinese consensus on Chloroquine Phosphate for New Coronavirus
Pneumonia. Diagnosis and Treatment Plan.
Chinese Journal of Tuberculosis and Respiratory Diseases. 2020, 43:
Multicenter Collaboration Group was formed to guide
and standardize the use of Chloroquine in Coronavirus pneumonia,
standardizing Chloroquine treatment at 500mg 2x day for 10 days.
of azithromycin was contraindicated.
20 March 2020
Scola B, Rolain
Hydroxychloroquine and azithromycin as a treatment of COVID-19: results
of an open-label non-randomized clinical trial.
J Antimicrob Agents. 2020
Mar 20:105949. doi: 10.1016/j.ijantimicag.2020.105949.
COVID-19 patients were included in a protocol from early March to March
16th, to receive 600mg of hydroxychloroquine daily and their
viral load in nasopharyngeal swabs was tested daily in a hospital
patients from another center were included as negative controls.
cases were treated in this study and showed a significant reduction of
the viral levels at D6-post inclusion compared to controls,
and much lower average carrying duration than reported of untreated
patients in the literature. Azithromycin added to hydroxychloroquine
was significantly more efficient for virus elimination.
sample size our survey shows that hydroxychloroquine treatment is
associated with viral load reduction/disappearance in
COVID-19 patients and its effect is reinforced by azithromycin,
20 March 2020
Mount Sinai health system treatment guidelines for SARS-CoV-2 infection
Last accessed on 20th March 2020.
Sinai Heath System establishes protocols for dosing and treatment of
COVID-19 patients using Chloroquine and Hydroxychloroquine.
27 March 2020
Gautret, J.C. Lagier, P. Parola, V.T. Hoang, T. Dupont, S. Honoré, A.
Stein, M. Million, B. La Scola, P. Brouqui, Didier Raoul. Hydroxychloroquine-Azithromycin
Treatment for COVID-19 Shown to be Effective in an 80-Patient Study
Infection, Marseille, France
March 27, 2020
hydroxychloroquine and azithromycin we
noted a clinical improvement in
all but one 86 year-old patient who died, and one 74 year still in ICU.
A rapid fall of nasopharyngeal viral load tested by qPCR was noted,
cultures from patient respiratory samples turning negative in 97.5%
patients at Day 5.
allowed patients to rapidly be discharged from highly contagious wards
mean length of stay of five days.
10 March 2020
A., Ingoglia G., Ippolito M., Giarratano A., Einav S. A systematic
review on the efficacy and safety of chloroquine for the treatment of
J Crit Care. 2020 Mar 10;(20):30390–30397.
review was made of six articles (one narrative letter, one in-vitro
study, one editorial, expert consensus paper, two national guideline
documents) and these clinical trials done in China.
(n = 30)
(n = 100)
HCQ 0.2 g BID × 14 days
(n = 120)
400 CQ BID 2
tablets placebo BID
(n = 100)
CQ 1.0 g × 2 days,
then 0.5 g × 12
0.2 g BID x 14 days
Severe COVID-19 pneumonia
(n = 80)
CQ Standard Rx
(n = 10)
(n = 100)
CQ Standard treatment
(n = 100)
(n = 100)
HCQ: 6 tablets (0.2 g/ 6 tablets/day
(n = 100)
HCQ Hydroxychloroquine 2 tablets/day
(n = 200)
HCQ Standard Rx Viral test
(n = 120)
HCQ tablets and placebo BID
ill COVID-19 pneumonia (n = 45)
2 tablets CQ BID- placebo BID
contacts with confirmed (n = 320)
(n = 60)
(n = 240)
HCQ Medium-dose group:
(n = 112)
CQ oxygen index during treatment;
(n = 78)
HCQ 0.2 g BID Lab testing
controlled trial (n = 205)
Mild-moderate CQ group:
CQ plus Lopinavir/ritonavir; Severe
Severe Lopinavir/Ritonavir group:
(n = 300)
Group 1: Hydroxychloroquine 0.1 g
oral BID; Group 2:
0.2 g oral BID Placebo control group: Starch
(n = 20)
chloroquine 0.5 g BID for 10 days 30-day specific mortality
(n = 520)
lopinavir/ritonavir or Arbidol or CQ
The Trial of Chloroquine in the Treatment of COVID-19 and Its Research
Progress in Forensic Toxicology.
2020 Mar 25;36(2). doi: 10.12116/j.issn.1004-5619.2020.02.001. [Epub
ahead of print]
is a long-established prescription drug that is often used clinically
to treat malaria and connective tissue diseases. The
antimalarial drug Chloroquine phosphate which has already been approved
to have an anti-SARS-CoV-2 effect and has been included in diagnostic
and therapeutic guidelines.
awareness of the risk of chloroquine phosphate causing acute poisoning
or even death should be strengthened. The
dosage used according to current clinical recommended dosage and course
of treatment are larger than that of previous treatment of malaria.
provinces have required close clinical monitoring of adverse reactions.
This paper reviews the pharmacological effects, poisoning and
toxicological mechanisms, in vivo metabolism and distribution, and
forensic issues of chloroquine drugs, in order to provide help to
forensic practice and clinical work
US prescribing information. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009768s037s045s047lbl.pdf
(Last accessed March 21, 2020)
Li, Zhiwei Xie, Weiyin Lin, Weiping Cai, et.al, An
exploratory randomized, controlled study on the efficacy and safety of
lopinavir/ritonavir or arbidol treating adult patients hospitalized
with mild/moderate COVID-19
to investigators, adding
hydroxychloroquine (HCQ), on top of conventional therapy didn’t shorten
the time to SARS-CoV-2 clearance in a 30-patient trial.
significant differences were observed across the two arms in terms of
the time it took to bring body temperature to normal or the number
of patients with disease progression as shown in CT scans.
a careful examination of the study reveals a more complicated
patients in the study's control group were actually treated with
other antiviral drugs at
the same time, including the HIV combo med Kaletra and the Russian flu
drug Arbidol. Most,
but not all, patients in the hydroxychloroquine group were also treated
with Arbidol. All patients also received interferon-alpha, thereby
completely invalidating any assessment of Chloroquine effects.
Caro F, Ascione
Is Hydroxychloroquine a possible post-exposure prophylaxis
drug to limit the transmission to health care workers exposed to
2020 Mar 24.
32211764 DOI: 10.1093/cid/ciaa320
and Hydroxychloroquine are able to inhibit replication at early stages
similar effect on early phases of Coronavirus infection has been
reported for other drugs proposed for SARS-CoV-2 treatment, which are
able to interfere only after cell infection.
believe that hydroxychloroquine can be effective in preventing
respiratory tract invasion in HCW and that hydroxychloroquine
administration as prophylactic agent could be particularly useful for
HCW attending to high risk procedures on respiratory tract in
profile, its ability to inhibit lung viral replication for a 10-day
period after only a 5- day cycle of therapy, and the large
amounts of knowledge in term of safety deriving from its use
for malaria prophylaxis and rheumatologic diseases permit to
recommend its pre-exposure or post-exposure use for those performing
procedures at high risk of viral diffusion in patients
with COVID-19 pneumonia.
Singh, and A.
and hydroxychloroquine in the treatment of COVID-19 with or without
diabetes: A systematic search and a narrative review with a special
reference to India and other developing countries.
Published online 2020 Mar26. doi: 10.1016/j.dsx.2020.03.011
systematic review of Hydroxychloroquine and COVID-19
Task Force Interim clinical guidelines for patients suspected of /
confirmed with COVID-19 infection.
on pharmacokinetic simulations, the recommended dosing of
hydroxychloroquine sulphate is 400mg BID on day 1, followed by 200mg
BID on day 2-5.
of the long elimination half-life of the drug (32–50 days), the
duration of treatment should not exceed 5 days to avoid accumulation of
hydroxychloroquine concentrations in plasma and tissues, and associated
increased risk of toxicity, and because there is no in vitro evidence
that longer courses improve drug activity on SARS-CoV-2.
Hu, Zongwei Zhang, Shan Jiang, Shoumeng Han, Dandan Yan, Ruhong Zhuang,
Ben Hu, Zhan Zhang
Efficacy of hydroxychloroquine in patients with COVID-19: results of a
randomized clinical trial doi:https://doi.org/10.1101/2020.03.22.20040758
regarding the in-vivo use of Hydroxychloroquine is limited. In COVID-19
infection. This study evaluated the efficacy of hydroxychloroquine
(HCQ) in the treatment of patients with COVID-19. From February 4 to
February 28, 2020, 62 patients suffering from COVID-19 were diagnosed
and admitted to Renmin Hospital of Wuhan University. All participants
were randomized in a parallel-group trial, 31 patients were assigned to
receive an additional 5-day HCQ (400 mg/d) treatment, Time
to clinical recovery (TTCR), clinical characteristics, and radiological
results were assessed at baseline and 5 days after treatment to
evaluate the effect of HCQ.
the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of
62) were female, the mean age was 44.7 (15.3) years. No difference in
the age and sex distribution between the control group and the HCQ
group. But for TTCR,
the body temperature recovery time and the cough remission time were
significantly shortened in the HCQ treatment group.
a larger proportion of patients with improved pneumonia in the HCQ
treatment group (80.6%, 25 of 31) compared with the control group
(54.8%, 17 of 31).
all 4 patients progressed to severe illness that occurred in the
control group. However, there were 2 patients with mild adverse
reactions in the HCQ treatment group. Significance: Among
patients with COVID-19, the use of HCQ could significantly shorten TTCR
and promote the absorption of pneumonia.
data is supportive of preliminary evidence suggesting a significant
reduction in the average length of hospital stay (ALOS) in
COVID-19 patients administered hydroxychloroquine (HCQ) alone.
crude data was generated by a multi-center data collection effort
conducted by Agilum
Healthcare Intelligence Inc.
in Brentwood, Tennessee and analyzed with respect to the COVID length
of hospital stay under various investigational treatments.
unpublished data was generated from a bell-curve of patient severities
encompassing all levels of severity. Hence, it only provides a gross
estimation of a Hydroxychloroquine effect in COVID-19 patients. However
it is supportive of the French Data released on 12 April 2020 as an
Cohort of 1061 COVID-18 cases treated with HCQ-AZ Combination with 9
day follow-up. IHU
Méditerranée Infection, Marseille.
cohort of 1061 COVID-19 patients, treated for at least 3 days with the
HCQ-AZ combination and a follow-up of at least 9 days was investigated.
Endpoints were death, worsening and viral shedding persistence.
March 3rd to April 9th, 2020, 59,655 specimens from 38,617 patients
were tested for COVID-19 by PCR. Of the 3,165 positive patients placed
in the care of our institute, 1061
previously unpublished patients met the inclusion criteria for a
Hydroxychloroquine –Azithromycin trial.
age was 43.6 years old and 492 were male (46.4%), As
in other studies, no cardiac toxicity was observed in this study.
poor outcome was observed for 46 patients (4.3%); -10
were transferred to intensive care units,
patients died (0.47%) (74-95 years old), 31 required 10 days of
hospitalization or more.
this group, 25 patients are now cured and 16 are still hospitalized
(98% of patients cured so far).
Baseline characteristics according to clinical and virological outcome
of 1061 patients treated with HCQ + AZ ≥ 3 days at IHU Méditerranée
infection Marseille, France with Day 0 between March 3 and March 31,
viral carriage at completion of treatment was observed in 47 patients
(4.4%) and was associated with a higher viral load and more advanced
disease at diagnosis (p < 10-2) but viral culture was negative at
day 10 and all but one were PCR-cleared at day 15.
clinical outcome was significantly associated to older age (OR 1.11),
initial higher severity (OR 10.05) and low Hydroxychloroquine serum
addition, both poor clinical and virological outcomes were associated
with patients taking selective beta-blocking agents and angiotensin II
receptor blockers (P<0.05) for Hypertension.
Gao, Hu, S., Update on use of Hydroxychloroquine to TREAT coronavirus
disease 2019 (COVID-19).
evidence from completed clinical studies indicates the prospects for
the treatment of COVID-19 by Chloroquine and Hydroxychloroquine
(indications Hydroxychloroquine is more effective).
has indicated its efficacy in mild and moderate COVID-19 cases.
is superior to Lopinavir/ritonavir in improving COVID-19 lung lesions.
has demonstrated significant efficacy in returning body temperature to
seems more effective than Chloroquine in a French study on reducing the
amount of virus in the body.
helps reduce the duration of cough, reduce the amount of virus in the
body and improve negative lung lesions on X-ray.
have already commented on the single paper involving 15 patients
subjected simultaneously to Interferon-Alpha, arbidol, and
lopinavir/ritonavir in the control group.
general, completed clinical studies have yielded promising results
regarding the safety and effectiveness of Chloroquine and
Hydroxychloroquine in the TREATMENT of COVID-19
of Bibliography Review
upon a successful peer review of the data presented in 1,061 COVID-19
patients, treated for at least 3 days with the HCQ-AZ combination in
the French Abstract released 12 April 2020, by D. Raoult of the
IHU Méditerranée Infection and a successful review of the
10 April 2020 paper by Zhaowei Chen et.al, ……
use of HCQ-AZ combination when
started immediately after diagnosis,
appears to be a safe an efficient treatment for COVID-19. It appears to
halt respiratory disease progression and length of hospital stay in
the context of an expanding COVID-19 pandemic, it is reasonable to
propose the EARLY
use of Hydroxychloroquine in attempt to reduce the number of COVID
patient hospitalization days, and hence provide an increased rate of
patient turnover and a more efficient use of limited hospital
finding in the gross data study done on 10 April 2020
showing a slightly prolonged Average Length of Hospital Stay (ALOS) in
the population group given HCQ/CQ/Azithromycin, requires further
can show the same cardiac conduction effects as Chloroquine in humans,
but there has not been a widespread aversion to its being prescribed.
Some 4,000 individuals have now been given what are considered to be
COVID doses of Hydroxychloroquine, and not one cardiac conduction
problem has been noted.
controls are used in many previous studies in medicine. In this
respect, the safety of Hydroxychloroquine is well
When the safe use of this drug is projected against its apparent effect
of decreasing the progression of early cases to ventilator use, it is
difficult to understand the reluctance of the authorities in charge of
U.S. pandemic management to recommend its use in early COVID-19
The effects of the chloroquines were first outlined 15 years ago by the
CDC’s own Special Pathogens Unit.