Chronic Hydroxychloroquine Therapy and COVID-19 Outcomes: A Retrospective Case-Control Analysis

Rangel et al., Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2020.10.098, Jan 2021
Mortality 25% improvement lower risk ← → higher risk Hospitalization 22% Hospitalization time 41% HCQ for COVID-19  Rangel et al.  PROPHYLAXIS Is pre-exposure prophylaxis with HCQ beneficial for COVID-19? Retrospective 153 patients in the USA Lower hospitalization with HCQ (not stat. sig., p=0.29) c19early.org Rangel et al., J. the American Academy.., Jan 2021 0 0.5 1 1.5 2+ RR
HCQ for COVID-19
1st treatment shown to reduce risk in March 2020, now with p < 0.00000000001 from 424 studies, used in 59 countries.
Lower risk for mortality, hospitalization, progression, recovery, cases, and viral clearance.
No treatment is 100% effective. Protocols combine treatments.
6,300+ studies for 210+ treatments. c19early.org
Meta Analysis
Retrospective 50 COVID-19 patients that take chronic HCQ, compared to a matched sample of patients not taking chronic HCQ, showing lower mortality and ICU admission, and shorter hospitalization for HCQ patients, but not statistically significant due to the small number of events.
The actual benefit for HCQ could be much larger. The study does not address the risk of being sick enough to visit the hospital. HCQ users are likely systemic autoimmune disease patients and authors do not adjust for the very different baseline risk for these patients. Other research shows that the risk of COVID-19 for systemic autoimmune disease patients is much higher overall, Ferri et al. show OR 4.42, p<0.0011.
Although the 25% lower mortality is not statistically significant, it is consistent with the significant 27% lower mortality [22‑31%] from meta analysis of the 256 mortality results to date.
Standard of Care (SOC) for COVID-19 in the study country, the USA, is very poor with very low average efficacy for approved treatments2. Only expensive, high-profit treatments were approved for early treatment. Low-cost treatments were excluded, reducing the probability of early treatment due to access and cost barriers, and eliminating complementary and synergistic benefits seen with many low-cost treatments.
This study is excluded in the after exclusion results of meta analysis: not fully adjusting for the different baseline risk of systemic autoimmune patients.
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risk of death, 25.1% lower, RR 0.75, p = 0.77, treatment 4 of 50 (8.0%), control 11 of 103 (10.7%), NNT 37, from all patients.
risk of hospitalization, 22.2% lower, RR 0.78, p = 0.29, treatment 17 of 50 (34.0%), control 45 of 103 (43.7%), NNT 10.
hospitalization time, 41.2% lower, relative time 0.59, p = 0.12, treatment 21, control 54.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Rangel et al., 10 Jan 2021, retrospective, USA, peer-reviewed, 5 authors.
$0 $500 $1,000+ Efficacy vs. cost for COVID-19 treatment protocols c19early.org December 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Bosnia-Herzegovina Ukraine Côte d'Ivoire Bulgaria Greece Slovakia Singapore Iceland New Zealand Czechia Mongolia Israel Trinidad and Tobago Hong Kong North Macedonia Belarus Qatar Panama Serbia CAR USA favored high-profit treatments.The average efficacy of treatments was very low.High-cost protocols reduce early treatment, andforgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
$0 $500 $1,000+ Efficacy vs. cost for COVID-19treatment protocols worldwide c19early.org December 2025 USA Russia Sudan Angola Colombia Kenya Mozambique Vietnam Peru Philippines Spain Brazil Italy France Japan Canada China Uzbekistan Nepal Ethiopia Iran Ghana Mexico South Korea Germany Bangladesh Saudi Arabia Algeria Morocco Yemen Poland India DR Congo Madagascar Thailand Uganda Venezuela Nigeria Egypt Bolivia Taiwan Zambia Fiji Ukraine Côte d'Ivoire Eritrea Bulgaria Greece Slovakia Singapore New Zealand Malawi Czechia Mongolia Israel Trinidad and Tobago North Macedonia Belarus Qatar Panama Serbia Syria USA favored high-profit treatments.The average efficacy was very low.High-cost protocols reduce early treatment,and forgo complementary/synergistic benefits. More effective More expensive 75% 50% 25% ≤0%
Abstract: J AM ACAD DERMATOL VOLUME 84, NUMBER 6 Medicine, Boston University School of Medicine, Massachusetts.e Drs Hartman and La are cofirst authors. Funding sources: Supported by an American Skin Association research grant (120795 to Dr Hartman). IRB approval status: Not applicable. Reprints not available from the authors. Correspondence to: Rebecca I. Hartman, MD, MPH, Harvard Medical School, BWH Department of Dermatology, 221 Longwood Ave, Boston, MA 02215 E-mail: rhartman@bwh.harvard.edu Conflicts of interest None disclosed. REFERENCES 1. Faries MB, Thompson JF, Cochran AJ, et al. Completion dissection or observation for sentinel-node metastasis in melanoma. N Engl J Med. 2017;376(23):2211-2222. 2. Wei EX, Chen L, Ma F, Keri J, Hu S. Recent dermatology visit is associated with thinner Breslow depth nodular melanomas. J Am Acad Dermatol. 2019;80(4):1143-1144. 3. Roetzheim RG, Lee JH, Ferrante JM, et al. The influence of dermatologist and primary care physician visits on melanoma outcomes among Medicare beneficiaries. J Am Board Fam Med. 2013;26(6):637-647. 4. Jackson GL, Melton LD, Abbott DH, et al. Quality of nonmetastatic colorectal cancer care in the Department of Veterans Affairs. J Clin Oncol. 2010;28(19):3176-3181. 5. Orkaby AR, Nussbaum L, Ho YL, et al. The burden of frailty among U.S. veterans and its association with mortality, 2002-2012. J Gerontol A Biol Sci Med Sci. 2019;74(8): 1257-1264. https://doi.org/10.1016/j.jaad.2020.12.069 Chronic hydroxychloroquine therapy and COVID-19 outcomes: A retrospective case-control analysis To the Editor: Hydroxychloroquine (HCQ) has failed to show significant therapeutic benefit for patients with coronavirus disease-2019 (COVID-19) in recent studies, although interest in this medication’s potential pre- and postprophylactic efficacy remains, with 1 retrospective study showing reduced COVID-19 infection among patients taking chronic HCQ.1,2 In this study, we sought to evaluate COVID-19 clinical outcomes in patients taking chronic HCQ for an underlying condition as well as in a matched cohort not taking HCQ at time of COVID-19 diagnosis. Research Letters 1769 Table I. Hydroxychloroquine indication, dosage, and duration at time of COVID-19 diagnosis HCQ indication, dosage, and duration (N = 50) HCQ indication Systemic lupus erythematosus Rheumatoid arthritis Connective tissue disease overlap syndromes €gren syndrome Sjo Mixed connective tissue disease Undifferentiated connective tissue disease Erythema nodosum during pregnancy Carcinoid Myalgic encephalomyelitis/ chronic fatigue syndrome Acquired hypogammaglobulinemia HCQ dosage 200 mg HCQ daily 200 mg HCQ 2 times daily (400 mg total) 200 mg HCQ 3 times daily (600 mg total) Mean duration of HCQ therapy before COVID-19 diagnosis (IQR) n (%) 17 (34.0) 11 (22.0) 9 (18.0) 6 (12.0) 2 (4.0) 1 (2.0) 1 (2.0) 1 (2.0) 1 (2.0) 1 (2.0) 13 (36.0) 36 (72.0) 1 (2.0) 28 (14.25-44.25) months COVID-19, Coronavirus disease-2019; HCQ, hydroxychloroquine; IQR, interquartile range. We identified all patients with severe acute respiratory syndrome coronavirus 2 seen at New York University from March to April 2020 using International Classification of Diseases, 10th revision codes and included patients taking HCQ for $6 weeks before their COVID-19 diagnosis. Control subjects were randomly selected from the remaining severe acute respiratory syndrome coronavirus 2epositive patients with automated matching for age, gender, and immunosuppressive medication using..
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