Pre-exposure hydroxychloroquine prophylaxis for COVID-19 in healthcare workers: a retrospective cohort
Keywords:COVID-19, Hydroxychloroquine, Pre-exposure prophylaxis, Healthcare workers
Background: While several trials are ongoing for treatment of Corona virus 2019 (COVID-19), scientific research on chemoprophylaxis is still lacking even though it has potential to flatten the curve allowing us time to complete research on vaccines.
Methods: This retrospective cohort study explores the potential of hydroxychloroquine (HCQ) as a pre- exposure prophylaxis for COVID-19 among 106 health care workers (HCW) exposed to COVID-19 patients, at a tertiary care hospital in India where there was an abrupt cluster outbreak within on duty personnel. HCWs who had voluntarily taken HCQ prior to exposure were considered one cohort while those who had not were considered to be the Control group. All participants with a verifiable high-risk contact history were tested for COVID-19 by RT- PCR.
Results: The two cohorts were comparable in terms of age, gender, co-morbidity and exposure. The primary outcome was incidence rates of RT-PCR positive COVID-19 infection among HCQ users and Controls.106 HCW were examined of whom 54 were HCQ users. The comparative analysis of incidence of infection between the two groups demonstrated that voluntary HCQ usage was associated with lesser likelihood of developing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection (4 out of 54 HCW), compared to those who were not on it (20 out of 52 HCW), χ2=14.59, p<0.001. None of the HCQ users noted any serious adverse effects.
Conclusions: The study demonstrated that voluntary pre- exposure HCQ prophylaxis by HCWs is associated with a statistically significant reduction in risk of SARS-CoV-2.
Worldometers.info, Dover, Delaware, U.S.A. COVID-19 Coronavirus Pandemic. 2020. Available from: https://www.worldometers.info/coronavirus. Accessed on 07 April, 2020.
Adalja A, Inglesby T. Broad-Spectrum Antiviral Agents: A Crucial Pandemic Tool. Expert Rev Anti Infect Ther. 2019;17(7):467-70.
Ianevski A, Andersen PI, Merits A, Bjørås M, Kainov D. Expanding the activity spectrum of antiviral agents. Drug Discov Today. 2019;24(5):1224-28.
Al-Bari MAA. Targeting endosomal acidification by chloroquine analogs as a promising strategy for the treatment of emerging viral diseases. Pharmacol Res Perspect. 2017;5(1):e00293.
McChesney EW. Animal toxicity and pharmacokinetics of hydroxychloroquine sulfate. Am J Med. 1983;75(1A):11-8.
Long L, Yang X, Southwood M, Lu J, Marciniak SJ, Dunmore BJ, et al. Chloroquine prevents progression of experimental pulmonary hypertension via inhibition of autophagy and lysosomal bone morphogenetic protein type II receptor degradation. Circ Res. 2013;112(8):1159-70.
Savarino A, Boelaert JR, Cassone A, Majori G, Cauda R. Effects of chloroquine on viral infections: an old drug against today's diseases? Lancet Infect Dis. 2003;3(11):722-7.
Yan Y, Zou Z, Sun Y, Li X, Xu KF, Wei Y, et al. Anti-malaria drug chloroquine is highly effective in treating avian influenza A H5N1 virus infection in an animal model. Cell Res. 2013;23(2):300-2.
Borba EF, Saad CG, Pasoto SG, Calich AL, Aikawa NE, Ribeiro AC, et al. Influenza A/H1N1 vaccination of patients with SLE: can antimalarial drugs restore diminished response under immunosuppressive therapy? Rheumatology (Oxford). 2012;51(6):1061-9.
Vincent MJ, Bergeron E, Benjannet S, Erickson BR, Rollin PE, Ksiazek TG, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69.
Berne MA, Somasundaran M, Sullivan JL, Luzuriaga K, Greenough TC, Choe H, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450-4.
Freund NT, Roitburd-Berman A, Sui J, Marasco WA, Gershoni JM. Reconstitution of the receptor-binding motif of the SARS coronavirus. Protein Eng Des Sel. 2015;28(12):567-75.
Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-73.
Liu J, Cao R, Xu M, Wang X, Zhang H, Hu H, et al. Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro. Cell Discov. 2020;6:16.
Mingo RM, Simmons JA, Shoemaker CJ, Nelson EA, Schornberg KL, D'Souza RS, et al. Ebola virus and severe acute respiratory syndrome coronavirus display late cell entry kinetics: evidence that transport to NPC1+ endolysosomes is a rate-defining step. J Virol. 2015 Mar;89(5):2931-43.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell. 2020;181(2):271-280.e8.
Magagnoli J, Narendran S, Pereira F, Cummings TH, Hardin JW, Sutton SS, et al. Outcomes of Hydroxychloroquine Usage in United States Veterans Hospitalized with COVID-19. Med (N Y). 2020.
Ministry of Health and Family Welfare, Government of India. Advisory on the use of Hydroxychloroquine as prophylaxis for SARS-CoV-2 Infection. 2020. https://www.mohfw.gov.in/pdf/AdvisoryontheuseofHydroxychloroquinasprophylaxisforSARSCoV2infection.pdf. Accessed on 07 April, 2020.
National Centre for Disease Control. SOP for Contact tracing COVID-19 cases. 2020. https://ncdc.gov.in/showfile.php?lid=538. Accessed on 07 April, 2020.
Indian Council of Medical Research. Multiplex Real-Time PCR for detection of SARS-CoV-2 using TaqPath COVID-19 Combo Kit (Applied Biosystems). https://www.icmr.gov.in/pdf/covid/labs/SARS_CoV2_using_TaqPath_COVID19_ComboKit.pdf. Accessed on 07 April, 2020.
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention. JAMA. 2020;323(13):1239-42.
Beigel JH, Tomashek KM, Dodd LE, Mehta AK, Zingman BS, Kalil AC, et al; ACTT-1 Study Group Members. Remdesivir for the Treatment of Covid-19 - Preliminary Report. N Engl J Med. 2020;NEJMoa2007764.
Covid19tracker.health.ny.gov. Workbook: NYS-COVID19-Tracker. 2020. https://covid19tracker.health.ny.gov/views/NYS-COVID19-Tracker/NYSDOHCOVID-19Tracker-Fatalities?%3Aembed=yes&%3Atoolbar=no&%3Atabs=n. Accessed on 07 April, 2020.
Tang W, Cao Z, Han M, Wang Z, Chen J, Sun W, et al. Hydroxychloroquine in patients with mainly mild to moderate coronavirus disease 2019: open label, randomised controlled trial. BMJ. 2020;369:m1849.
Hussain A, Kaler J, Dubey AK. Emerging Pharmaceutical Treatments of Novel COVID-19: A Review. Cureus. 2020;12(5):e8260.
Wang Y, Zhang D, Du G, Du R, Zhao J, Jin Y, et al. Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2020;395(10236):1569-78.
Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, et al. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020;382(19):1787-99.
McCaw JM, McVernon J. Prophylaxis or treatment? Optimal use of an antiviral stockpile during an influenza pandemic. Math Biosci. 2007;209(2):336-60.
Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, et al. 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). Clin Infect Dis. 2020;71(15):732-39.
Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020;30(3):269-71.
Chatterjee P, Anand T, Singh KJ, Rasaily R, Singh R, Das S, et al. Healthcare workers & SARS-CoV-2 infection in India: A case-control investigation in the time of COVID-19. Indian J Med Res. 2020;151(5):459-67.
Ministry of Health and Family Welfare, Government of India. Guidelines on rational use of Personal Protective Equipment. https://www.mohfw.gov.in/ pdf/GuidelinesonrationaluseofPersonalProtectiveEquipment.pdf. Accessed on 24 March, 2020.