Back to Journals » Infection and Drug Resistance » Volume 13

Flattening the Risk: Pre-Exposure Prophylaxis for COVID-19

Authors Stricker RB , Fesler MC

Received 27 May 2020

Accepted for publication 23 August 2020

Published 19 October 2020 Volume 2020:13 Pages 3689—3694


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eric Nulens

Raphael B Stricker, Melissa C Fesler

Union Square Medical Associates, San Francisco, CA, USA

Correspondence: Raphael B Stricker
Union Square Medical Associates, 450 Sutter Street, Suite 1504, San Francisco, CA 94108, USA
Tel +1 415-399-1035
Email [email protected]

Abstract: To date, more than 35 million people worldwide have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the agent of coronavirus disease 2019 (COVID-19), and more than one million have died in the COVID-19 pandemic. International economies are stalled and social isolation based on palpable fear of death remains the order of the day. The United States and other countries are moving toward resuming work activities and social interaction to boost economic recovery. While this makes financial sense, from a medical perspective our population has already suffered and will continue to suffer severe losses in the absence of a viable aggressive prophylaxis strategy for SARS-CoV-2. Herein, we present a plan to address this problem.

Keywords: coronavirus, SARS, COVID-19, prophylaxis


The medical approach to SARS-CoV-2 is based on three principles: prevention, early treatment and late treatment. We previously presented a novel plan to implement early treatment for COVID-19 on a large scale as needed.1 Although this plan may salvage patients with early disease, it is less practical than prevention for people who are resuming work activities and who may be exposed to SARS-CoV-2 via contact, aerosol and/or droplet transmission.2 As for late treatment, the high mortality rate of 50% or more for patients on respiratory support makes implementation of prevention and early treatment an urgent priority.3 Furthermore, the emergence of persistent debilitating symptoms in survivors indicates that COVID-19 is a complex illness that is best avoided.4 Residual risk of COVID-19 will likely persist in the future, and this risk is associated with additional global mental health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear.5,6 The medical costs of a poorly controlled COVID-19 pandemic are projected to reach hundreds of billions of dollars in the United States.7

Prophylaxis for viral infections traditionally relies on vaccines. Although a vaccine for COVID-19 would be an optimal solution, the prospects for a safe and effective vaccine are murky at best and probably not a viable option in the next two years due to mutational variation of the virus and potential vaccine enhancement of viral infection.8,9 Herd immunity to SARS-CoV-2 also may be difficult to achieve because the infection rate is too low.10,11 Therefore, an alternate prevention strategy is needed when social distancing is phased out during economic recovery. Drawing on lessons from the HIV/AIDS pandemic, we know that pre-exposure prophylaxis (PrEP) with antiviral agents is a viable strategy to prevent infection.12 In the case of HIV/AIDS, however, this treatment-intensive and expensive strategy only works because of the relatively small number of subjects at risk. For the COVID-19 pandemic, we need a more practical approach to prevention.

Based on worldwide experience with SARS-CoV-2, we now know that certain groups carry a higher risk of developing severe complications of COVID-19.3,13,14 These groups can be classified according to the following risk factors:

  • Hypertension
  • Diabetes
  • Obesity
  • Chronic kidney disease
  • Asthma/emphysema/smoking
  • Congestive heart failure
  • Liver cirrhosis
  • Malignancy/immune suppression
  • Age over 80 years old

In addition, medical personnel have more than three times the risk of acquiring the disease from repeated exposure to infected patients and household contacts.15,16 As schools reopen and asymptomatic children increase the risk of viral transmission, more teachers and parents will need protection against viral infection.17 Other high-risk groups include first responders, factory workers and sailors confined to close quarters, and prisoners.18 Individuals with certain genotypes may also have increased susceptibility to severe COVID-19.19 These subjects would benefit from a simple PrEP-type treatment for SARS-CoV-2.

Hydroxychloroquine PrEP

Where can we find a prophylactic treatment that is easy to use, inexpensive and already available? One answer lies in a medication that has generated significant controversy so far in the pandemic: hydroxychloroquine (HCQ). This medication has been used in combination with azithromycin for treatment of established SARS-CoV-2 infection, with variable results.20,21 There has been concern about cardiac and retinal toxicity with high-dose HCQ, especially because azithromycin increases blood levels of the medication.22,23 Furthermore, shortages of the two antimicrobials have occurred due to overprescribing in the face of the pandemic. Nevertheless, the combination appears to be effective in patients with early COVID-19, although it appears to be less effective in hospitalized patients with advanced disease.20,21 HCQ treatment was shown to protect multiple organs from inflammation in hospitalized COVID-19 patients.24 In one uncontrolled study, HCQ prophylaxis in a hospital setting with a known SARS-CoV-2 exposure prevented dissemination of viral infection.25

An overlooked property of HCQ is its extremely long half-life, estimated at up to 40 days with oral dosing.26,27 This extraordinary property has allowed the medication to be used for decades as weekly prophylaxis for malaria.28,29 Although HCQ-resistant malaria has eventually developed in parts of the world, the benefit of the medication is still recognized in terms of low cost, ease of use and limited side effects in areas with susceptible disease.2931 Malaria prophylaxis with HCQ may contribute in part to the reportedly low rate of COVID-19 infection seen so far in sub-Saharan Africa.32,33 Data from three randomized clinical trials using HCQ for the prevention and treatment of COVID-19 did not suggest significant safety concerns, and there were no sudden deaths in any trial.34 HCQ treatment is also considered safe for use in pregnancy and childhood diseases.35,36 Unfortunately, extrapolation of inpatient HCQ use to outpatient settings has muddied both the risks and benefits of this readily available preventive treatment for COVID-19.37

Based on these observations, we propose instituting a prophylactic regimen for SARS-CoV-2 in the high-risk patients listed above. The dose limit should be 400mg weekly based on malaria prophylaxis recommendations and continuing for one month or longer depending on the degree of social interaction and risk of viral exposure. The use of this prophylactic regimen will allow individuals to resume work with some modicum of protection against COVID-19. PrEP would also prevent high-risk individuals from acquiring infection from close contacts infected with the virus, and it would hopefully attenuate SARS-CoV-2 infection if it did occur.13 Although a higher-dose regimen might be more effective, higher dosing would also increase the risk of adverse events without clear benefit at this point in the pandemic.38,39 If symptoms of COVID-19 develop despite the use of PrEP, further treatment should be instituted immediately, as outlined in our previous publication.1

Recently three studies of HCQ prophylaxis in healthcare workers (HCWs) from India reported encouraging results. One cohort study found that 38% of untreated HCWs developed COVID-19 infection compared to 7% of HCWs treated with weekly HCQ PrEP (p<0.001).40 The second case–control study of HCWs found that four or more weekly doses of HCQ resulted in significantly less infection with SARS-CoV-2 (adjusted odds ratio 0.44, p<0.001).41 The third study was a questionnaire-based analysis showing that HCWs who had taken a full course of HCQ PrEP (seven or more weekly doses) had significantly less infection with SARS-CoV-2 compared to those who had taken either an incomplete course or no HCQ at all (p = 0.021).42

Additional clinical observations suggest that HCQ PrEP may be effective for COVID-19. In a multicenter retrospective study of 6,228 rheumatic disease patients from China, patients who were taking HCQ had a lower risk of SARS-CoV-2 infection compared to patients taking other disease-modifying anti-rheumatic drugs (odds ratio 0.09, p=0.044).43 Another population-based analysis of over 360,000 subjects from Portugal found that chronic HCQ treatment was associated with a significant decrease in SARS-CoV-2 infection (adjusted odds ratio 0.51, p=0.04).44 An observational study of 1,274 early outpatient COVID-19 cases in New Jersey found that a prescription of hydroxychloroquine reduced the risk of hospitalization by 47% (odds ratio 0.53). The benefit appeared to be lost if treatment was delayed more than two days after the onset of symptoms.45 In a retrospective cohort study of 32,109 rheumatic disease patients from the US Veterans Health Administration, the incidence of SARS-CoV-2 infection was equivalent regardless of chronic HCQ use (0.3% in users versus 0.4% in non-users), but mortality was significantly decreased in patients taking HCQ (odds ratio 0.70, p=0.0031).46 HCQ PrEP failed to prevent experimental viral infection in Syrian hamsters and macaque monkeys, but all of the animals cleared their infections and none died. Thus, the hamster and monkey PrEP models have questionable significance for humans.47,48

Larger randomized controlled trials (RCTs) of HCQ PrEP are ongoing in the United States and elsewhere.4952 The results of two RCTs that enrolled 1,615 HCWs were recently released, and among 1,053 subjects who received HCQ PrEP there were no hospitalizations, no deaths and no cardiac complications. In addition, once-weekly dosing appeared to be as effective as twice-weekly or daily dosing for HCQ PrEP. Because the studies were terminated prematurely they were underpowered to show a treatment benefit, however.53,54 Since RCTs require an average of 5.5 years for completion at an average cost of over a million dollars, it may take a long time to obtain conclusive results from these studies.5557 In the face of a public health crisis, it is important to consider life-saving approaches based on scientific logic and clinical availability even if definitive results are pending.21,58

Mefloquine PrEP

Unfortunately, HCQ has generated significant controversy resulting in the public perception that the medication is dangerous and ineffective. In light of this problem, weekly prophylaxis with mefloquine 250mg could be used instead. This oral medication has a half-life of about three weeks and appears to be active against SARS-CoV-2 in vitro, which makes it suitable for weekly antiviral prophylaxis.59,60 The troubling neuropsychiatric side effects of mefloquine make the drug a less attractive option for PrEP.

Ivermectin PrEP

Another option is the antiparasitic drug ivermectin. This antimicrobial agent with antiviral properties appears to be effective against SARS-CoV-2 in vitro and in vivo.6164 The half-life of ivermectin is 12–36 hours in humans, and its metabolites may persist for up to 12 days due to high liposolubility. It can be dosed daily or weekly at 0.15–0.2mg/kg with minimal side effects, but clinical PrEP trials for COVID-19 using ivermectin have not been organized to date, and appropriate antiviral dosing remains questionable.65 Individuals with specific gene mutations may have adverse reactions to ivermectin.66

Tafenoquine PrEP

Tafenoquine, a newer antimalarial agent that can be dosed weekly with a half-life of 2–3 weeks, has been suggested for COVID-19 PrEP, but the side effects and cost of this medication make it a less attractive candidate for widespread prophylaxis.67,68

Other Medication Options for PrEP

In patients with HIV/AIDS, treatment with tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) lowered the risk of COVID-19, but these medications are expensive and must be dosed daily.69 Therapy with convalescent plasma has been administered to severely ill COVID-19 patients and prophylaxis with plasma or neutralizing monoclonal antibodies has been suggested, but use of these nascent non-standardized treatments for PrEP has not been evaluated.7074

Barrier Protection

The efficacy and safety of barrier protection (primarily facemasks) in the COVID-19 pandemic continues to be debated, and formal studies in various settings have been recommended.75,76 For HCWs with high-risk patient exposure, facemasks were shown to be effective independent of other preventive measures.42 For the general population, facemasks appear to be less effective due to technical limitations, compliance issues and variable transmission risks.75,76 The theory of “variolation”, which states that population-wide masking may limit viral load exposure and thereby attenuate the severity of COVID-19, remains to be proven.77 Although not a perfect solution, medication-based PrEP should largely eliminate the drawbacks of barrier protection by providing consistent prophylaxis against viral infection for as long as the medication is used and the virus remains clinically susceptible.


As economies reopen, schools resume and passive social distancing becomes more difficult, there is an urgent need for active prophylaxis against COVID-19. PrEP modeled on malaria and HIV/AIDS prevention using readily available and clinically appropriate medication provides the means to fulfill this need in large populations at risk for viral infection. Until a vaccine can be found, PrEP for COVID-19 seems a logical and feasible choice for resumption of work activities and social interaction on a worldwide scale.


There is no funding to report.


The authors report no conflicts of interest in this work.


1. Stricker RB, Fesler MC. A novel plan to deal with SARS-CoV-2 and COVID-19 disease. J Med Virol. 2020;92:1394–1395. doi:10.1002/jmv.25945

2. Santarpia JL, Herrera VL, Rivera DN, et al. The infectious nature of patient-generated SARS-CoV-2 aerosol. MedRxiv. 2020. doi:10.1101/2020.07.13.20041632

3. Myers LC, Parodi SM, Escobar GJ, Liu VX. Characteristics of hospitalized adults with COVID-19 in an integrated health care system in California. JAMA. 2020;323(21):2195. doi:10.1001/jama.2020.7202

4. Tenforde MW, Kim SS, Lindsell CJ, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network — United States, March–June 2020. MMWR. 2020;69:993.

5. Bauchner H, Fontanarosa P. Thinking of risk in the era of COVID-19. JAMA. 2020;324(2):151. doi:10.1001/jama.2020.10242

6. Torales J, O’Higgins M, Castaldelli-Maia JM, Ventriglio A. The outbreak of COVID-19 coronavirus and its impact on global mental health. Int J Soc Psychiatry. 2020;66:317–320. doi:10.1177/0020764020915212

7. Lee BY. Coronavirus medical costs could soar into hundreds of billions as more Americans become infected. The Conversation. 2020. Available from: Accessed August 5, 2020.

8. Krammer F. SARS-CoV-2 vaccines in development. Nature. 2020.  doi:10.1038/s41586-020-2798-3

9. Farkas C, Fuentes-Villalobos F, Garrido JL, Haigh J, Barría MI. Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions. PeerJ. 2020;8:e9255. doi:10.7717/peerj.9255

10. Pollan M, Perez-Gomez B, Pastor-Barriuso R, et al. Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study. Lancet. 2020;396(10250):535–544. doi:10.1016/S0140-6736(20)31483-5

11. Kwok KO, Lai F, Wei WI, Wong SYS, Tang JWT. Herd immunity - estimating the level required to halt the COVID-19 epidemics in affected countries. J Infect. 2020;80(6):e32–e33. doi:10.1016/j.jinf.2020.03.027

12. Hillis A, Germain J, Hope V, McVeigh J, Van Hout MC. Pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM): a scoping review on PrEP service delivery and programming. AIDS Behav. 2020;24(11):3056–3070. doi:10.1007/s10461-020-02855-9

13. Dousa KM, Malavade SS, Furin J, et al. SARS-CoV-2 infection in a patient on chronic hydroxychloroquine therapy: implications for prophylaxis. IDCases. 2020;20:e00778. doi:10.1016/j.idcr.2020.e00778

14. Kass DA. COVID-19 and severe obesity: a big problem? Ann Intern Med. 2020. doi:10.7326/M20-5677

15. Steensels D, Oris E, Coninx L, et al. Hospital-wide SARS-CoV-2 antibody screening in 3056 staff in a tertiary center in Belgium. JAMA. 2020;324(2):195–197. doi:10.1001/jama.2020.11160

16. Nguyen LH, Drew DA, Graham MS, et al. Risk of COVID-19 among front-line health-care workers and the general community: a prospective cohort study. Lancet Public Health. 2020;5(9):e475–e483. doi:10.1016/S2468-2667(20)30164-X

17. Gaffney AW, Himmelstein D, Woolhandler S. Risk for severe COVID-19 illness among teachers and adults living with school-aged children. Ann Intern Med. 2020. doi:10.7326/M20-5413

18. Oran DP, Topol EJ. Prevalence of asymptomatic SARS-CoV-2 infection. A narrative review. Ann Intern Med. 2020;173(5):362–367. doi:10.7326/M20-3012

19. Zeberg H, Pääbo S.The major genetic risk factor for severe COVID-19 is inherited from Neanderthals. Nature. 2020. doi:10.1038/s41586-020-2818-3.

20. Million M, Lagier JC, Gautret P, et al. Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: a retrospective analysis of 1061 cases in Marseille, France. Travel Med Infect Dis. 2020;35:101738. doi:10.1016/j.tmaid.2020.101738

21. Risch HA. Early outpatient treatment of symptomatic, high-risk COVID-19 patients that should be ramped-up immediately as key to the pandemic crisis. Am J Epidemiol. 2020. doi:10.1093/aje/kwaa093

22. Jain R, Danziger LH. The macrolide antibiotics: a pharmacokinetic and pharmacodynamic overview. Curr Pharm Design. 2004;10:3045–3053. doi:10.2174/1381612043383322

23. Giudicessi JR, Noseworthy PA, Friedman PA, Ackerman MJ. Urgent guidance for navigating and circumventing the QTc prolonging and torsadogenic potential of possible pharmacotherapies for COVID-19. Mayo Clin Proc. 2020;95:1213–1221. doi:10.1016/j.mayocp.2020.03.024

24. Yu B, Li C, Chen P, Li J, Jiang H, Wang DW. Beneficial effects exerted by hydroxychloroquine in treating COVID-19 patients via protecting multiple organs. Sci China Life Sci. 2020. doi:10.1007/s11427-020-1782-1

25. Lee SH, Son H, Peck KR. Can post-exposure prophylaxis for COVID-19 be considered as an outbreak response strategy in long-term care hospitals? Int J Antimicrob Agents. 2020;55(6):105988. doi:10.1016/j.ijantimicag.2020.105988

26. Ducharme J, Fieger H, Ducharme MP, Khalil SK, Wainer IW. Enantioselective disposition of hydroxychloroquine after a single oral dose of the racemate to healthy subjects. Br J Clin Pharmacol. 1995;40:127–133. doi:10.1111/j.1365-2125.1995.tb05768.x

27. Lim HS, Im JS, Cho JY, et al. Pharmacokinetics of hydroxychloroquine and its clinical implications in chemoprophylaxis against malaria caused by plasmodium vivax. Antimicrob Agents Chemother. 2009;53:1468–1475. doi:10.1128/AAC.00339-08

28. Im JH, Huh K, Yoon CG, et al. Malaria control and chemoprophylaxis policy in the Republic of Korea Armed Forces for the previous 20 years (1997–2016). Malaria J. 2018;17:295. doi:10.1186/s12936-018-2449-4

29. Shippey EA, Wagler VD, Collamer AN. Hydroxychloroquine: an old drug with new relevance. Cleveland Clin J Med. 2018;85:459–467. doi:10.3949/ccjm.85a.17034

30. Yao X, Ye F, Zhang M, 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):732–739. doi:10.1093/cid/ciaa237

31. Spinelli FR, Ceccarelli F, Di Franco M, et al. To consider or not antimalarials as a prophylactic intervention in the SARS-CoV-2 (Covid-19) pandemic. Ann Rheum Dis. 2020;79:666–668. doi:10.1136/annrheumdis-2020-217367

32. Adegboye OA, Adekunle AI, Gayawan E. Early transmission dynamics of novel coronavirus (COVID-19) in Nigeria. Int J Environ Res Public Health. 2020;17(9):pii: E3054. doi:10.3390/ijerph17093054

33. Quaresima V, Naldini MM, Cirillo DM. The prospects for the SARS-CoV-2 pandemic in Africa. EMBO Mol Med. 2020;12. doi:10.15252/emmm.202012488

34. Lofgren SM, Nicol MR, Bangdiwala AS, et al. Safety of hydroxychloroquine among outpatient clinical trial participants for COVID-19. MedRxiv. 2020. doi:10.1101/2020.07.16.20155531

35. Sciascia S, Hunt BJ, Talavera-Garcia E, Lliso G, Khamashta MA, Cuadrado MJ. The impact of hydroxychloroquine treatment on pregnancy outcome in women with antiphospholipid antibodies. Am J Obstet Gynecol. 2016;214:273.e1–273.e8. doi:10.1016/j.ajog.2015.09.078

36. Braun S, Ferner M, Kronfeld K, Griese M. Hydroxychloroquine in children with interstitial (diffuse parenchymal) lung diseases. Pediatr Pulmonol. 2015;50:410–419. doi:10.1002/ppul.23133

37. Park JJH, Decloedt EH, Rayner CR, Cotton M, Mills EJ. Clinical trials of disease stages in COVID 19: complicated and often misinterpreted. Lancet Glob Health. 2020;8(10):e1249–e1250. doi:10.1016/S2214-109X(20)30365-X

38. Al-Kofahi M, Jacobson P, Boulware DR, et al. Finding the dose for hydroxychloroquine prophylaxis for COVID-19; the desperate search for effectiveness. Clin Pharmacol Ther. 2020;108(4):766–769. doi:10.1002/cpt.1874

39. Bonow RO, Hernandez AF, Turakhia M. Hydroxychloroquine, coronavirus disease 2019, and QT prolongation. JAMA Cardiol. 2020;5(9):986. doi:10.1001/jamacardio.2020.1782

40. Bhattacharya R, Chowdhury S, Mukherjee R, et al. Pre exposure hydroxychloroquine use is associated with reduced COVID19 risk in healthcare workers. MedRxiv. 2020. doi:10.1101/2020.06.09.20116806

41. Chatterjee P, Anand T, Singh KJ, et al. Healthcare workers and SARS-CoV-2 infection in India: a case-control investigation in the time of COVID-19. Indian J Med Res.2020;151(5):459-467.doi:10.4103/ijmr.IJMR_2234_20.

42. Khurana A, Kaushal GP, Gupta R, Verma V, Sharma K, Kohli M. Prevalence and clinical correlates of COVID-19 outbreak among health care workers in a tertiary level hospital in Delhi. MedRxiv. 2020. doi:10.1101/2020.07.21.20159301

43. Zhong J, Shen G, Yang H, et al. COVID-19 in patients with rheumatic disease in Hubei province, China: a multicentre retrospective observational study. Lancet Rheumatol. 2020;2(9):e557–e564. doi:10.1016/S2665-9913(20)30227-7

44. Ferreira A, Oliveira-e-Silva A, Bettencourt P. Chronic treatment with hydroxychloroquine and SARS-CoV-2 infection. MedRxiv. 2020. doi:10.1101/2020.06.26.20056507

45. Ip A, Ahn J, Zhou Y, et al. Hydroxychloroquine in the treatment of outpatients with mildly symptomatic COVID-19: a multi-center observational study. MedRxiv. 2020. doi:10.1101/2020.08.20.20178772

46. Gentry CA, Humphrey MB, Thind SK, Hendrickson SC, Kurdgelashvili G, Williams RJ II. Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study. Lancet Rheumatol. 2020.doi:10.1016/S2665-9913(20)30305-2.

47. Rosenke K, Jarvis MA, Feldmann F, et al. Hydroxychloroquine proves ineffective in hamsters and macaques infected with SARS- CoV-2. BioRxiv. 2020. doi:10.1101/2020.06.10.145144

48. Maisonnasse P, Guedj J, Contreras V, et al. Hydroxychloroquine use against SARS-CoV-2 infection in non-human primates. Nature. 2020;585(7826):584–587. doi:10.1038/s41586-020-2558-4

49. O’Neill WW. Will hydroxychloroquine impede or prevent COVID-19 (WHIP COVID-19). 2020. Available from: NLM identifier: NCT04341441. Accessed August 3, 2020.

50. Wright JK, Tan DHS, Walmsley SL, et al. Protecting frontline health care workers from COVID-19 with hydroxychloroquine pre-exposure prophylaxis: a structured summary of a study protocol for a randomised placebo-controlled multisite trial in Toronto, Canada. Trials. 2020;21:647. doi:10.1186/s13063-020-04577-8

51. Hazan S A study of hydroxychloroquine, vitamin C, vitamin D, and zinc for the prevention of COVID-19 infection (HELPCOVID-19). 2020. Available from: NLM identifier: NCT04335084. Accessed September 25, 2020.

52. Infante M, Ricordi C, Alejandro R, Caprio M, Fabbri A. Hydroxychloroquine in the COVID-19 pandemic era: in pursuit of a rational use for prophylaxis of SARS-CoV-2 infection. Expert Rev Anti Infect Ther. 2020. doi:10.1080/14787210.2020.1799785

53. Abella BS, Jolkovsky EL, Biney BT, Uspal JE, Hyman MC, Frank I, et al. Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers: A randomized clinical trial. JAMA Intern Med. 2020. doi:10.1001/jamainternmed.2020.6319.

54. Rajasingham R, Bangdiwala AS, Nicol MR, Skipper CP, Pastick KA, Axelrod ML,et al. Hydroxychloroquine as pre-exposure prophylaxis for COVID-19 in healthcare workers: a randomized trial. MedRxiv. 2020. doi:10.1101/2020.09.18.20197327

55. Pham Q, Wikjer D, Cafazzo JA, Eng P. Beyond the randomized controlled trial: a review of alternatives in mHealth clinical trial methods. JMIR Mhealth Uhealth. 2016;4:e107. doi:10.2196/mhealth.5720

56. Johnston SC, Rootenberg JD, Katrak S, Smith WS, Elkins JS. Effect of a US National Institutes of Health programme of clinical trials on public health and costs. Lancet. 2006;367:1319–1327. doi:10.1016/S0140-6736(06)68578-4

57. Pundi K, Perino AC, Harrington RA, Krumholz HM, Turakhia MP. Characteristics and strength of evidence of COVID-19 studies registered on JAMA Intern Med. 2020. doi:10.1001/jamainternmed.2020.2904

58. Song P, Karako T. COVID-19: real-time dissemination of scientific information to fight a public health emergency of international concern. Biosci Trends. 2020;14:1–2. doi:10.5582/bst.2020.01056

59. Schlagenhauf P, Hatz C, Behrens R, et al. Mefloquine at the crossroads? Implications for malaria chemoprophylaxis in Europe. Travel Med Infect Dis. 2015;13:192–196. doi:10.1016/j.tmaid.2015.03.010

60. Fan HH, Wang LQ, Liu WL, et al. Repurposing of clinically approved drugs for treatment of coronavirus disease 2019 in a 2019-novel coronavirus (2019-nCoV) related coronavirus model. Chin Med J (Engl). 2020;133(9):1051–1056. doi:10.1097/CM9.0000000000000797

61. Yang SNY, Atkinson SC, Wang C, et al. The broad spectrum antiviral ivermectin targets the host nuclear transport importin α/β1 heterodimer. Antiviral Res. 2020;177:104760. doi:10.1016/j.antiviral.2020.104760

62. Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020;178:104787. doi:10.1016/j.antiviral.2020.104787

63. Sharun K, Dhama K, Patel SK, et al. Ivermectin, a new candidate therapeutic against SARS-CoV-2/COVID-19. Ann Clin Microbiol Antimicrob. 2020;19(1):23. doi:10.1186/s12941-020-00368-w

64. Rajter JC, Sherman M, Fatteh N, Vogel F, Sacks J, Rajter JJ. ICON (Ivermectin in COvid Nineteen) study: use of ivermectin is associated with lower mortality in hospitalized patients with COVID19. MedRxiv. 2020. doi:10.1101/2020.06.06.20124461

65. Bray M, Rayner C, Noël F, Jans D, Wagstaff K. Ivermectin and COVID-19: a report in Antiviral Research, widespread interest, an FDA warning, two letters to the editor and the authors’ responses. Antiviral Res. 2020;178:104805. doi:10.1016/j.antiviral.2020.104805

66. Baudou E, Lespine A, Durrieu G, et al. Serious ivermectin toxicity and human ABCB1 nonsense mutations. N Engl J Med. 2020;383:787–789. doi:10.1056/NEJMc1917344

67. Alshaban F. A recommendation for the use of chloroquine, hydroxychloroquine, primaquine, or tafenoquine for prophylaxis against the 2019 novel coronavirus (COVID-19) with note to the ophthalmic considerations. Eye Res. 2020;6:S7–S10. doi:10.16964/er.v6i1.99

68. Dow GS, Luttick A, Fenner J, Wesche D, Yeo KR, Rayner C. Tafenoquine inhibits replication of SARS-Cov-2 at pharmacologically relevant concentrations in vitro. BioRxiv. 2020. doi:10.1101/2020.07.12.199059

69. Del Amo J, Polo R, Moreno S, et al. Incidence and severity of COVID-19 in HIV-positive persons receiving antiretroviral therapy – a cohort study. Ann Intern Med. 2020. doi:10.7326/M20-3689

70. Casadevall A, Pirofski LA. The convalescent sera option for containing COVID-19. J Clin Invest. 2020;130:1545–1548. doi:10.1172/JCI138003

71. Li L, Zhang W, Hu Y, et al. Effect of convalescent plasma therapy on time to clinical improvement in patients with severe and life-threatening COVID-19. A randomized clinical trial. JAMA. 2020;324(5):460. doi:10.1001/jama.2020.10044

72. Liu M, Chen Z, Dai M-Y, et al. Lessons learned from early compassionate use of convalescent plasma on critically ill patients with Covid-19. Transfusion. 2020:1–7. doi:10.1111/trf.15975

73. Liu L, Wang P, Nair MS, et al. Potent neutralizing antibodies directed to multiple epitopes on SARS-CoV-2 spike. Nature. 2020;584(7821):450–456. doi:10.1038/s41586-020-2571-7

74. Ledford H. Antibody therapies could be a bridge to a coronavirus vaccine - but will the world benefit? Nature. 2020;584(7821):333–334. doi:10.1038/d41586-020-02360-y

75. Esposito S, Principi N, Leung CC, Migliori GB. Universal use of face masks for success against COVID-19: evidence and implications for prevention policies. Eur Respir J. 2020;55:2001260. doi:10.1183/13993003.01260-2020

76. Schünemann HJ, Akl EA, Chou R, et al. Use of facemasks during the COVID-19 pandemic. Lancet Respir Med. 2020. doi:10.1016/S2213-2600(20)30352-0

77. Gandhi M, Rutherford GW. Facial masking for Covid-19 — potential for “variolation” as we await a vaccine. N Engl J Med. 2020. doi:10.1056/NEJMp2026913

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