Prevention and Prophylaxis of SARS-CoV-2 Infection
Last Updated: July 17, 2020
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies; III = Expert opinion
General Prevention Measures
Most transmissions of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are thought to occur through respiratory droplets, and the risk of transmission can be reduced by covering coughs and sneezes and maintaining a distance of at least 6 feet from others. When consistent distancing is not possible, face coverings may further reduce the spread of droplets from infectious individuals to others. Frequent handwashing is also effective in reducing the risk of acquisition.1 Health care providers should follow the Centers for Disease Control and Prevention (CDC) recommendations for infection control and appropriate use of personal protective equipment.2
Vaccines for SARS-CoV-2 are aggressively being pursued. Vaccine development is typically a lengthy process, often requiring multiple candidates before one proves to be safe and effective. To address the current pandemic, several platforms are being used to develop candidate vaccines for Phase 1/2 trials; those that show promise are rapidly moving into Phase 3 trials. Several standard platforms, such as inactivated vaccines, live-attenuated vaccines, and protein subunit vaccines, are being pursued. Some novel approaches are being investigated, including DNA-based and RNA-based strategies and replicating and nonreplicating vector strategies, with the hope of identifying a safe and effective vaccine that can be used in the near future.3,4
- The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use of any agents for SARS-CoV-2 pre-exposure prophylaxis (PrEP), except in a clinical trial (AIII).
At present, no known agent that is administered before exposure (i.e., as PrEP) can prevent SARS-CoV-2 infection. Clinical trials are investigating several agents, including emtricitabine plus tenofovir alafenamide or tenofovir disoproxil fumarate, hydroxychloroquine, and supplements such as zinc, vitamin C, and vitamin D. Studies of monoclonal antibodies that target SARS-CoV-2 are in development. Please check ClinicalTrials.gov for the latest information.
- The Panel recommends against the use of any agents for SARS-CoV-2 post-exposure prophylaxis (PEP), except in a clinical trial (AIII).
At present, no known agent can prevent SARS-CoV-2 infection after exposure (i.e., as PEP). Potential options for PEP that are currently under investigation include chloroquine, hydroxychloroquine, lopinavir/ritonavir, nitazoxanide, vitamin super B-complex, and vitamin D. Other strategies that are in development include the use of SARS-CoV-2 monoclonal antibodies and convalescent plasma. Please check ClinicalTrials.gov for the latest information.
Clinical Trial Data
Both chloroquine and hydroxychloroquine have in vitro activity against SARS-CoV and SARS-CoV-2.5,6 A small cohort study without a control group has suggested that hydroxychloroquine might reduce the risk of household transmission.7
A randomized, double-blind, controlled trial enrolled 821 participants using an internet-based survey. Study participants had either high or moderate risk of occupational exposures (66% of participants) or household exposures (34% of participants). High-risk exposure was defined as being within 6 feet of an individual with confirmed SARS-CoV-2 infection for more than 10 minutes while not wearing a face mask or eye shield (87.6% of participants), and moderate-risk exposure was defined as the same exposure while wearing a face mask but no eye shield (12.4% of participants).8
Participants were randomized to receive placebo or hydroxychloroquine sulfate given once at a relatively high dose of 800 mg, followed by 600 mg 6 to 8 hours later, then 600 mg once daily for 4 additional days. Because enrollment was done online, study drugs were sent by overnight mail, resulting in more than 50% of participants initiating their first dose 3 to 4 days after exposure to SARS-CoV-2.8
A total of 107 participants had a primary outcome of symptomatic illness, with SARS-CoV-2 infection confirmed by molecular test or by the development of a compatible, COVID-19-related syndrome based on CDC criteria. Due to limited access to molecular diagnostic testing, confirmation of infection occurred for only 16 of the 107 participants (15%). There was no statistically significant difference between the incidences of a primary outcome in the hydroxychloroquine and placebo groups (11.8% vs. 14.3%, respectively; P = 0.35). There were more adverse events in the hydroxychloroquine group; mostly nausea, loose stools, and abdominal discomfort, with no serious adverse reactions or cardiac arrhythmias.8
This study had several important limitations, including:
- Initiation of therapy was delayed for at least 3 days after exposure to SARS-CoV-2 in the majority of participants.
- Only 15% of participants who reached the primary outcome had SARS-CoV-2 infection confirmed by molecular diagnostics.
- The study population was young (with a median age of 40 years) and consisted of participants who had a relatively low risk of severe COVID-19.
It is notable that while high doses of hydroxychloroquine were associated with an increase in the frequency of adverse events, the reported adverse events were mostly mild, with no serious events reported.
- Centers for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19): how to protect yourself & others. 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html?CDC_AA_refVal=https%3A%2F%2Fwww.cdc.gov%2Fcoronavirus%2F2019-ncov%2Fprepare%2Fprevention.html. Accessed July 10, 2020.
- Centers for Disease Control and Prevention. Coronavirus disease 2019 (COVID-19): infection control guidance for healthcare professionals about coronavirus (COVID-19). 2020. Available at: https://www.cdc.gov/coronavirus/2019-ncov/hcp/infection-control.html. Accessed July 10, 2020.
- Lurie N, Saville M, Hatchett R, Halton J. Developing COVID-19 vaccines at pandemic speed. N Engl J Med. 2020;382(21):1969-1973. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32227757.
- World Health Organization. Draft landscape of COVID-19 candidate vaccines. 2020. Available at: https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines. Accessed July 10, 2020.
- 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. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32150618.
- Vincent MJ, Bergeron E, Benjannet S, et al. Chloroquine is a potent inhibitor of SARS coronavirus infection and spread. Virol J. 2005;2:69. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16115318.
- 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. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32305587.
- Boulware DR, Pullen MF, Bangdiwala AS, et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for COVID-19. N Engl J Med. 2020. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32492293.