Covid-19: the crisis of personal protective equipment in the USBMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1367 (Published 03 April 2020) Cite this as: BMJ 2020;369:m1367
All rapid responses
The World Health Organization (WHO) defined the coronavirus disease 2019 (COVID-19) epidemic, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a public health emergency of international concern.  The spread of COVID-19 is reaching alarming figures worldwide. As of 24 March this year, more than 334,000 cases of COVID-19 have been confirmed in a total of 189 countries. Overall, more than 14,600 deaths have been reported thus far, with a case fatality rate of 4.4%.  In such a situation, it is essential to forecast the epidemic trend in order to take adequate healthcare measures.
The attack rate (AR) (i.e., the percentage of exposed patients who will eventually become infected) is a metric that may help to estimate this trend. The AR of SARS-CoV2 is still a matter of debate. The WHO reported an AR of about 3-10%  in household contacts of SARS-CoV-2 patients in the Guangdong Province of China, which is similar to that of influenza viruses (about 10%).
In the absence of a vaccine, the strategy of epidemic containment lays mainly in the isolation of both cases and contacts and in social distancing of the entire population. Many countries have taken a series of exceptional containment measures including locking down entire cities. However, with the likely exception of China, such measures have not been sufficient to block the spread of SARS-CoV-2 infection. In fact, several countries continue to report outbreaks, thereby forcing governments to adopt extraordinary public health measures. The ongoing increase in the number of COVID-19 cases risks bringing national health systems to the brink of collapse, and could lead to disastrous social and economic consequences.
In this context, a post-exposure prophylaxis (PEP) approach may help to reduce the spread of theCOVID-19 epidemic. This procedure consists in the administration of drugs to a subject who has been exposed to an infected patient in the attempt to reduce the risk of becoming infected. The drugs administered are often the same drugs used to treat patients. This strategy is not novel. Indeed, it is well established in the setting of acute viral respiratory infections. For example, oseltamivir and zanamivir, two antivirals used to treat influenza, are administered to exposed subjects to reduce the risk of secondary cases. In a meta-analysis, oseltamivir and zanamivir prevented influenza in 67-89% of subjects who underwent PEP. 
With respect to the coronavirus responsible for the SARS epidemic in 2002-2004, no pharmacological prevention strategies were implemented beyond such non-specific measures as active symptom monitoring or home quarantine. Notably, in the setting of the coronavirus responsible for the Middle East Respiratory Syndrome (MERS), a study conducted in South Korea evaluated whether PEP was effective in preventing MERS in healthcare workers (HCWs) after unprotected exposure to infected patients.  The study enrolled 22 HCWs receiving ribavirin plus lopinavir/ritonavir within 80 hours (median 36 hours) of unprotected exposure in the previous 14 days. No HCW in the PEP arm contracted MERS versus 6/21cases in the control (non-PEP) arm (0% vs 28.6%, p=0.009).  Twenty-one/22 PEP HCWs experienced adverse effects, but all were mild. Moreover, there were no discontinuations,  and the risk/benefit ratio was considered reasonable.
To date, there is no approved treatment for COVID-19. Several trials are now evaluating the effects of various types of COVID-19 treatment but, to our knowledge, only a few studies have been designed to evaluate a prophylactic approach in COVID-19. 
Given the worldwide spread of the COVID-19 epidemic, the lack of treatment and the excellent results of the MERSstudy,  it seems reasonable to evaluate whether a PEP approach could reduce the spread of the infection. However, several aspects remain to be established before conducting such a trial, i.e., the drug to administer, the interval between exposure and PEP onset, the dosage and the duration of administration. The drug to use should be one of those currently under study--namely, lopinavir/ritonavir, chloroquine, remdesivir, darunavir/ritonavir, ribavirin, arbidol, neuraminidase inhibitors, peptide (EK1), and RNA synthesis inhibitors. Although these drugs were developed for a vast array of indications, they are now being repurposed to counter COVID-19 based on potential in vitroefficacy. 
Another issue is the design of the study. A randomized controlled trial would reveal whether the PEP strategy is effective or not in containing COVID-19. However, such a design is probably non-viable, at least in countries with a high burden of cases and the consequential heavy social resonance. In such settings, a study comparing the attack rate before and after PEP onset in the area under study could provide initial proof of efficacy. Potential enrolees would be people who are in contact with COVID-19 patients, already identified by health authorities, or HCWs after unprotected exposure to COVID-19 patients. In ordinary times, such a study should follow proof of in vitro and in vivo activity of the drug and its therapeutic efficacy. In the present exceptional times, any promising approach should be urgently exploited to contain the epidemic.
In conclusion, should a study of PEP demonstrate efficacy in decreasing the circulation of SARS-CoV-2, this approach could be widely implemented to help contain the epidemic and reduce the global burden of the disease.
1 WHO. Coronavirus Disease (COVID-19) - events as they happen. Updated 23 March 2020. 2020. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-a... . Accessed March 24, 2020.
2 https://experience.arcgis.com/experience/685d0ace521648f8a5beeeee1b9125c... March 24, 2020.
3 WHO. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) https://www.who.int/docs/default-source/coronaviruse/who-china-joint-mis... .Accessed March 24, 2020.
4 Okoli GN, Otete HE, Beck CR, Nguyen-Van-Tam JS. Use of neuraminidase inhibitors for rapid containment of influenza: a systematic review and meta-analysis of individual and household transmission studies. PLoS ONE. 2014;9(12): e113633.
5 Park SY, Lee JS, Son JS, et al. Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers. J Hosp Infect. 2019;101(1): 42–6.
6 NIH. ClinicalTrials.gov https://clinicaltrials.gov/ct2/results?cond=COVID-19.Accessed March 24, 2020.
7 Harrison C. Coronavirus puts drug repurposing on the fast track. [published online Feb 27,2020] Nature Biotechnology.doi:10.1038/d41587-020-00003-1.
Competing interests: No competing interests