Hydroxychloroquine found ineffective as post-exposure SARS-CoV-2 prophylaxis

By Dr. Ananya Mandal, MDDec 10 2020

Over 69.41 million people around the world have been infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, of these, over 1.49 million people have lost their lives. The spread of the virus from person to person is rapid and has brought the economies of major nations to their knees due to public health measures preventing human movement over the last few months.

Hydroxychloroquine prophylaxis to prevent COVID-19 had gathered interest during the initial phases of the pandemic early this year (2020). Studies quickly proved it to be less than effective in preventing the infection or reducing viral load or severe disease in infected persons.

Now, a study on the utility of hydroxychloroquine as prophylaxis against COVID-19, has been released in the latest issue of Annals of Internal Medicine.

Study: Hydroxychloroquine as Postexposure Prophylaxis to Prevent Severe Acute Respiratory Syndrome Coronavirus 2 Infection. Image Credit: Article Graphical Abstract / AIM

Background

As of now, no antiviral or therapeutic drugs are available against SARS-CoV-2. Several initial laboratory studies, as well as clinical studies, have suggested that hydroxychloroquine – an antimalarial and a drug useful in certain immunological arthritis – could be effective against SARS-CoV-2. Because of this evidence, the agent has been tested as prophylaxis against COVID-19.

Transmission

The SARS-CoV-2 infection is highly contagious and is rapidly transmitted from person to person. In many with the infection, no symptoms or mild acute symptoms may be present. Asymptomatic persons can still transmit the infection due to close contact. These transmissions are one of the major causes of such epidemic growth in the number of infections.

The authors of this study write, “Within households, the incidence of SARS-CoV-2 is high: 10% to 30% of household contacts acquire infection.” Non-pharmacological measures of prevention of the infection include “physical distancing, mask use, ventilation and handwashing.” The authors of the study say that the search for pharmaceutical agents to prevent the spread of infection has been ongoing for the better part of this year.

Postexposure prophylaxis (PEP)

Postexposure prophylaxis (PEP) refers to a medication that is given to persons who are exposed to viral infections. PEPs have been tried in viral infections in the past, such as influenza and HIV. Effective PEP for SARS-CoV-2 could thus help prevent the spread of the infection.

Hydroxychloroquine

Hydroxychloroquine is an analog of chloroquine that has been in use for over 60 years. In vitro studies have shown that standard dosing of chloroquine inhibits SARS-CoV-2 replication. The present study was conducted to see if hydroxychloroquine could act as an effective PEP against SARS-CoV-2.

Study design

This was a multicenter, double-blind, controlled, household-randomized trial testing the efficacy of hydroxychloroquine PEP among close contacts of persons with diagnosed SARS-CoV-2 infection.

For this study, close contacts that had been recently exposed to an infected person were included. The time frame of exposure was within 96 hours. For half the participants, a regimen of hydroxychloroquine 400mg was administered once daily for 3 days, followed by 200 mg per day for 11 days. The other group of participants received ascorbic acid or Vitamin C 500mg per day, followed by 250mg per day. This Vitamin C group was considered to be a placebo or control group.

For all participants, mid-turbinate swabs were collected on days 1 to 14 for SARS-CoV-2 polymerase chain reaction (PCR) testing. The primary outcome of the study was a positive PCR test among participants who had tested negative when enrolled in the study after exposure.

Findings

For this study, a total of 671 households were included between March and August 2020. Of the participants, 407 (from 337 households) were assigned to the Hydroxychloroquine group and 422 participants (from 334 households) were allocated to the control group.

Results showed

• On day 14, 91 percent and 92 percent swabs were collected from hydroxychloroquine and control groups, respectively.
• A total of 689 participants (89 percent) participants who were SARS-CoV-2 negative at enrolment in the study tested positive. No difference was found between the two study groups.
• By day 14, there were 53 events compared to 45 events in the Hydroxychloroquine group and control group, respectively. The adjusted hazard ratio was 1.10 (95% CI, 0.73 to 1.66)
• Adverse effects due to the use of the drugs were seen in 66 participants (16.2 percent) in the Hydroxychloroquine group compared to 46 (10.9 percent) among the control group.

Conclusions and implications

The study was a ‘rigorous randomized controlled trial’ among persons exposed to SARS-CoV-2 infection. Results showed that Hydroxychloroquine did not prove to be an effective post-exposure prophylaxis to prevent the infection among contacts.