Discussion
retinopathy, G6PD-deficient, rheumatoid arthritis, systemic lupus erythematosusHCQ, SARS-CoV-2 infection, illness, palpitation, haemolysis
RETINOPATHY, RHEUMATOID ARTHRITIS, VIRUS, CARDIAC ARRHYTHMIAS, SARS-COV-2 INFECTION, RECURRENCE, DISEASE, EVENT, CARDIAC EVENTS, LOSS OF VISION, HYPOGLYCAEMIA
In this randomized, double-blind placebo-controlled clinical trial, 1168 asymptomatic individuals of high risk household direct contact with the laboratory-proven COVID-19 cases received PEP with either HCQ or Placebo and followed up for 4 weeks for the detection of new onset COVID-19. We found that PEP with HCQ was not associated with significant reduction in incidence of new onset COVID-19 as compared to the Placebo. Vaccines against COVID-19 came with great hope for the prevention of COVID-19 as well as reduction of the severity of illness and subsequent decrease in mortality. Even after more than a year of vaccine roll-out, many countries are going through multiple waves of the pandemic adding further assault to already traumatised human lives. Despite covering more than 66% of the population with full 2-dose vaccination, countries like the USA, UK and India have no respite from the surge of new COVID-19 casesHCQ generated sense of belief for the treatment and prevention of COVID-19 due to its in vitro virucidal action against SARS-CoV-2Presently evidence emerged against the therapeutic benefit of HCQ in hospitalised COVID-19 patients in term of recovery and prevention of mortalityBoulware et al. defined COVID-19 cases as symptomatic illness supported by a positive molecular assay or COVID-19-related symptoms, but asymptomatic presentation of COVID-19 is also very frequentIn Boulware et al. the majority (66.4%) of participants were HCW. There is still scarcity of RCT, exploring PEP with HCQ for the prevention of SARS-CoV-2 infection in high-risk household direct contacts of COVID-19 cases. The present study aimed to evaluate the efficacy of HCQ as PEP for prevention of COVID-19, particularly in asymptomatic household direct contacts of the laboratory-confirmed COVID-19 cases. Though, the HCW related to COVID-19 patient care and the household direct contacts of COVID-19 cases are at risk for SARS-CoV-2 infection, they have a comparatively different risk category. HCWs are expected to participate in COVID-19 patient care after wearing personal protective equipments, usually for a fixed duty hours, and can retain a safe distance from the patients as per feasibility. The household contacts get exposure to COVID-19 unknowingly without any precautions or personal protective equipment, as the patients are either family members or friends or relatives, and they live with COVID-19 patients for days to weeks without retaining a safe distance. Therefore, household direct contact possesses a greater risk for COVID-19 compared to HCW and incidence of COVID-19 after exposure may differ in HCW and household direct contact. So the HCW were excluded from the present study.In a household RCT, Barnabas et al. concluded that PEP with HCQ was not efficacious for the prevention of COVID-19Additionally, a Cluster-Randomized Trial concluded that PEP with HCQ did not prevent SARS-CoV-2 infection in asymptomatic direct contact of COVID-19 casesSafety has always been a concern against the use of HCQ as it can cause life-threatening cardiac arrhythmias, QT prolongation, retinopathy causing loss of vision, hypoglycaemia, and haemolysis in G6PD-deficient patients. However, these side effects are not common in conventional practice and HCQ has been found to be safe with prolonged lifelong use in rheumatoid arthritis and systemic lupus erythematosusHCQ was also tried unsuccessfully against the previous corona virus pandemic (MARS) and perhaps COVID-19 is not the last corona virus pandemic either. Despite the unfavorable results of HCQ for the treatment and prevention of COVID-19, the practice of irrational use of HCQ for the prevention of COVID-19 still continues in many countriesHCQ remains a myth only as it couldn’t produce sufficient in vivo evidence in favor of its benefit against COVID-19. But, at the same time it opens the gate for further research in search of newer and efficacious anti-viral drugs or repurposing of the established drugs against SARS-CoV-2 making us more efficient in defeating this ongoing pandemic. Till then, vaccination, increasing social awareness about the disease and better adherence to the use of face mask, maintaining adequate social distancing and hand hygiene are the best way for the prevention of COVID-19, breaking the chain of transmission of COVID-19 in communityLimitation of the study was, being a single center clinical trial raised doubt regarding the representation of large diverse Indian population. However, being a tertiary care center, the PGIMER caters to multiple states which include Punjab, Haryana, Himachal Pradesh, Uttarakhand, Uttar Pradesh, Jammu & Kashmir, Rajasthan and Bihar, representing large and diverse parts of India.The event number (primary end point) was lower than expected. The sample size may have been inadequate to exclude small but clinically meaningful decreases in the incidence of SARS-CoV-2 infection in high risk individuals.Follow-up ECG could not be done to detect new onset QT prolongation. Only one patient had a self-limiting episode of palpitation without recurrence, and none of the participants reported any symptoms related to any acute cardiac events.Majority of the participants represented a younger (18–45 years) age group (84.4%) with less representation for older age groups who may have contrasting risk factors for COVID-19 than younger population, and only 3 participants from > 45 years age group had COVID-19 (Table In conclusion, PEP with HCQ is not advantageous for the prevention of COVID-19 in asymptomatic household direct contact of the laboratory-confirmed COVID-19 cases. Though HCQ is a safer drug, the practice of irrational and indiscriminate use of HCQ for COVID-19 should be restrained with better pharmacovigilance till further supportive evidence emerges. Till then, mass vaccination, increasing social awareness and use of face masks, social distancing and personal hygiene are the best ways for the prevention of COVID-19.