Effect of quantitative real-time RT-PCR reaction sensitivity in determining the efficacy of HCQ prophylaxis for COVID-19

Sir,

We read the article by Chatterjee et al1 published recently on HCQ prophylaxis for COVID-19. We congratulate the authors for this successful study, but make a comment on the research methodology.

In this case-control study, the authors designated symptomatic healthcare workers (HCWs) testing positive on the quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) for SARS-CoV-2 as cases and symptomatic HCWs who tested negative on qRT-PCR for SARS-CoV-2 as controls. The differentiating factor of the two groups is the result of the qRT-PCR test. Other population characteristics have been appropriately matched. However, previous research shows very low sensitivity of the qRT-PCR for SARS-CoV-2. Ai et al2 found that initial qRT-PCR pharyngeal swab sensitivity ranged from 66 to 80 per cent. Fang et al3 found qRT-PCR sensitivity of 71 per cent compared to chest computed tomography (CT) sensitivity of 98 per cent. Many suspected cases with typical clinical features and identical specific CT images have elicited false negatives by qRT-PCR4. As a result, many national public health institutes and hospital systems have detailed multifactored diagnostic approaches to diagnose symptomatic patients suspected of having SARS-CoV-2. The Centers for Disease Control and Prevention, USA, for example, in the guidance to clinicians includes laboratory and radiographic findings alongside viral testing as diagnostic procedures to be used in conjunction to diagnose SARS-CoV-25.

Thus, given this background, it is inaccurate to use the qRT-PCR test as a standalone diagnostic procedure to designate the studied healthcare worker population into case and control groups. It introduces the likelihood of diagnostic error and as a result, undermines the subsequent analysis on occupational exposure, personal protective equipment (PPE) and prophylactic HCQ.