Towards an accurate and systematic characterisation of persistently asymptomatic infection with SARS-CoV-2

Meyerowitz, Eric A; Richterman, Aaron; Bogoch, Isaac I; Low, Nicola; Cevik, Muge

People with persistently asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection experience no symptoms throughout the course of infection, and pre-symptomatic individuals become infectious days before they report symptoms. Transmission of SARS-CoV-2 from individuals without symptoms contributes to pandemic spread, but the extent of transmission from persistently asymptomatic individuals remains unknown. We describe three methodological issues that hinder attempts to estimate this proportion. First, incomplete symptom assessment probably overestimates the asymptomatic fraction. Second, studies with inadequate follow-up misclassify pre-symptomatic individuals. Third, serological studies might identify people with previously unrecognised infection, but reliance on poorly defined antibody responses and retrospective symptom assessment might result in misclassification. We provide recommendations regarding definitions, detection, documentation, and follow-up to improve the identification and evaluation of people with persistently asymptomatic SARS-CoV-2 infection and their contacts. Accurate characterisation of the persistently asymptomatic fraction of infected individuals might shed light on COVID-19 pathogenesis and transmission dynamics, and inform public health responses.