The immunology of asymptomatic SARS-CoV-2 infection: what are the key questions?

Abstract

An important challenge during the COVID-19 pandemic has been to understand asymptomatic disease and the extent to which this may be a source of transmission. As asymptomatic disease is by definition hard to screen for, there is a lack of clarity about this aspect of the COVID-19 spectrum. Studies have considered whether the prevalence of asymptomatic disease is determined by differences in age, demographics, viral load, duration of shedding, and magnitude or durability of immunity. It is clear that adaptive immunity is strongly activated during asymptomatic infection, but some features of the T cell and antibody response may differ from those in symptomatic disease. Areas that need greater clarity include the extent to which asymptomatic disease leads to persistent symptoms (long COVID), and the quality, quantity and durability of immune priming required to confer subsequent protection.

SARS-CoV-2 reinfections: Overview of efficacy and duration of natural and hybrid immunity

“…Moreover, differentiation between persistent COVID-19 and reinfection is challenging, in particular in older persons ( Ringlander et al, 2021 ). It is also not entirely clear whether disease severity of the initial SARS-CoV-2 infection significantly modifies the risk of reinfections, but it should be noted that even asymptomatic SARS-CoV-2 infections elicit a strong immunological response ( Boyton and Altmann, 2021 ; Garrido et al, 2021 ; Murillo-Zamora et al, 2021a ; Schuler et al, 2021 ; Spicer et al, 2021 ).…”

“…Taken together, there is accumulating evidence that reinfections may be significantly less severe than primary infections with SARS-CoV-2, a finding with huge implications for the COVID-19 pandemic and its evolution into an endemic phase. Reduced clinical severity of SARS-CoV-2 reinfections makes, of course, also sense from a biological point of view, as a previously primed immune system should be better prepared for a re-challenge with this virus ( Boyton and Altmann, 2021 ; Castro Dopico et al, 2022 ; Cromer et al, 2021 ; Milne et al, 2021 ).…”

Rapid synchronous type 1 IFN and virus-specific T cell responses characterize first wave non-severe SARS-CoV-2 infections

“…Perhaps more importantly, we still have very limited insights into the potential role of adaptive immune responses in early protection against disease in the first epidemic wave. 4 These are of particular interest because they may inform the design of the next generation of vaccines with potential to provide cross-reactive immunity to future variants. We recently reported T cell responses in a subset of individuals associated with evidence for very early termination of infection before detectable viral replication or even seroconversion.…”

Tuftsin: a natural molecule against SARS-CoV-2 infection

“…It is worth noting that there were many asymptomatic and mild infectors during the pandemic. It is clear that innate and adaptive immunity functions during asymptomatic infection; however, the mechanism of the T cell and antibody response is unclear 30,31 .…”