Urgent need to understand re-infection of SARS-CoV-2May 8, 2021
Recent studies published by Andrew G Letizia and team (N Engl J Med 2020; 383:2407-2416 and Lancet Respir Med. 2021) look at subsequent infection risks for SARS-CoV-2 in healthy young adults who may have had previous anti-spike IgG antibodies. The study followed Marine recruits as part of the prospective COViD-19 Health Response for Marines study (CHARM) for 6 weeks after an initial two-week, supervised quarantine. Researchers performed serology and RT-PCR tests for SARS-CoV-2 on the Marines regularly during the period.
A waning immunity may result in re-infection, viral persistence, or reactivation, but among young healthy individuals, this seems less likely. The definition of re-infection or relapse or recurrence by positive RT-PCR result will have clinical and epidemiological implications for treatment and infection control.
Re-infection is usually observed in many respiratory viruses, primarily due to the high variability of viruses (e.g., influenza virus).
In the case of SARS-CoV-1 and the Middle East Respiratory Syndrome coronavirus (MERS-CoV), the specific antibodies were detected up to 24 or 34 months in survivors. This resulted in negligible risk of second exposure.
For endemic coronaviruses, immunity is temporary and re-infection is reported after experimental or natural infections. In this study of closed settings, the rate of new SARS-CoV-2 RT-PCR positive results was significantly (80%) less (p<0.001)) among seropositive individuals, suggesting that seropositive people may have important, but limited, protection from new infection. It was found that the degree of protection fell with an increase in age. Another important observation was that the rate of new SARS-CoV-2 RT-PCR positive cases was 1.1 per person-year, suggesting that COVID-19 does not provide near universal and long-lasting protective immunity unlike in cases of other viral infections like measles.
This study also showed that recurrent infection was inversely correlated to anti-spike IgG antibody titers, and neutralizing antibodies were lower in second-time RT-PCR positive Marines than in negative subjects. Due to the heterogeneity of the immune responses in these study subjects, seropositivity alone could not guarantee effective SARS-CoV-2 neutralisation or protection against subsequent infection. This is an important finding that will have a large impact on how we view re-infection, especially with new variants. It will be important to study nAb efficacy for initial infections as well as for re-infection by variants. It was observed that subsequent infections were generally asymptomatic or oligosymptomatic and thus needed repeated RT-PCR tests rather than just an evaluation of symptoms. As there is a high percentage of asymptomatic infections among young adults, they might be a major source of transmission in the community. Thus, all efforts must be made to reduce the risk of virus transmission from young asymptomatic individuals. This study by Letizia and team does give an important understanding of re-infections, but much more needs to be addressed in terms of frequency, clinical relevance, transmission and the impact on immune responses. We need more studies in each country to study these aspects immediately to be prepared for further, large-scale re-infections.