Sustained neutralising antibodies in the Wuhan population suggest durable protection against SARS-CoV-2.

SARS-CoV-2 infections were first reported in Wuhan, China, in 2019, and quickly became a global pandemic, as declared on March 11, 2020. SARS-CoV-2 is highly infectious and COVID-19 is variable in its presentation, with many infected individuals, as detected by viral nucleic acid screening, being asymptomatic.

In The Lancet, Zhenyu He and colleagues report their cross-sectional study of serological responses of more than 9500 individuals from 3600 households in Wuhan, the early epicentre for the COVID-19 outbreak. The study was initiated shortly after lockdown in Wuhan ceased in April, 2020, with follow-up over two timepoints (June and October–December, 2020). In this cross-sectional, longitudinal serosurvey of Wuhan residents, the authors estimated the penetration of the virus into the community who were selected using a population-stratified, random-sampling approach. They also examined the development and durability of SARS-CoV-2 neutralising antibodies, the putative correlate of protection in COVID-19.

In the Wuhan population sampled by He and colleagues, 532 (5·6%) of 9542 participants were positive for pan-immunoglobulins against SARS-CoV-2 at baseline, giving an adjusted seroprevalence of 6·92% (higher than an earlier report, which estimated a seroprevalence of 3·2–3·8%). More than 80% of those surveyed who were seropositive were asymptomatic. As a city of 11 million people with 9 million residents as estimated during lockdown, quick extrapolation of these estimates suggests that approximately 622 800 individuals in Wuhan would have been infected as of April, 2020, far exceeding the cumulative number of confirmed cases in Wuhan (50 333 as of April 17, 2020). If the seroconversion rate is an accurate reflection of exposure to SARS-CoV-2, the apparent disparity between low case numbers and high seroconversion rate seems to suggest that most seroconverted individuals produced antibodies to SARS-CoV-2 after asymptomatic infection. Accordingly, by occupation group, the highest seroconversion rate was seen in health workers and in those with known COVID-19 contacts in the past 5 months. This observation suggests a relay of exposure that frequently resulted in asymptomatic transmission chains because, when the full population of Wuhan was screened in May, 2020, few additional, asymptomatic cases were detected compared with the known number of confirmed cases in April, 2020. Although separating transmitting from non-transmitting asymptomatic individuals with COVID-19 is probably impractical, the transmission outcomes from these two patient cohorts would suggest that different management regimens might be considered.

He and colleagues detected neutralising antibodies in 39·8% of the seropositive subgroup; encouragingly, the proportion was sustained over the 9-month study period, indicating that putative protection was durable when it occurred. Moreover, titres of neutralising antibodies were lower in individuals who had asymptomatic infections, compared with those with symptomatic infection and confirmed cases. The reason why those with asymptomatic disease developed lower neutralising antibody titres than those with symptomatic disease might be simply explained by different levels of exposure to SARS-CoV-2 antigens. Whether the levels of neutralising antibodies, or their transient appearance, also affected the so-called transmissibility potential would require further investigation.

Efficient global management of COVID-19 will probably succeed or fail on the basis of the immunity induced by natural infection and, especially, vaccination. Given the relative paucity of neutralising antibodies through natural infection, the study by He and colleagues reinforces the need for effective COVID-19 vaccines in the population-level control of the disease. The extraordinary, rapid, and effective control measures implemented in Wuhan might have restricted the spread of the virus, but also reduced naturally acquired herd immunity by truncating the development of sustained neutralising antibodies. Although other national and local governments have used alternate and usually less effective strategies to control the spread of SARS-CoV-2, even in highly endemic communities the prevalence of disease is usually less 1%, but has increased to 23% in some communities.9, 10, 11, 12 He and colleagues‘ findings suggest that herd immunity will likely not develop after natural transmission in settings where infection control mechanisms are successfully introduced, underscoring the importance of effective vaccination strategies to control the spread of COVID-19.

This study is an important milestone in the description of SARS-CoV-2 infection and our understanding of immunity in the pandemic. He and colleagues have provided a much deeper understanding of natural seroconversion in a key city in the pandemic and their findings also underscore the remarkable achievement of the Chinese public health system in controlling the Wuhan outbreak of COVID-19 at a time when testing, tracing, and treatment resources were much less developed.