Sustained neutralising antibodies in the Wuhan population suggest durable protection against SARS-CoV-2
Authors: Richard Strugnell, Nancy Wang
Journal: The Lancet (2021)

SARS-CoV-2 infections were first reported in Wuhan, China, in 2019,1Huang C Wang Y Li X et al.Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.Lancet. 2020; 395: 497-506Summary Full Text Full Text PDF PubMed Scopus (33099) Google Scholar and quickly became a global pandemic, as declared on March 11, 2020.2Cucinotta D Vanelli M WHO declares COVID-19 a pandemic.Acta Biomed. 2020; 91: 157-160PubMed Google Scholar SARS-CoV-2 is highly infectious3Petersen E Koopmans M Go U et al.Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics.Lancet Infect Dis. 2020; 20: e238-e244Summary Full Text Full Text PDF PubMed Scopus (850) Google Scholar 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 colleagues4He Z Ren L Yang J et al.Seroprevalence and humoral immune durability of anti-SARS-CoV-2 antibodies in Wuhan, China: a longitudinal, population-level, cross-sectional study.Lancet. 2021; 397: 1075-1084Summary Full Text Full Text PDF PubMed Scopus (175) Google Scholar 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-19.5Garcia-Beltran WF Lam EC Astudillo MG et al.COVID-19-neutralizing antibodies predict disease severity and survival.Cell. 2021; 184: 476-488Summary Full Text Full Text PDF PubMed Scopus (448) Google Scholar 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,6Xu X Sun J Nie S et al.Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China.Nat Med. 2020; 26: 1193-1195Crossref PubMed Scopus (309) Google Scholar 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,6Xu X Sun J Nie S et al.Seroprevalence of immunoglobulin M and G antibodies against SARS-CoV-2 in China.Nat Med. 2020; 26: 1193-1195Crossref PubMed Scopus (309) Google Scholar 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, 20207Health Commission of Hubei ProvinceEpidemic situation of new COVID-19 in Hubei Province on April 17, 2020.http://wjw.hubei.gov.cn/bmdt/ztzl/fkxxgzbdgrfyyq/xxfb/202004/t20200418_2234341.shtmlDate accessed: January 25, 2021Google Scholar). 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, 2020.8Cao S Gan Y Wang C et al.Post-lockdown SARS-CoV-2 nucleic acid screening in nearly ten million residents of Wuhan, China.Nat Commun. 2020; 115917Crossref PubMed Scopus (118) Google Scholar 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.9Ripperger TJ Uhrlaub JL Watanabe M et al.Orthogonal SARS-CoV-2 serological assays enable surveillance of low-prevalence communities and reveal durable humoral immunity.Immunity. 2020; 53: 925-933Summary Full Text Full Text PDF PubMed Scopus (230) Google Scholar, 10Gidding HF Machalek DA Hendry AJ et al.Seroprevalence of SARS-CoV-2-specific antibodies in Sydney after the first epidemic wave in 2020.Med J Aust. 2021; (published online Feb 3.)https://doi.org/10.5694/mja2.50940Crossref PubMed Scopus (19) Google Scholar, 11Poustchi H Darvishian M Mohammadi Z et al.SARS-CoV-2 antibody seroprevalence in the general population and high-risk occupational groups across 18 cities in Iran: a population-based cross-sectional study.Lancet Infect Dis. 2020; (published online Dec 15.)https://doi.org/10.1016/S1473-3099(20)30858-6Summary Full Text Full Text PDF PubMed Scopus (112) Google Scholar, 12Bajema KL Wiegand RE Cuffe K et al.Estimated SARS-CoV-2 seroprevalence in the US as of September 2020.JAMA Intern Med. 2020; (published online Nov 24.)https://doi.org/10.1001/jamainternmed.2020.7976Crossref PubMed Scopus (190) Google Scholar 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. We declare no competing interests. Seroprevalence and humoral immune durability of anti-SARS-CoV-2 antibodies in Wuhan, China: a longitudinal, population-level, cross-sectional study6·92% of a cross-sectional sample of the population of Wuhan developed antibodies against SARS-CoV-2, with 39·8% of this population seroconverting to have neutralising antibodies. Our durability data on humoral responses indicate that mass vaccination is needed to effect herd protection to prevent the resurgence of the epidemic. Full-Text PDF