8-in-10 seropositive people in study were asymptomatic

The first long-term seroprevalence study from Wuhan, China—where the world’s first Covid-19 cases were identified in December of 2019—suggested much higher SARS-CoV-2 seropositivity in the first months of the outbreak than case numbers suggested at the time.

Adjusted seropositivity among randomly selected Wuhan residents enrolled in the study was close to 7% soon after a citywide lockdown lifted in April 2020, with 8 of 10 (82%) people with antibodies never developing Covid-19 symptoms in the longitudinal, cross-sectional study.

This suggests that close to 629,000 of the estimated 9 million people in Wuhan during the lock down were infected by April, which is much higher than the roughly 50,000 confirmed cases in the city at the time.

Two-out-of-five (40%) antibody-positive study participants developed neutralizing antibodies, and this remained stable from April until at least October through December.

The study, which included participants living in all 13 districts of Wuhan, was published online Thursday, March 18, in The Lancet.

“The proportions of participants who were positive for IgG and neutralizing antibodies were stable for at least 9 months after exposure, regardless of whether individuals were asymptomatic, which indicates that passive and active immune strategies could be considered to protect the at-risk population from severe infection,” wrote researcher Zhenyu He, PhD, of the Wuhan Center for Disease Control and Prevention, Wuhan, China, and colleagues.

In a written press statement, principal researcher Chen Wang, MD, noted that early seroprevalence findings in Wuhan and in other populations across the globe indicate that there may be large discrepancies between reported cases of Covid-19 and SARS-CoV-2 infections.

“Even at the epicenter of the pandemic in China, with more than 50,000 confirmed cases as of April 8, 2020, the estimated seroprevalence in Wuhan remains low, and around 40% of people with antibodies develop neutralizing antibodies, suggesting there is still lack of immunity in the population,” Wang said.

In commentary published with the study, Covid-19 vaccine researchers Professor Richard Strugnell and Nancy Wang, PhD, of Australia’s University of Melbourne, wrote that the findings confirm the key role of vaccines in the efficient global management of Covid-19.

“Given the relative paucity of neutralizing 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,” they wrote. “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 neutralizing antibodies.”

They added that findings from this study and other population-wide seroprevalence studies suggest that herd immunity will not occur in areas with successful infection control measures, “underscoring the importance of effective vaccination strategies to control the spread of Covid-19.”

A total of 4,600 households in Wuhan were randomly selected for the study, with 3,599 families (9,702 individuals) attending the baseline visit in April of 2020. A total of 9,542 participants from 3,556 families were included in the analysis, with 532 people (5.6%) found to have SARS-CoV-2 antibodies (baseline adjusted prevalence, 6.92%, 95% CI, 6.41-7.43). A total of 82.1% of antibody positive participants were asymptomatic.

Among the other main findings:

  • Thirteen percent of the seropositive people were positive for IgM antibodies, close to 16% were positive for IgA antibodies, 100% were positive for IgG antibodies, and close to 40% were positive for neutralizing antibodies at baseline.
  • The proportion of people who were positive for pan-immunoglobulins who had neutralizing antibodies in April remained stable for the two follow-up visits (162 [44.6%] of 363 in June 2020, and 187 [41.2%] of 454 in October–December 2020).
  • Based on data from 335 people who attended all three follow-up visits and who were positive for pan-immunoglobulins, neutralizing antibody levels did not significantly decrease over the study period (median 1/5.6 at baseline vs 1/5.6 at first follow-up [P=1.0] and 1/6.3 at second follow-up [P=0.29]).
  • Neutralizing antibody titres were lower, however, in asymptomatic people compared to confirmed cases and symptomatic individuals.

Although titres of IgG decreased over time, the proportion of people who had IgG antibodies did not decrease substantially from baseline to subsequent visits.

Women in the study had slightly higher seroprevalence than men (adjusted seroprevalence 7.70% vs. 6.22%, respectively) and older people (≥66 years) had the highest seroprevalence of any age group (adjusted seroprevalence, 9.51%; 95% CI, 7.51-11.51).

A study limitation cited by the researchers was the inability to identify the timing of infection, given that the vast majority of seropositive study participants were asymptomatic. They noted that because few cases of Covid-19 were reported in Wuhan between mid-March and April 2020 due to strict infection control measures, it is reasonable to assume that the baseline samples were collected at least 4 weeks after antibody production in most cases.

In their commentary, Strugnell and Wang wrote that the study represents “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,” they concluded.

  1. Adjusted seropositivity among randomly selected Wuhan residents enrolled in the study was close to 7% soon after a citywide lockdown lifted in April of 2020, with 8 of 10 (82%) people with antibodies never developing Covid-19 symptoms in a longitudinal, cross-sectional study.

  2. Two-out-of-five (40%) antibody-positive study participants developed neutralizing antibodies which remained stable from April until at least October through December.

Salynn Boyles, Contributing Writer, BreakingMED™

This study was funded by the Chinese Academy of Medical Sciences & Peking Union Medical College, National Natural Science Foundation, and Chinese Ministry of Science and Technology.

The researchers and commentary writers declared no relevant competing interests related to this study.

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