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Serological follow-up of SARS-CoV-2 asymptomatic subjects

Our take —

This study among mildly, pre-symptomatic, or asymptomatically infected individuals provides further evidence that antibody responses to SARS-Cov-2 infection frequently wane or never reach detectable levels within a short period following active SARS-CoV-2 infection within a substantial number of individuals. While purportedly focused on asymptomatic infections, both pre-symptomatic and mildly symptomatic individuals were included within this study. As the host immune response may contribute to differences between asymptomatic, mildly symptomatic, and severe SARS-CoV-2 infection, it remains unclear whether the estimates obtained by this study accurately reflect SARS-CoV-2-specific serology within asymptomatic individuals.

Study design

Prospective Cohort

Study population and setting

This serology-focused study examined a subset of individuals from the University of Milan personnel-based UNICORN study in Lombardy, Italy. This analysis focused on 31 out of 197 asymptomatic individuals initially enrolled in UNICORN with evidence of prior or current SARS-CoV-2 infection on the day of enrollment. These individuals purportedly had no symptoms 14 days prior to and including the day of recruitment, which involved both a nasal swab and serological test for SARS-CoV-2. A second plasma sample and a questionnaire was obtained 8 weeks after the baseline sample to assess the proportion of individuals who developed or retained immunoglobulins (Ig) or antibodies specific to the spike-receptor binding domain (RBD) of SARS-CoV-2.

Summary of Main Findings

Of 197 asymptomatic individuals screened, 31 individuals were initially positive for SARS-CoV-2 infection via nasal swab or serology and of these 29 underwent a secondary serological assessment eight weeks after the initial testing. Among 21 individuals with an active asymptomatic infection at baseline (positive nasal swab), 52.3% (11/21) never had detectable SARS-CoV-2-specific antibodies while 80% of these baseline PCR positive individuals had no evidence of circulating Ig against SARS-Cov-2 eight weeks later. Roughly two-thirds of individuals with a positive baseline serology test (11/17) did not have SARS-CoV-2-specific IgG eight weeks later. Overall, the majority of individuals with evidence of asymptomatic SARS-CoV-2 infection did not have antibodies against the RBD-spike protein when serologically assessed eight weeks later.

Study Strengths

This study utilized data from the previously well described UNICORN cohort study during the initial surge of the SARS-CoV-2 pandemic in Milan, Italy. The serological tests used by the investigators were appropriate, and the study benefits from Ig-specific tests screening for multiple types of antibodies (IgM and IgG).


This study purports to explore the serological dynamics of asymptomatic SARS-CoV-2 infected individuals, however it remains unclear whether the individuals included within this study were truly asymptomatic. Many of the included individuals reported experiencing fevers (37.9%), episodes of upper/lower airway infections, and are characterized within the discussion as ‘subjects with a mild SARS-CoV-2 infection’. The distinction between asymptomatic, pre-symptomatic (1 individual reported a fever and upper airway infection days after their initial positive SARS-CoV-2 nasal swab), and mildly symptomatic infection is of critical importance, and coupled with the small sample size, suggests that these findings may not accurately reflect the serological dynamics of asymptomatic SARS-CoV-2 infection.

Value added

This study supports similar findings related to the transient nature of host antibody responses to SARS-CoV-2, suggesting that among asymptomatic or mildly symptomatic individuals, a significant proportion of infections may result in rapidly waning antibody responses or fail to induce detectable antibody responses within eight weeks.

This review was posted on: 11 January 2021