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

Abstract

SARS-CoV-2 symptoms are non-specific and can range from asymptomatic presentation to severe pneumonia. Asymptomatic subjects carrying SARS-CoV-2 often remain undiagnosed and it is still debated whether they develop immunoglobulins (Ig) and how long they persist. The aim of this study was to investigate the development and persistence of antibodies against SARS-CoV-2 in asymptomatic subjects infected by the virus. This follow-up study was performed on the 31 asymptomatic subjects who presented a positive nasal swab or serology against SARS-CoV-2 (Ig against Spike-RBD) in the first part of the UNICORN study (March 2020) aimed at attesting previous or current contacts with the virus in the personnel of the University of Milan. Eight weeks after the first Ig measure, these subjects were invited to donate a second blood sample for testing serum antibodies (IgM, IgG and total antibodies) and to fill-in a structured questionnaire. About 80% of asymptomatic subjects did not present circulating immunoglobulins against SARS-CoV-2 after 8 weeks from a positive nasal swab against the virus. Moreover, in more than 40% of these subjects, no Ig against SARS-CoV-2 were detected at any time. Finally, about two third of subjects with immunoglobulins at baseline did not present IgG against SARS-CoV-2 after 8 weeks. The majority of subjects who developed an asymptomatic SARS-CoV-2 infection do not present antibodies against the RBD-spike protein after 8 weeks of follow-up. These data should be taken into account for the interpretation of the serological evidences on SARS-CoV-2 that are emerging nowadays.

Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2

“…In our analysis, IgM detectability was less sensitive and reproducible than IgGs across multiple LFAs, possibly due to both lower IgM titres, and lower limits of detection for the IgM LFAs. Waning antibody responses have been reported in some SARS-CoV-2-infected individuals (41)(42)(43)(44). Furthermore, reported cases of re-infection with SARS-CoV-2 suggest that prior exposure, and even seroconversion, do not universally protect against SARS-CoV-2 infection (44,45).…”

“…Waning antibody responses have been reported in some SARS-CoV-2-infected individuals (41)(42)(43)(44). Furthermore, reported cases of re-infection with SARS-CoV-2 suggest that prior exposure, and even seroconversion, do not universally protect against SARS-CoV-2 infection (44,45). This could result from low antibody titers as shown in an immunocompromised patient (46), low durability of infection-induced antibodies (42)(43)(44), or low neutralizing potential of SARS-CoV-2 infection-induced antibodies in some individuals (34).…”

“…A positive serological result does not necessarily mean active infection (23,31,49). Although combined use of molecular and seroconversion results can be used to con rm the diagnosis of symptomatic and hospitalized individuals (35), a positive serological test in the absence of symptoms dissociates the presence of the antibodies from the time of infection (44). Additionally, it is important to understand the implication of false positive and false negative results, particularly in the context of a low to mid-prevalence disease such as COVID-19 (25).…”

Evaluation of serological lateral flow assays for severe acute respiratory syndrome coronavirus-2

“…Furthermore, reported cases of re-infection with SARS-CoV-2 suggest that prior exposure, and even seroconversion, do not universally protect against SARS-CoV-2 infection 54, 55, 56 . This could result from low antibody titers as shown in an immunocompromised patient 57 , low durability of infection-induced antibodies 52, 53, 54 , or low neutralizing potential of SARS-CoV-2 antibodies in some individuals 44 . IgG and IgM antibodies may also target irrelevant epitopes outside the spike and receptor binding domains, and consequently be less efficient at intercepting infection by the virus 58 .…”

“…A positive serological result does not necessarily mean active infection 31, 41, 60 . Although combined use of molecular and seroconversion results can be used to confirm the diagnosis of symptomatic and hospitalized individuals 45 , a positive serological test in the absence of symptoms dissociates the presence of the antibodies from the time of infection 54 . Additionally, it is important to understand the implication of false positive and false negative results, particularly in the context of a low-prevalence disease such as COVID-19 35 .…”