SARS-CoV-2 Antibody Dynamics and B-Cell Memory Response Over-Time in COVID-19 Convalescent Subjects

Background: Worldwide spread of COVID-19 disease highlights the need for assessment of long-term humoral immunity in convalescent subjects. Objectives: Evaluate IgG SARS-CoV-2 antibody response and B-cell memory response over-time in COVID-19 convalescent subjects. Methods: Blood samples were collected from a cohort of subjects recovering from COVID-19 disease and from healthy subjects that donated blood. SARS-CoV-2 IgG antibodies were quantitatively detected by ELISA using anti-S1 spike IgG. SARS-CoV-2 spike-specific IgG memory B-cells were evaluated in a randomly selected group of COVID-19 recovering subjects by reversed B-cell FluroSpot based on human IgG SARS-CoV-2 receptor-binding domain. Statistical analysis was performed with clinical variables and time post COVID-19 infection. Results: We evaluated 392 COVID-19 convalescent subjects and 180 healthy subjects for SARS-CoV-2 antibody response. No antibody response was detected in 6.7% of COVID-19 convalescent subjects. Over a period of 9 months the level of antibodies decreased by 50% but stabilized at 6 months and prevailed a protective level up to 9 months. No differences were found regarding IgG SARS-COV-2 antibody levels for age, gender, and major blood types, over-time. COVID-19 asymptomatic subjects did not differ in antibody level overtime from subjects with mild to severe disease. Repeated paired IgG SARS-COV-2 antibody level analyses disclosed that over 6 and 9 months, 15.3% and 15.8% of subjects became SARS-COV-2 IgG seronegative, respectively, all with low antibody level at 3 months. Rate of antibody decline was not affected by age, gender, or clinical symptomatology.  Memory B-cell response up to 9 months post COVID-19 infection was undetectable in 31.8% of subjects with no correlation to age, SARS-COV-2 antibody level or time post-infection. Conclusions: Our findings are of importance regarding health care decisions related to the magnitude of protective humoral immunity and the need of vaccination in COVID-19 convalescent subjects particularly in subjects with SARS-COV-2 antibody decay or absence of B-cell memory response. Funding Statement: The Laura Schwarz-Kipp Research Chair of Autoimmune Diseases, Sackler School of Medicine, Tel-Aviv University and Nitzan Research Foundation, Sheba Medical Center, Israel. Declaration of Interests: The authors declare no competing interest. Ethics Approval Statement: This study was approved by Sheba Institutional Review Board SMC- 750320) and informed consent was obtained from all enrolled participants.