ABSTRACT
Background: Understanding the adaptive immune response to SARS-CoV-2, kinetics, persistence and their relationship with the disease severity would be crucial in order to predict recurrences, reinfections and could serve in the design of vaccination strategies. We sought to characterize IgG and neutralizing antibodies (NAbs) against SARS-CoV-2 in patients who were admitted to hospital with COVID-19 disease. Methods: All patients admitted between March-April 2020 with moderate, severe and critical SARS-CoV-2 pneumonia were prospectively studied. Clinical, laboratory data and IgG against SARS-CoV-2 levels were assessed at baseline (upon admission) and months 1, 3 and 6. NAbs were assessed at month 1, 3 and 6. IgG against the SARS-CoV-2 spike (S) protein was measured in serum by chemiluminescence (LIAISON® SARS-CoV-2 S1/S2, DiaSorin) and results were expressed in arbitrary units (AU)/mL. The neutralizing activity of plasma samples was analyzed in a 293T/hACE2 cell infection test using a surrogate viral inhibition assay that uses human immunodeficiency virus type 1 (HIV-1)-based virus expressing SARS-CoV-2 S protein and Luciferase. For neutralization assays, pseudoviruses were incubated with increasing plasma dilutions (range 1/60-1/14,580) in order to obtain the ID50 values. Results: A total of 110 patients who were discharged from hospital were recruited. Median (range) age was 61 (57-71);61.2% were male and most reported comorbidities were hypertension (39.6%), diabetes (24.3%) and obesity (19.8%). Median time from symptoms onset to admission was 9 days (range 7-11). Median (range) IgG levels (AU/mL) at baseline and months 1, 3 and 6 were 48 (28-81), 168 (134-210), 140 (112-171) and 146 (104-206) respectively. No significant differences were observed in median IgG fold change values up to month 6 among severity groups. Median (range) ID50 values for NAbs at months 1, 3 and 6 were 3938 (1958-6407), 4344 (2335-6752) and 424 (124-1022) respectively. NAb titers presented a significant decrease (overall-10.2-fold change from maximal values) without differences among severity groups (Figure 1 a and b). No reinfections occurred. Conclusion: Specific humoral immune response to SARS CoV-2 in patients requiring hospital admission characterizes for a clear peak between 30 and 90 days after admission followed by a significant decline in titer of NAbs by day 180 regardless of disease severity. Longer follow-up may help to determine the longevity of the specific immune response.