Temporal trends and differences of SARS-CoV-2-specific antibody responses in symptomatic and asymptomatic subjects: a longitudinal study from Umbria in Italy

Abstract

Objectives: Dynamics of antibody responses following SARS-CoV-2 infection are controversial in terms of immunity and persistence. We aimed to assess longitudinally the trend of antibody serological titres, their correlation with clinical severity as well as clinical reinfection during a follow-up.

Design: Longitudinal cohort, 12 months follow-up study.

Setting: USL Umbria 2.

Participants: Consecutive subjects aged 15-75 who were discharged with the diagnosis of Sars-Cov-2 from the hospitals of the AUSL Umbria 2, or resulted positive to a PCR test for SARS-CoV-2 infection with or without symptoms were recruited. SARS-CoV-2 serological testing for antibodies targeting the Nucleocapside and Spike proteins were determined.

Results: Of 184 eligible subjects, 149 were available for evaluation: 17 were classified as oligo/asymptomatic, 107 as symptomatic, 25 as hospital admitted. Participants differed in terms of signs and symptoms as well as treatment. Overall there was a significant difference in terms of antibody titres between groups (anti-S: p<0.00; anti-N: p=0.019). Median anti-S titres in the symptomatic and hospital admitted participants were significantly higher compared with the oligo/asymptomatic participants. During follow-up, the median titre of anti-S antibodies did not show significant variations (p=0.500) and the difference within groups remained constant overtime. Subjects that showed an anti-S titre above the threshold of 12 U/mL were 88.7% at first visit and 88.2% at last follow-up. Anti-N values were higher in the hospital admitted participants compared with the other two groups. Anti-N titre reduced constantly overtime (p<0.001) and across the three groups of participants. The percentage of the subjects with serological titre above threshold (<1.4 U/mL) decreased from 74.5%% to 29.2% (p<0.001). None of the participants developed clinically evident reinfection.

Conclusion: Anti-N and anti-S correlate well with clinical severity. While anti-N declines overtime, anti-S antibodies persist for at least 1 year.

Keywords: COVID-19; immunology; infectious diseases; virology.

Figure 1

Study screening process.

Figure 2

Duration (in days) of signs and symptoms across the three groups of participants. Numbers in denominators are participants available at follow-up. Oligo-symptomatic patients are those with symptoms enduring for less than 3 days or with only one symptom (anosmia/ageusia or asthenia). Symptomatic patients are those with one more symptom lasting at least 3 days and without any hospital admission.

Figure 3

Ab-anti-S titre across the three groups of participants compared across the three periods of follow-up (estimated means and 95% CI). Oligosymptomatic patients are those with symptoms enduring for less than 3 days or with only one symptom (anosmia/ageusia or asthenia) Symptomatic patients are those with one more symptom lasting at least 3 days and without any hospital admission.

Figure 4

Ab-anti-N titre across the three groups of participants compared across the three periods of follow-up (estimated means and 95% CI). Oligosymptomatic patients are those with symptoms enduring for less than 3 days or with only one symptom (anosmia/ageusia or asthenia) symptomatic patients are those with one more symptom lasting at least 3 days and without any hospital admission.