Abstract
This contribution explores in a new statistical perspective the antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 141 coronavirus disease 2019 (COVID-19) patients exhibiting a broad range of clinical manifestations. This cohort accurately reflects the characteristics of the first wave of the SARS-CoV-2 pandemic in Italy. We determined the IgM, IgA, and IgG levels towards SARS-CoV-2 S1, S2, and NP antigens, evaluating their neutralizing activity and relationship with clinical signatures. Moreover, we longitudinally followed 72 patients up to 9 months postsymptoms onset to study the persistence of the levels of antibodies. Our results showed that the majority of COVID-19 patients developed an early virus-specific antibody response. The magnitude and the neutralizing properties of the response were heterogeneous regardless of the severity of the disease. Antibody levels dropped over time, even though spike reactive IgG and IgA were still detectable up to 9 months. Early baseline antibody levels were key drivers of the subsequent antibody production and the long-lasting protection against SARS-CoV-2. Importantly, we identified anti-S1 IgA as a good surrogate marker to predict the clinical course of COVID-19. Characterizing the antibody response after SARS-CoV-2 infection is relevant for the early clinical management of patients as soon as they are diagnosed and for implementing the current vaccination strategies.
Highlights
In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the causative agent of the coronavirus disease 2019 (COVID-19)
The cohort consisted of 141 COVID-19 individuals enrolled between February and August 2020, including patients admitted at San Raffaele Hospital in the COVID-19 clinical-biological case series study (COVID-BioB) (ClinicalTrialsgov identifier NCT04318366), and healthcare workers from care-home residents in Lombardia, Piemonte, and Liguria regions (Table 1)
The median age was 56 years, and males and females were balanced distributed (48.2% and 51.8%, respectively). They experienced a wide range of clinical manifestations, ranging from asymptomatic (13.5%), mild (36.9%, WHO scores 1 and 2), moderate (34%, WHO scores 3 and 4), and severe (15.6%, WHO scores 5 and 6) symptoms
Summary
In December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the causative agent of the coronavirus disease 2019 (COVID-19). It became clear very quickly that COVID-19 was characterized by highly variable clinical manifestations ranging from asymptomatic to mild and moderate, while progressing to respiratory and multiorgan failure in certain patients, even leading to death [1]. IgM, IgA, and IgG targeting the viral spike (S) and nucleoprotein (NP) are sequentially or concomitantly generated promptly after infection [2, 3]. Antibody production reduces the risk of severe disease and neutralizing antibodies (nAbs) represent important correlates of protection against viral infections [4]. Several studies examined the magnitude, the dynamic, the persistence, and the functions of SARS-CoV-2specific antibodies; the evidences are not concordant across the studies [5,6,7]
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