Defining the features and duration of antibody responses to SARS-CoV-2 infection associated with disease severity and outcome

Abstract

SARS-CoV-2-specific antibodies, particularly those preventing viral spike receptor binding domain (RBD) interaction with host angiotensin-converting enzyme 2 (ACE2) receptor, can neutralize the virus. It is, however, unknown which features of the serological response may affect clinical outcomes of COVID-19 patients. We analyzed 983 longitudinal plasma samples from 79 hospitalized COVID-19 patients and 175 SARS-CoV-2-infected outpatients and asymptomatic individuals. Within this cohort, 25 patients died of their illness. Higher ratios of IgG antibodies targeting S1 or RBD domains of spike compared to nucleocapsid antigen were seen in outpatients who had mild illness versus severely ill patients. Plasma antibody increases correlated with decreases in viral RNAemia, but antibody responses in acute illness were insufficient to predict inpatient outcomes. Pseudovirus neutralization assays and a scalable ELISA measuring antibodies blocking RBD-ACE2 interaction were well correlated with patient IgG titers to RBD. Outpatient and asymptomatic individuals’ SARS-CoV-2 antibodies, including IgG, progressively decreased during observation up to five months post-infection.

Absent or insufficient anti-SARS-CoV-2 S antibodies at ICU admission are associated to higher viral loads in plasma, antigenemia and mortality in COVID-19 patients

“…Results from Li et al also support the role of antibodies in controlling SARS-CoV-2 replication, since they found higher frequencies of anti-S receptorbinding domain (RBD)-specific IgG levels in those recovered patients who were SARS CoV-2 RNA negative than those who were RNA positive in respiratory samples[10]. In agreement with our results, Röltgen K et al found that increases in plasma anti-SARS-CoV-2 S antibodies correlated with decreases in viral RNAemia along the course of COVID-19[2]. In a small study with 39 patients (critically and non-critically ill), Ogata AF et al found a…”

“…From the clinical point of view, recent evidence suggests that anti-SARS-CoV-2 S antibodies could play a role in protecting against severe disease in patients with COVID-19 [2].…”

“…The impact of antibody levels on mortality risk in COVID-19 is controversial. In the study from Röltgen K et al, antibody responses in acute illness were not related with patients` outcomes[2]. In contrast, Hashem AM et al reported significantly higher levels of anti-S1 and -N IgG and IgM antibodies in patients with fatal outcomes[11].Nonetheless, these studies include a mixture of mild, moderate and severe patients, with only a limited representation of critically ill patients.…”

Kinetics and correlates of the neutralizing antibody response to SARS-CoV-2

“…The cohort consists primarily (91.69%) of patients with mild COVID-19 therefore representing the predominant clinical course of this disease 6 . Since higher disease severity was shown to correlate with higher antibody responses 14,42 , cohorts mainly composed of hospitalized individuals have limited applicability on the majority of COVID-19 cases 20,35,43,44 . Moreover, to our knowledge this is the most comprehensive study (n=963), in which neutralizing antibody activity has been reported to date with the next largest study having analyzed 4-5 fold less individuals at a single time point 45 .…”

Kinetics and Correlates of the Neutralizing Antibody Response to SARS-CoV-2

“…The cohort consists primarily (91.69%) of patients with mild COVID-19 therefore representing the predominant clinical course of this disease 6 . Since higher disease severity was shown to correlate with higher antibody responses 14,42 , cohorts mainly composed of hospitalized individuals have limited applicability on the majority of COVID-19 cases 20,35,43,44 . Moreover, to our knowledge this is the most comprehensive study (n = 963), in which neutralizing antibody activity has been reported to date with the next largest study having analyzed 4-5 fold less individuals at a single time point 45 The broad spectrum of neutralizing activity developed in COVID-19 recovered individuals may impact the level of protective immunity.…”