Resolution of viral load in mild COVID-19 patients is associated with both innate and adaptive immune responses

Abstract

Over 90% of the COVID-19 patients manifest mild/moderate symptoms or are asymptomatic. Although comorbidities and dysregulation of immune response have been implicated in severe COVID-19, the host factors that associate with asymptomatic or mild infections have not been characterized. We have collected serial samples from 23 hospitalized COVID-19 patients with mild symptoms and measured the kinetics of SARS-CoV-2 viral load in respiratory samples and markers of inflammation in serum samples. We monitored seroconversion during the acute phase of illness and quantitated the amount of total IgG against the receptor-binding domain of SARS-CoV-2 and estimated the virus neutralization potential of these antibodies. Viral load decreased by day 8 in all the patients but the detection of viral RNA in saliva samples did not correlate well with viral RNA detection in nasopharyngeal/oropharyngeal swab samples. 25% of the virus-positive patients had no detectable neutralizing antibodies in the serum and in other cases, the efficiency of antibodies to neutralize SARS-CoV-2 B1.1.7 strain was lower as compared to the circulating virus isolate. Decrease in viral load coincided with increase in neutralizing antibodies and interferon levels in serum. Most patients showed no increase in inflammatory cytokines such as IL-1β or IL-6, however, elevated levels of IL-7 and other inflammatory mediators such as TNF-α and IL-8 was observed. These data suggest that most mild infections are associated with absence of inflammation coupled with an active innate immune response, T-cell activation and neutralizing antibodies.

Antibody response after a single dose of BBV152 vaccine negatively correlates with pre-existing antibodies and induces a significant but low levels of neutralizing antibodies to Omicron variant

“…The GMT of RBD antibodies increased significantly from 109 (95% CI: 76, 156) to 206 (95% CI: 163, 260) in baseline seropositive (Figure 1A) subjects, however, the increase in the GMT of N antibodies was from 18 (95% CI: 12, 25) to 25 (95% CI: 20, 31) which was not significant (Figure 1B). We next measured the virus neutralizing antibody titers against the SARS-CoV-2 B.6 lineage virus from 2020 4 (designated as WT) and B.1.617.2 (Delta variant) isolates in 9 both the baseline and post-single dose vaccination samples by focus reduction neutralization titer (FRNT) assay. Overall GMT of neutralizing antibodies increased after one dose of BBV152 vaccination for both WT virus and delta variant (Table 1).…”

“…We next measured the virus neutralizing antibody titers against the SARS-CoV-2 B.6 lineage virus from 2020 4 (designated as WT) and B.1.617.2 (Delta variant) isolates in both the baseline and post-single dose vaccination samples by focus reduction neutralization titer (FRNT) assay. Overall GMT of neutralizing antibodies increased after one dose of BBV152 vaccination for both WT virus and delta variant (Table 1).…”

“…However, the participants of our study were all non-vaccinated individuals and we cannot rule out the possibility that vaccination of these individuals after further reduction in antibody titers would have induced a better antibody response. It has been estimated that neutralizing antibodies are a good correlate of protection and contribute to about 60% of the protective efficacy of a vaccine which indicates that the cellular responses play a critical synergistic role along with antibodies in mediating protection from SARS-CoV-2 VoCs 4,5,16 . Some of the recent studies have also shown that heterologous boosting mounts a robust immune response to VoCs 20 .…”

“…Informed consent was obtained from all the participants. Viruses SARS-CoV-2 to B.6 and delta lineage virus isolation has been described earlier [3][4][5] . SARS-CoV-2 Omicron isolate (sub-lineage BA.1) was obtained from Leo Poon 6 .…”

“…Recombinant spike protein receptor binding domain (RBD) ELISA was performed as described earlier 4,10 . Recombinant spike protein Receptor Binding Domain (RBD) antigen of SARS-CoV-2 were coated onto 96-well polystyrene plate (0.1µg/well) and incubate coated plate at 4 o C for 18-22 hours.…”