Immune cell landscape in symptomatic and asymptomatic SARS-CoV-2 infected adults and children in urban Dhaka, Bangladesh.

OBJECTIVES: The study of cellular immunity to SARS-CoV-2 is crucial for evaluating the course of the COVID-19 disease and for improving vaccine development. We aimed to assess the phenotypic landscape of circulating lymphocytes and mononuclear cells in adults and children who were seropositive to SARS-CoV-2 in the past 6 months. METHODS: Blood samples (n = 350) were collected in a cross-sectional study in Dhaka, Bangladesh (Oct 2020-Feb 2021). Plasma antibody responses to SARS-CoV-2 were determined by an electrochemiluminescence immunoassay while lymphocyte and monocyte responses were assessed using flow cytometry including dimensionality reduction and clustering algorithms. RESULTS: SARS-CoV-2 seropositivity was observed in 52% of adults (18-65 years) and 56% of children (10-17 years). Seropositivity was associated with reduced CD3+T cells in both adults (beta(ß) = -2.86; 95% Confidence Interval (CI) = -5.98, 0.27) and children (ß = -8.78; 95% CI = -13.8, -3.78). The frequencies of T helper effector (CD4+TEFF) and effector memory cells (CD4+TEM) were increased in seropositive compared to seronegative children. In adults, seropositivity was associated with an elevated proportion of cytotoxic T central memory cells (CD8+TCM). Overall, diverse manifestations of immune cell dysregulations were more prominent in seropositive children compared to adults, who previously had COVID-like symptoms. These changes involved reduced frequencies of CD4+TEFF cells and CD163+CD64+ classical monocytes, but increased levels of intermediate or non-classical monocytes, as well as CD8+TEM cells in symptomatic children. CONCLUSION: Seropositive individuals in convalescence showed increased central and effector memory T cell phenotypes and pro-resolving/healing monocyte phenotypes compared to seronegative subjects. However, seropositive children with a previous history of COVID-like symptoms, displayed an ongoing innate inflammatory trait.

Antibodies to Commonly Circulating Viral Pathogens Modulate Serological Response to Severe Acute Respiratory Syndrome Coronavirus 2 Infection

The purpose of this study was to determine the seropositivity of circulating viral pathogens and their association with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) seropositivity. In a cross-sectional design, inhabitants (aged 10-60 years) of the slum and surrounding non-slum areas of Dhaka and Chattogram Metropolitan cities in Bangladesh were enrolled from October 2020 to February 2021. Antibodies to SARS-CoV-2, influenza B, parainfluenza, respiratory syncytial virus (RSV), human coronavirus HKU1 (HCoV-HKU1), dengue and chikungunya viruses were determined in plasma. The association of SARS-CoV-2 seropositivity with seropositivity to other viruses was assessed using the multi-variate logistic regression model. Seroprevalence of SARS-CoV-2, influenza B, RSV, dengue, chikungunya, HCoV-HKU1 and the parainfluenza virus were 68.3%, 98%, 50.0%, 16.5%, 15.5%, 3.36% and 0.0%, respectively. Individuals seropositive for RSV had lower odds (OR = 0.60;95% CI= 0.49, 0.73) of SARS-CoV-2 seropositivity compared to RSV-seronegative individuals. Conversely, higher odds of SARS-CoV-2 seropositivity were observed in participants seropositive for dengue (OR= 1.73;95% CI = 1.14, 2.66, only in slum) or chikungunya (OR = 1.48;95% CI = 1.11, 1.95) compared to their seronegative counterparts. The study findings indicated that exposure to vector-borne virus dengue or chikungunya enhance, while antibodies to respiratory virus RSV decrease, the serological response to SARS-CoV-2.

Comparison of the Immune Responses to COVID-19 Vaccines in Bangladeshi Population.

BACKGROUND: The adaptive immune response is a crucial component of the protective immunity against SARS-CoV-2, generated after infection or vaccination. METHODS: We studied antibody titers, neutralizing antibodies and cellular immune responses to four different COVID-19 vaccines, namely Pfizer-BioNTech, Moderna Spikevax, AstraZeneca and Sinopharm vaccines in the Bangladeshi population (n = 1780). RESULTS: mRNA vaccines Moderna (14,655 ± 11.3) and Pfizer (13,772 ± 11.5) elicited significantly higher anti-Spike (S) antibody titers compared to the Adenovector vaccine AstraZeneca (2443 ± 12.8) and inactivated vaccine Sinopharm (1150 ± 11.2). SARS-CoV-2-specific neutralizing antibodies as well as IFN-γ-secreting lymphocytes were more abundant in Pfizer and Moderna vaccine recipients compared to AstraZeneca and Sinopharm vaccine recipients. Participants previously infected with SARS-CoV-2 exhibited higher post-vaccine immune responses (S-specific and neutralizing antibodies, IFN-γ-secreting cells) compared to uninfected participants. Memory B (BMEM), total CD8+T, CD4+ central memory (CD4+CM) and T-regulatory (TREG) cells were more numerous in AstraZeneca vaccine recipients compared to other vaccine recipients. Plasmablasts, B-regulatory (BREG) and CD4+ effector (CD4+EFF) cells were more numerous in mRNA vaccine recipients. CONCLUSIONS: mRNA vaccines generated a higher antibody response, while a differential cellular response was observed for different vaccine types, suggesting that both cellular and humoral responses are important in immune monitoring of different types of vaccines.