Determining clinical biomarkers to predict long-term SARS-CoV-2 antibody response among COVID-19 patients in Bangladesh.

Background: Information on antibody responses following SARS-CoV-2 infection, including the magnitude and duration of responses, is limited. In this analysis, we aimed to identify clinical biomarkers that can predict long-term antibody responses following natural SARS-CoV-2 infection. Methodology: In this prospective study, we enrolled 100 COVID-19 patients between November 2020 and February 2021 and followed them for 6 months. The association of clinical laboratory parameters on enrollment, including lactate dehydrogenase (LDH), neutrophil-lymphocyte ratio (NLR), C-reactive protein (CRP), ferritin, procalcitonin (PCT), and D-dimer, with predicting the geometric mean (GM) concentration of SARS-CoV-2 receptor-binding domain (RBD)-specific IgG antibody at 3 and 6 months post-infection was assessed in multivariable linear regression models. Result: The mean ± SD age of patients in the cohort was 46.8 ± 14 years, and 58.8% were male. Data from 68 patients at 3 months follow-up and 55 patients at 6 months follow-up were analyzed. Over 90% of patients were seropositive against RBD-specific IgG till 6 months post-infection. At 3 months, for any 10% increase in absolute lymphocyte count and NLR, there was a 6.28% (95% CI: 9.68, -2.77) decrease and 4.93% (95% CI: 2.43, 7.50) increase, respectively, in GM of IgG concentration, while any 10% increase for LDH, CRP, ferritin, and procalcitonin was associated with a 10.63, 2.87, 2.54, and 3.11% increase in the GM of IgG concentration, respectively. Any 10% increase in LDH, CRP, and ferritin was similarly associated with an 11.28, 2.48, and 3.0% increase in GM of IgG concentration at 6 months post-infection. Conclusion: Several clinical biomarkers in the acute phase of SARS-CoV-2 infection are associated with enhanced IgG antibody response detected after 6 months of disease onset. The measurement of SARS-CoV-2 specific antibody responses requires improved techniques and is not feasible in all settings. Baseline clinical biomarkers can be a useful alternative as they can predict antibody response during the convalescence period. Individuals with an increased level of NLR, CRP, LDH, ferritin, and procalcitonin may benefit from the boosting effect of vaccines. Further analyses will determine whether biochemical parameters can predict RBD-specific IgG antibody responses at later time points and the association of neutralizing antibody responses.

Transmission of SARS-CoV-2 in the Population Living in High- and Low-Density Gradient Areas in Dhaka, Bangladesh.

Community transmission of SARS-CoV-2 in densely populated countries has been a topic of concern from the beginning of the pandemic. Evidence of community transmission of SARS-CoV-2 according to population density gradient and socio-economic status (SES) is limited. In June-September 2020, we conducted a descriptive longitudinal study to determine the community transmission of SARS-CoV-2 in high- and low-density areas in Dhaka city. The Secondary Attack Rate (SAR) was 10% in high-density areas compared to 20% in low-density areas. People with high SES had a significantly higher level of SARS-CoV-2-specific Immunoglobulin G (IgG) antibodies on study days 1 (p = 0.01) and 28 (p = 0.03) compared to those with low SES in high-density areas. In contrast, the levels of seropositivity of SARS-CoV-2-specific Immunoglobulin M (IgM) were comparable (p > 0.05) in people with high and low SES on both study days 1 and 28 in both high- and low-density areas. Due to the similar household size, no differences in the seropositivity rates depending on the population gradient were observed. However, people with high SES showed higher seroconversion rates compared to people with low SES. As no difference was observed based on population density, the SES might play a role in SARS-CoV-2 transmission, an issue that calls for further in-depth studies to better understand the community transmission of SARS-CoV-2.

Correlation of antigen-specific immune response with disease severity among COVID-19 patients in Bangladesh.

Coronavirus disease 2019 (COVID-19) is a protean disease causing different degrees of clinical severity including fatality. In addition to humoral immunity, antigen-specific T cells may play a critical role in defining the protective immune response against SARS-CoV-2, the virus that causes this disease. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell-specific immune responses, we sought to evaluate the activation-induced marker (AIM) and the status of different immune cell subsets during a COVID-19 infection. We analyzed a total of 115 participants, which included participants with asymptomatic, mild, moderate, and severe clinical symptoms. We observed decreased mucosal-associated invariant T (MAIT) cell frequency on the initial days of the COVID-19 infection in symptomatic patients compared to asymptomatic patients. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of the disease compared to both asymptomatic patients and healthy individuals. Moreover, we found a significant increase of AIM+ (both OX40+CD137+ and OX40+CD40L+) CD4+ T cells in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (especially spike peptides) compared to pre-pandemic controls who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIMs (CD137+CD69+), which indicates the exhaustion of CD8+ T cells during a COVID-19 infection. These findings suggest that patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T-cell response against shared viral determinants that ultimately induced T cells to mount further immune responses to SARS-CoV-2.

Life-Course Approach to Vaccination in Bangladesh for Meeting the Health and Health-Related Sustainable Development Goals: A Commentary.

Bangladesh is entering from low-income to lower-middle-income status in 2020, and this will be completed in the next 5 years. With gross national income growing, vaccines will need to be procured through private market for the Expanded Program on Immunization. A cost-benefit analysis is needed to evaluate vaccine demand in different socioeconomic groups in the country, to inform this procurement. Moreover, disease burden studies and awareness of importance of specific vaccines are needed as we move forward. A life-course approach to vaccination may enable whole society to realize the full potential of vaccination and address most significant threats to its success over time.

Longevity of memory B cells and antibodies, as well as the polarization of effector memory helper T cells, are associated with disease severity in patients with COVID-19 in Bangladesh.

The longevity of immune responses induced by different degrees of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides information important to understanding protection against coronavirus disease 2019 (COVID-19). Here, we report the persistence of SARS-CoV-2 spike receptor-binding domain (RBD) specific antibodies and memory B cells recognizing this antigen in sequential samples from patients in Bangladesh with asymptomatic, mild, moderate and severe COVID-19 out to six months following infection. Since the development of long-lived memory B cells, as well as antibody production, is likely to be dependent on T helper (Th) cells, we also investigated the phenotypic changes of Th cells in COVID-19 patients over time following infection. Our results show that patients with moderate to severe COVID-19 mounted significant levels of IgG antibodies out to six months following infection, while patients with asymptomatic or mild disease had significant levels of IgG antibodies out to 3 months following infection, but these then fell more rapidly at 6 months than in patients with higher disease severity. Patients from all severity groups developed circulating memory B cells (MBCs) specific to SARS-CoV-2 spike RBD by 3 months following infection, and these persisted until the last timepoint measured at 6 months. A T helper cell response with an effector memory phenotype was observed following infection in all symptomatic patients, while patients with asymptomatic infection had no significant increases in effector Th1, Th2 and Th17 effector memory cell responses. Our results suggest that the strength and magnitude of antibody and memory B cells induced following SARS-CoV-2 infection depend on the severity of the disease. Polarization of the Th cell response, with an increase in Th effector memory cells, occurs in symptomatic patients by day 7 following infection, with increases seen in Th1, Th2, Th17 and follicular helper T cell subsets.

COVID-19 Risk Perception and Prevention Practices among High- and Low-Density Populations in Bangladesh: A Mixed-Methods Study.

We aimed to explore coronavirus disease 2019 (COVID-19) risk perception and prevention practices among people living in high- and low-population density areas in Dhaka, Bangladesh. A total of 623 patients with confirmed COVID-19 agreed to participate in the survey. Additionally, we purposively selected 14 participants from diverse economic and occupational groups and conducted qualitative interviews for them accordingly. Approximately 70% of the respondents had low socioeconomic status. Among the 623 respondents, 146 were from low-density areas, and 477 were from high-density areas. The findings showed that study participants perceived COVID-19 as a punishment from the Almighty, especially for non-Muslims, and were not concerned about its severity. They also believed that coronavirus would not survive in hot temperatures or negatively impact Bangladeshis. This study revealed that people were reluctant to undergo COVID-19 testing. Family members hid if anyone tested positive for COVID-19 or did not adhere to institutional isolation. The findings showed that participants were not concerned about COVID-19 and believed that coronavirus would not have a devastating impact on Bangladeshis; thus, they were reluctant to follow prevention measures and undergo testing. Tailored interventions for specific targeted groups would be relevant in mitigating the prevailing misconceptions.

Correlation of antigen-specific immune response with disease severity among COVID-19 patients in Bangladesh

Coronavirus disease 2019 (COVID-19) is a protean disease causing different degrees of clinical severity including fatality. In addition to humoral immunity, antigen-specific T cells may play a critical role in defining the protective immune response against SARS-CoV-2, the virus that causes this disease. As a part of a longitudinal cohort study in Bangladesh to investigate B and T cell-specific immune responses, we sought to evaluate the activation-induced marker (AIM) and the status of different immune cell subsets during a COVID-19 infection. We analyzed a total of 115 participants, which included participants with asymptomatic, mild, moderate, and severe clinical symptoms. We observed decreased mucosal-associated invariant T (MAIT) cell frequency on the initial days of the COVID-19 infection in symptomatic patients compared to asymptomatic patients. However, natural killer (NK) cells were found to be elevated in symptomatic patients just after the onset of the disease compared to both asymptomatic patients and healthy individuals. Moreover, we found a significant increase of AIM+ (both OX40+CD137+ and OX40+CD40L+) CD4+ T cells in moderate and severe COVID-19 patients in response to SARS-CoV-2 peptides (especially spike peptides) compared to pre-pandemic controls who are unexposed to SARS-CoV-2. Notably, we did not observe any significant difference in the CD8+ AIMs (CD137+CD69+), which indicates the exhaustion of CD8+ T cells during a COVID-19 infection. These findings suggest that patients who recovered from moderate and severe COVID-19 were able to mount a strong CD4+ T-cell response against shared viral determinants that ultimately induced T cells to mount further immune responses to SARS-CoV-2.

Covishield vaccine induces robust immune responses in Bangladeshi adults.

Objective: To evaluate severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-specific antibody responses after Covishield vaccination for 6 months after vaccination. Design: SARS-CoV-2-specific antibody responses were assessed by enzyme-linked immunosorbent assay of the recombinant receptor-binding domain of SARS-CoV-2 in 381 adults given the Covishield vaccine at baseline (n=119), 1 month (n=126) and 2 months (n=75) after the first dose, 1 month after the second dose (n=161), and monthly for 3 additional months. Results: Over 51% of participants were seropositive at baseline (before vaccination with Covishield), and almost all participants (159/161) became seropositive 1 month after the second dose. Antibody levels peaked 1 month after receipt of the second dose of vaccine, and decreased by 4 months after the first dose; the lowest responses were found 6 months after the first dose, although antibody responses and responder frequencies remained significantly higher compared with baseline (P<0.0001). Compared with younger participants, older participants had lower antibody responses 6 months after the first dose of vaccine (P<0.05). Participants who had previous SARS-CoV-2 infection showed robust higher antibody responses after vaccination. Conclusions: These findings help to elucidate the longevity of vaccine-specific antibody responses following vaccination with Covishield, and provide information relevant to the planning of booster doses after the initial two doses of vaccine.

Transmission of SARS-CoV-2 in the Population Living in High- and Low-Density Gradient Areas in Dhaka, Bangladesh

Community transmission of SARS-CoV-2 in densely populated countries has been a topic of concern from the beginning of the pandemic. Evidence of community transmission of SARS-CoV-2 according to population density gradient and socio-economic status (SES) is limited. In June–September 2020, we conducted a descriptive longitudinal study to determine the community transmission of SARS-CoV-2 in high- and low-density areas in Dhaka city. The Secondary Attack Rate (SAR) was 10% in high-density areas compared to 20% in low-density areas. People with high SES had a significantly higher level of SARS-CoV-2-specific Immunoglobulin G (IgG) antibodies on study days 1 (p = 0.01) and 28 (p = 0.03) compared to those with low SES in high-density areas. In contrast, the levels of seropositivity of SARS-CoV-2-specific Immunoglobulin M (IgM) were comparable (p > 0.05) in people with high and low SES on both study days 1 and 28 in both high- and low-density areas. Due to the similar household size, no differences in the seropositivity rates depending on the population gradient were observed. However, people with high SES showed higher seroconversion rates compared to people with low SES. As no difference was observed based on population density, the SES might play a role in SARS-CoV-2 transmission, an issue that calls for further in-depth studies to better understand the community transmission of SARS-CoV-2.

Genome Sequences of 25 SARS-CoV-2 Sublineage B.1.1.529 Omicron Strains in Bangladesh.

We report the coding-complete genome sequences of 25 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sublineage B.1.1.529 Omicron strains obtained from Bangladeshi individuals in samples collected between December 2021 and January 2022. Genomic data were generated by Nanopore sequencing using the amplicon sequencing approach developed by the ARTIC Network.

Seroprevalence of SARS-CoV-2 antibodies in Bangladesh related to novel coronavirus infection.

Design: A cross-sectional study was conducted amongst household members in 32 districts of Bangladesh to build knowledge about disease epidemiology and seroepidemiology of coronavirus disease 2019 (COVID-19). Objective: Antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were assessed in people between April and October 2020. Results: The national seroprevalence rates of immunoglobulin G (IgG) and IgM were estimated to be 30.4% and 39.7%, respectively. In Dhaka, the seroprevalence of IgG was 35.4% in non-slum areas and 63.5% in slum areas. In areas outside of Dhaka, the seroprevalence of IgG was 37.5% in urban areas and 28.7% in rural areas. Between April and October 2020, the highest seroprevalence rate (57% for IgG and 64% for IgM) was observed in August. IgM antibody was more prevalent in younger participants, while older participants had more frequent IgG seropositivity. Follow-up specimens from patients with COVID-19 and their household members suggested that both IgG and IgM seropositivity increased significantly at day 14 and day 28 compared with day 1 after enrolment. Conclusions: SARS-CoV-2 had spread extensively in Bangladesh by October 2020. This highlights the importance of monitoring seroprevalence data, particularly with the emergence of new SARS-CoV-2 variants over time.

SARS-CoV-2 Seroprevalence before Delta Variant Surge, Chattogram, Bangladesh, March-June 2021.

A March-June 2021 representative serosurvey among Sitakunda subdistrict (Chattogram, Bangladesh) residents found an adjusted prevalence of severe acute respiratory syndrome coronavirus 2 antibodies of 64.1% (95% credible interval 60.0%-68.1%). Before the Delta variant surge, most residents had been infected, although cumulative confirmed coronavirus disease incidence was low.

Hepatitis E in Bangladesh: Insights From a National Serosurvey.

BACKGROUND: Hepatitis E virus (HEV) genotypes 1 and 2 are a major cause of avoidable morbidity and mortality in South Asia. Despite the high risk of death among infected pregnant women, scarce incidence data has been a contributing factor to global policy recommendations against the introduction of licensed hepatitis E vaccines, one of the only effective prevention tools. METHODS: We tested serum from a nationally representative serosurvey in Bangladesh for anti-HEV immunoglobulin G and estimated seroprevalence. We used Bayesian geostatistical models to generate high-resolution maps of seropositivity and examined variability in seropositivity by individual-level, household-level, and community-level risk factors using spatial logistic regression. RESULTS: We tested serum samples from 2924 individuals from 70 communities representing all divisions of Bangladesh and estimated a national seroprevalence of 20% (95% confidence interval [CI], 17%-24%). Seropositivity increased with age and male sex (odds ratio, 2.2 male vs female; 95% CI, 1.8-2.8). Community-level seroprevalence ranged widely (0-78%) with higher seroprevalence in urban areas, including Dhaka, with a 3.0-fold (95% credible interval, 2.3-3.7) higher seroprevalence than the rest of the country. CONCLUSIONS: Hepatitis E infections are common throughout Bangladesh. Strengthening surveillance for hepatitis E, especially in urban areas, can provide additional evidence to appropriately target interventions.

Disease characteristics and serological responses in patients with differing severity of COVID-19 infection: A longitudinal cohort study in Dhaka, Bangladesh.

BACKGROUND: COVID-19 caused by SARS-CoV-2 ranges from asymptomatic to severe disease and can cause fatal and devastating outcome in many cases. In this study, we have compared the clinical, biochemical and immunological parameters across the different disease spectrum of COVID-19 in Bangladeshi patients. METHODOLOGY/PRINCIPAL FINDINGS: This longitudinal study was conducted in two COVID-19 hospitals and also around the community in Dhaka city in Bangladesh between November 2020 to March 2021. A total of 100 patients with COVID-19 infection were enrolled and classified into asymptomatic, mild, moderate and severe cases (n = 25/group). In addition, thirty age and sex matched healthy participants were enrolled and 21 were analyzed as controls based on exclusion criteria. After enrollment (study day1), follow-up visits were conducted on day 7, 14 and 28 for the cases. Older age, male gender and co-morbid conditions were the risk factors for severe COVID-19 disease. Those with moderate and severe cases of infection had low lymphocyte counts, high neutrophil counts along with a higher neutrophil-lymphocyte ratio (NLR) at enrollment; this decreased to normal range within 42 days after the onset of symptom. At enrollment, D-dimer, CRP and ferritin levels were elevated among moderate and severe cases. The mild, moderate, and severe cases were seropositive for IgG antibody by day 14 after enrollment. Moderate and severe cases showed significantly higher IgM and IgG levels of antibodies to SARS-CoV-2 compared to mild and asymptomatic cases. CONCLUSION/SIGNIFICANCE: We report on the clinical, biochemical, and hematological parameters associated with the different severity of COVID-19 infection. We also show different profile of antibody response against SARS-CoV-2 in relation to disease severity, especially in those with moderate and severe disease manifestations compared to the mild and asymptomatic infection.

Prevalence of COVID-19 in Bangladesh, April to October 2020-a cross-sectional study.

Objective: The aim of this study was to estimate the proportion of symptomatic and asymptomatic laboratory-confirmed coronavirus disease 2019 (COVID-19) cases among the population of Bangladesh. Methods: A cross-sectional survey was conducted in Dhaka City and other districts of Bangladesh between April 18 and October 12, 2020. A total of 32 districts outside Dhaka were randomly selected, and one village and one mahalla was selected from each district; 25 mahallas were selected from Dhaka City. From each village or mahalla, 120 households were enrolled through systematic random sampling. Results: A total of 44 865 individuals were interviewed from 10 907 households. The majority (70%, n = 31 488) of the individuals were <40 years of age. Almost half of the individuals (49%, n = 21 888) reported more than four members in their household. It was estimated that 12.6% (n = 160) of the households had one or more severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals, among whom 0.9% (n = 404) of individuals had at least one COVID-19-like symptom, at the national level. The prevalence of COVID-19 in the general population was 6.4%. Among the SARS-CoV-2-positive individuals, 87% were asymptomatic. Conclusions: The substantial high number of asymptomatic cases all over Bangladesh suggests that community-level containment and mitigation measures are required to combat COVID-19. Future studies to understand the transmission capability could help to define mitigation and control measures.

Antibody responses after COVID-19 infection in patients who are mildly symptomatic or asymptomatic in Bangladesh.

OBJECTIVES: Studies on serological responses following coronavirus disease-2019 (COVID-19) have been published primarily in individuals who are moderately or severely symptomatic, but there are few data from individuals who are mildly symptomatic or asymptomatic. METHODS: We measured IgG, IgM, and IgA to the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by using enzyme-linked immunosorbent assay in mildly symptomatic (n = 108) and asymptomatic (n = 63) on days 1, 7, 14, and 30 following RT-PCR confirmation in Bangladesh and when compared with pre-pandemic samples, including healthy controls (n = 73) and individuals infected with other viruses (n = 79). RESULTS: Mildly symptomatic individuals developed IgM and IgA responses by day 14 in 72% and 83% of individuals, respectively, while 95% of individuals developed IgG response, and rose to 100% by day 30. In contrast, individuals infected with SARS-CoV-2 but who remained asymptomatic developed antibody responses significantly less frequently, with only 20% positive for IgA and 22% positive for IgM by day 14, and 45% positive for IgG by day 30 after infection. CONCLUSIONS: These results confirm immune responses are generated following COVID-19 who develop mildly symptomatic illness. However, those with asymptomatic infection do not respond or have lower antibody levels. These results will impact modeling needed for determining herd immunity generated by natural infection or vaccination.