Showing papers by "Tarun Bhatnagar published in 2021"

SARS-CoV-2 Sero-Prevalence Among General Population and Healthcare Workers in India, December 2020 - January 2021

Abstract: Background: Repeated cross-sectional serosurveys in the same geographic area establish the trend of the evolving pandemic. We present the findings of the third round of a national serosurvey to estimate the seroprevalence of SARS-CoV-2 infection among the general population and health care workers of India. Methods: We conducted the third population-based serosurvey between Dec 18, 2020 and Jan 6, 2021 in the same 700 villages or wards from 70 districts in 21 states across India, which were selected for the first and second serosurveys. We enrolled from each district, at least 400 individuals aged ≥ 10 years from general population and 100 HCWs from sub-district level public health facilities. Serum samples from general population were tested for the presence of IgG antibodies against nucleocapsid (N) and spike protein (S1-RBD) of SARS-CoV-2 using the Abbott and Siemens assays respectively, whereas sera from HCWs were tested for anti-S1-RBD. For general population, sera positive for either of the antibodies were considered positive, while sera positive for anti-S1-RBD were considered as positive for HCW. Weighted seroprevalence estimates were adjusted for sensitivity and specificity of respective assays. Findings: Of the 28,598 sera from general population, 4585 (16%) had IgG antibodies against N, 6647 (23.2%) against S1-RBD and 7436 (26%) against either. The weighted and assay characteristic adjusted seroprevalence against either of the antibodies was 24.1 (95%CI: 23.0% to 25.3%). Seroprevalence was lower in rural areas (21.4%, 95% CI: 20.3% to 22.6%) compared to urban non-slum (29.4%, 95% CI: 26.9% - 32.1%) and slum areas (34.6%, 95% CI: 31.0% to 38.3%). Among 7385 HCWs, the seroprevalence of anti-S1-RBD IgG antibodies was 25.6% (95% CI: 23.5% to 27.8%). Interpretation: Nearly one in four individuals aged 10 years or older from general population as well as HCWs were exposed to SARS-CoV-2 by December 2020 amounting to 271 million infections in India. Funding Statement: Indian Council of Medical Research Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare no competing interests Ethics Approval Statement: The project was approved by Institutional Human Ethics Committee at ICMR-National Institute of Epidemiology.

Optimal governance and implementation of vaccination programmes to contain the COVID-19 pandemic

Abstract: Since the recent introduction of several viable vaccines for SARS-CoV-2, vaccination uptake has become the key factor that will determine our success in containing the COVID-19 pandemic. We argue that game theory and social network models should be used to guide decisions pertaining to vaccination programmes for the best possible results. In the months following the introduction of vaccines, their availability and the human resources needed to run the vaccination programmes have been scarce in many countries. Vaccine hesitancy is also being encountered from some sections of the general public. We emphasize that decision-making under uncertainty and imperfect information, and with only conditionally optimal outcomes, is a unique forte of established game-theoretic modelling. Therefore, we can use this approach to obtain the best framework for modelling and simulating vaccination prioritization and uptake that will be readily available to inform important policy decisions for the optimal control of the COVID-19 pandemic.

Population-Based Serosurvey for Severe Acute Respiratory Syndrome Coronavirus 2 Transmission, Chennai, India.

Abstract: We conducted a cross-sectional survey to estimate the seroprevalence of IgG against severe acute respiratory syndrome coronavirus 2 in Chennai, India. Among 12,405 serum samples tested, weighted seroprevalence was 18.4% (95% CI 14.8%-22.6%). These findings indicate most of the population of Chennai is still susceptible to this virus.

Dynamic alterations in monocyte numbers, subset frequencies and activation markers in acute and convalescent COVID-19 individuals.

Abstract: Monocytes are thought to play an important role in host defence and pathogenesis of COVID-19. However, a comprehensive examination of monocyte numbers and function has not been performed longitudinally in acute and convalescent COVID-19. We examined the absolute counts of monocytes, the frequency of monocyte subsets, the plasma levels of monocyte activation markers using flowcytometry and ELISA in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the absolute counts of total monocytes and the frequencies of intermediate and non-classical monocytes increases from Days 15-30 to Days 61-90 and plateau thereafter. In contrast, the frequency of classical monocytes decreases from Days 15-30 till Days 121-150. The plasma levels of sCD14, CRP, sCD163 and sTissue Factor (sTF)-all decrease from Days 15-30 till Days 151-180. COVID-19 patients with severe disease exhibit higher levels of monocyte counts and higher frequencies of classical monocytes and lower frequencies of intermediate and non-classical monocytes and elevated plasma levels of sCD14, CRP, sCD163 and sTF in comparison with mild disease. Thus, our study provides evidence of dynamic alterations in monocyte counts, subset frequencies and activation status in acute and convalescent COVID-19 individuals.

Factors associated with mortality among moderate and severe patients with COVID-19 in India: a secondary analysis of a randomised controlled trial.

Abstract: Objective Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce. We analysed the factors associated with mortality in a cohort of moderately and severely ill patients with COVID-19 enrolled in a randomised trial on convalescent plasma. Design Secondary analysis of data from a Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease. Setting 39 public and private hospitals across India during the study period from 22 April to 14 July 2020. Participants Of the 464 patients recruited, two were lost to follow-up, nine withdrew consent and two patients did not receive the intervention after randomisation. The cohort of 451 participants with known outcome at 28 days was analysed. Primary outcome measure Factors associated with all-cause mortality at 28 days after enrolment. Results The mean (SD) age was 51±12.4 years; 76.7% were males. Admission Sequential Organ Failure Assessment score was 2.4±1.1. Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98.9%, 8.4% and 4.0%, respectively. The 28-day mortality was 14.4%. Median time from symptom onset to hospital admission was similar in survivors (4 days; IQR 3–7) and non-survivors (4 days; IQR 3–6). Patients with two or more comorbidities had 2.25 (95% CI 1.18 to 4.29, p=0.014) times risk of death. When compared with survivors, admission interleukin-6 levels were higher (p 10 (9.97, 3.65–27.13, p 1.0 mg/L (2.50, 1.14–5.48, p=0.022), ferritin ≥500 ng/mL (2.67, 1.44–4.96, p=0.002) and lactate dehydrogenase ≥450 IU/L (2.96, 1.60–5.45, p=0.001) were significantly associated with death. Conclusion In this cohort of moderately and severely ill patients with COVID-19, severity of illness, underlying comorbidities and elevated levels of inflammatory markers were significantly associated with death. Trial registration number CTRI/2020/04/024775.

Multi-country cross-sectional study of colonization with multidrug-resistant organisms: protocol and methods for the Antibiotic Resistance in Communities and Hospitals (ARCH) studies.

Abstract: Antimicrobial resistance is a global health emergency. Persons colonized with multidrug-resistant organisms (MDROs) are at risk for developing subsequent multidrug-resistant infections, as colonization represents an important precursor to invasive infection. Despite reports documenting the worldwide dissemination of MDROs, fundamental questions remain regarding the burden of resistance, metrics to measure prevalence, and determinants of spread. We describe a multi-site colonization survey protocol that aims to quantify the population-based prevalence and associated risk factors for colonization with high-threat MDROs among community dwelling participants and patients admitted to hospitals within a defined population-catchment area. Researchers in five countries (Bangladesh, Chile, Guatemala, Kenya, and India) will conduct a cross-sectional, population-based prevalence survey consisting of a risk factor questionnaire and collection of specimens to evaluate colonization with three high-threat MDROs: extended-spectrum cephalosporin-resistant Enterobacteriaceae (ESCrE), carbapenem-resistant Enterobacteriaceae (CRE), and methicillin-resistant Staphylococcus aureus (MRSA). Healthy adults residing in a household within the sampling area will be enrolled in addition to eligible hospitalized adults. Colonizing isolates of these MDROs will be compared by multilocus sequence typing (MLST) to routinely collected invasive clinical isolates, where available, to determine potential pathogenicity. A colonizing MDRO isolate will be categorized as potentially pathogenic if the MLST pattern of the colonizing isolate matches the MLST pattern of an invasive clinical isolate. The outcomes of this study will be estimates of the population-based prevalence of colonization with ESCrE, CRE, and MRSA; determination of the proportion of colonizing ESCrE, CRE, and MRSA with pathogenic characteristics based on MLST; identification of factors independently associated with ESCrE, CRE, and MRSA colonization; and creation an archive of ESCrE, CRE, and MRSA isolates for future study. This is the first study to use a common protocol to evaluate population-based prevalence and risk factors associated with MDRO colonization among community-dwelling and hospitalized adults in multiple countries with diverse epidemiological conditions, including low- and middle-income settings. The results will be used to better describe the global epidemiology of MDROs and guide the development of mitigation strategies in both community and healthcare settings. These standardized baseline surveys can also inform future studies seeking to further characterize MDRO epidemiology globally.

Recovery of Memory B-cell Subsets and Persistence of Antibodies in Convalescent COVID-19 Patients.

Abstract: It is essential to examine the longevity of the defensive immune response engendered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. We examined the SARS-CoV-2-specific antibody responses and ex vivo memory B-cell subsets in seven groups of individuals with COVID-19 classified based on days since reverse-transcription polymerase chain reaction confirmation of SARS-CoV-2 infection. Our data showed that the levels of IgG and neutralizing antibodies started increasing from days 15 to 30 to days 61 to 90, and plateaued thereafter. The frequencies of naive B cells and atypical memory B cells decreased from days 15 to 30 to days 61 to 90, and plateaued thereafter. In contrast, the frequencies of immature B cells, classical memory B cells, activated memory B cells, and plasma cells increased from days 15 to 30 to days 61 to 90, and plateaued thereafter. Patients with severe COVID-19 exhibited increased frequencies of naive cells, atypical memory B cells, and activated memory B cells, and lower frequencies of immature B cells, central memory B cells, and plasma cells when compared with patients with mild COVID-19. Therefore, our data suggest modifications in memory B-cell subset frequencies and persistence of humoral immunity in convalescent individuals with COVID-19.

Monitoring the trend of SARS-CoV-2 seroprevalence in Chennai, India, July and October 2020

Abstract: Background: The first serosurvey conducted in Chennai, India in July 2020 reported sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2) prevalence of 18.4%. The aim of this study was to estimate the seroprevalence in the month of October 2020. Methods: We conducted a survey in 153 streets covering 51 wards and all 15 zones of the city and enrolled from each street 40 individuals >= 10 y of age. We collected 3-5 ml of venous blood and tested for anti-nucleocapsid (N) immunoglobulin (IgG) antibodies using a SARS-CoV-2 IgG assay. We estimated the weighted seroprevalence of SARS-CoV-2 infection and adjusted for test characteristics. Results: Of the 6366 sera tested, 2052 were positive for anti-N IgG antibodies. The weighted seroprevalence after adjusting for test characteristics was 30.1% (95% confidence interval [CI] 24.7 to 36.1). There was wide variation in the seroprevalence between wards, ranging from 11.0% (95% CI 5.6 to 16.4) to 48.1% (95% CI 39.5 to 56.7). Conclusions: The seroprevalence of SARS-CoV-2 infection in Chennai nearly doubled between July and October 2020.

Prevalence of Igg Antibodies Against SARS-CoV-2 Among the General Population and Healthcare Workers in India, June–July 2021

Abstract: Background: India witnessed a severe second wave of COVID-19 during March and June 2021. We did the fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged >=6 years and health care workers (HCWs). Methods: We did a cross-sectional study between 14 June and 6 July 2021 in 700 clusters in the same 70 districts across 21 states/Union Territory. From each district, a minimum of 400 individuals aged >=6 years from general population and 100 HCWs from the district public health facilities were included. The serum samples were tested for the presence of IgG antibodies against S1-RBD and nucleocapsid protein of SARS-CoV-2 using chemiluminescence immunoassay. We estimated the weighted and test adjusted seroprevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein along with 95% CI. Findings: Of the 28,975 sera tested, the weighted and test adjusted prevalence of IgG antibodies against S1-RBD and/or nucleocapsid protein among the general population aged >=6 years was 67.6% (95% CI: 66.4 – 68.7). The seroprevalence increased with age and was not different in rural and urban areas. Compared to unvaccinated adults (62.3%, 95% CI: 60.9 – 63.7), seroprevalence was significantly higher among individuals who received one (81.0%, 95% CI: 79.6 - 82.3) and two doses (89.8%, 95% CI: 88.4 - 91.1). The seroprevalence of IgG antibodies among 7,252 health care workers was 85.2% (95% CI: 83.5 - 86.7). Interpretation: Nearly one third of the population is still seronegative. It is necessary to accelerate the coverage of COVID-19 vaccination among adults and continue adherence to non-pharmaceutical interventions. Funding: Indian Council of Medical Research. Declaration of Interest: None to declare. Ethical Approval: The Institutional Human Ethics Committee of the ICMR National Institute of Epidemiology, Chennai approved the study protocol.

Assessing of the Factors Associated with Mortality Among the Patients of PLACID Trial (A Phase II, Open Label, Randomized Controlled Trial to Assess the Safety and Efficacy of Convalescent Plasma to Limit COVID-19 Associated Complications in Moderate Disease)

Abstract: Background: Large data on the clinical characteristics and outcome of COVID-19 in the Indian population are scarce We analyzed the factors associated with mortality in a cohort of moderately ill COVID-19 patients enrolled in a multicentre randomized trial on convalescent plasma Methods: Demographic, clinical, laboratory, treatment, and outcome data were extracted from electronic records Factors associated with mortality were explored using univariate and multivariable Cox regression analysis and expressed as hazard ratio (HR) with 95% confidence intervals (CI) Findings: The mean (SD) age of the cohort (n=451) was 51±12·4 years; 76·7% were male Admission SOFA score was 2·4±1·1 Non-invasive ventilation, invasive ventilation and vasopressor therapy were required in 98·9%, 8·4% and 4·0% respectively The 28 day all-cause mortality was 14·4% Median time from symptom onset to hospital admission was similar (p=10) in survivors (4 days; IQR 3-7) and non survivors (4 days; IQR 3-6) Patients with two or more co-morbidities had 2·25 (95%CI:1·17–4·32, p=0·014) times risk of death When compared with survivors, admission IL-6 levels were higher (p 10 (9·38, 3·67-24·0,p 1·0mg/l (2·51,1·14-5·51,p=0·022), ferritin>500ng/ml (2·66,1·46-4·85,p=0·001) and LDH≥450 IU/L (2·96,1·61-5·45,p=0·001) were significantly associated with death Interpretation: In this cohort of moderately ill COVID-19 patients, severity of illness, underlying co-morbidities and higher levels of inflammatory markers were significantly associated with death Trial Registration: The trial protocol was registered with the Clinical Trial Registry of India (CTRI/2020/04/024775) Funding: This study was funded by Indian Council of Medical Research, an autonomous government funded medical research council Declaration of Interests: No other author has any competing financial or non-financial interest Ethics Approval Statement: Ethical approval was obtained from the ICMR Central Ethics Committee on Human Research 326 (CECHR-002/2020) as well as from the Institutional Review Boards (IRB) /Institutional Ethics 327 Committees of all the participating hospitals

Outbreak of ceftriaxone-resistant Salmonella enterica serotype Typhi-Tiruchirappalli, Tamil Nadu, India, June 2018

Abstract: Objectives In May 2018, a laboratory network for antimicrobial resistance (AMR) surveillance in Tamil Nadu, India, detected a cluster of Salmonella enterica serotype Typhi (S. Typhi) isolates resistant to ceftriaxone. We investigated to describe the epidemiology and identify risk factors for the outbreak. Methods We conducted unmatched case-control studies. We defined a case as illness (fever with abdominal pain, diarrhea or vomiting) in a person with blood culture-confirmed ceftriaxone-resistant S. Typhi isolated between January 1 and July 4, 2018 in Tiruchirappalli, Tamil Nadu. We interviewed cases using a semi-structured questionnaire to identify common exposures to food, water and places visited. Results We identified 7 cases (5 men) during March 25–June 8, 2018, median age 23 years (range: 12–42); all were hospitalized, none died. Eating at Restaurant A (odds ratio [OR]=22) and chicken gravy (OR=16) was associated with illness. Of the 10 workers at Restaurant A, stool culture from 8 did not detect S. Typhi; 2 did not consent to provide samples. Five water samples around the restaurant showed low or no residual chlorine content. Conclusions The investigation highlights the value of AMR surveillance in detecting emerging pathogens and the need for timely investigations, along with strengthening food safety.