Post-campaign coverage evaluation of a measles and rubella supplementary immunization activity in five districts in India, 2019-2020.

BACKGROUND: In alignment with the Measles and Rubella (MR) Strategic Elimination plan, India conducted a mass measles and rubella vaccination campaign across the country between 2017 and 2020 to provide a dose of MR containing vaccine to all children aged 9 months to 15 years. We estimated campaign vaccination coverage in five districts in India and assessed campaign awareness and factors associated with vaccination during the campaign to better understand reasons for not receiving the dose. METHODS AND FINDINGS: Community-based cross-sectional serosurveys were conducted in five districts of India among children aged 9 months to 15 years after the vaccination campaign. Campaign coverage was estimated based on home-based immunization record or caregiver recall. Campaign coverage was stratified by child- and household-level risk factors and descriptive analyses were performed to assess reasons for not receiving the campaign dose. Three thousand three hundred and fifty-seven children aged 9 months to 15 years at the time of the campaign were enrolled. Campaign coverage among children aged 9 months to 5 years documented or by recall ranged from 74.2% in Kanpur Nagar District to 90.4% in Dibrugarh District, Assam. Similar coverage was observed for older children. Caregiver awareness of the campaign varied from 88.3% in Hoshiarpur District, Punjab to 97.6% in Dibrugarh District, Assam, although 8% of children whose caregivers were aware of the campaign were not vaccinated during the campaign. Failure to receive the campaign dose was associated with urban settings, low maternal education, and lack of school attendance although the associations varied by district. CONCLUSION: Awareness of the MR vaccination campaign was high; however, campaign coverage varied by district and did not reach the elimination target of 95% coverage in any of the districts studied. Areas with lower coverage among younger children must be prioritized by strengthening the routine immunization programme and implementing strategies to identify and reach under-vaccinated children.

Factors associated with unexplained sudden deaths among adults aged 18-45 years in India - A multicentric matched case-control study.

BACKGROUND OBJECTIVES: In view of anecdotal reports of sudden unexplained deaths in India's apparently healthy young adults, linking to coronavirus disease 2019 (COVID-19) infection or vaccination, we determined the factors associated with such deaths in individuals aged 18-45 years through a multicentric matched case-control study. METHODS: This study was conducted through participation of 47 tertiary care hospitals across India. Cases were apparently healthy individuals aged 18-45 years without any known co-morbidity, who suddenly (<24 h of hospitalization or seen apparently healthy 24 h before death) died of unexplained causes during 1 st October 2021-31 st March 2023. Four controls were included per case matched for age, gender and neighborhood. We interviewed/perused records to collect data on COVID-19 vaccination/infection and post-COVID-19 conditions, family history of sudden death, smoking, recreational drug use, alcohol frequency and binge drinking and vigorous-intensity physical activity two days before death/interviews. We developed regression models considering COVID-19 vaccination ≤42 days before outcome, any vaccine received anytime and vaccine doses to compute an adjusted matched odds ratio (aOR) with 95 per cent confidence interval (CI). RESULTS: Seven hundred twenty nine cases and 2916 controls were included in the analysis. Receipt of at least one dose of COVID-19 vaccine lowered the odds [aOR (95% CI)] for unexplained sudden death [0.58 (0.37, 0.92)], whereas past COVID-19 hospitalization [3.8 (1.36, 10.61)], family history of sudden death [2.53 (1.52, 4.21)], binge drinking 48 h before death/interview [5.29 (2.57, 10.89)], use of recreational drug/substance [2.92 (1.1, 7.71)] and performing vigorous-intensity physical activity 48 h before death/interview [3.7 (1.36, 10.05)] were positively associated. Two doses lowered the odds of unexplained sudden death [0.51 (0.28, 0.91)], whereas single dose did not. INTERPRETATION CONCLUSIONS: COVID-19 vaccination did not increase the risk of unexplained sudden death among young adults in India. Past COVID-19 hospitalization, family history of sudden death and certain lifestyle behaviors increased the likelihood of unexplained sudden death.

Household catastrophic health expenditure for COVID-19 during March-August 2021, in South India: a cross-sectional study.

BACKGROUND: The Coronavirus disease 2019 (COVID-19) pandemic increased the utilisation of healthcare services. Such utilization could lead to higher out-of-pocket expenditure (OOPE) and catastrophic health expenditures (CHE). We estimated OOPE and the proportion of households that experienced CHE by conducting a cross-sectional survey of 1200 randomly selected confirmed COVID-19 cases. METHODS: A cross-sectional survey was conducted by telephonic interviews of 1200 randomly selected COVID-19 patients who tested positive between 1 March and 31 August 2021. We collected household-level information on demographics, income, expenditure, insurance coverage, direct medical and non-medical costs incurred toward COVID-19 management. We estimated the proportion of CHE with a 95% confidence interval. We examined the association of household characteristics; COVID-19 cases, severity, and hospitalisation status with CHE. A multivariable logistic regression analysis was conducted to ascertain the effects of variables of interest on the likelihood that households face CHE due to COVID-19. RESULTS: The mean (95%CI) OOPE per household was INR 122,221 (92,744-1,51,698) [US$1,643 (1,247-2,040)]. Among households, 61.7% faced OOPE, and 25.8% experienced CHE due to COVID-19. The odds of facing CHE were high among the households; with a family member over 65 years [OR = 2.89 (2.03-4.12)], with a comorbid individual [OR = 3.38 (2.41-4.75)], in the lowest income quintile [OR = 1.82 (1.12-2.95)], any member visited private hospital [OR = 11.85 (7.68-18.27)]. The odds of having CHE in a household who have received insurance claims [OR = 5.8 (2.81- 11.97)] were high. Households with one and more than one severe COVID-19 increased the risk of CHE by more than two-times and three-times respectively [AOR = 2.67 (1.27-5.58); AOR = 3.18 (1.49-6.81)]. CONCLUSION: COVID-19 severity increases household OOPE and CHE. Strengthening the public healthcare and health insurance with higher health financing is indispensable for financial risk protection of households with severe COVID-19 from CHE.

Evaluating the effect of measles and rubella mass vaccination campaigns on seroprevalence in India: a before-and-after cross-sectional household serosurvey in four districts, 2018-2020.

BACKGROUND: India did phased measles-rubella supplementary immunisation activities (MR-SIAs; ie, mass-immunisation campaigns) targeting children aged 9 months to less than 15 years. We estimated measles-rubella seroprevalence before and after the MR-SIAs to quantify the effect on population immunity and identify remaining immunity gaps. METHODS: Between March 9, 2018 and March 19, 2020 we did community-based, cross-sectional serosurveys in four districts in India before and after MR-SIAs. 30 villages or wards were selected within each district, and one census enumeration block from each was selected as the survey cluster. Households were enumerated and 13 children in the younger age group (9 months to <5 years) and 13 children in the older ager group (5 to <15 years) were randomly selected by use of computer-generated random numbers. Serum samples were tested for IgG antibodies to measles and rubella viruses by enzyme immunoassay. FINDINGS: Specimens were collected from 2570 children before the MR-SIA and from 2619 children afterwards. The weighted MR-SIA coverage ranged from 73·7% to 90·5% in younger children and from 73·6% to 93·6% in older children. Before the MR-SIA, district-level measles seroprevalence was between 80·7% and 88·5% among younger children in all districts, and between 63·4% and 84·5% among older children. After the MR-SIA, measles seroprevalence among younger children increased to more than 90% (range 91·5 to 96·0) in all districts except Kanpur Nagar, in which it remained unchanged 80·4%. Among older children, measles seroprevalence increased to more than 90·0% (range 93·7% to 96·5%) in all districts except Hoshiarpur (88·7%). A significant increase in rubella seroprevalence was observed in all districts in both age groups, with the largest effect in Dibrugarh, where rubella seroprevalence increased from 10·6% to 96·5% among younger children. INTERPRETATION: Measles-rubella seroprevalence increased substantially after the MR-SIAs but the serosurvey also identified remaining gaps in population immunity. FUNDING: The Bill & Melinda Gates Foundation and Indian Council of Medical Research.

Restoration of dendritic cell homeostasis and Type I/Type III interferon levels in convalescent COVID-19 individuals.

BACKGROUND: Plasmacytoid and myeloid dendritic cells play a vital role in the protection against viral infections. In COVID-19, there is an impairment of dendritic cell (DC) function and interferon secretion which has been correlated with disease severity. RESULTS: In this study, we described the frequency of DC subsets and the plasma levels of Type I (IFNα, IFNß) and Type III Interferons (IFNλ1), IFNλ2) and IFNλ3) in seven groups of COVID-19 individuals, classified based on days since RT-PCR confirmation of SARS-CoV2 infection. Our data shows that the frequencies of pDC and mDC increase from Days 15-30 to Days 61-90 and plateau thereafter. Similarly, the levels of IFNα, IFNß, IFNλ1, IFNλ2 and IFNλ3 increase from Days 15-30 to Days 61-90 and plateau thereafter. COVID-19 patients with severe disease exhibit diminished frequencies of pDC and mDC and decreased levels of IFNα, IFNß, IFNλ1, IFNλ2 and IFNλ3. Finally, the percentages of DC subsets positively correlated with the levels of Type I and Type III IFNs. CONCLUSION: Thus, our study provides evidence of restoration of homeostatic levels in DC subset frequencies and circulating levels of Type I and Type III IFNs in convalescent COVID-19 individuals.

Community voices around COVID-19 vaccine in Chennai, India: A qualitative exploration during early phase of vaccine rollout.

Background & objectives: Globally, vaccination is considered as an important public health strategy to mitigate the impact of the COVID-19 pandemic. The purpose of the current study was to conduct an in-depth inquiry to explore perceptions of community members around COVID-19 vaccines in the southern city of Chennai, Tamil Nadu. This was conducted during the early phase of the vaccine rollout programme in India. Methods: A qualitative investigation was conducted between January-February 2021 through in-depth interviews. Healthcare workers, religious leaders, community influencers, local administrators and representatives of marginalized communities were included. The key informant interview guides and probes explored five domains; (i) vaccine availability, (ii) trust in COVID-19 vaccines, (iii) vaccine-related concerns, (iv) health/risk balance and (v) vaccine prioritization. Transcripted interviews were coded using a thematic approach and analyzed manually as well as with the help of ATLAS.ti 9 software. Results: Eagerness to receive COVID-19 vaccines amongst some of the respondents was linked with freedom from fear, possible restoration of normalcy, protection of family and ability to travel and work abroad. Concerns around threat of emergence of new variants, damage caused by such viral mutants and trust in policymakers were other facilitatory influencers for vaccine uptake. On the other hand, doubts surrounding safety and fear of side effects of COVID-19 vaccine were the feeders to vaccine hesitancy. Lack of accurate information, sensational media reports and rumours exacerbated this fear and provoked anxiety among people. Apprehensions around COVID-19 vaccine in the wake of its rapid development and approval for use and reluctance to take it during the declining phase of the epidemic were identified as other inhibitory factors. Participants underlined the importance of having responsive communication strategies in place focussing on vaccine safety. Making vaccines available to people free of cost and ensuring wider access were other programmatic suggestions. Interpretation & conclusions: In conclusion, our study findings suggest that it is essential to remain engaged with communities and execute evidence-based information dissemination strategy about the safety and efficacy of the vaccines. We identified that it is also imperative to sensitize and train media professionals on how to report side effects related to vaccines. Responsive communication strategies will thus have the potential to serve as a key public health approach pertaining to future pandemic preparedness as well as to manage the demands of clinical and public health issues in an ongoing pandemic situation.

Experiences of sharing results of community based serosurvey with participants in a district of Maharashtra, India.

A growing number of organisations, including medical associations, recommend that research subjects should be given the option of being informed about the general outcome and results of the study. We recently completed a study involving nine serosurveys from 2018 to 2020 in five districts of India among three age groups (children 9 months to < 5 years; 5 to < 15 years of age, and women 15 to < 50 years of age before and after the measles and rubella (MR) vaccination campaigns). In Palghar district of Maharashtra all individuals in 30 selected clusters were enumerated, and 13 individuals per age group were randomly sampled. We established the procedures to return the results to the respondents for each stage of the survey. Of the 1,166 individuals selected for the measles and rubella serosurvey, 971 (83%) agreed to participate and were enrolled. Participants were informed that they will only be contacted if they test seronegative for measles and/or rubella antibodies. Overall, 140 individuals enrolled in the survey tested seronegative for IgG antibodies to measles and/or rubella viruses; were provided the reports and informed to seek medical advice. Upon follow up by phone, 10% (14) of the 140 participants reported to have been vaccinated. In this paper we discuss the procedures, experiences and considerations in returning results to participants in a community-based measles and rubella serosurvey. Although the lessons learned are specific to post measles-rubella vaccine campaign serosurvey in India, they might be helpful to those contemplating sharing results to participants of large scale survey settings.

Previous SARS-CoV-2 Infection Status Among the Current RT-PCR-Positive Individuals Affected During the Second Wave of COVID-19 Infections in Chennai, India.

India witnessed a very strong second wave of coronavirus disease 2019 (COVID-19) during March and June 2021. Newly emerging variants of concern can escape immunity and cause reinfection. We tested newly diagnosed COVID-19 cases during the second wave in Chennai, India for the presence of Immunoglobulin G (IgG) antibodies to estimate the extent of re-infection. Of the 902 unvaccinated COVID-19 positive individuals, 53 (26.5%) were reactive for IgG antibodies and non-reactive for Immunogobulin M (IgM) antibodies. Among the 53 IgG-positive individuals, the interval between symptom onset (or last contact with the known case in case of asymptomatic) was <5 days in 29 individuals, ≥5 days in 11 individuals, while 13 asymptomatic individuals did not know their last contact with a positive case. The possible re-infections ranged between 3.2% (95% CI: 2.2-4.5%) and 4.3% (95% CI: 3.4-6.2%). The findings indicate that re-infection was not a major reason of the surge in cases during second wave. The IgG seropositivity among recently diagnosed unvaccinated COVID-19 patients could provide early indications about the extent of re-infections in the area.

Enablers and barriers towards ensuring routine immunization services during the COVID-19 pandemic: findings from a qualitative study across five different states in India.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to disruption in delivering routine healthcare services including routine immunization (RI) worldwide. Understanding the enablers and barriers for RI services during a pandemic is critically important to develop context-appropriate strategies to ensure uninterrupted routine services. METHODS: A community-based, cross-sectional descriptive study was conducted in five different states of India, nested within an ongoing multicentric study on RI. Telephone in-depth interviews among 56 health workers were carried out and the data were analyzed using a content analysis method. RESULTS: During the COVID-19 pandemic, healthcare providers encountered many challenges at the health system, community and individual level when rendering RI services. Challenges like the limited availability of personal protective equipment and vaccines, deployment for COVID-19 duty at system level, the difficulty in mobilizing people in the community, fear among people at community level, mobility restrictions and limited family support, as well as the stress and stigma at individual level, were barriers to providing RI services. By contrast, the issuing of identification cards to health staff, engaging community volunteers, the support given to health workers by their families and training on COVID-19, were factors that enabled health workers to maintain RI services during the pandemic. CONCLUSIONS: When addressing the COVID-19-related public health emergency, we should not lose sight of the importance of services like RI.

Seroprevalence of IgG antibodies against SARS-CoV-2 in India, March 2020 to August 2021: a systematic review and meta-analysis.

INTRODUCTION: India experienced 2 waves of COVID-19 pandemic caused by SARS-CoV-2 and reported the second highest caseload globally. Seroepidemiologic studies were done to track the course of the pandemic. We systematically reviewed and synthesized the seroprevalence of SARS-CoV-2 in the Indian population. METHODS: We included studies reporting seroprevalence of IgG antibodies against SARS-CoV-2 from March 1, 2020 to August 11, 2021 and excluded studies done only among patients with COVID-19 and vaccinated individuals. We searched published databases, preprint servers, and government documents using a combination of keywords and medical subheading (MeSH) terms of "Seroprevalence AND SARS-CoV-2 AND India". We assessed risk of bias using the Newcastle-Ottawa scale, the appraisal tool for cross-sectional studies (AXIS), the Joanna Briggs Institute (JBI) critical appraisal tool, and WHO's statement on the Reporting of Seroepidemiological Studies for SARS-CoV-2 (ROSES-S). We calculated pooled seroprevalence along with 95% Confidence Intervals (CI) during the first (March 2020 to February 2021) and second wave (March to August 2021). We also estimated seroprevalence by selected demographic characteristics. RESULTS: We identified 3821 studies and included 53 studies with 905379 participants after excluding duplicates, screening of titles and abstracts and full-text screening. Of the 53, 20 studies were of good quality. Some of the reviewed studies did not report adequate information on study methods (sampling = 24% (13/53); laboratory = 83% [44/53]). Studies of 'poor' quality had more than one of the following issues: unjustified sample size, nonrepresentative sample, nonclassification of nonrespondents, results unadjusted for demographics and methods insufficiently explained to enable replication. Overall pooled seroprevalence was 20.7% in the first (95% CI = 16.1 to 25.3) and 69.2% (95% CI = 64.5 to 73.8) in the second wave. Seroprevalence did not differ by age in first wave, whereas in the second, it increased with age. Seroprevalence was slightly higher among women in the second wave. In both the waves, the estimate was higher in urban than in rural areas. CONCLUSION: Seroprevalence increased by 3-fold between the 2 waves of the pandemic in India. Our review highlights the need for designing and reporting studies using standard protocols.

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

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.

Implementing Serosurveys in India: Experiences, Lessons Learned, and Recommendations.

Serological surveillance for vaccine-preventable diseases, such as measles and rubella, can provide direct measures of population immunity across age groups, identify gaps in immunity, and document changes in immunity over time. Rigorously conducted, representative household serosurveys provide high-quality estimates with minimal bias. However, they can be logistically challenging, expensive, and have higher refusal rates than vaccine coverage surveys. This article shares lessons learned through implementing nine measles and rubella household serosurveys in five districts in India-the challenges faced, the potential impact on results, and recommendations to facilitate the conduct of serosurveys. Specific lessons learned arose from challenges related to community mobilization owing to lack of cooperation in certain settings and populations, limitations of outdated census information, nonresponse due to refusal or unavailability during survey enumeration and enrollment, data collection issues, and specimen collection and handling issues. Although some experiences are specific to serosurveys in India, these lessons are generalizable to other household surveys, particularly vaccination coverage and serosurveys conducted in low- and middle-income settings.

Age- & sex-specific infection fatality ratios for COVID-19 estimated from two serially conducted community-based serosurveys, Chennai, India, 2020.

Background & objectives: Infection fatality ratio (IFR) is considered a more robust and reliable indicator than case fatality ratio for severity of SARS-CoV-2 infection. Age- and sex-stratified IFRs are crucial to guide public health response. Infections estimated through representative community-based serosurveys would gauge more accurate IFRs than through modelling studies. We describe age- and sex-stratified IFR for COVID-19 estimated through serosurveys conducted in Chennai, India. Methods: Two community-based serosurveys were conducted among individuals aged ≥10 yr during July and October 2020 in 51 of the 200 wards spread across 15 zones of Chennai. Total number of SARS-CoV-2 infections were estimated by multiplying the total population of the city aged ≥10 yr with the weighted seroprevalence and IFR was calculated by dividing the number of deaths with the estimated number of infections. Results: IFR was 17.3 [95% confidence interval (CI): 14.1-21.6] and 16.6 (95% CI: 13.8-20.2) deaths/10,000 infections during July and October 2020, respectively. Individuals aged 10-19 years had the lowest IFR [first serosurvey (R1): 0.2/10,000, 95% CI: 0.2-0.3 and second serosurvey (R2): 0.2/10,000, 95% CI: 0.1-0.2], and it increased with age and was highest among individuals aged above 60 yr (R1: 140.0/10,000, 95% CI: 107.0-183.8 and R2: 111.2/10,000, 95% CI: 89.2-142.0). Interpretation & conclusions: Our findings suggested that the IFR increased with age and was high among the elderly. Therefore, elderly population need to be prioritized for public health interventions including vaccination, frequent testing in long-term care facilities and old age homes, close clinical monitoring of the infected and promoting strict adherence to non-pharmaceutical interventions.

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

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.