"Design and implementation challenges of massive open online course on research methods for Indian medical postgraduates and teachers -descriptive analysis of inaugural cycle".

BACKGROUND: In view of the growing popularity, reach and access for Massive Open Online Courses (MOOCs), India's apex body for medical education, the National Medical Commission (NMC) mandated uniform foundational course on research methods for the medical post graduates (PGs) and faculty members of the medical institutions under NMC as MOOC. This course is a pioneering effort in the field of India's PG medical education. NMC entrusted Indian Council of Medical Research (ICMR)-National Institute of Epidemiology (NIE) to design and offer the MOOC, named as Basic Course in Biomedical Research (BCBR). We describe the experience of designing and that of implementation challenges in the inaugural cycle of the course. METHODS: The course objective was to inculcate the fundamental concepts in research methods covering epidemiology and biostatistics in the form of video lectures, resource materials, discussion forum, assignments, feedback and a final proctored examination. The course was delivered over 16 weeks through MOOCs platform under the Indian Ministry of Education. We reviewed records, documents and faculty notes and described the course conceptualization, development, design and implementation process. We abstracted information from course portal on enrolment profile of the participants, self-reported course feedback (structured and open-ended on format, lectures and quality of contents), examination registration form, scores obtained in the assignments/examination and that of the participant queries. We described quantitative data using descriptive statistics. We presented the thematic analysis of qualitative data from open-ended questions in the feedback system and that of email interactions. RESULTS: The inaugural cycle (September-December 2019) was taken by 24,385 participants. Majority, 15,879 (65%) were from medical background. 13,242 (54%) were medical postgraduates and 2637 (11%) were medical teachers. Among the enrolled, 14,720 (60%) cleared the assignments. A total of 11,392 (47%), 8,205 (62%) medical PGs and 896 (34%) faculty members successfully completed the course. Feedback from 1305 (5%) participants had mean score of 4.5/5 (±0.7) for quality of teaching. We faced challenges in customizing the course for medical participants, unawareness among target group, digital illiteracy and the ongoing pandemic. CONCLUSIONS: During the inaugural cycle of the online Basic Course in Biomedical Research course, nearly half of the enrolled participants successfully completed and received the certificate. India's MOOC for enhancing research capabilities of future medical researchers encountered successes and challenges. Lessons learnt from the inaugural cycle will guide future directions and to address larger issues in terms of sustainability and replication by stakeholders in medical education in India or elsewhere.

Enhanced SARS-CoV-2-Specific CD4+ T Cell Activation and Multifunctionality in Late Convalescent COVID-19 Individuals.

Background: Examination of CD4+ T cell responses during the natural course of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection offers useful information for the improvement of vaccination strategies against this virus and the protective effect of these T cells. Methods: We characterized the SARS-CoV-2-specific CD4+ T cell activation marker, multifunctional cytokine and cytotoxic marker expression in recovered coronavirus disease 2019 (COVID-19) individuals. Results: CD4+ T-cell responses in late convalescent (>6 months of diagnosis) individuals are characterized by elevated frequencies of activated as well as mono, dual- and multi-functional Th1 and Th17 CD4+ T cells in comparison to early convalescent (<1 month of diagnosis) individuals following stimulation with SARS-CoV-2-specific antigens. Similarly, the frequencies of cytotoxic marker expressing CD4+ T cells were also enhanced in late convalescent compared to early convalescent individuals. Conclusion: Our findings from a low-to middle-income country suggest protective adaptive immune responses following natural infection of SARS-CoV-2 are elevated even at six months following initial symptoms, indicating the CD4+ T cell mediated immune protection lasts for six months or more in natural infection.

Predictors of mortality among hospitalized COVID-19 patients and risk score formulation for prioritizing tertiary care-An experience from South India.

BACKGROUND: We retrospectively data-mined the case records of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients hospitalized to a tertiary care centre to derive mortality predictors and formulate a risk score, for prioritizing admission. METHODS AND FINDINGS: Data on clinical manifestations, comorbidities, vital signs, and basic lab investigations collected as part of routine medical management at admission to a COVID-19 tertiary care centre in Chengalpattu, South India between May and November 2020 were retrospectively analysed to ascertain predictors of mortality in the univariate analysis using their relative difference in distribution among 'survivors' and 'non-survivors'. The regression coefficients of those factors remaining significant in the multivariable logistic regression were utilised for risk score formulation and validated in 1000 bootstrap datasets. Among 746 COVID-19 patients hospitalised [487 "survivors" and 259 "non-survivors" (deaths)], there was a slight male predilection [62.5%, (466/746)], with a higher mortality rate observed among 40-70 years age group [59.1%, (441/746)] and highest among diabetic patients with elevated urea levels [65.4% (68/104)]. The adjusted odds ratios of factors [OR (95% CI)] significant in the multivariable logistic regression were SaO2<95%; 2.96 (1.71-5.18), Urea ≥50 mg/dl: 4.51 (2.59-7.97), Neutrophil-lymphocytic ratio (NLR) >3; 3.01 (1.61-5.83), Age ≥50 years;2.52 (1.45-4.43), Pulse Rate ≥100/min: 2.02 (1.19-3.47) and coexisting Diabetes Mellitus; 1.73 (1.02-2.95) with hypertension and gender not retaining their significance. The individual risk scores for SaO2<95-11, Urea ≥50 mg/dl-15, NLR >3-11, Age ≥50 years-9, Pulse Rate ≥100/min-7 and coexisting diabetes mellitus-6, acronymed collectively as 'OUR-ARDs score' showed that the sum of scores ≥ 25 predicted mortality with a sensitivity-90%, specificity-64% and AUC of 0.85. CONCLUSIONS: The 'OUR ARDs' risk score, derived from easily assessable factors predicting mortality, offered a tangible solution for prioritizing admission to COVID-19 tertiary care centre, that enhanced patient care but without unduly straining the health system.

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.

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

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.

Exploration of population ecological factors related to the spatial heterogeneity of dengue fever cases diagnosed through a national network of laboratories in India, 2017.

Background & objectives: Dengue virus (DENV) transmission is known to be influenced by the environmental conditions. During 2017, the Viral Research and Diagnostic Laboratories (VRDLs) tested 78,744 suspected dengue fever (DF) patients, of whom, 21,260 were laboratory confirmed. The objectives of the study were to evaluate the hypothesis that spatial heterogeneity existed for DF patients and to identify significant determinants of DENV transmission in various districts across the Indian States during 2017. Methods: Laboratory confirmed DF cases were analysed from 402 districts spread across the Indian States. The determinants for DF transmission included in the model were population density, proportion of population living in rural areas, proportion o f forest cover area to the total geographical area, proportion of persons not able to read and write and who were aged greater than seven years; the climatic variables considered were minimum, maximum and average temperature, precipitation and cumulative rainfall. The spatial heterogeneity was assessed using spatial regression analysis. Results: DF cases showed strong spatial dependency, with Moran's I=4.44 (P <0.001). The robust measure for spatial lag (6.55; P=0.01) was found to be the best model fit for the data set. Minimum temperature and cumulative rainfall were significant predictors. Interpretation & conclusions: A significant increase in the number of dengue cases has occurred when the minimum temperature was 23.0-25.8°C and the cumulative rainfall 118.14-611.64 mm across the Indian districts. Further in-depth investigations incorporating more number of demographic, ecological and socio-economic factors would be needed for robust conclusions.