Severity and mortality associated with COVID-19 among children hospitalised in tertiary care centres in India: a cohort study

Background It is critical to identify high-risk groups among children with COVID-19 from low-income and middle-income countries (LMICs) to facilitate the optimum use of health system resources. The study aims to describe the severity and mortality of different clinical phenotypes of COVID-19 in a large cohort of children admitted to tertiary care hospitals in India, Methods Children aged 0-19 years with evidence of SARS-CoV-2 infection (real time polymerase chain reaction or rapid antigen test positive) or exposure (anti-SARS-CoV-2 antibody, or history of contact with SARS-CoV-2) were enrolled in the study, between January 2021 and March 2022 across five tertiary hospitals in India.. All study participants enrolled prospectively and retrospectively were followed up for three months after discharge. COVID-19 was classified into severe (Multisystem Inflammatory Syndrome in Children (MIS-C), severe acute COVID-19, ‘unclassified') or non-severe disease. The mortality rates were estimated in different phenotypes. Findings Among 2468 eligible children enrolled, 2148 were hospitalised Signs of illness were present in 1688 (79%) children with 1090 (65%) having severe disease. High mortality was reported in MIS-C (18·6%), severe acute COVID-19 (13·3%) and the unclassified severe COVID-19 disease (12·3%). Mortality remained high (17·5%) when modified MIS-C criteria was used. Non-severe COVID-19 disease had 14·1% mortality when associated with comorbidity. Interpretation Our findings have important public health implications for low resource settings. The high mortality underscores the need for better preparedness for timely diagnosis and management of COVID-19. Children with associated comorbidity or coinfections are a vulnerable group and need special attention. MIS-C requires context specific diagnostic criteria for low resource settings. It is important to evaluate the clinical, epidemiological and health system-related risk factors associated with severe COVID-19 and mortality in children from LMICs. Funding Department of Biotechnology, Govt of India and Department of Maternal, Child and Adolescent Health and Aging, WHO, Geneva.

Demographic comparison of the first, second and third waves of COVID-19 in a tertiary care hospital at Jaipur, India.

Background: Coronavirus disease 2019 (COVID-19) infection in India demonstrated three peaks in India, with differences in presentation and outcome in all the three waves. The aim of the paper was to assess differences in the epidemiological, clinical features and outcomes of patients with COVID-19 presenting at a tertiary care hospital in the three waves at Jaipur, India. Methods: This was a retrospective study conducted at a tertiary care hospital at Jaipur, India. Demographic, clinical features and outcomes were compared of confirmed COVID-19 cases admitted during the first wave (16-7-2020 to 31-1-2021), second wave (16-3-2021 to 6-5-2021) and third wave (1-1-22 to 20-2-22) of the outbreak. Results: There were 1006 cases, 639 cases and 125 cases admitted during the three waves, respectively. The cases presenting in the second wave were significantly younger, with significantly higher prevalence of symptoms such as fever, cough, sore throat, nausea, vomiting, headache, muscle ache, loss of appetite and fatigue (P < 0.05). A significantly higher proportion of patients received Remdesivir in the second wave (P < 0.001). However, in the second wave, the use of low molecular weight heparin, plasma therapy, non-invasive and invasive ventilator were higher (P < 0.001). Co-morbid conditions were significantly higher in the admitted patients during the third wave (P < 0.05). Radiological scores were similar in second and third wave, significantly higher than the first wave. Lymphopenia and rise of inflammatory markers including C-reactive protein and interleukin-6 were more evident in the second wave (P < 0.001). The mean mortality, hospital stay and air-leak complications were also significantly higher in the second wave (P < 0.001). Conclusions: The second wave was more vicious in terms of symptoms, inflammatory markers, radiology, complications, requirement of ventilation and mortality. Mutation in the virus, lack of immunity and vaccination at the time point of second wave could have been the possible causes. The ferocity of the second wave has important implications for the government to formulate task forces for effective management of such pandemics.

Humoral antibody kinetics with ChAdOx1-nCOV (Covishield™) and BBV-152 (Covaxin™) vaccine among Indian Healthcare workers: A 6-month longitudinal cross-sectional Coronavirus Vaccine-induced antibody titre (COVAT) study.

BACKGROUND AND AIMS: There is limited data available on longitudinal humoral antibody dynamics following two doses of ChAdOx1-nCOV (Covishield™) and BBV-152 (Covaxin™) vaccine against SARS-CoV-2 among Indians. METHODS: We conducted a 6-month longitudinal study in vaccinated healthcare workers by serially measuring quantitative anti-spike antibody at 3-weeks, 3-months and 6-months after the completion of second dose. Geometric mean titer (GMT) and linear mixed models were used to assess the dynamics of antibody levels at 6 months. RESULTS: Of the 481 participants, GMT of anti-spike antibody decreased by 56% at 6-months regardless of age, gender, blood group, body-mass index and comorbidities in 360 SARS-CoV-2 naive individuals but significantly more in hypertensives. Participants with past infection had significantly higher GMT at all time points compared to the naive individuals. Among SARS-CoV-2 naive cohorts, a significantly higher GMT was noted amongst the Covishield recipients at all time points, but there was a 44% decline in GMT at 6-month compared to the peak titer period. Decline in GMT was insignificant (8%) in Covaxin recipients at 6-month despite a lower GMT at all time points vs. Covishield. There was 5.6-fold decrease in seropositivity rate at 6-month with both vaccines. Participants with type 2 diabetes mellitus have a lower seropositivity rate at all the time points. Seropositivity rate was significantly higher with Covishield vs. Covaxin at all time points except at 6-month where Covaxin recipients had a higher seropositivity rate but no difference noted in propensity-matched analysis. CONCLUSIONS: There is waning humoral antibody response following two doses of either vaccine at six months. Covishield recipients had a higher anti-spike antibody GMT compared with Covaxin at all-time points, however a significant decline in antibody titers was seen with Covishield but not with Covaxin at 6-months.

Antibody response after first and second-dose of ChAdOx1-nCOV (CovishieldTM®) and BBV-152 (CovaxinTM®) among health care workers in India: The final results of cross-sectional coronavirus vaccine-induced antibody titre (COVAT) study.

BACKGROUND: We assessed the humoral immune response of both ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) vaccines in Indian health care workers (HCW). METHODS: A Pan-India, Cross-sectional, Coronavirus Vaccine-induced Antibody Titre (COVAT) study was conducted that measured SARS-CoV-2 anti-spike binding antibody quantitatively, 21 days or more after the first and second dose of two vaccines in both severe acute respiratory syndrome (SARS-CoV-2) naïve and recovered HCW. Primary aim was to analyze antibody response (seropositivity rate, Geometric Mean Titre [GMT] and 95% Confidence Interval [CI]) following each dose of both vaccines and its correlation to age, sex, blood group, body mass index (BMI) and comorbidities. Here we report the results of anti-spike antibody response after first and two completed doses. RESULTS: Among the 515 HCW (305 Male, 210 Female) who took two doses of both vaccines, 95.0% showed seropositivity to anti-spike antibody. However, both seropositivity rate and GMT (95% CI) of anti-spike antibody was significantly higher in Covishield vs. Covaxin recipients (98.1 vs. 80.0%; 129.3 vs. 48.3 AU/mL; both p < 0.001). This difference persisted in 457 SARS-CoV-2 naïve and propensity-matched (age, sex and BMI) analysis of 116 participants. Age > 60-years, males, people with any comorbidities, and history of hypertension (HTN) had a significantly less anti-spike antibody GMT compared to age ≤ 60 years, females, no comorbidities and no HTN respectively, after the completion of two doses of either vaccine. Gender, presence of comorbidities, and vaccine type were independent predictors of antibody seropositivity rate and anti-spike antibody titre levels in multiple logistic and log transformed linear regression analysis. Both vaccine recipients had similar solicited mild to moderate adverse events and none had severe or unsolicited side effects. CONCLUSIONS: Both vaccines elicited good immune response after two doses, although seropositivity rates and GMT of anti-spike antibody titre was significantly higher in Covishield compared to Covaxin recipients.

Spatial network based model forecasting transmission and control of COVID-19.

The SARS-CoV-2 driven infectious novel coronavirus disease (COVID-19) has been declared a pandemic by its brutal impact on the world in terms of loss on human life, health, economy, and other crucial resources. To explore more about its aspects, we adopted the S E I R D (Susceptible-Exposed-Infected-Recovered-Death) pandemic spread with a time delay on the heterogeneous population and geography in this work. Focusing on the spatial heterogeneity, epidemic spread on the framework of modeling that incorporates population movement within and across the boundaries is studied. The entire population of interest in a region is divided into small distinct geographical sub regions, which interact using migration networks across boundaries. Utilizing the time delay differential equations based model estimations, we analyzed the spread dynamics of disease in India. The numerical outcomes from the model are validated using real time available data for COVID-19 cases. Based on the developed model in the framework of the recent data, we verified total infection cases in India considering the effect of nationwide lockdown at the onset of the pandemic and its unlocking by what seemed to be the end of the first wave. We have forecasted the total number of infection cases in two extreme situations of nationwide no lockdown and strict lockdown scenario. We expect that in future for any change in the key parameters, due to the regional differences, predictions will lie within the bounds of the above mentioned extreme plots. We computed the approximate peak infection in forwarding time and relative timespan when disease outspread halts. The most crucial parameter, the time-dependent generalization of the basic reproduction number, has been estimated. The impact of the social distancing and restricted movement measures that are crucial to contain the pandemic spread has been extensively studied by considering no lockdown scenario. Our model suggests that attaining a reduction in the contact rate between susceptible and infected individuals by practicing strict social distancing is one of the most effective control measures to manage COVID-19 spread in India. The cases can further decrease if social distancing is followed in conjunction with restricted movement.

Network synchronization, stability and rhythmic processes in a diffusive mean-field coupled SEIR model.

Connectivity and rates of movement have profound effect on the persistence and extinction of infectious diseases. The emerging disease spread rapidly, due to the movement of infectious persons to some other regions, which has been witnessed in case of novel coronavirus disease 2019 (COVID-19). So, the networks and the epidemiology of directly transmitted infectious diseases are fundamentally linked. Motivated by the recent empirical evidence on the dispersal of infected individuals among the patches, we present the epidemic model SEIR (Susceptible-Exposed-Infected-Recovered) in which the population is divided into patches which form a network and the patches are connected through mean-field diffusive coupling. The corresponding unstable epidemiology classes will be synchronized and achieve stable state when the patches are coupled. Apart from synchronization and stability, the coupled model enables a range of rhythmic processes such as birhythmicity and rhythmogenesis which have not been investigated in epidemiology. The stability of Disease Free Equilibrium (or Endemic Equilibrium) is attained through cessation of oscillation mechanism namely Oscillation Death (OD) and Amplitude Death (AD). Corresponding to identical and non-identical epidemiology classes of patches, the different steady states are obtained and its transition is taking place through Hopf and transcritical bifurcation.

Alternative Strategy Adopted in Practical Assessment for Pathology Postgraduate Certification Examination Amidst COVID-19 Nationwide Lockdown: An Indian Experience with a Novel Hybrid Method of Assessment.

BACKGROUND: A major concern and challenge faced by the educational institution during coronavirus disease (COVID-19) pandemic and consequent lockdown is the timely conduct of the summative assessment. Unlike cognitive assessment, real-time practical assessment through online mode, without compromising principles of assessment is difficult. This study was performed to analyze an alternative hybrid approach adopted for the postgraduate practical summative assessment in pathology. MATERIALS AND METHODS: Evaluation of the process of summative assessment was done where internal and external examiners synchronously assessed examinees real-time on-site (face to face) and off-site (remotely through live videoconferencing) respectively. A pre-validated questionnaire on a novel approach for assessment and feedback (with close-ended on 5-point Likert scale and open-ended questions) were administered to nine participants comprising three final year postgraduates in pathology, four examiners (two internal and two externals) and two technical experts from the Department of Pathology. Overall scores obtained by all examinees were recorded. A pre-validated questionnaire and feedback were administered to the participants to assess the novel approach to assessment. RESULTS: The mean performance score obtained by examinees was 63.5% in the summative assessment. Feedback analysis revealed that 85% of participants strongly agreed and the rest (15%) agreed that essential minor deviations introduced in this novel mode of assessment did not compromise basic principles and goals of assessment. Quality of assessment through this mode of assessment was graded as good to excellent. All participants responded that this mode of examination may be applied in the future under similar circumstances. CONCLUSION: This study concludes that an alternative novel hybrid method of real-time synchronous assessment with on-site and off-site examiners may be a feasible and successful model for conducting summative assessment and can be practiced in time of need.