Prediction models based on miRNA-disease relationship: Diagnostic relevance to multiple diseases including COVID-19.

BACKGROUND: Small, non-coding microRNAs, usually of 20-25 nucleotides, are known to regulate the post-transcriptional gene expression, which has a significant role in human biological processes, including immune-biogenesis, homeostasis and infection control as differential expression of such miRNAs is responsible for fine-tuning the organismic development. METHODS: A search of bibliographic databases was carried out with a focused question on microRNA-Disease Prediction. A deductive qualitative content analysis approach was further employed to assess the research's overall outcomes, review articles on prediction tools in miRNA-Diseases, and analyse the interventions. RESULTS: Diagnosis and therapeutics of diseases and miRNA prediction methods hold importance in identifying the regulatory mechanisms. Collections of efficient miRNA prediction methods to identify miRNA-mRNA-disease regulatory relationships have been presented through this review, consolidating the potential of miRNAs as a diagnostic and prognostic biomarker of multiple diseases, including COVID-19. CONCLUSIONS: The role of miRNA in the aetiology and pathogenesis of wide-range of pathologies, including viral, bacterial to chronic diseases such as cancer, is quite feasible through the modern tools in bioinformatics which has been elaborated focusing upon miRNA-disease prediction methods and their application potential establishing miRNAs as a robust and reliable biomarker in clinico-medical studies.

Evaluation of T and B cell immunophenotyping and antibody response post Covid-19 vaccination.

PURPOSE: To evaluate T and B cell subsets and IgG antibodies in response to SARS-CoV-2 post COVID-19 vaccination. METHODS: A total of 50 healthy adults (18-60 years) receiving anti-SARS-CoV-2 vaccination (COVISHIELD) were recruited for the study. Blood samples were collected from participants at 3 time points; just before vaccination (Visit 0, V0), just before booster dose (Visit 1, V1) and 6th month after 1st dose (Visit 2, V2). Peripheral blood mononuclear cell isolation was done and evaluated for T and B cell subsets by Flow cytometry. Quantitative determination of IgG antibodies to SARS-CoV-2 was done by Chemiluminescence immunoassay in all samples. Final data for all three visits was available for 37 participants who remained healthy. Ethics approval was obtained from Medanta Institution of Ethics Committee vide MICR No. 1290/2021 dated 24th May 2021. RESULTS: Mean age of the participants was 34.6 â€‹± â€‹5.7 years (Range: 24-45 years). Highly significant improvement in SARS-CoV-2 IgG levels was observed after each visit {Mean IgG: (V0 v/s. V1: 133.8 â€‹± â€‹339.2AU/ml v/s. 434.5 â€‹± â€‹519.2AU/ml; p-value â€‹= â€‹0.003) and V0 v/s. V2: 133.8 â€‹± â€‹339.2AU/ml v/s. 420.9 â€‹± â€‹394.2AU/ml; p-value â€‹= â€‹0.002) Between visits 0 and 1, the mean value for CD4 Naïve T cells showed significant increase, while CD4 central memory (CM) T cells showed significant decrease. Between visits 0 and 2 the mean values for CD4 Naïve T cells, CD8 Naïve T cells and Pre germinal centre (Pre GC) B cells showed significant increase. During the same period the mean values for CD4CM, CD8 effector memory (EM) and CD8 CM T cells showed significant decrease. CONCLUSION: It is concluded that both, humoral and cellular immunity, play an important role in maintaining immunity against COVID-19 infection, following COVISHIELD vaccination. Moreover, in subjects with normalisation of antibody levels post vaccination, persistence of T cell subsets may still offer some immunity.

Clinico-Epidemiologic Characteristics of Patients Reported in the Mycotic Infections in COVID-19 Registry.

We update results from the Mycotic Infections in COVID-19 (MUNCO) Registry, May-September 2021. Data collection from May to September 2021 yielded 728 cases from India, Nepal, Bangladesh, Thailand, and the United States. The cases consisted of mostly mucormycosis (97.6%), primarily rhinocerebral, and were analyzed to investigate clinical characteristics associated with negative outcomes. Patients were mostly diabetic (85%) and male (76%), with significant mortality (11.7%). All patients received treatment of coronavirus disease 2019 (COVID-19) as well as antifungal treatment. The crude mortality rate was 11.3% for mucormycosis and 22.7% formixed infections. This study demonstrates the utility of online databases in the collection of high-caliber data.

Investigating stigma during the COVID-19 pandemic: Living conditions, social determinants and experiences of infection among employees at a tertiary referral cancer centre.

AIM: Healthcare workers (HCWs) have reported negative social experiences during the COVID-19 pandemic; however, this data is largely from medical personnel. We examined living conditions, social determinants, and experiences during the COVID-19 pandemic among all cadres of employees who had recovered from COVID-19 at a tertiary referral cancer hospital in India. METHODS: We conducted a mixed methods study combining a questionnaire-based survey followed by semi-structured interviews with open-ended questions, among hospital staff who recovered from COVID-19 between April and November 2020. We initially administered a 79-point survey to all participants; based on their responses, we used purposive sampling to identify 60 interview participants. The primary aim of the study was to examine the impact of socio-economic factors on experiences and potential stigma faced by staff during the COVID-19 pandemic. RESULTS: We surveyed 376 participants including doctors (10 %), nurses (20 %), support staff (29 %), administrators (18 %) and scientists/technicians (22 %). Of these, 126 (34 %) participants reported negative social experiences. Stigmatisation was lower among doctors compared to other professions, decreased in the second half of the study period, and was more among those living in less affluent surroundings. Interviews revealed 3 types of negative social experiences: neighbourhood tensions around restrictions of mobility, social distancing, and harassment. CONCLUSIONS: The first phase of the COVID-19 pandemic in India led to considerable negative social experiences among hospital employees, especially those lower in the socio-economic hierarchy, which was fuelled by restrictions imposed by the government and pressure on local neighbourhoods. POLICY SUMMARY: It is important to not just document and count stigma experiences during global pandemics, but also to examine sociologically the conditions under which and the processes through which stigma happens.

Seroprevalence of Covid-19 infection among healthcare workers: A study from a tertiary care hospital in the National Capital Region of India.

Background Seroprevalence studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide information on the target populations for vaccination. We aimed to evaluate the seroprevalence among healthcare workers (HCWs) at our tertiary care institution and to identify parameters that may affect it. Method We assessed seroprevalence of SARS-CoV-2 by the chemiluminescence immunoassay test among 3258 HCW in our hospital and evaluated as per gender, age, their previous Covid-19 diagnosis, role in hospital and type/risk of exposure. Results Of 3258 participants, 46.2% (95% CI 44.4%- 47.9%) were positive for SARS-CoV-2 IgG antibodies (i.e. IgG ≥15 AU/ml). Higher seroprevalence was seen in non-clinical HCWs (50.2%) than in clinical HCWs (41.4%, p=0.0001). Furthermore, people with a history of Covid-19 were found to have significantly higher antibody levels (p=0.0001). Among the HCWs, doctors and nurses had lower relative risk (RR) of acquiring Covid-19 infection (RR=0.82; 95% CI 0.76-0.89) compared to non-clinical HCWs. Conclusion Seroprevalence in HCWs at our hospital was 46.2%. Clinical HCWs had lower seroprevalence compared to non-clinical HCWs. Previous history of Covid-19 almost doubled the seropositivity, particularly in those with current infection.

Comparative study of different machine learning algorithms for chronic kidney disease prediction

Chronic kidney disease (CKD) is a huge problem on the health-care system due to its growing occurrence, high risk of process to final phase kidney disease, and increased death rate. It is gradually increasing into a major public health problem. An early diagnostic method to measure renal function is necessary and highly needed in many respects. Machine Learning technique uses understanding of various key medical problems, including diabetes projection, heart observation, and coronavirus detection. Machine learning may be a better solution to achieve higher performance in the prediction of CKD and may be effective for other diseases as well. The main purpose of this study is to determine the optimal and appropriate machine learning techniques which may effectively identify and predict the CKD status. The dataset from Kaggle has been used for this study. Machine learning models such as Random Forest, Decision Tree and SVM have been used in this research to predict chronic kidney disease. Therefore, the results showed that Random Forest provides the highest accuracy in identifying chronic kidney disease. The overall accuracy of an algorithms used in this research is basically greater than that of previous research, intimating that this research is also more reliable than previous model.

Factors Associated with Mortality in Coronavirus-Associated Mucormycosis: Results from Mycotic Infections in COVID-19 (MUNCO) Online Registry.

BACKGROUND: COVID-19-associated mucormycosis (CAM) is associated with high morbidity and mortality. MUNCO is an international database used to collect clinical data on cases of CAM in real time. Preliminary data from the Mycotic Infections in COVID-19 (MUNCO) online registry yielded 728 cases from May to September 2021 in four South Asian countries and the United States. A majority of the cases (694; 97.6%) consisted of a mucormycosis infection. The dataset allowed for the analysis of the risk factors for adverse outcomes from CAM and this analysis is presented in this paper. METHODS: The submission of cases was aided by a direct solicitation and social media online. The primary endpoints were full recovery or death measured on day 42 of the diagnosis. All patients had histopathologically confirmed CAM. The groups were compared to determine the contribution of each patient characteristic to the outcome. Multivariable logistic regression models were used to model the probability of death after a CAM diagnosis. RESULTS: The registry captured 694 cases of CAM. Within this, 341 could be analyzed as the study excluded patients with an unknown CAM recovery status due to either an interruption or a lack of follow up. The 341 viable cases consisted of 258 patients who survived after the completion of treatment and 83 patients who died during the period of observation. In a multivariable logistic regression model, the factors associated with an increased risk of mortality include old age (OR = 1.04, 95% CI 1.02-1.07, p = 0.001), history of diabetes mellitus (OR 3.5, 95% CI 1.01-11.9, p = 0.02) and a lower BMI (OR 0.9, 95% CI 0.82-0.98, p = 0.03). Mucor localized to sinus disease was associated with 77% reduced odds of death (OR = 0.23, 95% CI 0.09-0.57, p = 0.001), while cerebral mucor was associated with an increased odds of death (OR = 10.96, 95% CI 4.93-24.36, p = ≤0.0001). CONCLUSION: In patients with CAM, older age, a history of diabetes and a lower body mass index is associated with increased mortality. Disease limited to the sinuses without a cerebral extension is associated with a lower risk of mortality. Interestingly, the use of zinc and azithromycin were not associated with increased mortality in our study.

A case control investigation of COVID-19 associated mucormycosis in India.

BACKGROUND: Increased occurrence of mucormycosis during the second wave of COVID-19 pandemic in early 2021 in India prompted us to undertake a multi-site case-control investigation. The objectives were to examine the monthly trend of COVID-19 Associated Mucormycosis (CAM) cases among in-patients and to identify factors associated with development of CAM. METHODS: Eleven study sites were involved across India; archived records since 1st January 2021 till 30th September 2021 were used for trend analysis. The cases and controls were enrolled during 15th June 2021 to 30th September 2021. Data were collected using a semi-structured questionnaire. Among 1211 enrolled participants, 336 were CAM cases and 875 were COVID-19 positive non-mucormycosis controls. RESULTS: CAM-case admissions reached their peak in May 2021 like a satellite epidemic after a month of in-patient admission peak recorded due to COVID-19. The odds of developing CAM increased with the history of working in a dusty environment (adjusted odds ratio; aOR 3.24, 95% CI 1.34, 7.82), diabetes mellitus (aOR: 31.83, 95% CI 13.96, 72.63), longer duration of hospital stay (aOR: 1.06, 95% CI 1.02, 1.11) and use of methylprednisolone (aOR: 2.71, 95% CI 1.37, 5.37) following adjustment for age, gender, occupation, education, type of houses used for living, requirement of ventilatory support and route of steroid administration. Higher proportion of CAM cases required supplemental oxygen compared to the controls; use of non-rebreather mask (NRBM) was associated as a protective factor against mucormycosis compared to face masks (aOR: 0.18, 95% CI 0.08, 0.41). Genomic sequencing of archived respiratory samples revealed similar occurrences of Delta and Delta derivates of SARS-CoV-2 infection in both cases and controls. CONCLUSIONS: Appropriate management of hyperglycemia, judicious use of steroids and use of NRBM during oxygen supplementation among COVID-19 patients have the potential to reduce the risk of occurrence of mucormycosis. Avoiding exposure to dusty environment would add to such prevention efforts.

Safety, immunogenicity & effectiveness of the COVID-19 vaccine among healthcare workers in a tertiary care hospital.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic has caused significant global morbidity and mortality. As the vaccination was rolled out with prioritization on healthcare workers (HCWs), it was desirable to generate evidence on effectiveness of vaccine in prevailing real-life situation for policy planning. The objective of the study was to evaluate the safety, effectiveness and immunogenicity of COVID-19 vaccination among HCWs in a tertiary care hospital. METHODS: This prospective observational study was undertaken on the safety, immunogenicity and effectiveness of the ChAdOx1 nCoV- 19 coronavirus vaccine (Recombinant) during the national vaccine roll out in January-March 2021, in a tertiary care hospital, New Delhi, India. RESULTS: The vaccine was found to be safe, with local pain, fever and headache as the most common adverse events of milder nature which generally lasted for two days. The adverse events following vaccination were lower in the second dose as compared to the first dose. The vaccine was immunogenic, with seropositivity, which was 51 per cent before vaccination, increasing to 77 per cent after single dose and 98 per cent after two doses. Subgroup analysis indicated that those with the past history of COVID-19 attained seropositivity of 98 per cent even with single dose. The incidence of reverse transcription (RT)-PCR positive COVID-19 was significantly lower among vaccinated (11.7%) as compared to unvaccinated (22.2%). Seven cases of moderate COVID-19 needing hospitalization were seen in the unvaccinated and only one such in the vaccinated group. The difference was significant between the fully vaccinated (10.8%) and the partially vaccinated (12.7%). The hazard of COVID-19 infection was higher among male, age >50 yr and clinical role in the hospital. After adjustment for these factors, the hazard of COVID-19 infection among unvaccinated was 2.09 as compared to fully vaccinated. Vaccine effectiveness was 52.2 per cent in HCWs. INTERPRETATION & CONCLUSIONS: ChAdOx1 nCoV-19 coronavirus vaccine (Recombinant) was safe, immunogenic as well as showed effectiveness against the COVID-19 disease (CTRI/2021/01/030582).

Severity and Cardiac Involvement in Multisystem Inflammatory Syndrome in Children.

Multisystem inflammatory syndrome in children (MIS-C) occurs secondary to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A retrospective study, involving 6 tertiary-care centers in Haryana, was conducted to evaluate the clinical features, severity, laboratory findings, and outcomes of patients with MIS-C. Disease severity was graded (mild/moderate/severe) and presence of cardiac abnormalities noted. Patients with and without cardiac abnormalities and with and without severe disease were compared. Forty-eight children with MIS-C were included (median age - 9.5 y). Fever (100%), gastrointestinal (83.3%) and mucocutaneous (50%) symptoms were common. Only 16.7% patients had previous history of documented SARS-CoV-2 infection/contact. Severe disease and cardiac abnormalities were seen in 47.9% and 54.2% patients, respectively. NT-proBNP > 1286.5 pg/mL and thrombocytopenia (≤ 119500/µL) were significant risk factors for severe MIS-C. Forty-five patients (93.8%) recovered and 3 died. Median hospitalization duration was 7 d (5-9.5). MIS-C must be considered as a possibility in any febrile child, even if a positive epidemiological history is absent. High NT-proBNP and thrombocytopenia are significant risk factors for severe MIS-C. (Trial Registration: The study was registered with the Clinical Trials Registry, India (CTRI/2021/09/036491)).

Alleviating Work Exhaustion, Improving Professional Fulfillment, and Influencing Positivity Among Healthcare Professionals During COVID-19: A Study on Sudarshan Kriya Yoga

Demanding work-life and excessive workload, the conflict between professional and personal lives, problems with patients and those related to the occurrence of death and high risk for their own life are a few factors causing burnout, disengagement, and dissatisfaction in the professional lives of healthcare professionals (HCPs). The situation worsened during the COVID-19 pandemic. It is of utmost importance to find effective solutions to mitigate the stress and anxiety adversely affecting the mental well-being and professional lives of HCPs. This study was designed to examine the efficacy of Sudarshan Kriya Yoga (SKY) for alleviating work exhaustion, improving Professional Fulfillment, and influencing positivity among HCPs during COVID-19. In a comparative observation before the intervention (Pre), after the intervention (Post), and 30 days after the intervention (Day 30) in the Experimental Group (29 physicians) and Control Group (27 physicians), it was found that immediately after SKY, HCPs experienced a significant improvement in Professional Fulfillment (p = 0.009), work exhaustion (0.008), positive affect (p = 0.02), and negative affect (p < 0.001) compared to the Control Group. The effect of SKY continued until Day 30 for Professional Fulfillment and had positive and negative effects. Findings suggest that SKY elevated Professional Fulfillment among HCPs during the COVID-19 pandemic and reduced their work exhaustion and the negative effect on their mental health. SKY can aid HCPs in maintaining their well-being when faced with unprecedented challenges.

Internship in the year of Covid-19: what has changed in internship dynamics?

The purpose of this research is to understand the changes in internship dynamics of MBA students in 2020 who undertook virtual full-time internships as compared to previous years when interns were required to be present physically. Sample was collected from two set of interns;one set interns were working through virtual internship and the second set were working on traditional model of on- site internship. For data collection, structured questionnaire was used. Data was collected on various parameters of internship processes and experience. The result from the current findings suggests that the experience of both set of interns differ significantly. This paper will essentially evaluate whether virtual full-time internships have been able to contribute, create & shape internship experience effectively for interns & understand which dimensions such as learning, productivity, communication, etc have seen changes due to the nature of work being changed. Research material in this area is limited, mainly due to students experiencing a remote working style in their internships for the first time which is why this research will be quite valuable for various stakeholders.

Ayurvedic clinical profile of COVID-19 - A preliminary report.

BACKGROUND: Ayurvedic clinical profiling of COVID-19 is a pre-requisite to develop standalone and integrative treatment approaches. At present, Ayurvedic clinicians do not have access to COVID-19 patients in clinical settings. In these circumstances, a preliminary clinical profiling of COVID-19 based on review of modern medical and classical Ayurvedic literature with inputs from Allopathic clinicians treating COVID-19 patients assumes significance. OBJECTIVES: This paper aims to develop an Ayurvedic clinical profile of COVID-19 by literature review supported by analysis of clinical data of a cohort of COVID-19 patients. METHODS: The typical clinical presentation of COVID-19 was categorized based on a cluster of symptoms with reference to "Interim Clinical Guidance for Management of Patients with confirmed corona virus disease (COVID-19)" released by the US CDC. As the clinical presentation is found to vary widely, research papers reporting clinical symptoms of patient samples from different parts of the world were also reviewed to identify outliers and atypical presentations. Case records of fourteen COVID-19 patients treated at Medanta Hospital, Gurgaon were analyzed to compare symptomatology with data obtained from published literature. Further, a careful correlation was done with the data collected from selected Ayurvedic classical texts and expert views of clinical practitioners to arrive at a preliminary Ayurvedic clinical profile of COVID-19. RESULTS: COVID-19 can be understood from the Ayurvedic perspective as vatakapha dominant sannipatajvara of agantu origin with pittanubandha. The asymptomatic, presymptomatic, mild, moderate, severe and critical stages of COVID-19 with varying clinical presentations have been analysed on the basis of nidana, dosa, dusya, nidanapañcaka and satkriyakala to present a preliminary clinical profile of the disease. CONCLUSION: In this paper, we have demonstrated that a preliminary clinical profiling of COVID-19 from the Ayurvedic perspective is possible through literature review supported by discussions with Allopathic clinicians as well as examination of patient case records. The provisional diagnosis proposed can be further developed with continued review of literature, wider cooperation and teamwork with Allopathic physicians and access to clinical data as well as direct clinical assessment of COVID-19 patients.

A pilot clinical study of an add-on Ayurvedic formulation containing Tinospora cordifolia and Piper longum in mild to moderate COVID-19.

BACKGROUND: After declaration of COVID- 19 as pandemic by WHO, countries adopted several measures to contain the spread as well as test and treat the patients. Further, as no effective management protocols to address this pandemic were available, a need was felt to explore the integration of modern and traditional medicines to treat COVID- 19 cases. OBJECTIVE: To undertake a study with Ayurveda formulation as add on to existing standard of care (SOC) and to compare the outcomes in terms of patient acceptability, the time to clinical recovery, hospital stay as well as any signs of drug-herb interaction between the Ayurveda formulation and the SOC. MATERIAL AND METHODS: An exploratory nonrandomized prospective study has been undertaken for comparing the outcomes of traditional Ayurvedic classical formulation of Tinospora cordifolia (Guduchi) and Piper longum (Pippali) as an add on to standard of care (SOC) using modern medicine with SOC alone. This has been done in mild and moderate COVID- 19 cases, at a tertiary care integrative Medicine hospital in the National Capital Region, Gurgaon, India. The outcomes have been evaluated in terms of the duration of hospital stay, the time to clinical recovery, safety and non- interference/interaction of Ayurvedic and Further, long term impact of COVID- 19 treatment has been evaluated using quality of life questionnaire after 3 months of discharge. RESULTS: Findings of present study reveals that the Ayurveda add-on formulation of T. cordifolia (Guduchi) and P. longum (Pippali) has reduced the length of hospital stay and improve the recovery time. General feeling of wellbeing and activity levels were better in the 3 month follow-up post discharge in the Ayurveda add-on group. CONCLUSION: Addition of Ayurveda formulation has reduced the time of recovery and duration of hospital stay. However, this formulation needs further investigated to provide more information on effective and safe herbal add-on to SOC for better outcomes to treatment of COVID-19 disease.

Vaccine Breakthrough Infections by SARS-CoV-2 Variants after ChAdOx1 nCoV-19 Vaccination in Healthcare Workers.

This study elucidated the clinical, humoral immune response and genomic analysis of vaccine breakthrough (VBT) infections after ChAdOx1 nCoV-19/Covishield vaccine in healthcare workers (HCWs). Amongst 1858 HCWs, 1639 had received either two doses (1346) or a single dose (293) of ChAdOx1 nCoV-19 vaccine. SARS-CoV-2 IgG antibodies and neutralizing antibodies were measured in the vaccinated group and the development of SARS-CoV-2 infection was monitored.Forty-six RT-PCR positive samples from the 203 positive samples were subjected to whole genome sequencing (WGS). Of the 203 (10.92%) infected HCWs, 21.46% (47/219) were non-vaccinated, which was significantly more than 9.52% (156/1639) who were vaccinated and infection was higher in doctors and nurses. Unvaccinated HCWs had 1.57 times higher risk compared to partially vaccinated HCWs and 2.49 times higher risk than those who were fully vaccinated.The partially vaccinated were at higher risk than the fully vaccinated (RR 1.58). Antibody non-response was seen in 3.44% (4/116), low antibody levels in 15.51% (18/116) and medium levels were found in 81.03% (94/116). Fully vaccinated HCWs had a higher antibody response at day 42 than those who were partially vaccinated (8.96 + 4.00 vs. 7.17 + 3.82). Whole genome sequencing of 46 samples revealed that the Delta variant (B.1.617.2) was predominant (69.5%). HCWs who had received two doses of vaccine showed better protection from mild, moderate, or severe infection, with a higher humoral immune response than those who had received a single dose. The genomic analysis revealed the predominance of the Delta variant (B.1.617.2) in the VBT infections.

Tocilizumab plus standard care versus standard care in patients in India with moderate to severe COVID-19-associated cytokine release syndrome (COVINTOC): an open-label, multicentre, randomised, controlled, phase 3 trial.

BACKGROUND: Global randomised controlled trials of the anti-IL-6 receptor antibody tocilizumab in patients admitted to hospital with COVID-19 have shown conflicting results but potential decreases in time to discharge and burden on intensive care. Tocilizumab reduced progression to mechanical ventilation and death in a trial population enriched for racial and ethnic minorities. We aimed to investigate whether tocilizumab treatment could prevent COVID-19 progression in the first multicentre randomised controlled trial of tocilizumab done entirely in a lower-middle-income country. METHODS: COVINTOC is an open-label, multicentre, randomised, controlled, phase 3 trial done at 12 public and private hospitals across India. Adults (aged ≥18 years) admitted to hospital with moderate to severe COVID-19 (Indian Ministry of Health grading) confirmed by positive SARS-CoV-2 PCR result were randomly assigned (1:1 block randomisation) to receive tocilizumab 6 mg/kg plus standard care (the tocilizumab group) or standard care alone (the standard care group). The primary endpoint was progression of COVID-19 (from moderate to severe or from severe to death) up to day 14 in the modified intention-to-treat population of all participants who had at least one post-baseline assessment for the primary endpoint. Safety was assessed in all randomly assigned patients. The trial is completed and registered with the Clinical Trials Registry India (CTRI/2020/05/025369). FINDINGS: 180 patients were recruited between May 30, 2020, and Aug 31, 2020, and randomly assigned to the tocilizumab group (n=90) or the standard care group (n=90). One patient randomly assigned to the standard care group inadvertently received tocilizumab at baseline and was included in the tocilizumab group for all analyses. One patient randomly assigned to the standard care group withdrew consent after the baseline visit and did not receive any study medication and was not included in the modified intention-to-treat population but was still included in safety analyses. 75 (82%) of 91 in the tocilizumab group and 68 (76%) of 89 in the standard care group completed 28 days of follow-up. Progression of COVID-19 up to day 14 occurred in eight (9%) of 91 patients in the tocilizumab group and 11 (13%) of 88 in the standard care group (difference -3·71 [95% CI -18·23 to 11·19]; p=0·42). 33 (36%) of 91 patients in the tocilizumab group and 22 (25%) of 89 patients in the standard care group had adverse events; 18 (20%) and 15 (17%) had serious adverse events. The most common adverse event was acute respiratory distress syndrome, reported in seven (8%) patients in each group. Grade 3 adverse events were reported in two (2%) patients in the tocilizumab group and five (6%) patients in the standard care group. There were no grade 4 adverse events. Serious adverse events were reported in 18 (20%) patients in the tocilizumab group and 15 (17%) in the standard care group; 13 (14%) and 15 (17%) patients died during the study. INTERPRETATION: Routine use of tocilizumab in patients admitted to hospital with moderate to severe COVID-19 is not supported. However, post-hoc evidence from this study suggests tocilizumab might still be effective in patients with severe COVID-19 and so should be investigated further in future studies. FUNDING: Medanta Institute of Education and Research, Roche India, Cipla India, and Action COVID-19 India.

Genomic characterization and epidemiology of an emerging SARS-CoV-2 variant in Delhi, India.

Delhi, the national capital of India, experienced multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreaks in 2020 and reached population seropositivity of >50% by 2021. During April 2021, the city became overwhelmed by COVID-19 cases and fatalities, as a new variant, B.1.617.2 (Delta), replaced B.1.1.7 (Alpha). A Bayesian model explains the growth advantage of Delta through a combination of increased transmissibility and reduced sensitivity to immune responses generated against earlier variants (median estimates: 1.5-fold greater transmissibility and 20% reduction in sensitivity). Seropositivity of an employee and family cohort increased from 42% to 87.5% between March and July 2021, with 27% reinfections, as judged by increased antibody concentration after a previous decline. The likely high transmissibility and partial evasion of immunity by the Delta variant contributed to an overwhelming surge in Delhi.

Brain Stress Mapping in COVID-19 Survivors Using MR Spectroscopy: New Avenue of Mental Health Status Monitoring$.

Coronavirus (COVID-19) has emerged as a human catastrophe worldwide, and it has impacted human life more detrimentally than the combined effect of World Wars I and II. Various research studies reported that the disease is not confined to the respiratory system but also leads to neurological and neuropsychiatric disorders suggesting that the virus is potent to affect the central nervous system (CNS). Moreover, the damage to CNS may continue to rise even after the COVID-19 infection subsides which may further induce a long-term impact on the brain, resulting in cognitive impairment. Neuroimaging techniques is the ideal platform to detect and quantify pathological manifestations in the brain of COVID-19 survivors. In this context, a scheme based on structural, spectroscopic, and behavioral studies could be executed to monitor the gradual changes in the brain non-invasively due to COVID-19 which may further help in quantifying the impact of COVID-19 on the mental health of the survivors. Extensive research is required in this direction for identifying the mechanism and implications of COVID-19 in the brain. Cohort studies are urgently required for monitoring the effects of this pandemic on individuals of various subtypes longitudinally.