Survival After Invasive or Conservative Management of Stable Coronary Disease.

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing. METHODS: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol. RESULTS: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease. CONCLUSIONS: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04894877.

Initial Invasive or Conservative Strategy for Stable Coronary Disease.

BACKGROUND: Among patients with stable coronary disease and moderate or severe ischemia, whether clinical outcomes are better in those who receive an invasive intervention plus medical therapy than in those who receive medical therapy alone is uncertain. METHODS: We randomly assigned 5179 patients with moderate or severe ischemia to an initial invasive strategy (angiography and revascularization when feasible) and medical therapy or to an initial conservative strategy of medical therapy alone and angiography if medical therapy failed. The primary outcome was a composite of death from cardiovascular causes, myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. A key secondary outcome was death from cardiovascular causes or myocardial infarction. RESULTS: Over a median of 3.2 years, 318 primary outcome events occurred in the invasive-strategy group and 352 occurred in the conservative-strategy group. At 6 months, the cumulative event rate was 5.3% in the invasive-strategy group and 3.4% in the conservative-strategy group (difference, 1.9 percentage points; 95% confidence interval [CI], 0.8 to 3.0); at 5 years, the cumulative event rate was 16.4% and 18.2%, respectively (difference, -1.8 percentage points; 95% CI, -4.7 to 1.0). Results were similar with respect to the key secondary outcome. The incidence of the primary outcome was sensitive to the definition of myocardial infarction; a secondary analysis yielded more procedural myocardial infarctions of uncertain clinical importance. There were 145 deaths in the invasive-strategy group and 144 deaths in the conservative-strategy group (hazard ratio, 1.05; 95% CI, 0.83 to 1.32). CONCLUSIONS: Among patients with stable coronary disease and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of ischemic cardiovascular events or death from any cause over a median of 3.2 years. The trial findings were sensitive to the definition of myocardial infarction that was used. (Funded by the National Heart, Lung, and Blood Institute and others; ISCHEMIA ClinicalTrials.gov number, NCT01471522.).

India's tryst with salt: Dandi march to low sodium salts.

Salt plays a critical role in India's past as well as its present, from Dandi March to its role as a vehicle for micronutrient fortification. However, excess salt intake is a risk factor for high blood pressure and cardiovascular diseases (CVDs). Indians consume double the World Health Organization recommended daily salt (<5 g). India has committed to a 30 per cent reduction in sodium intake by 2025. Evidence based strategies for population sodium intake reduction require a moderate reduction in salt in - home cooked foods, packaged foods and outside-home foods. Reducing the sodium content in packaged food includes policy driven interventions such as front-of-package warning labels, food reformulation, marketing restrictions and taxation on high sodium foods. For foods outside of the home, setting standards for foods purchased and served by schemes like mid-day meals can have a moderate impact. For home cooked foods (the major source of sodium), strategies include advocacy for reducing salt intake. In addition to mass media campaigns for awareness generation, substituting regular salt with low sodium salt (LSS) has the potential to reduce salt intake even in the absence of a major shift in consumer behaviour. LSS substitution effectively lowers blood pressure and thus reduces the risk of CVDs. Further research is required on the effect of LSS substitutes on patients with chronic kidney disease. India needs an integrated approach to sodium reduction that uses evidence based strategies and can be implemented sustainably at scale. This will be possible only through scientific research, governmental leadership and a responsive evidence-to-action approach through a multi-stakeholder coalition.

A comparison of the quality of images of chest X-ray between handheld portable digital X-ray & routinely used digital X-ray machine.

Background & objectives: Chest X-ray (CXR) is an important screening tool for pulmonary tuberculosis (TB). Accessibility to CXR facilities in difficult-to-reach and underserved populations is a challenge. This can potentially be overcome by deploying digital X-ray machines that are portable. However, these portable X-ray machines need to be validated before their deployment in the field. Here, we compare the image quality of CXR taken by a newly developed handheld X-ray machine with routinely used reference digital X-ray machine through the conduct of a feasibility study. Methods: A total of 100 participants with suspected pulmonary TB were recruited from the outpatient departments of a medical college and a community health centre in Agra. Each participant underwent CXR twice, once with each machine. Both sets of de-identified images were independently read by two radiologists, who were blinded to the type of X-ray machine used. The primary outcome was agreement between image qualities produced by these two machines. Results: The intra-observer (radiologist) agreements regarding the status of the 15 CXR parameters ranged between 74 per cent and 100 per cent, with an unweighted mean of 87.2 per cent (95% confidence interval: 71.5-100). The median Cohen's kappa values for intra-observer agreement were 0.62 and 0.67 for radiologists 1 and 2, respectively. In addition, on comparison of the overall median score of quality of the image, the handheld machine images had a higher score for image quality. Interpretation & conclusions: The current study shows that a handheld X-ray machine, which is easy to use and can potentially be carried to any area, produces X-ray images with quality that is comparable to digital X-ray machines routinely used in health facilities.

Outcomes of Participants With Diabetes in the ISCHEMIA Trials.

BACKGROUND: Among patients with diabetes and chronic coronary disease, it is unclear if invasive management improves outcomes when added to medical therapy. METHODS: The ISCHEMIA (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) trials (ie, ISCHEMIA and ISCHEMIA-Chronic Kidney Disease) randomized chronic coronary disease patients to an invasive (medical therapy + angiography and revascularization if feasible) or a conservative approach (medical therapy alone with revascularization if medical therapy failed). Cohorts were combined after no trial-specific effects were observed. Diabetes was defined by history, hemoglobin A1c ≥6.5%, or use of glucose-lowering medication. The primary outcome was all-cause death or myocardial infarction (MI). Heterogeneity of effect of invasive management on death or MI was evaluated using a Bayesian approach to protect against random high or low estimates of treatment effect for patients with versus without diabetes and for diabetes subgroups of clinical (female sex and insulin use) and anatomic features (coronary artery disease severity or left ventricular function). RESULTS: Of 5900 participants with complete baseline data, the median age was 64 years (interquartile range, 57-70), 24% were female, and the median estimated glomerular filtration was 80 mL·min-1·1.73-2 (interquartile range, 64-95). Among the 2553 (43%) of participants with diabetes, the median percent hemoglobin A1c was 7% (interquartile range, 7-8), and 30% were insulin-treated. Participants with diabetes had a 49% increased hazard of death or MI (hazard ratio, 1.49 [95% CI, 1.31-1.70]; P<0.001). At median 3.1-year follow-up the adjusted event-free survival was 0.54 (95% bootstrapped CI, 0.48-0.60) and 0.66 (95% bootstrapped CI, 0.61-0.71) for patients with diabetes versus without diabetes, respectively, with a 12% (95% bootstrapped CI, 4%-20%) absolute decrease in event-free survival among participants with diabetes. Female and male patients with insulin-treated diabetes had an adjusted event-free survival of 0.52 (95% bootstrapped CI, 0.42-0.56) and 0.49 (95% bootstrapped CI, 0.42-0.56), respectively. There was no difference in death or MI between strategies for patients with diabetes versus without diabetes, or for clinical (female sex or insulin use) or anatomic features (coronary artery disease severity or left ventricular function) of patients with diabetes. CONCLUSIONS: Despite higher risk for death or MI, chronic coronary disease patients with diabetes did not derive incremental benefit from routine invasive management compared with initial medical therapy alone. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Efficacy, safety, and lot-to-lot immunogenicity of an inactivated SARS-CoV-2 vaccine (BBV152): interim results of a randomised, double-blind, controlled, phase 3 trial.

BACKGROUND: We report the clinical efficacy against COVID-19 infection of BBV152, a whole virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) in Indian adults. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre, phase 3 clinical trial in 25 Indian hospitals or medical clinics to evaluate the efficacy, safety, and immunological lot consistency of BBV152. Adults (age ≥18 years) who were healthy or had stable chronic medical conditions (not an immunocompromising condition or requiring treatment with immunosuppressive therapy) were randomised 1:1 with a computer-generated randomisation scheme (stratified for the presence or absence of chronic conditions) to receive two intramuscular doses of vaccine or placebo administered 4 weeks apart. Participants, investigators, study coordinators, study-related personnel, the sponsor, and nurses who administered the vaccines were masked to treatment group allocation; an unmasked contract research organisation and a masked expert adjudication panel assessed outcomes. The primary outcome was the efficacy of the BBV152 vaccine in preventing a first occurrence of laboratory-confirmed (RT-PCR-positive) symptomatic COVID-19 (any severity), occurring at least 14 days after the second dose in the per-protocol population. We also assessed safety and reactogenicity throughout the duration of the study in all participants who had received at least one dose of vaccine or placebo. This report contains interim results (data cutoff May 17, 2021) regarding immunogenicity and safety outcomes (captured on days 0 to 56) and efficacy results with a median of 99 days for the study population. The trial was registered on the Indian Clinical Trials Registry India, CTRI/2020/11/028976, and ClinicalTrials.gov, NCT04641481 (active, not recruiting). FINDINGS: Between Nov 16, 2020, and Jan 7, 2021, we recruited 25 798 participants who were randomly assigned to receive BBV152 or placebo; 24 419 received two doses of BBV152 (n=12 221) or placebo (n=12 198). Efficacy analysis was dependent on having 130 cases of symptomatic COVID-19, which occurred when 16 973 initially seronegative participants had at least 14 days follow-up after the second dose. 24 (0·3%) cases occurred among 8471 vaccine recipients and 106 (1·2%) among 8502 placebo recipients, giving an overall estimated vaccine efficacy of 77·8% (95% CI 65·2-86·4). In the safety population (n=25 753), 5959 adverse events occurred in 3194 participants. BBV152 was well tolerated; the same proportion of participants reported adverse events in the vaccine group (1597 [12·4%] of 12 879) and placebo group (1597 [12·4%] of 12 874), with no clinically significant differences in the distributions of solicited, unsolicited, or serious adverse events between the groups, and no cases of anaphylaxis or vaccine-related deaths. INTERPRETATION: BBV152 was highly efficacious against laboratory-confirmed symptomatic COVID-19 disease in adults. Vaccination was well tolerated with no safety concerns raised in this interim analysis. FUNDING: Bharat Biotech International and Indian Council of Medical Research.

Characterizing the third wave of COVID-19: An analysis from the National Clinical Registry of COVID-19.

Background & objectives: Data from the National Clinical Registry for COVID-19 (NCRC) were analyzed with an aim to describe the clinical characteristics, course and outcomes of patients hospitalized with COVID-19 in the third wave of the pandemic and compare them with patients admitted earlier. Methods: The NCRC, launched in September 2020, is a multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized COVID-19 patients were captured in an electronic data portal from 38 hospitals across India. Patients enrolled during December 16, 2021 to January 17, 2022 were considered representative of the third wave of COVID-19 and compared with those registered during November 15 to December 15, 2021, representative of the tail end of the second wave. Results: Between November 15, 2021 and January 17, 2022, 3230 patients were recruited in NCRC. Patients admitted in the third wave were significantly younger than those admitted earlier (46.7±20.5 vs. 54.6±18 yr). The patients admitted in the third wave had a lower requirement of drugs including steroids, interleukin (IL)-6 inhibitors and remdesivir as well as lower oxygen supplementation and mechanical ventilation. They had improved hospital outcomes with significantly lower in-hospital mortality (11.2 vs. 15.1%). The outcomes were better among the fully vaccinated when compared to the unvaccinated or partially vaccinated. Interpretation & conclusions: The pattern of illness and outcomes were observed to be different in the third wave compared to the last wave. Hospitalized patients were younger with fewer comorbidities, decreased symptoms and improved outcomes, with fully vaccinated patients faring better than the unvaccinated and partially vaccinated ones.

Development of the India COVID-19 vaccine tracker.

COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11, 2020. Since then, efforts were initiated to develop safe and effective vaccines. Till date, 11 vaccines have been included in the WHO's emergency use list. The emergence and spread of variant strains of SARS-CoV-2 has altered the disease transmission dynamics, thus creating a need for continuously monitoring the real-world effectiveness of various vaccines and assessing their overall impact on disease control. To achieve this goal, the Indian Council of Medical Research (ICMR) along with the Ministry of Health and Family Welfare, Government of India, took the lead to develop the India COVID-19 Vaccination Tracker by synergizing three different public health databases: National COVID-19 testing database, CoWIN vaccination database and the COVID-19 India portal. A Vaccine Data Analytics Committee (VDAC) was constituted to advise on various modalities of the proposed tracker. The VDAC reviewed the data related to COVID-19 testing, vaccination and patient outcomes available in the three databases and selected relevant data points for inclusion in the tracker, following which databases were integrated, using common identifiers, wherever feasible. Multiple data filters were applied to retrieve information of all individuals ≥18 yr who died after the acquisition of COVID-19 infection with or without vaccination, irrespective of the time between vaccination and test positivity. Vaccine effectiveness (VE) against the reduction of mortality and hospitalizations was initially assessed. As compared to the hospitalization data, mortality reporting was found to be much better in terms of correctness and completeness. Therefore, hospitalization data were not considered for analysis and presentation in the vaccine tracker. The vaccine tracker thus depicts VE against mortality, calculated by a cohort approach using person-time analysis. Incidence of COVID-19 deaths among one- and two-dose vaccine recipients was compared with that among unvaccinated groups, to estimate the rate ratios (RRs). VE was estimated as 96.6 and 97.5 per cent, with one and two doses of the vaccines, respectively, during the period of reporting. The India COVID-19 Vaccination Tracker was officially launched on September 9, 2021. The high VE against mortality, as demonstrated by the tracker, has helped aid in allaying vaccine hesitancy, augmenting and maintaining the momentum of India's COVID-19 vaccination drive.

Restless legs syndrome/Willis-Ekbom disease among patients with resistant hypertension versus stroke patients-a prospective study.

BACKGROUND: Epidemiological studies have shown an increased prevalence and incidence of hypertension as well as a higher incidence of stroke among patients suffering from RLS. The objective of this study was to estimate the prevalence of RLS among patients with resistant hypertension (RH) and compare the clinical characteristics of these patients with patients of stroke pre-existing RLS and with patients with primary RLS presenting to the Sleep clinic. METHODS: Consecutive patients with RH (without any identifiable cause on extensive work up) and consecutive in-patients with stroke were enrolled over a 3-year-period. Patients with RH fulfilling revised-IRLSSG-criteria for RLS comprised group 1 and those with stroke and RLS formed group 2. These were compared with patients diagnosed to have idiopathic RLS (iRLS) (Group 3). Prevalence of RLS in groups 1 and 2 and RLS characteristics in all groups were compared. RESULTS: Sixteen out of 56 RH patients (29%) formed group 1 and 43 out 346 of stroke patients (12%) formed group 2, while 43 consecutive iRLS patients were included in group 3. Age was significantly higher, with male dominance in group 2. Median age at symptom onset was significantly lower in group 1. Positive family history was similar in RH and iRLS patients and was significantly less common in stroke patients. Asymmetrical/unilateral distribution of symptoms was significantly more common in stroke group, compared to RH and iRLS groups. CONCLUSION: This study demonstrated a high prevalence of RLS among patients with resistant hypertension. RLS characteristics are different from those in patients with stroke, and very similar to primary RLS.

The International Collaboration for Research methods Development in Oncology (CReDO) workshops: shaping the future of global oncology research.

Low-income and middle-income countries (LMICs) have a disproportionately high burden of cancer and cancer mortality. The unique barriers to optimum cancer care in these regions necessitate context-specific research. The conduct of research in LMICs has several challenges, not least of which is a paucity of formal training in research methods. Building capacity by training early career researchers is essential to improve research output and cancer outcomes in LMICs. The International Collaboration for Research methods Development in Oncology (CReDO) workshop is an initiative by the Tata Memorial Centre and the National Cancer Grid of India to address gaps in research training and increase capacity in oncology research. Since 2015, there have been five CReDO workshops, which have trained more than 250 oncologists from India and other countries in clinical research methods and protocol development. Participants from all oncology and allied fields were represented at these workshops. Protocols developed included clinical trials, comparative effectiveness studies, health services research, and observational studies, and many of these protocols were particularly relevant to cancer management in LMICs. A follow-up of these participants in 2020 elicited an 88% response rate and showed that 42% of participants had made progress with their CReDO protocols, and 73% had initiated other research protocols and published papers. In this Policy Review, we describe the challenges to research in LMICs, as well as the evolution, structure, and impact of CReDO and other similar workshops on global oncology research.

Seroprevalence of IgG antibodies against SARS-CoV-2 among the general population and healthcare workers in India, June-July 2021: A population-based cross-sectional study.

BACKGROUND: India began COVID-19 vaccination in January 2021, initially targeting healthcare and frontline workers. The vaccination strategy was expanded in a phased manner and currently covers all individuals aged 18 years and above. India experienced a severe second wave of COVID-19 during March-June 2021. We conducted a fourth nationwide serosurvey to estimate prevalence of SARS-CoV-2 antibodies in the general population aged ≥6 years and healthcare workers (HCWs). METHODS AND FINDINGS: We did a cross-sectional study between 14 June and 6 July 2021 in the same 70 districts across 20 states and 1 union territory where 3 previous rounds of serosurveys were conducted. From each district, 10 clusters (villages in rural areas and wards in urban areas) were selected by the probability proportional to population size method. From each district, a minimum of 400 individuals aged ≥6 years from the general population (40 individuals from each cluster) 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 SARS-CoV-2, along with 95% CIs, based on the presence of antibodies to S1-RBD and/or nucleocapsid protein. Of the 28,975 individuals who participated in the survey, 2,892 (10%) were aged 6-9 years, 5,798 (20%) were aged 10-17 years, and 20,285 (70%) were aged ≥18 years; 15,160 (52.3%) participants were female, and 21,794 (75.2%) resided in rural areas. 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% to 68.7%). Seroprevalence increased with age (p < 0.001) and was not different in rural and urban areas (p = 0.822). Compared to unvaccinated adults (62.3%, 95% CI 60.9% to 63.7%), seroprevalence was significantly higher among individuals who had received 1 vaccine dose (81.0%, 95% CI 79.6% to 82.3%, p < 0.001) and 2 vaccine doses (89.8%, 95% CI 88.4% to 91.1%, p < 0.001). The seroprevalence of IgG antibodies among 7,252 HCWs was 85.2% (95% CI 83.5% to 86.7%). Important limitations of the study include the survey design, which was aimed to estimate seroprevalence at the national level and not at a sub-national level, and the non-participation of 19% of eligible individuals in the survey. CONCLUSIONS: Nearly two-thirds of individuals aged ≥6 years from the general population and 85% of HCWs had antibodies against SARS-CoV-2 by June-July 2021 in India. As 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.

Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate Safety and Therapeutic Efficacy of Angiogenesis Induced by Intraarterial Autologous Bone Marrow-Derived Stem Cells in Patients with Severe Peripheral Arterial Disease.

PURPOSE: To evaluate safety and efficacy of angiogenesis induced by intraarterial autologous bone marrow-derived stem cell (BMSC) injection in patients with severe peripheral arterial disease (PAD). MATERIALS AND METHODS: Eighty-one patients with severe PAD (77 men), including 56 with critical limb ischemia (CLI) and 25 with severe claudication, were randomized to receive sham injection (group A) or intraarterial BMSC injection at the site of occlusion (group B). Primary endpoints included improvement in ankle-brachial index (ABI) of > 0.1 and transcutaneous pressure of oxygen (TcPO2) of > 15% at mid- and lower foot at 6 mo. Secondary endpoints included relief from rest pain, > 30% reduction in ulcer size, and reduction in major amputation in patients with CLI and > 50% improvement in pain-free walking distance in patients with severe claudication. RESULTS: Technical success was achieved in all patients, without complications. At 6 mo, group B showed more improvements in ABI of > 0.1 (35 of 41 [85.37%] vs 13 of 40 [32.50%]; P < .0001) and TcPO2 of > 15% at the midfoot (35 of 41 [85.37%] vs 17 of 40 [42.50%]; P = .0001] and lower foot (37 of 41 [90.24%] vs 19 of 40 [47.50%]; P < .0001). No patients with CLI underwent major amputation in group B, compared with 4 in group A (P = .0390). No significant difference was observed in relief from rest pain or > 30% reduction in ulcer size among patients with CLI or in > 50% improvement in pain-free walking distance among patients with severe claudication. CONCLUSIONS: Intraarterial delivery of autologous BMSCs is safe and effective in the management of severe PAD.

SARS-CoV-2 re-infection: development of an epidemiological definition from India.

The current investigation was conducted with the objective to develop an epidemiological case definition of possible severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) re-infection and assess its magnitude in India. The epidemiological case definition for SARS-CoV-2 re-infection was developed from literature review of data on viral kinetics. For achieving second objective, the individuals who satisfied the developed case definition for SARS-CoV-2 re-infection were contacted telephonically. Taking available evidence into consideration, re-infection with SARS-CoV-2 in our study was defined as any individual who tested positive for SARS-CoV-2 on two separate occasions by either molecular tests or rapid antigen test at an interval of at least 102 days with one negative molecular test in between. In this archive based, telephonic survey, 58 out of 1300 individuals (4.5%) fulfilled the above-mentioned definition; 38 individuals could be contacted with healthcare workers (HCWs) accounting for 31.6% of the cases. A large proportion of participants was asymptomatic and had higher Ct value during the first episode. While SARS-CoV-2 re-infection is still a rare phenomenon, there is a need for epidemiological definition of re-infection for establishing surveillance systems and this study contributes to such a goal.Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) re-infection is an emerging concern and there is a need to define it. Therefore, working epidemiological case definition for re-infection was developed and its magnitude was explored via archive-based, telephonic survey. Re-infection with SARS-CoV-2 was defined as two positive tests at an interval of at least 102 days with one interim negative test. Thirty-eight of the 58 eligible patients could be contacted with 12 (31.6%) being HCWs. Majority of the participants were asymptomatic and had higher Ct value during their first episode. To conclude, a working epidemiological case definition of SARS-CoV-2 re-infection is important to strengthen surveillance. The present investigation contributes to this goal and records reinfection in 4.5% of SARS-CoV-2 infected individuals in India.

Plausibility of a third wave of COVID-19 in India: A mathematical modelling based analysis.

BACKGROUND & OBJECTIVES: In the context of India's ongoing resurgence of COVID-19 (second wave since mid-February 2021, following the subsiding of the first wave in September 2020), there has been increasing speculation on the possibility of a future third wave of infection, posing a burden on the healthcare system. Using simple mathematical models of the transmission dynamics of SARS-CoV-2, this study examined the conditions under which a serious third wave could occur. METHODS: Using a deterministic, compartmental model of SARS-CoV-2 transmission, four potential mechanisms for a third wave were examined: (i) waning immunity restores previously exposed individuals to a susceptible state, (ii) emergence of a new viral variant that is capable of escaping immunity to previously circulating strains, (iii) emergence of a new viral variant that is more transmissible than the previously circulating strains, and (iv) release of current lockdowns affording fresh opportunities for transmission. RESULTS: Immune-mediated mechanisms (waning immunity, or viral evolution for immune escape) are unlikely to drive a severe third wave if acting on their own, unless such mechanisms lead to a complete loss of protection among those previously exposed. Likewise, a new, more transmissible variant would have to exceed a high threshold (R0>4.5) to cause a third wave on its own. However, plausible mechanisms for a third wave include: (i) a new variant that is more transmissible and at the same time capable of escaping prior immunity, and (ii) lockdowns that are highly effective in limiting transmission and subsequently released. In both cases, any third wave seems unlikely to be as severe as the second wave. Rapid scale-up of vaccination efforts could play an important role in mitigating these and future waves of the disease. INTERPRETATION & CONCLUSIONS: This study demonstrates plausible mechanisms by which a substantial third wave could occur, while also illustrating that it is unlikely for any such resurgence to be as large as the second wave. Model projections are, however, subject to several uncertainties, and it remains important to scale up vaccination coverage to mitigate against any eventuality. Preparedness planning for any potential future wave will benefit by drawing upon the projected numbers based on the present modelling exercise.

Comparison of the immunogenicity & protective efficacy of various SARS-CoV-2 vaccine candidates in non-human primates.

BACKGROUND & OBJECTIVES: The COVID-19 pandemic has emerged as a global public health crisis and research groups worldwide are engaged in developing vaccine candidates to curb its transmission, with a few vaccines having progressed to advanced stages of clinical trials. The aim of this systematic review was to compare immunogenicity and protective efficacy of various SARS-CoV-2 vaccine candidates tested in non-human primate (NHP) models. METHODS: Literature on effect of SARS-CoV-2 vaccines in NHP models reported on PubMed and preprint platforms (medRxiv and bioRxiv) till October 22, 2020, was searched with the following terms: coronavirus vaccine, COVID-19 vaccine, SARS-CoV-2 vaccine, nonhuman primate, and rhesus macaque. RESULTS: Our search yielded 19 studies, which reported immune response elicited by 18 vaccine candidates in NHP. All the vaccines induced detectable neutralizing antibody (NAb) titres in the serum of vaccinated animals, with some showing effective viral clearance from various organs. The vaccinated animals also showed nil to mild histopathological changes in their lungs compared to placebo groups in the trials that performed necropsy. INTERPRETATION & CONCLUSIONS: Our findings highlighted onset of quick immunogenicity and protective efficacy of mRNA-1273, followed by Ad26.CoV2.S, NVX-CoV2373, BNT162b2, RBD and BBV152 vaccine candidates in preclinical trials as compared to the others. NHP data also showed correlation with clinical trial data available for a few vaccines. Preclinical trials of COVID-19 vaccine candidates in NHPs yielded promising results, with some candidates faring better than others.

Antibody responses to the BBV152 vaccine in individuals previously infected with SARS-CoV-2: A pilot study.

Background & objectives: Vaccination against SARS-CoV-2 is a recommendation from the World Health Organization as the foremost preference in the current situation to control the COVID-19 pandemic. BBV152 is one of the approved vaccines against SARS-CoV-2 in India. In this study, we determined SARS-CoV-2-specific antibody levels at day 0 (baseline, before vaccination), day 28 ± 2 post-first dose (month 1) and day 56 ± 2 post-first dose (month 2) of BBV152 whole-virion-inactivated SARS-CoV-2 recipients, and compared the antibody responses of individuals with confirmed pre-vaccination SARS-CoV-2 infection to those individuals without prior evidence of infection. Methods: Blood samples were collected from 114 healthcare professionals and frontline workers who received BBV152 vaccine from February to May & June 2021. Prior infection with SARS-CoV-2 was determined at baseline. Serum samples were used to estimate SARS-CoV-2 nucleoprotein-specific IgG [IgG (N)], spike protein-specific IgG [IgG (S)] and neutralizing antibodies (NAb). Results: Participants with previous SARS-CoV-2 infection after a single vaccine dose elicited IgG (N) and IgG (S) antibody levels along with NAb binding inhibition responses levels were similar to infection-naïve vaccinated participants who had taken two doses of vaccine. Interpretation & conclusions: Our preliminary data suggested that a single dose of BBV152-induced humoral immunity in previously infected individuals was equivalent to two doses of the vaccine in infection-naïve individuals. However, these findings need to be confirmed with large sized cohort studies.

Clinical profile of hospitalized COVID-19 patients in first & second wave of the pandemic: Insights from an Indian registry based observational study.

Background & objectives: India witnessed a massive second surge of COVID-19 cases since March 2021 after a period of decline from September 2020. Data collected under the National Clinical Registry for COVID-19 (NCRC) were analysed to describe the differences in demographic and clinical features of COVID-19 patients recruited during these two successive waves. Methods: The NCRC, launched in September 2020, is an ongoing multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized, confirmed COVID-19 patients were captured in an electronic data portal from 41 hospitals across India. Patients enrolled during September 1, 2020 to January 31, 2021 and February 1 to May 11, 2021 constituted participants of the two successive waves, respectively. Results: As on May 11, 2021, 18961 individuals were recruited in the registry, 12059 and 6903 reflecting in-patients from the first and second waves, respectively. Mean age of the patients was significantly lower in the second wave [48.7 (18.1) yr vs. 50.7 (18.0) yr, P<0.001] with higher proportion of patients in the younger age group intervals of <20, and 20-39 yr. Approximately 70 per cent of the admitted patients were ≥ 40 yr of age in both waves of the pandemic. The proportion of males were slightly lower in second wave as compared to the first [4400 (63.7%) vs. 7886 (65.4%), P=0.02]. Commonest presenting symptom was fever in both waves. In the second wave, a significantly higher proportion [2625 (48.6%) vs. 4420 (42.8%), P<0.003] complained of shortness of breath, developed ARDS [422(13%) vs. 880 (7.9%), P<0.001], required supplemental oxygen [1637 (50.3%) vs. 4771 (42.7%), P<0.001], and mechanical ventilation [260 (15.9%) vs. 530 (11.1%), P<0.001]. Mortality also significantly increased in the second wave [OR: 1.35 (95% CI: 1.19, 1.52)] in all age groups except in <20 yr. Interpretation & conclusions: The second wave of COVID-19 in India was slightly different in presentation than the first wave, with a younger demography, lesser comorbidities, and presentation with breathlessness in greater frequency.

Global Hunger Index does not really measure hunger - An Indian perspective.

The Global Hunger Index (GHI) is calculated and disseminated annually. India, which is the 5th largest economy in the world and has a good ranking in many other indicators, has a poor ranking based on this index. After a critical review of the appropriateness of the indicators used in GHI, the Indian Council of Medical Research has the viewpoint that the indicators of undernourishment, stunting, wasting and child mortality do not measure hunger per se. Referring to this index as a Hunger Index, and thereby ranking countries is not appropriate, since many of the measures that are used to evolve an index that measures hunger are probably contextual. Countries should therefore evolve their own measures that are suitable for their own context.

White paper on smokeless tobacco & women's health in India.

Smokeless tobacco (SLT) use is widespread across many nations and populations, and India shares more than three-quarters of the global burden of SLT consumption. Tobacco use in India has been largely viewed as a male-dominant behaviour. However, evidence from medical, social and behavioural sciences show significant SLT use among women and young girls. This paper highlights key dimensions of SLT use among women in India including prevalence and determinants, the health effects arising from SLT use and cessation behaviours. The paper concludes by providing recommendations with the aim of setting research priorities and policy agenda to achieve a tobacco-free society. The focus on women and girls is essential to achieve the national targets for tobacco control under the National Health Policy, 2017, and Sustainable Development Goals 3 of ensuring healthy lives and promote well-being for all.

Perspectives for repurposing drugs for the coronavirus disease 2019.

The newly emerged 2019 novel coronavirus (CoV), named as severe acute respiratory syndrome CoV-2 (SARS-CoV-2), like SARS-CoV (now, SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV), has been associated with high infection rates with over 36,405 deaths. In the absence of approved marketed drugs against coronaviruses, the treatment and management of this novel CoV disease (COVID-19) worldwide is a challenge. Drug repurposing that has emerged as an effective drug discovery approach from earlier approved drugs could reduce the time and cost compared to de novo drug discovery. Direct virus-targeted antiviral agents target specific nucleic acid or proteins of the virus while host-based antivirals target either the host innate immune responses or the cellular machineries that are crucial for viral infection. Both the approaches necessarily interfere with viral pathogenesis. Here we summarize the present status of both virus-based and host-based drug repurposing perspectives for coronaviruses in general and the SARS-CoV-2 in particular.