Diabetes and tuberculosis syndemic in India: A narrative review of facts, gaps in care and challenges.

Both diabetes mellitus (DM) and tuberculosis (TB) are prevalent all across in India. TB-DM comorbidity has emerged as a syndemic and needs more attention in India considering gaps in screening, clinical care, and research. This paper is intended to review published literature on TB and DM in India to understand the burden of the dual epidemic and its trajectory and to obtain perspectives on the gaps, constraints, and challenges in care and treatment of this dual epidemic. A literature search was carried out on PubMed, Scopus, and Google Scholar, using the key words 'Tuberculosis' OR 'TB' AND 'Diabetes' OR 'Diabetes Mellitus' AND 'India', focusing on the research published between the year 2000 to 2022. The prevalence of DM is high in patients with TB. Quantitative data on the epidemiological situation of TB/DM in India such as incidence, prevalence, mortality, and management are lacking. During the last 2 years convergence of TB-DM syndemic with the COVID-19 pandemic has increased cases with uncontrolled DM but also made coordinated control of TB-DM operationally difficult and of low effectiveness. Research regarding TB-DM comorbidity is required in the context of epidemiology and management. Detection and bidirectional screening are aggressively warranted. Management of DM in those with TB-DM comorbidity needs more efforts, including training and supervision of frontline workers.

Reactive arthritis following COVID-19 current evidence, diagnosis, and management strategies.

BACKGROUND: Immune-mediated conditions associated to Corona Virus Disease-19 (COVID-19) have been reported, including vasculitis, antiphospholipid antibody syndrome, myositis, and lupus. Emerging studies have reported the potential occurrence of reactive arthritis in patients previously infected with COVID-19. This systematic review summarised the current evidence on the occurrence of reactive arthritis in patients previously infected by COVID-19. METHODS: This study was conducted according to the 2020 PRISMA guidelines. All the clinical investigations describing the occurrence of reactive arthritis following COVID-19 were accessed. In September 2022, the following databases were accessed: PubMed, Web of Science, Google Scholar, Embase. The generalities of the study were extracted: author, year and journal of publication, country of the main author, study design, sample size, mean age, number of women, main results of the study. The following data on COVID-19 severity and management were retrieved: type of treatment, hospitalization regimes (inpatient or outpatient), admission to the intensive care unit, need of mechanical ventilation, pharmacological management. The following data on reactive arthritis were collected: time elapsed between COVID-19 infection to the onset of reactive arthritis symptoms (days), pharmacological management, type of arthritis (mono- or bilateral, mono- or polyarticular), extra-articular manifestations, presence of tenosynovitis or enthesitis, synovial examination at microscopic polarised light, imaging (radiography, magnetic resonance, sonography), clinical examination, laboratory findings. RESULTS: Data from 27 case reports (54 patients) were retrieved, with a mean age of 49.8 ± 14.5 years. 54% (29 of 54 patients) were women. The mean time span between COVID-19 infection and the occurrence of reactive arthritis symptoms was 22.3 ± 10.7 days. Between studies diagnosis and management of reactive arthritis were heterogeneous. Symptoms resolved within few days in all studies considered. At last follow-up, all patients were minimally symptomatic or asymptomatic, and no additional therapy or attentions were required by any patient. CONCLUSION: Poor evidence suggests that COVID-19 could target the musculoskeletal system causing reactive arthritis at its post infectious stage. COVID-19 can act as a causative agent or as a trigger for development of reactive arthritis even without presence of antibodies of rheumatological disorders. Treating physicians should have a high index of suspicion while treating post infectious COVID-19 patient with arthralgia. LEVEL OF EVIDENCE: Level IV, systematic review.

SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion.

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era.

Vitamins C and D and COVID-19 Susceptibility, Severity and Progression: An Evidence Based Systematic Review.

Background and Objectives: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis and related clinical consequences are still unclear. Early diagnosis and dynamic monitoring of prognostic factors are essential to improve the ability to manage COVID-19 infection. This study aimed to provide an account of the role played by vitamins C and D on the onset, progression and severity of COVID-19. Clinical features and infection-related risk factors are also briefly discussed. Material and Methods: In March 2022, the main online databases were accessed. All the articles that investigate the possible role of vitamins C and D on COVID-19 susceptibility, severity and progression were considered. Results: The current evidence on vitamin C and D supplementation in patients with COVID-19 infection is inconsistent and controversial. In some studies, vitamins were used as coadjuvant of a formal experimental therapy, while in others as main treatment. Ethnicity and hospital setting (inpatient/outpatient) were also variable. Moreover, there was no consensus between studies in administration protocol: high heterogeneity in dosage, administration, and duration of the treatment were evident. Finally, some studies administered vitamins pre- and/or during COVID infection, in patients with different risk factors and infection severity. Conclusions: While waiting to develop a targeted, safe and effective therapy, it is important to investigate individual predisposition and proper disease management. Concluding, available data on the use of nutraceuticals in COVID-19 are inconsistent. However, there is a lack of evidence-based guidelines which recommend vitamin C and D supplementation in patients with COVID-19, and results from high quality randomised controlled trials (RCTs) are inconsistent. Current investigations so far are mostly observational, and include a relatively small sample size which can lead to biased results. Large-scale multicentre studies are therefore needed.

Symptomatic post-vaccination SARS-CoV-2 infections in healthcare workers- A multicenter cohort study.

BACKGROUND AND AIMS: During the COVID-19 vaccination program in India, the healthcare workers were given the first priority. There are concerns regarding the occurrence of breakthrough infections after vaccination. We aimed to investigate the effictiveness of COVID-19 vaccines in preventing and reducing the severity of post-vaccination infections. METHODS: This retrospective test-negative case-control study examined 28342 vaccinated healthcare workers for symptomatic SARS-CoV-2 infections between January 16 to June 15, 2021. They worked at 43 Apollo Group hospitals in 24 Indian cities. These cohorts received either ChAdOx nCOV-19 (Recombinant) or the whole virion inactivated Vero cell vaccines. Various demographic, vaccination related and clinical parameters were evaluated. RESULTS: Symptomatic symptomatic post-vaccination infections occurred in a small number of vaccinated cohorts (5.07%, p < 0.001), and these were predominantly mild and did not result in hospitalization (p < 0.0001), or death. Both vaccines provided similar protection, with symptomatic infections in 5.11% and 4.58%, following ChAdOx nCOV-19 (Recombinant) and the whole virion inactivated Vero cell vaccines, respectively (p < 0.001). Nursing and Clinical staff and cohorts >50 years contracted more infections (p < 0.001). Two-dose vaccination has significantly lower odds of developing symptomatic infection (0.83, 95%CI - 0.72 to 0.97). Maximum infections occurred during the peak of the second COVID-19 wave from mid-April to May 2021 (p < 0.001). No significant difference existed in the infection between sex, vaccine type, and the number of vaccine doses received (p ≥ 0.05). CONCLUSION: Symptomatic infections occurred in a small percentage of healthcare workers after COVID vaccination. Vaccination protected them from not only infection but also severe disease.

Bibliometric analysis of COVID-19 related publications in Indian orthopaedic journals.

BACKGROUND: The COVID-19 pandemic has resulted in an infodemic about the novel coronavirus SARS-CoV-2 outbreak to build knowledge and develop mitigation strategies. In addition, scientific journals across the world have studied the impact of COVID-19 on trauma and orthopaedics. METHODS: A cross-sectional, bibliometric analysis of the literature was undertaken on COVID-19 related articles from three Pubmed and Scopus indexed orthopaedic journals from India, namely, Indian Journal of Orthopaedics(IJO),Journal of Clinical Orthopaedics and Trauma(JCOT), and Journal of Orthopaedics (JOO), in May 2021. All the article types and study designs were included for this review. The authors, institutions, countries, keywords, and co-authorship mapping were studied. RESULTS: A total of 112 COVID-19 related documents were retrieved. Period of these publications was from 2nd April 2020 to 31st May 2021. Vaishya R. (n = 16) was the most cited author, and Indraprastha Apollo Hospitals (n = 16) was the most cited research Institution. India led the list of countries in academic publication output. On keyword mapping, telemedicine was the most prominent Medical Subject Headings (MeSH) search word. CONCLUSION: The Indian orthopedic journals have addressed the impact of COVID-19 on orthopaedic practice in India and aborad whilst continuing to publish knowledge about basic science and clinical orthopaedic research studies. The JCOT has outperformed and become the most leading orthopaedic journal from India during the pandemic. COVID -19 articles have been fast tracked, open accessed and attracted more citations in reduced duration of time compared to non-COVID-19 papers.

Bibliometric analysis of the top 50 most cited publications of the Journal of Clinical Orthopaedics and Trauma.

BACKGROUND: The Journal of Clinical Orthopaedics and Trauma (JCOT) is one of the top three orthopaedic journals from India. We set out to analyse the top 50 cited articles from JCOT since indexing in PubMed and Scopus. METHODS: We looked into the bibliometrics of the top 50 cited articles and compared citations from PubMed and Scopus, and depicted outputs from VOS viewer analysis on co-authorship and keywords. RESULTS: Total citations for top-cited articles were 1076 in numbers, with a maximum of 103.2016 and 2018 were the most productive years. The major contribution was from India with 74%, followed by the USA. New Delhi published maximally at 72%. Clinical topics and narrative reviews were the most common types of studies. Trauma and Adult reconstruction was the most common sub-specialities, and Level 4 was the most frequent level of study. The basic science and COVID-19 related articles received the maximum citations. The authors from Indraprastha Apollo Hospitals published the maximum number of top-50 cited articles in the JCOT. CONCLUSIONS: There is a steady increase in the number of publications in the JCOT, with an increasing number of citation counts. Both the Indian and foreign authors have been publishing in this journal at a comparative rate. Although the citation counts in Scopus are more than those in PubMed for given articles, more than 80% of articles are listed in both databases as top 50 cited articles. The majority of top-cited articles belonged to trauma and adult reconstruction, level III studies, and narrative reviews.

SARS-CoV-2 infection after COVID-19 immunization in healthcare workers: A retrospective, pilot study.

BACKGROUND & OBJECTIVES: COVID-19 pandemic has taken a significant toll on the health of the people across the globe, including India, and is still continuing with its rapidly evolving second wave. Although the COVID-19 vaccines effectively prevent infection, yet some cases of infections have been reported post-vaccination, raising concerns about their efficacy and safety. This study was aimed to investigate the occurrence of SARS-CoV-2 infection among the symptomatic-vaccinated healthcare workers (HCWs) and to analyze the severity of their disease. METHODS: This retrospective study was done at a single multispecialty hospital, on the HCWs who have had COVID-19 vaccination, during the initial period of the vaccination drive (January 16 to April 24, 2021). The symptomatic post-vaccination infections in these HCWs were evaluated. RESULTS: Eighty five of 3235 (2.63%) vaccinated HCWs acquired the SARS-CoV-2 infection after vaccination, during the study period. Of these, 65 (76.5%) were fully vaccinated (FV), and 20 (23.5%) were partially vaccinated (PV) and the protection rate of vaccination was 97.4 per cent [95 % confidence interval (CI)=96.8-97.9]. The odds ratio of acquiring infection among females was higher at 1.84 (95% CI=1.17-2.88; P=0.008) mainly because of their greater involvement in the patient care as nursing personnel. The chances of infections were the highest in the medical and nursing personnel, as compared to paramedical, administrative and supporting staff (P<0.001). Among the HCWs studied, only two required hospitalization (0.06%), none needed an intensive care unit (ICU) admission and there were no deaths. INTERPRETATION & CONCLUSIONS: The COVID-19 infection after vaccination occurred in a smaller subset (2.63%) of HCWs, in both PV and the FV groups. These infections were primarily minor and did not lead to severe disease. Overall, the vaccination with ChAdOx1 nCoV-19 vaccine (recombinant) prevented SARS-CoV-2 severe infection in the HCWs, leading to ICU admission and deaths.

Multivariable mortality risk prediction using machine learning for COVID-19 patients at admission (AICOVID).

In Coronavirus disease 2019 (COVID-19), early identification of patients with a high risk of mortality can significantly improve triage, bed allocation, timely management, and possibly, outcome. The study objective is to develop and validate individualized mortality risk scores based on the anonymized clinical and laboratory data at admission and determine the probability of Deaths at 7 and 28 days. Data of 1393 admitted patients (Expired-8.54%) was collected from six Apollo Hospital centers (from April to July 2020) using a standardized template and electronic medical records. 63 Clinical and Laboratory parameters were studied based on the patient's initial clinical state at admission and laboratory parameters within the first 24 h. The Machine Learning (ML) modelling was performed using eXtreme Gradient Boosting (XGB) Algorithm. 'Time to event' using Cox Proportional Hazard Model was used and combined with XGB Algorithm. The prospective validation cohort was selected of 977 patients (Expired-8.3%) from six centers from July to October 2020. The Clinical API for the Algorithm is  http://20.44.39.47/covid19v2/page1.php being used prospectively. Out of the 63 clinical and laboratory parameters, Age [adjusted hazard ratio (HR) 2.31; 95% CI 1.52-3.53], Male Gender (HR 1.72, 95% CI 1.06-2.85), Respiratory Distress (HR 1.79, 95% CI 1.32-2.53), Diabetes Mellitus (HR 1.21, 95% CI 0.83-1.77), Chronic Kidney Disease (HR 3.04, 95% CI 1.72-5.38), Coronary Artery Disease (HR 1.56, 95% CI - 0.91 to 2.69), respiratory rate > 24/min (HR 1.54, 95% CI 1.03-2.3), oxygen saturation below 90% (HR 2.84, 95% CI 1.87-4.3), Lymphocyte% in DLC (HR 1.99, 95% CI 1.23-2.32), INR (HR 1.71, 95% CI 1.31-2.13), LDH (HR 4.02, 95% CI 2.66-6.07) and Ferritin (HR 2.48, 95% CI 1.32-4.74) were found to be significant. The performance parameters of the current model is at AUC ROC Score of 0.8685 and Accuracy Score of 96.89. The validation cohort had the AUC of 0.782 and Accuracy of 0.93. The model for Mortality Risk Prediction provides insight into the COVID Clinical and Laboratory Parameters at admission. It is one of the early studies, reflecting on 'time to event' at the admission, accurately predicting patient outcomes.