Tuberculosis endemicity and BCG vaccination: Protection against COVID-19.

The coronavirus disease 2019 (COVID-19) has affected different countries in a differential manner. The host susceptibility and host factors are important parameters for this variability. This study aimed to assess the effect of tuberculosis (TB) endemicity and Bacille Calmette-Guerin (BCG) coverage on COVID-19. Available data regarding TB incidence, BCG coverage (as per the World Health Organization), and COVID-19 incidence of 168 countries as of 19th September 2021. Countries were divided into four cohorts based upon annual TB incidence and BCG coverage and COVID-19 incidence and case fatality rates were compared using the Kruskal-Wallis test. Countries with low TB incidence and low BCG coverage had the highest COVID-19 incidence per lac population. However, no significant difference was seen in COVID-19 cases fatality rate. Higher TB incidence and BCG coverage were associated with lesser incidence of COVID-19. This result paves the way for research into pathogenesis and host immune response in COVID-19.

Temporal evolution of diaphragm thickness and diaphragm excursion among subjects hospitalized with COVID-19: A prospective observational study.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has an affinity for the angiotensin-converting enzyme 2 (ACE2) receptors, which are present abundantly on the diaphragm. This study aims to describe temporal changes in diaphragmatic thickness and excursion using ultrasonography in subjects with acute COVID-19. METHODS: This prospective observational study included adults hospitalized with COVID-19 in the past 48 hours. The diaphragm thickness at end-expiration (DTE), diaphragm thickening fraction (DTF), and diaphragm excursion during tidal breathing (DE) and maximal inspiration (DEmax) were measured using ultrasonography daily for 5 days. The changes in DTE, DTF, DE, and Demax from day 1 to day 5 were assessed. RESULTS: This study included 64 adults (62.5% male) with a mean (SD) age of 50.2 (17.5) years. A majority (91%) of the participants had mild or moderate illness. The median (IQR) DTE, DTF (%), DE and Demax on day 1 were 2.2 (1.9, 3.0) mm, 21.5% (14.2, 31.0), 19.2 (16.5, 24.0) mm, and 26.7 (22.0, 30.2) mm, respectively. On day 5, there was a significant reduction in the DTE (p=0.002) with a median (IQR) percentage change of -15.7% (-21.0, 0.0). The DTF significantly increased on day 5 with a median (IQR) percentage change of 25.0% (-19.2, 98.4), p=0.03. There was no significant change in DE and Demax from day 1 to day 5, with a median (IQR) percentage change of 3.6% (-5.2, 15) and 0% (-6.7, 5.9), respectively. CONCLUSIONS: Non-intubated patients with COVID-19 exhibited a temporal decline in diaphragm thickness with increase in thickening fraction over 5 days of hospital admission. Further research is warranted to assess the impact of COVID-19 pneumonia on diaphragmatic function.

Covid-19 presenting as isolated severe thrombocytopenia in an HIV-lymphoma survivor.

Coronavirus disease has myriad manifestations and can present with predominantly extrapulmonary manifestations. We describe a 50-year-old man, a person living with HIV (PLHA), a non-Hodgkin lymphoma survivor, who presented with isolated severe thrombocytopenia. He was found to have immune-mediated thrombocytopenia, and showed excellent response to intravenous immunoglobulins.

The Effectiveness of SARS-CoV-2 Vaccination in Preventing Severe Illness and Death - Real-world Data from a Cohort of Patients Hospitalized with COVID-19.

Background: While long-term studies on the correlates of protection, vaccine effectiveness, and enhanced surveillance are awaited for SARS-CoV-2 vaccine, studies on breakthrough infections help understand the nature and course of this illness among vaccinated individuals and guide in public health preparedness. This study aims to compare the differences in the hospitalization outcomes SARS-CoV-2 infection of fully vaccinated individuals with with those of unvaccinated and partially vaccinated individuals. Materials and Methods: Single institution observational cohort study. This study compared the differences in clinical, biochemical parameters and the hospitalization outcomes of 53 fully vaccinated individuals with those of unvaccinated (1464) and partially vaccinated (231) individuals, among a cohort of 2,080 individuals hospitalized with SARS-CoV-2 infection. Descriptive statistics and propensity-score weighted multivariate logistic regression analysis adjusting for clinical and laboratory parameters were used to compare the differences and to identify factors associated with outcomes. Results: Completing the course of vaccination protected individuals from developing severe COVID-19 as evidenced by lower proportions of those with hypoxia, abnormal levels of inflammatory markers, requiring ventilatory support, and death compared to unvaccinated and partially vaccinated individuals. There were no differences in these outcomes among patients who received either vaccine type approved in India. Conclusions: Efforts should be made to improve the vaccination rates as a timely measure to prepare for the upcoming waves of this highly transmissible pandemic. Vaccination rates of the communities may also guide in the planning of the health needs and appropriate use of medical resources.

A Delphi consensus statement for the management of post-COVID interstitial lung disease.

INTRODUCTION: As millions of people worldwide recover from COVID-19, a substantial proportion continue to have persistent symptoms, pulmonary function abnormalities, and radiological findings suggestive of post-COVID interstitial lung disease (ILD). To date, there is limited scientific evidence on the management of post-COVID ILD, necessitating a consensus-based approach. AREAS COVERED: A panel of experts in pulmonology and thoracic radiology was constituted. Key questions regarding the management of post-COVID ILD were identified. A search was performed on PubMed and EMBASE and updated till 1 March 2022. The relevant literature regarding the epidemiology, pathophysiology, diagnosis and treatment of post-COVID ILD was summarized. Subsequently, suggestions regarding the management of these patients were framed, and a consensus was obtained using the Delphi approach. Those suggestions which were approved by over 80% of the panelists were accepted. The final document was approved by all panel members. EXPERT OPINION: Dedicated facilities should be established for the care of patients with post-COVID ILD. Symptom screening, pulmonary function testing, and thoracic imaging have a role in the diagnosis. The pharmacologic and non-pharmacologic options for the management of post-COVID ILD are discussed. Further research into the pathophysiology and management of post-COVID ILD will improve our understanding of this condition.

Non-coding RNA in idiopathic interstitial pneumonia and Covid-19 pulmonary fibrosis.

Pulmonary fibrosis is the key feature of majority of idiopathic interstitial pneumonias (IIPs) as well as many patients with post-COVID-19. The pathogenesis of pulmonary fibrosis is a complex molecular process that involves myriad of cells, proteins, genes, and regulatory elements. The non-coding RNA mainly miRNA, circRNA, and lncRNA are among the key regulators of many protein coding genes and pathways that are involved in pulmonary fibrosis. Identification and molecular mechanisms, by which these non-coding RNA molecules work, are crucial to understand the molecular basis of the disease. Additionally, elucidation of molecular mechanism could also help in deciphering a potential diagnostic/prognostic marker as well as therapeutic targets for IIPs and post-COVID-19 pulmonary fibrosis. In this review, we have provided the latest findings and discussed the role of these regulatory elements in the pathogenesis of pulmonary fibrosis associated with Idiopathic Interstitial Pneumonia and Covid-19.

Clinical profile and in-hospital outcomes of COVID-19 among adolescents at a tertiary care hospital in India.

Introduction: We aimed to describe the clinical profile and risk factors for severe disease in adolescents hospitalised with coronavirus disease 2019 (COVID-19). Methods: A retrospective analysis of an admitted cohort of COVID-19 patients was performed at a tertiary hospital in North India. Adolescents aged 12-18 years who were hospitalised during the first wave (March-December, 2020) and the second wave (March-June, 2021) were included. Data on the demographic details, clinical presentation, laboratory parameters, disease severity at admission, treatments received, and in-hospital outcomes were retrieved. Results: The study included 197 adolescents with a median [inter-quartile range (IQR)] age of 15 (13-17) years, of whom 117 (59.4%) were male. Among these, 170 (86.3%) were admitted during the first wave. Underlying co-morbidities were present in nine (4.6%) patients. A total of 60 (30.9%) patients were asymptomatic. In the severity grading, 148 (84.6%) had mild, 16 (9.1%) had moderate, and 11 (6.3%) had severe disease. Fever (14.9%) and cough (14.9%) were the most commonly encountered symptoms. The median (IQR) duration of hospital stay was 10 (8-13) days, and six (3.1%) patients died in the hospital. Conclusion: Adolescents admitted with COVID-19 had predominantly asymptomatic or mild disease, and the mortality rate was 3.1%.

Silent Hypoxia in Coronavirus disease-2019: Is it more dangerous? -A retrospective cohort study.

Background: Hypoxia in patients with COVID-19 is one of the strongest predictors of mortality. Silent hypoxia is characterised by the presence of hypoxia without dyspnoea. Silent hypoxia has been shown to affect the outcome in previous studies. Methods: This was a retrospective study of a cohort of patients with SARS-CoV-2 infection who were hypoxic at presentation. Clinical, laboratory and treatment parameters in patients with silent hypoxia and dyspnoeic hypoxia were compared. Multivariate logistic regression models were fitted to identify the factors predicting mortality. Results: Among 2080 patients with COVID-19 admitted to our hospital, 811 patients were hypoxic with SpO2 <94% at the time of presentation. Among them, 174 (21.45%) did not have dyspnoea since the onset of COVID-19 symptoms. Further, 5.2% of patients were completely asymptomatic for COVID-19 and were found to be hypoxic only on pulse oximetry. The case fatality rate in patients with silent hypoxia was 45.4% as compared to 40.03% in dyspnoeic hypoxic patients (P = 0.202). The odds ratio of death was 1.1 (95% CI: 0.41-2.97) in the patients with silent hypoxia after adjusting for baseline characteristics, laboratory parameters, treatment and in-hospital complications, which did not reach statistical significance (P = 0.851). Conclusion: Silent hypoxia may be the only presenting feature of COVID-19. As the case fatality rate is comparable between silent and dyspnoeic hypoxia, it should be recognised early and treated as aggressively. Because home isolation is recommended in patients with COVID-19, it is essential to use pulse oximetry in the home setting to identify these patients.

Impact of various hematological and biochemical parameters on mortality in coronavirus disease 2019 (COVID-19): A single-center study from North India.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), which causes coronavirus disease 2019 (COVID-19), has rapidly evolved into a pandemic, affecting more than 90 million people and more than 1.9 million deaths worldwide. Despite extensive study, the prognostic role of various hematological and biochemical parameters remains unclear. Methods: This study was carried out at a COVID care facility in Delhi. The demographic and clinical information, laboratory parameters (hematological, biochemical, and inflammatory), and the treatment of admitted COVID-19 patients during first wave were collected from electronic medical records and were subsequently analyzed. Results: Between March 2020 and November 2020, a total of 5574 patients were admitted to hospital due to COVID-19. Majority (77.2%) were male and had a mean (standard deviation [SD]) age of 38.9 (14.9) years. The mean (SD) duration of hospital stay was significantly higher in nonsurvivors. Out of the entire cohort, 8.7% of the patients had comorbidities, whereas 47.1% of the patients were asymptomatic at presentation. Compared to the survivors, the nonsurvivors had a significantly higher proportion of comorbidities and were more likely to be symptomatic. Patients who died during hospital stay had significantly higher relative neutrophil percent and neutrophil-lymphocyte ratio and lower lymphocyte percent. The patients who died had significantly higher levels of ferritin, D-dimer, and fibrinogen. Conclusions: Analysis of various hematological and inflammatory parameters can provide useful prognostic information among COVID-19-affected patients. It can also help in identifying patients who merit aggressive institutional care and thereby potentially mitigate the mortality.

Non-Coding RNA in Idiopathic Interstitial Pneumonia and Covid-19 Pulmonary Fibrosis (preprint)

Pulmonary fibrosis is the major manifestation of idiopathic interstitial pneumonia as well as post-COVID-19 complications. The pathogenesis of PF is a complex molecular process that involves many types of cells, proteins, genes, and regulatory elements. The non-coding RNA is the main regulatory element in this process which mainly includes;miRNA, circRNA, and lncRNA. These regulatory elements control the expression of many important genes and various pathways that are involved in the pathogenesis of pulmonary fibrosis. Identification and molecular mechanisms by which these non-coding RNA molecules works are very important because they do not only help to understand the molecular basis of the disease but could also serve as a potential diagnostic/prognostic marker as well as therapeutic targets. In this review, we have provided the latest findings and discussed the role of these regulatory elements in various biological processes and pathways involved in the pathogenesis of pulmonary fibrosis associated with IIPs and Covid-19.

Tocilizumab for COVID-19: A systematic review and meta-analysis of randomized controlled trials.

The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I2 value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.

Clinical features, demography, and predictors of outcomes of SARS-CoV-2 infection at a tertiary care hospital in India: A cohort study.

BACKGROUND: The "second wave" of the COVID-19 pandemic hit India from early April 2021 to June 2021. We describe the clinical features, treatment trends, and baseline laboratory parameters of a cohort of patients with SARS-CoV-2 infection and their association with the outcome. METHODS: This was a retrospective cohort study. Multivariate logistic regression models were fitted to identify clinical and biochemical predictors of developing hypoxia, deterioration during the hospital stay, and death. RESULTS: A total of 2080 patients were included. The case fatality rate was 19.5%. Among the survivors, the median duration of hospital stay was 8 (5-11) days. Out of 853 (42.3%%) of patients who had COVID-19 acute respiratory distress syndrome at presentation, 340 (39.9%) died. Patients aged >45 years had higher odds of death as compared to the 18-44 years age group. Vaccination reduced the odds of death by 40% (odds ratio [OR] [95% confidence interval [CI]]: 0.6 [0.4-0.9], P = 0.032). Patients with hyper inflammation at baseline as suggested by leukocytosis (OR [95% CI]: 2.1 [1.5-3.1], P < 0.001), raised d-dimer >500 mg/dL (OR [95% CI]: 3.2 [2.2-4.7], P < 0.001), and raised C-reactive peptide >0.5 mg/L (OR [95% CI]: 3.7 [2.2-13], P = 0.037) had higher odds of death. Patients who were admitted in the 2nd week had lower odds and those admitted in the 3rd week had higher odds of death. CONCLUSION: This study shows that vaccination status and early admission during the inflammatory phase can change the course of illness of these patients. Improving vaccination rates and early admission of patients with moderate and severe COVID-19 can improve the outcomes.

Impact of Latent Tuberculosis on Severity and Outcomes in Admitted COVID-19 Patients.

Background There is limited data on coronavirus disease 2019 (COVID-19) and latent tuberculosis infection (LTBI). Methodology We analyzed data of admitted COVID-19 patients evaluated for LTBI to examine the impact of LTBI on severity, laboratory parameters, and COVID-19 outcome. Prospectively collected data were analyzed for 60 patients who were administered the Mantoux tuberculosis skin test (TST) using five tuberculin units of purified protein derivative. All patients were administered TST irrespective of Bacille Calmette-Guérin (BCG) vaccination status. Comorbidities, clinical features, radiologic involvement, laboratory parameters, and clinical course were analyzed concerning LTBI. Results The mean age was 45.9 (±15.2) years, and 35 (58.3%) patients had non-severe disease. The vast majority (n = 56/60; 93.3%) had been vaccinated with single-dose BCG in infancy or early childhood, as per national immunization guidelines. LTBI was diagnosed in 15 (25%) patients. LTBI prevalence was lower in severe (n = 1/25; 4%) than non-severe (n = 14/35; 40%) COVID-19 (p = 0.01) patients. LTBI patients had lower percentage neutrophil count, higher lymphocyte percentage, higher monocyte count, lower neutrophil-lymphocyte (NL) ratio, lower alanine aminotransferase, lower C-reactive protein, and lesser radiologic involvement compared to those without LTBI (p < 0.05). Similarly, among the mild COVID-19 subgroup, those with LTBI had higher lymphocyte and monocyte counts and lesser radiologic involvement than those without LTBI (p < 0.05). Conclusions LTBI patients appear to have milder disease, higher lymphocyte and monocyte count, higher NL ratio, and lesser radiographic involvement. This observation needs to be studied in larger studies using interferon release assays.

Single-dose oral ivermectin in mild and moderate COVID-19 (RIVET-COV): A single-centre randomized, placebo-controlled trial.

INTRODUCTION: Ivermectin is an antiparasitic drug which has in-vitro efficacy in reducing severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) viral load. Hence, Ivermectin is under investigation as a repurposed agent for treating COVID-19. METHODS: In this pilot, double blind, randomized controlled trial, hospitalized patients with mild-to-moderate COVID-19 were assigned to a single oral administration of an elixir formulation of Ivermectin at either 24 mg or 12 mg dose, or placebo in a 1:1:1 ratio. The co-primary outcomes were conversion of RT-PCR to negative result and the decline of viral load at day 5 of enrolment. Safety outcomes included total and serious adverse events. The primary outcomes were assessed in patients who had positive RT-PCR at enrolment (modified intention-to-treat population). Safety outcomes were assessed in all patients who received the intervention (intention-to-treat population). RESULTS: Among the 157 patients randomized, 125 were included in modified intention-to-treat analysis. 40 patients each were assigned to Ivermectin 24 mg and 12 mg, and 45 patients to placebo. The RT-PCR negativity at day 5 was higher in the two Ivermectin arms but failed to attain statistical significance (Ivermectin 24 mg, 47.5%; 12 mg arm, 35.0%; and placebo arm, 31.1%; p-value = 0.30). The decline of viral load at day 5 was similar in each arm. No serious adverse events occurred. CONCLUSIONS: In patients with mild and moderate COVID-19, a single oral administration of Ivermectin did not significantly increase either the negativity of RT-PCR or decline in viral load at day 5 of enrolment compared with placebo.

Candidate immunomodulators for COVID-19: Heat-killed Mycobacterium w and BCG vaccine.

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