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.

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 Comprehensive Assessment of Self-Reported Post COVID-19 Symptoms Among Beneficiaries of Hospital Employee Scheme at a Tertiary Healthcare Institution in Northern India.

Purpose: With millions of people being affected by COVID-19, people living with post COVID-19 clinical symptoms (PCS) are expected to rise further. The primary aim of the study was to comprehensively assess self-reported PCS and its associated risk factors among beneficiaries of Hospital Employee Scheme of a tertiary healthcare institution in Delhi. Patients and Methods: An online cross-sectional study was conducted using a semi-structured questionnaire developed by employing nominal group technique among individuals aged 18 years and above who were novel SARS-CoV-2 positive from January to April 2021. Participants were telephoned first, before sending the online survey link. Socio-demographic data, information on PCS along with potential risk factors, pre-existing morbidities, vaccination status, severity of acute illness and management were collected between June and July 2021. PCS was presented as relative frequency; Chi-Square test and odds ratio; adjusted values were used to rule out any association between PCS and predictors. Results: In total, 773 of 1801 eligible participants responded to the survey (completion rate 42.9%), with a median age of 34 years (IQR 27-44). Males accounted for 56.4% and PCS was present in 33.2%. The most prevalent symptoms were fatigue (79.3%), arthralgia (33.4%), myalgia (29.9%), hair loss (28.0%), headache (27.2%), breathlessness (25.3%), and sleep disturbance (25.3%). The prevalence of PCS was reduced to 12.8% at 12 weeks. Female gender, older age, oxygen supplementation, severity of acute illness, and pre-existing co-morbidities were positively associated with PCS. Vaccination (second dose) reduced the odds of developing PCS by 39% compared to unvaccinated participants (aOR 0.61; 95% CI 0.40-0.96). Conclusion: PCS affects almost all organ systems of the body, regardless of the severity of acute COVID-19 illness. Two doses of vaccine hel reduce the development of PCS.

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.

Effectiveness of an inactivated virus-based SARS-CoV-2 vaccine, BBV152, in India: a test-negative, case-control study.

BACKGROUND: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection. METHODS: We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%. FINDINGS: Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61). INTERPRETATION: This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

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.

Low-dose radiation therapy for COVID-19 pneumonia: a pilot study.

OBJECTIVES: The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. METHODS: From June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of ≥5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. RESULTS: All patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3 to 7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. CONCLUSION: The results of our pilot study suggest that LDRT is feasible in COVID-19 patients having moderate to severe disease. Its clinical efficacy may be tested by conducting randomized controlled trials. ADVANCES IN KNOWLEDGE: LDRT has shown promising results in COVID-19 pneumonia and should be researched further through randomized controlled trials.

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.

NA.

Efficacy and safety of antivirals for Covid-19: A systematic review and meta-analysis.

Background: Coronavirus disease 2019 (Covid-19) has led to a severe medical, social and economic crisis globally. Use of antivirals has given inconsistent results; thus systematic summaries of available evidence are required for any recommendations for treatment. We conducted a systematic review and meta-analysis on the use of antivirals for Covid-19. Methods: The databases we searched were-Medline, Embase, Cochrane CENTRAL and Medrxiv. Title/abstract screening, full-text screening and data abstraction were carried out in duplicate by two researchers. Pooled effect sizes and 95% confidence intervals (CI) were calculated using the Mantel-Haenszel method of random effects for meta-analysis. Results: Twenty studies were found eligible for inclusion: 6 randomized controlled trials, 9 cohort studies and 5 case series. Moderate-quality evidence suggests a likely clinical benefit from the use of remdesivir in improving the number of recoveries (RR 1.18; 95% CI 1.07-1.31; I2 = 0%) and time to recovery in days (median -3.02; 95% CI -4.98 to -1.07; I2 = 97%). A possibility of lower mortality is suggested by low-quality evidence with remdesivir (RR 0.74; 95% CI 0.40-1.37, I2 = 58%). Moderate-quality evidence suggests no certain benefit of using lopinavir/ritonavir for Covid-19 compared to arbidol, lopinavir/ritonavir combined with arbidol or other medications used as controls. Conclusion: Further evidence from randomized controlled trials is required for all antivirals to treat Covid-19. At present, remdesivir seems more promising than other antivirals.

Convalescent plasma therapy for Covid-19: A systematic review.

Background: Covid-19 has emerged as a pandemic affecting more than 20 million people till date with few, if any, proven therapy. Convalescent plasma (CP) containing antibodies against the virus has been used with some success. We did a systematic review to synthesize the available data on CP therapy for treatment of Covid-19 to study the efficacy and safety outcomes. Methods: Two reviewers searched the published and pre-published literature between 1 January 2019 and 23 June 2020 for studies comparing the use of CP with standard therapy for Covid-19 patients. Data from the selected studies were abstracted and analysed for efficacy and safety outcomes. Critical appraisal of the evidence was done by using the Joanna Briggs Institute tool and the quality of evidence was graded as per GRADE. Results: We found 13 case series and 1 randomized trial that fulfilled our search criteria. Of the 12 case series with a total of 264 patients that reported the efficacy outcomes, 11 studies showed favourable results with survival benefit. The only RCT with 103 patients did not show any mortality benefit but was terminated early prior to complete enrolment. A single large study of 5000 patients reported safety outcomes and showed no major adverse events in patient streated with CP. Conclusion: There is very low-quality evidence to suggest efficacy and safety of CP in patients with Covid-19 infection. Well-designed randomized trials are urgently needed to provide robust data.

Anti-interleukin-6 therapies for Covid-19: A systematic review, critical appraisal and meta-analysis.

Background: . Coronavirus disease 2019 (Covid-19) has emerged as a pandemic by end-January 2020. Of the infected patients, 10%-15% may develop severe or critical illness. So far, no definite treatment is available for Covid-19. Cytokine release syndrome may underlie the pathogenesis of severe and critical disease. Anti-interleukin (IL)-6 therapies are being tried to improve clinical outcomes. Methods: . We did a systematic review to identify the available literature on anti-IL-6 therapies in the treatment of Covid-19 and used the GRADE method to assess the quality of evidence. Results: . Four case series and 10 case reports were identified. On critical assessment, we found that these studies reported some beneficial effect of anti-IL-6 therapy, but all the studies had a high risk of bias. The pooled estimate showed that 42% of patients improved but with a very wide confidence interval (CI) (95% CI 1%-91%) and substantial heterogeneity (I2 = 95%). The overall quality of evidence was graded as 'very low'. Conclusions: . Although promising, anti-IL-6 therapy for Covid-19 needs to be tested in randomized controlled trials to provide robust evidence.