Th17 overexpression in severe COVID-19: a prospective observational study.

INTRODUCTION: The objective of the study was to determine T-cell subtypes, Natural Killer cell activity and cytokines in COVID-19 patients with mild to moderate disease and compare them between patients who had recovered and those who had progressed to severe disease. METHODS: Peripheral blood samples of COVID-19 patients were collected at the time of hospital admission and after one week. These samples were analysed for interleukins (IL-6, IL-17a) using chemiluminescence ELISA. The T-cell subsets (T naïve, T regulatory, Th17, Th1, Th2, CD8+ T cells] were studied using flow cytometry. Mild, moderate and severe COVID-19 are defined as per CDC guidelines. RESULTS: Nineteen COVID-19-positive patients were enrolled between June 2020 to December 2021. Nine had mild COVID-19 and 10 had moderate COVID-19 at recruitment. All mild cases recovered without progression to severe disease, while five patients from the moderate group progressed to severe disease. Overall, there is a decrease in lymphocyte count in patients with moderate-severe disease, but the ratio of Th17 [5.91 (2.69-12.01)] was higher compared to Th1 [1.12 (0.27-3.13)] and Th2[2.34 (2-3.5)]. The high baseline level of IL-6 observed in patients with moderate disease leads to the proliferation of more Th17 type of CD4+ T-cells(p=0.002) and suppression of Treg cells. A higher Th17 subset leads to neutrophilic inflammation in patients with severe COVID-19. CONCLUSION: Interpretation conclusions: Higher baseline IL-6 leads to depletion of regulatory T-cells, Th1 Th2 CD4 cells. IL-6 leads to the proliferation of Th17 type of CD4+ subsets in moderate COVID-19. Higher Th17 cells in moderate COVID-19 patients lead to the production of IL-17a, which may result in intense neutrophilic inflammatory response and cytokine storm.

A study on the morbid histopathological changes in COVID-19 patients with or without comorbidities using minimally invasive tissue sampling.

COVID-19 causes morbid pathological changes in different organs including lungs, kidneys, liver, and so on, especially in those who succumb. Though clinical outcomes in those with comorbidities are known to be different from those without-not much is known about the differences at the histopathological level. To compare the morbid histopathological changes in COVID-19 patients between those who were immunocompromised (Gr 1), had a malignancy (Gr 2), or had cardiometabolic conditions (hypertension, diabetes, or coronary artery disease) (Gr 3), postmortem tissue sampling (minimally invasive tissue sampling [MITS]) was done from the lungs, kidney, heart, and liver using a biopsy gun within 2 hours of death. Routine (hematoxylin and eosin) and special staining (acid fast bacilli, silver methanamine, periodic acid schiff) was done besides immunohistochemistry. A total of 100 patients underwent MITS and data of 92 patients were included (immunocompromised: 27, malignancy: 18, cardiometabolic conditions: 71). In lung histopathology, capillary congestion was more in those with malignancy, while others like diffuse alveolar damage, microthrombi, pneumocyte hyperplasia, and so on, were equally distributed. In liver histopathology, architectural distortion was significantly different in immunocompromised; while steatosis, portal inflammation, Kupffer cell hypertrophy, and confluent necrosis were equally distributed. There was a trend towards higher acute tubular injury in those with cardiometabolic conditions as compared to the other groups. No significant histopathological difference in the heart was discerned. Certain histopathological features were markedly different in different groups (Gr 1, 2, and 3) of COVID-19 patients with fatal outcomes.

Risk Factors of Severity and Mortality Among COVID-19 Patients: A Prospective Observational Study From a Tertiary Care Center.

Introduction The COVID-19 pandemic has been a major public health threat for the past three years. The RNA virus has been constantly evolving, changing the manifestations and progression of the disease. Some factors which impact the progression to severe COVID-19 or mortality include comorbidities such as diabetes mellitus, hypertension, and obesity. In this study, we followed a cohort of patients to evaluate the risk factors leading to severe manifestations and mortality from COVID-19. Methodology We conducted a prospective observational study of 589 COVID-19 patients to assess the risk factors associated with the severity and mortality of the disease. Results In our cohort, 83.5% were male, with a median age (p25, p75) of 39.71 (30-48) years. The most common comorbidities included diabetes mellitus (7.8%) and hypertension (7.9%). About 41.7% had an asymptomatic disease, and of the symptomatic, 45% were mild, 6% moderate, and 7% severe. The mortality rate was 4.1%. Risk factors for severity included breathlessness (p=0.02), leukocytosis (p=0.02), and deranged renal function (p=0.04). Risk factors for mortality included older age (p=0.04), anemia (p=0.02), and leukocytosis (p=0.02). Conclusions COVID-19 commonly leads to asymptomatic or mild illness. The major factors we found that were associated with severity include breathlessness at presentation, leukocytosis, and deranged renal functions. The factors associated with mortality include older age, anemia, and leukocytosis.

ACE2 protein expression in lung tissues of severe COVID-19 infection.

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity.

Clinical profile of ChAdOx1 nCoV-19- and BBV152-vaccinated individuals among hospitalized COVID-19 patients: a pair-matched study.

Background: COVID-19 infections among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-vaccinated individuals are of clinical concern, especially in those requiring hospitalization. Such real-world data on ChAdOx1 nCoV-19- and BBV152-vaccinated individuals are scarce. Hence, there is an urgent need to understand their clinical profile and outcomes. Methods: A 1:1 pair-matched study was performed among vaccinated and unvaccinated COVID-19 patients admitted between March 2021 and June 2021 at a tertiary care centre in New Delhi, India. The vaccinated group (received at least one dose of ChAdOx1 nCoV-19 or BBV152) was prospectively followed till discharge or death and matched [for age (±10 years), sex, baseline disease severity and comorbidities] with a retrospective group of unvaccinated patients admitted during the study period. Paired analysis was done to look for clinical outcomes between the two groups. Results: The study included a total of 210 patients, with 105 in each of the vaccinated and unvaccinated groups. In the vaccinated group, 47 (44.8%) and 58 (55.2%) patients had received ChAdOx1 nCoV-19 and BBV152, respectively. However, 73 patients had received one dose and 32 had received two doses of the vaccine. Disease severity was mild in 36.2%, moderate in 31.4% and severe in 32.4%. Two mortalities were reported out of 19 fully vaccinated individuals. All-cause mortality in the vaccinated group was 8.6% (9/105), which was significantly lower than the matched unvaccinated group mortality of 21.9% (23/105), p = 0.007. Vaccination increased the chances of survival (OR = 3.8, 95% CI: 1.42-10.18) compared to the unvaccinated group. Conclusion: In the second wave of the pandemic predominated by delta variant of SARS CoV-2, vaccination reduced all-cause mortality among hospitalized patients, although the results are only preliminary.

Prevalence of Long COVID-19 and its Impact on Quality of Life Among Outpatients With Mild COVID-19 Disease at Tertiary Care Center in North India.

Literature is lacking on the spectrum of symptoms of long COVID-19 (defined as symptoms persisting beyond 28 days of diagnosis) and its impact on quality of life. This single-center, cross-sectional study included mild COVID-19 cases as determined by a positive real-time reverse transcription polymerase chain reaction test. Patients were contacted at least 28 days after diagnosis and were interviewed telephonically using semi-structured questionnaires for duration of symptoms, fatigue using Fatigue Severity Scale (FSS) and quality of life using the World Health Organization Quality of Life: Brief Version (WHOQOL-BREF). A total of 251 COVID-19 patients were included; of which 169 (67.3%) were males. The mean age of the patients was 35.8 years (SD = 12.5). The prevalence of long COVID-19 was 28.2% (n = 71, 95% CI: 23.0-34.2). The most common symptoms involved the musculoskeletal system (12.7%), upper respiratory tract (7.6%), and fatigue among 17 (6.8%) patients. Patients with long COVID-19 had significantly higher FSS score and lower WHOQOL-BREF score compared to the patients without long COVID-19 (<28 days).

Outcomes of HFNC Use in COVID-19 Patients in Non-ICU Settings: A Single-center Experience.

How to cite this article: Aggarwal A, Arora U, Mittal A, Aggarwal A, Singh K, Ray A, et al.Outcomes of HFNC Use in COVID-19 Patients inNon-ICU Settings: A Single-center Experience. Indian J Crit Care Med 2022;26(4):528-530.

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.

Efficacy of add-on Ayurveda and Yoga intervention in health care workers of tertiary care hospital during COVID-19: Randomized controlled trial.

BACKGROUND: The present study aimed to evaluate the safety and prophylactic efficacy of add-on Comprehensive Ayurveda and mindfulness-based Yoga (CAY) regimen to standard care among HealthCare Workers (HCWs) against COVID-19. MATERIALS AND METHODS: This prospective single-blind (outcome assessor-blinded) RCT was conducted in tertiary care hospital in Delhi during July 2020-April 2021. HCWs of both sexes were randomized to add-on CAY intervention or control group. The primary outcomes were the incidence of confirmed COVID-19 positive cases and influenza-like illness events (ILI). Secondary outcomes were anxiety (GAD-7), depression (PHQ-9), and quality of life (SF-36) at the end of 12 weeks. RESULTS: Three hundred fifty-six participants (181 in intervention and 175 in the control group) were randomized. With the modified intention to treat approach, we analyzed 309 participants. The mean age for the intervention and control group was 39.3 ± 10.1 and 36.6 ± 10 years, respectively. Incidence of COVID-19 event was higher in control group compared to CAY group (16 of 164 [9.8%] vs. 11 of 145 [7.6%]; P = 0.50). The incidence of ILI events was also higher in the control group as compared to the CAY group (14 of 164 [8.5%] vs 9 of 145 [6.2%]). The health change domain of the SF-36 questionnaire showed statistically significant improvement in the CAY group as compared to the control group (P < 0.01). CONCLUSION: Incidence of COVID-19 and ILI events was lower in the CAY group compared with the contr ol group, though the difference is not statistically significant.

Clinicoepidemiological Features and Mortality Analysis of Deceased Patients with COVID-19 in a Tertiary Care Center.

BACKGROUND AND OBJECTIVE: A large number of studies describing the clinicoepidemiological features of coronavirus disease-2019 (COVID-19) patients are available but very few studies have documented similar features of the deceased. This study was aimed to describe the clinicoepidemiological features and the causes of mortality of COVID-19 deceased patients admitted in a dedicated COVID center in India. METHODOLOGY: This was a retrospective study done in adult deceased patients admitted in COVID ICU from April 4 to July 24, 2020. The clinical features, comorbidities, complications, and causes of mortality in these patients were analyzed. Pediatric deceased were analyzed separately. RESULTS: A total of 654 adult patients were admitted in the ICU during the study period and ICU mortality was 37.7% (247/654). Among the adult deceased, 65.9% were males with a median age of 56 years [interquartile range (IQR), 41.5-65] and 94.74% had one or more comorbidities, most common being hypertension (43.3%), diabetes mellitus (34.8%), and chronic kidney disease (20.6%). The most common presenting features in these deceased were fever (75.7%), cough (68.8%), and shortness of breath (67.6%). The mean initial sequential organ failure assessment score was 9.3 ± 4.7 and 24.2% were already intubated at the time of admission. The median duration of hospital stay was 6 days (IQR, 3-11). The most common cause of death was sepsis with multi-organ failure (55.1%) followed by severe acute respiratory distress syndrome (ARDS) (25.5%). All pediatric deceased had comorbid conditions and the most common cause of death in this group was severe ARDS. CONCLUSION: In this cohort of adult deceased, most were young males with age less than 65 years with one or more comorbidities, hypertension being the most common. Only 5% of the deceased had no comorbidities. Sepsis with multi-organ dysfunction syndrome was the most common cause of death. HOW TO CITE THIS ARTICLE: Aggarwal R, Bhatia R, Kulshrestha K, Soni KD, Viswanath R, Singh AK, et al. Clinicoepidemiological Features and Mortality Analysis of Deceased Patients with COVID-19 in a Tertiary Care Center. Indian J Crit Care Med 2021; 25(6):622-628.

Hydroxychloroquine pre-exposure prophylaxis for COVID-19 among healthcare workers: Initial experience from India.

Background: Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities. Objectives: Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19. Methods: Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3-7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results. Results: Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3-9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (P < 0.001). Odds ratio with HCQ intake was 0.34 (95% CI 0.13-0.83, P = 0.01) and the number needed to treat was 12. Conclusion: HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19.

Risk factors for Coronavirus disease-associated mucormycosis.

BACKGROUND: The epidemiology of the Coronavirus-disease associated mucormycosis (CAM) syndemic is poorly elucidated. We aimed to identify risk factors that may explain the burden of cases and help develop preventive strategies. METHODS: We performed a case-control study comparing cases diagnosed with CAM and taking controls as recovered COVID 19 patients who did not develop mucormycosis. Information on comorbidities, glycemic control, and practices related to COVID-19 prevention and treatment was recorded. Multivariate regression analysis was used to identify independent predictors. RESULTS: A total of 352 patients (152 cases and 200 controls) diagnosed with COVID-19 during April-May 2021 were included. In the CAM group, symptoms of mucormycosis began a mean of 18.9 (SD 9.1) days after onset of COVID-19, and predominantly rhino-sinus and orbital involvement was present. All, but one, CAM cases had conventional risk factors of diabetes and steroid use. On multivariable regression, increased odds of CAM were associated with the presence of diabetes (adjusted OR 3.5, 95% CI 1.1-11), use of systemic steroids (aOR 7.7, 95% CI 2.4-24.7), prolonged use of cloth and surgical masks (vs. no mask, aOR 6.9, 95%CI 1.5-33.1), and repeated nasopharyngeal swab testing during the COVID-19 illness (aOR 1.6, 95% CI 1.2-2.2). Zinc therapy was found to be protective (aOR 0.05, 95%CI 0.01-0.19). Notably, the requirement of oxygen supplementation or hospitalization did not affect the risk of CAM. CONCLUSION: Judicious use of steroids and stringent glycemic control are vital to preventing mucormycosis. Use of clean masks, preference for N95 masks if available, and minimizing swab testing after the diagnosis of COVID-19 may further reduce the incidence of CAM.

Atypical bacterial co-infections among patients with COVID-19: A study from India.

Emerging evidence shows co-infection with atypical bacteria in coronavirus disease 2019 (COVID-19) patients. Respiratory illness caused by atypical bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila may show overlapping manifestations and imaging features with COVID-19 causing clinical and laboratory diagnostic issues. We conducted a prospective study to identify co-infections with SARS-CoV-2 and atypical bacteria in an Indian tertiary hospital. From June 2020 to January 2021, a total of 194 patients with laboratory-confirmed COVID-19 were also tested for atypical bacterial pathogens. For diagnosing M. pneumoniae, a real-time polymerase chain reaction (PCR) assay and serology (IgM ELISA) were performed. C. pneumoniae diagnosis was made based on IgM serology. L. pneumophila diagnosis was based on PCR or urinary antigen testing. Clinical and epidemiological features of SARS-CoV-2 and atypical bacteria-positive and -negative patient groups were compared. Of the 194 patients admitted with COVID-19, 17 (8.8%) were also diagnosed with M. pneumoniae (n = 10) or C. pneumoniae infection (n = 7). Confusion, headache, and bilateral infiltrate were found more frequently in the SARS CoV-2 and atypical bacteria co-infection group. Patients in the M. pneumoniae or C. pneumoniae co-infection group were more likely to develop ARDS, required ventilatory support, had a longer hospital length of stay, and higher fatality rate compared to patients with only SARS-CoV-2. Our report highlights co-infection with bacteria causing atypical pneumonia should be considered in patients with SARS-CoV-2 depending on the clinical context. Timely identification of co-existing pathogens can provide pathogen-targeted treatment and prevent fatal outcomes of patients infected with SARS-CoV-2 during the current pandemic.

Post COVID-19 sequelae: A prospective observational study from Northern India.

Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO2 ≤ 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID.

Role of systemic corticosteroids in preventing hypoxia among patients with mild COVID-19: An observational study.

Use of systemic corticosteroids is well-established in COVID-19 patients with hypoxia; however, there is scant data on its role in patients with mild disease and prolonged symptoms as a measure to prevent disease progression. The aim of this study is to evaluate the role of systemic corticosteroids in preventing hypoxia (SpO2 ≤ 93% on room-air) among mild COVID-19 patients. An observational study was conducted among symptomatic COVID-19 patients taking oral corticosteroids and attending institute teleconsultation facility between 10th-30th June 2021. Patients who were already on corticosteroids for other indication or required oxygen supplementation before or within 24-hours of initiation of corticosteroids were excluded. A total of 140 consecutive symptomatic COVID-19 patients were included. Higher baseline C-reactive protein (OR: 1.03, 95% CI: 1.02-1.06, p < 0.001) and early systemic corticosteroid (within 7 days) initiation (OR: 6.5, 95% CI: 2.1-20.1, p = 0.001) were independent risk factors for developing hypoxia (SpO2 ≤ 93%). Progression to hypoxia was significantly higher in patients who received corticosteroids before day 7 of illness (36.7%, 95% CI, 23.4-51.7%) compared to ≥ 7 of illness (14.3%, 95% CI, 7.8-23.2%) for persistent fever. Systemic corticosteroids within 7 days from symptom-onset were harmful and increased the risk of progression to hypoxia, whereas it may decrease the risk of progression when administered on or beyond 7 days in patients with mild COVID-19 and persistent symptoms. A well-designed randomised controlled trial is required to validate the findings.

Comparison of High-Flow Nasal Cannula and Noninvasive Ventilation in Acute Hypoxemic Respiratory Failure Due to Severe COVID-19 Pneumonia.

BACKGROUND: Efficacy of high-flow nasal cannula (HFNC) over noninvasive ventilation (NIV) in severe coronavirus disease 2019 (COVID-19) pneumonia is not known. We aimed to assess the incidence of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure due to COVID-19 treated with either HFNC or NIV. METHODS: This was a single-center randomized controlled trial performed in the COVID-19 ICU of a tertiary care teaching hospital in New Delhi, India. One hundred and nine subjects with severe COVID-19 pneumonia presenting with acute hypoxemic respiratory failure were recruited and allocated to either HFNC (n = 55) or NIV (n = 54) arm. Primary outcome was intubation by 48 h. Secondary outcomes were improvement in oxygenation by 48 h, intubation rate at day 7, and in-hospital mortality. RESULTS: Baseline characteristics and [Formula: see text]/[Formula: see text] ratio were similar in both the groups. Intubation rate at 48 h was similar between the groups (33% NIV vs 20% HFNC, relative risk 0.6, 95% CI 0.31-1.15, P = .12). Intubation rate at day 7 was lower in the HFNC (27.27%) compared to the NIV group (46.29%) (relative risk 0.59, 95% CI 0.35-0.99, P = .045), and this difference remained significant after adjustment for the incidence of chronic kidney disease and the arterial pH (adjusted OR 0.40, 95% CI 0.17-0.93, P = .03). Hospital mortality was similar between HFNC (29.1%) and NIV (46.2%) group (relative risk 0.6, 95% CI 0.38-1.04, P = .06). CONCLUSIONS: We were not able to demonstrate a statistically significant improvement of oxygenation parameters nor of the intubation rate at 48 h between NIV and HFNC. These findings should be further tested in a larger randomized controlled trial. The study was registered at the Clinical Trials Registry of India (www.ctri.nic.in; reference number: CTRI/2020/07/026835) on July 27, 2020.

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.

Atypical bacterial co-infections among patients with COVID-19: A study from India

Abstract Emerging evidence shows co-infection with atypical bacteria in coronavirus disease 2019 (COVID-19) patients. Respiratory illness caused by atypical bacteria such as Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella pneumophila may show overlapping manifestations and imaging features with COVID-19 causing clinical and laboratory diagnostic issues. We conducted a prospective study to identify co-infections with SARS-CoV-2 and atypical bacteria in an Indian tertiary hospital. From June 2020 to January 2021, a total of 194 patients with laboratory-confirmed COVID-19 were also tested for atypical bacterial pathogens. For diagnosing M. pneumoniae, a real-time polymerase chain reaction (PCR) assay and serology (IgM ELISA) were performed. C. pneumoniae diagnosis was made based on IgM serology. L. pneumophila diagnosis was based on PCR or urinary antigen testing. Clinical and epidemiological features of SARS-CoV-2 and atypical bacteria-positive and -negative patient groups were compared. Of the 194 patients admitted with COVID-19, 17 (8.8%) were also diagnosed with M. pneumoniae (n?=?10) or C. pneumoniae infection (n?=?7). Confusion, headache, and bilateral infiltrate were found more frequently in the SARS CoV-2 and atypical bacteria co-infection group. Patients in the M. pneumoniae or C. pneumoniae co-infection group were more likely to develop ARDS, required ventilatory support, had a longer hospital length of stay, and higher fatality rate compared to patients with only SARS-CoV-2. Our report highlights co-infection with bacteria causing atypical pneumonia should be considered in patients with SARS-CoV-2 depending on the clinical context. Timely identification of co-existing pathogens can provide pathogen-targeted treatment and prevent fatal outcomes of patients infected with SARS-CoV-2 during the current pandemic.

Gargle lavage & saliva: Feasible & cheaper alternatives to nasal & throat swabs for diagnosis of COVID-19.

Background & objectives: In the present scenario, the most common sample for diagnosis of COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) is nasal and throat swab (NTS). Other sampling options such as gargle lavage have found limited application in clinical use mostly because of unavailability of an appropriate gargling liquid. This study was conducted to assess the stability of SARS-CoV-2 RNA in normal saline at 4°C that can serve as a gargling liquid as well as a transport medium. The study also looked at the agreement between NTS and gargle lavage/saliva for the detection of SARS-CoV-2. Methods: In 29 consecutive real-time RT-PCR (rRT-PCR) positive COVID-19 patients, paired NTS, gargle and saliva samples were taken. Samples were processed by rRT-PCR for the detection of SARS-CoV-2 RNA. To assess the SARS-CoV-2 RNA stability in normal saline, gargle lavage specimens were divided into two aliquots; one subset of the specimen was run within 4-6 h along with the routine samples (NTS and saliva) and the other subset was stored at 4°C and processed after 24-30 h. Agreement between cycle threshold (Ct) values from both the runs was compared using Bland-Altman (BA) analysis. Results: The positivity rates of rRT-PCR in NTS, saliva and gargle lavage samples were 82.7 (24/29), 79.3 (23/29) and 86.2 per cent (25/29), respectively. BA plot showed a good agreement between the Ct values of fresh and stored gargle samples, stipulating that there were no significant differences in the approximate viral load levels between the fresh and stored gargle lavage samples (bias: E gene -0.64, N gene -0.51, ORF gene -0.19). Interpretation & conclusions: Our study results show stability of SARS-CoV-2 RNA in the gargle samples collected using normal saline up to 24-30 h. Gargle lavage and saliva specimen collection are cost-effective and acceptable methods of sampling for the detection of SARS-CoV-2 RNA by rRT-PCR. These simplified, inexpensive and acceptable methods of specimen collection would reduce the cost and workload on healthcare workers for sample collection.