Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Sarcoidosis presenting as bilateral optic neuritis after ChAdOx1 nCoV-19 vaccination.

Sarcoidosis is an idiopathic granulomatous disease and can virtually affect any organ system. Multiple factors, including tubercular antigens organic and environmental exposures, have been implicated in its pathogenesis. In addition to drugs, sarcoid-like reactions have been reported following varicella and influenza vaccination. Few reports of erythema nodosum and Lofgren syndrome have been reported after the COVID19 vaccination, though no histologic diagnosis was pursued in these cases. We herein report a case of sarcoidosis presenting with bilateral acute onset vision loss with a temporal association with COVID19 vaccination (ChadOx-1 n-COV, COVISHIELDTM). Symptoms started within two weeks of receiving the vaccine. Alternate causes for optic neuritis were excluded. Transbronchial lung biopsy showed the presence of non-caseating epithelioid cell granulomas. The patient received high-dose corticosteroids immediately after diagnosis, albeit with incomplete clinical improvement in vision on a three-month follow-up. In conclusion, we report a novel case of sarcoidosis-related optic neuritis following COVID19 vaccination.

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.

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.

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%.

Statin and aspirin as adjuvant therapy in hospitalised patients with SARS-CoV-2 infection: a randomised clinical trial (RESIST trial).

BACKGROUND: Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There is a need for a randomised controlled trial. METHODS: In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement ≥ 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. RESULTS: The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit [Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46]. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. CONCLUSIONS: Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration. Trial Registry Number CTRI/2020/07/026791 ( http://ctri.nic.in ; registered on 25/07/2020).

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.

Pneumothorax and pneumomediastinum in patients with COVID-19: A retrospective study from tertiary care institute in India.

COVID-19 is associated with rarer extra-parenchymal manifestations, namely pneumothorax (PTX) and pneumomediastinum (PM) leading to complications and increased mortality. The study aims to describe the prevalence, risk factors for mortality, radiological characteristics and outcome of PTX/PM in patients admitted with COVID-19. This was a retrospective, single-centre, observational study in patients with confirmed COVID-19 presenting with non-iatrogenic PTX/PM from April 2020 to May 2021. Details pertaining to demographics, presentation, radiological characteristics, management and outcome were collected. Cases were classified into spontaneous and barotraumatic PTX/PM and a between-group comparison was performed using Chi-square and t-test. A total of 45 cases (mean age: 53.2 years, 82% males) out of 8,294 confirmed COVID-19 patients developed PTX/PM, the calculated incidence being 0.54%. 29 cases had spontaneous PTX/PM and the remaining 17 cases were attributed to barotrauma. The most common comorbidities were diabetes-mellitus (65.3%) and hypertension (42.3%). The majority of the cases had large PTX (62.1%) with tension in 8 cases (27.5%). There were predominant right-sided pneumothoraces and five were diagnosed with bronchopleural fistula. 37.7% of cases had associated subcutaneous emphysema. The median duration of PTX/PM from symptom onset was delayed at 22.5 and 17.6 days respectively. The mean CT severity score (CTSS) was 20.5 (± 4.9) with fibrosis (53.8%), bronchiectatic changes (50%) and cystic-cavitary changes (23%). There was no statistically significant difference between the spontaneous and barotrauma cohort. 71% of cases died and the majority belonged to the barotrauma cohort. It is imperative to consider the possibility of PTX/PM in patients having COVID-19, especially in those with deterioration in the disease course, both in spontaneously breathing and mechanically ventilated patients. These patients may also have a high incidence of death, reflecting the gravity of COVID-19.

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.

Detection of SARS-CoV2 virus using the real-time reverse transcriptase polymerase chain reaction in semen and seminal plasma from men with active COVID-19 infection - A pilot study.

INTRODUCTION: SARS-CoV-2 has been detected in various body fluids. Its presence in semen has been tested with contradictory results. This study aimed to detect the presence of SARS-CoV-2 virus using the real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) in semen and seminal plasma from men with active COVID-19 infection. METHODS: In a cross-sectional study at a COVID facility, men aged 20-45 years with active COVID-19 infection provided semen samples within 7 days of symptom onset or 5 days of nasopharyngeal rRT-PCR test positivity in asymptomatic men. Testing of SARS-CoV-2 was performed using rRT-PCR and semen analysis was done for sperm counts and motility as per the WHO (2010) standards. RESULTS: A total of 37 men with a mean age of 32.2 ± 5.6 years were tested. SARS CoV-2 virus could not be isolated in any of the samples. Further, microscopic analysis done on 17 samples showed normal semen parameters during the active phase of disease. CONCLUSION: Men with mild COVID-19 disease or asymptomatic individuals do not shed virus in their semen, ruling out sexual contact as a mode of transmission in this subset of population.

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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Clinical Profile and Risk Factors for Severe Disease in 402 Children Hospitalized with SARS-CoV-2 from India: Collaborative Indian Pediatric COVID Study Group.

INTRODUCTION: There is a lack of large multicentric studies in children with COVID-19 from developing countries. We aimed to describe the clinical profile and risk factors for severe disease in children hospitalized with COVID-19 from India. METHODS: In this multicentric retrospective study, we retrieved data related to demographic details, clinical features, including the severity of disease, laboratory investigations and outcome. RESULTS: We included 402 children with a median (IQR) age of 7 (2-11) years. Fever was the most common symptom, present in 38.2% of children. About 44% had underlying comorbidity. The majority were asymptomatic (144, 35.8%) or mildly symptomatic (219, 54.5%). There were 39 (9.7%) moderate-severe cases and 13 (3.2%) deaths. The laboratory abnormalities included lymphopenia 25.4%, thrombocytopenia 22.1%, transaminitis 26.4%, low total serum protein 34.7%, low serum albumin 37.9% and low alkaline phosphatase 40%. Out of those who were tested, raised inflammatory markers were ferritin 58.9% (56/95), c-reactive protein 33.3% (41/123), procalcitonin 53.5% (46/86) and interleukin-6 (IL-6) 76%. The presence of fever, rash, vomiting, underlying comorbidity, increased total leucocyte count, thrombocytopenia, high urea, low total serum protein and raised c-reactive protein was factors associated with moderate to severe disease. CONCLUSION: Fever was the commonest symptom. We identified additional laboratory abnormalities, namely lymphopenia, low total serum protein and albumin and low alkaline phosphatase. The majority of the children were asymptomatic or mildly symptomatic. We found high urea and low total serum protein as risk factors for moderate to severe disease for the first time.

Acute hypoxemia due to lung collapse in COVID-19: the role of therapeutic bronchoscopy.

Bronchoscopy is an aerosol-generating procedure and involves a high risk of transmission of SARS-CoV-2 to health care workers. There are very few indications for performing bronchoscopy in a patient with confirmed COVID-19. These include atelectasis, foreign body aspiration, and suspected superinfection in immunocompromised patients. Proper use of standard personal protective equipment is mandatory to reduce the risk of transmission to health care workers. In this article, we describe a case of acute lung collapse in a 16-year-old boy with cerebral palsy who was infected with COVID-19. This patient responded to therapeutic bronchoscopy and had complete resolution of lung collapse within 24 hours of the procedure.

Effect of proning in patients with COVID-19 acute hypoxemic respiratory failure receiving noninvasive oxygen therapy.

BACKGROUND: Novel coronavirus (SARS-CoV-2) infection is associated with hypoxemic respiratory failure. Mechanical ventilation (MV) is reported to have high mortality in SARS-CoV-2 acute respiratory distress syndrome. We aimed to investigate whether awake prone positioning (PP) can improve oxygenation and prevent intubation when employed early. METHODS: This prospective interventional study included proven coronavirus disease 2019 (COVID-19) patients with room air saturation 93% or less. The primary outcome was the rate of intubation between the two groups. The secondary outcomes included ROX index (SpO2/FiO2%/respiratory rate, breaths/min) at 30 min following the intervention, ROX index at 12 h, time to recovery of hypoxemia, and mortality. RESULTS: A total of 45 subjects were included (30 cases and 15 controls) with a mean (standard deviation [SD]) age of 53.1 (11.0) years. The age, comorbidities, and baseline ROX index were similar between the two groups. The median duration of PP achieved was 7.5 h on the 1st day. The need for MV was higher in the control group (5/15; 33.3%) versus prone group (2/30; 6.7%). At 30 min, there was a statistically significant improvement in the mean (SD) ROX index of cases compared with that of the controls (10.7 [3.8] vs. 6.7 [2.6], P < 0.001). No significant adverse effects related to intervention were noted. CONCLUSION: Awake PP is associated with significant improvement in oxygenation and may reduce the need for MV in subjects with COVID-19.