ReCOVer study: A Cross-sectional Observational Study to Identify the Rehabilitation Need in Post-discharge COVID-19 Survivors (preprint)

IntroductionWith the increasing number of Coronavirus disease-2019 (COVID-19) cases there is simultaneous increase in recovered cases too. There are many post-covid complications where need for rehabilitation intervention is very conspicuous especially pulmonary, neurological complications. Hence data are of utmost importance to find out those rehabilitation needs among post-covid survivors. Methods and analysisReCOVer (Rehabilitation Need in Post-discharge COVID-19 Survivors), a cross-sectional observational study protocol has been planned to find out rehab-need by assessing International Classification of Functioning, Disability and Health (ICF) core data set, COVID-19 Yorkshire Rehab Screen (C19-YRS) tool, The Post-COVID-19 Functional Status (PCFS) scale, barriers to functional independence and rehab services (affordability & availability). Post-discharge (minimum 1 weeks) Covid patients (required hospitalisation) will be included in the study. Study will be conducted through Telerehabilitation facility. Study will conform to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines. Ethics and disseminationStudy received ethical approval from Institute Ethics Committee, All India Institute of Medical Sciences (AIIMS), New Delhi, India. Findings will be disseminated at scientific conferences/meetings, peer-reviewed journals, and to relevant stakeholders including the ministry of health (if required).

Clinical correlation of lung ultrasound profiles in patients with COVID-19 infection (preprint)

BackgroundLung ultrasound is a popular point of care test that correlates well with computed tomography for lung pathologies. While previous studies have shown its ability to detect COVID-19 related lung pathology, we aimed to evaluate the utility of lung ultrasound in the triage and prognostication of COVID-19 patients by determining its ability to predict clinical severity and outcomes. MethodsThis was a prospective, cross-sectional, observational, single centre study done at JPNATC and AIIMS, New Delhi, India. Consenting eligible patients aged 18 years or more were included if hospitalised with microbiologically confirmed COVID-19 and classified as mild, moderate (respiratory rate >24/min OR SpO2<94% on room air) and severe COVID-19 (respiratory rate >30/min OR SpO2<90% on room air) at the time of enrolment. The lungs were systematically assessed with ultrasound after division into 14 zones (4 anteriorly, 4 axillary and 6 posteriorly). Clinical and laboratory parameters including arterial blood gas analysis at the time of evaluation were recorded. Patients were followed till death or discharge. The primary objective was to determine the correlation between clinical severity and lung ultrasound profiles (no. of A, B and C profiles, and the total number of areas involved). Secondary objectives included assessment of the correlation between lung ultrasound profiles and clinical outcomes and development of a statistical model incorporating ultrasound and clinical parameters to allow prediction of COVID-19 related severity and outcomes. FindingsBetween October 1, 2020, and January 31,2021, patients were screened for inclusion and total n=60 patients were evaluated and included in the final analysis. The most common abnormality seen were B lines, seen in at least one zone in n=53 (88.33%) of cases. A median of 9 (IQR: 5-12) zones of the 14 assessed had a B-profile. The total number of abnormal areas (zones with a B or C profile) correlated significantly with the PaO2/FiO2 ratio ({rho}= -0.7232, p<0.0001) and SpO2/FiO2 ratio ({rho}= -0.6866, p<0.0001), and differed significantly between mild and moderate vs severe cases (p=0.0026 mild vs moderate, p<0.0001 mild vs severe, p=0.0175 moderate vs severe). The total number of B lines were predictors of mortality (p=0.0188, OR 1.03, 95% CI 1.003-1.060). Statistical models that incorporated total number of B-lines, CRP and anticoagulation use could predict mortality (p=0.0124, pseudo R2=0.1740) with an AUC= 0.7682 (95% CI=0.6176-0.9188), and the total number of involved areas and LDH levels could distinguish severe disease from mild/moderate disease (p<0.0001, Pseudo R2=0.3822), AUC = 0.8743 (95% CI=0.7752-0.9733). A simplified cut off of [≥]6 involved areas (of the 14 assessed) was 100% sensitive and 52% specific for differentiating severe disease from mild and moderate ones. InterpretationIn patients with COVID-19, increasing involvement of the lungs as assessed by ultrasonography correlates significantly with clinical severity and outcomes. These findings may be utilized in future prospective studies to validate the use of lung ultrasound to triage and prognosticate patients with COVID-19 infection. Author ApprovalAll authors have seen and approved the manuscript Competing interestsThere are no potential competing interests Data availability StatementAll data referred to in the manuscript shall be provided when asked for. DisclaimersThe authors have nothing to disclose Funding statementNo funding source was involved.

Clinical Correlation of Lung Ultrasound Profiles in Patients with COVID-19 Infection (preprint)

Background: Lung ultrasound is a popular point of care test that correlates well with computed tomography for lung pathologies. While previous studies have shown its ability to detect COVID-19 related lung pathology, we aimed to evaluate the utility of lung ultrasound in the triage and prognostication of COVID-19 patients by determining its ability to predict clinical severity and outcomes.Methods: This was a prospective, cross-sectional, observational, single centre study done at JPNATC and AIIMS, New Delhi, India. Consenting eligible patients aged 18 years or more were included if hospitalised with microbiologically confirmed COVID-19 and classified as mild, moderate (respiratory rate >24/min OR SpO2<94% on room air) and severe COVID-19 (respiratory rate >30/min OR SpO2 <90% on room air) at the time of enrolment. The lungs were systematically assessed with ultrasound after division into 14 zones (4 anteriorly, 4 axillary and 6 posteriorly). Clinical and laboratory parameters including arterial blood gas analysis at the time of evaluation were recorded. Patients were followed till death or discharge. The primary objective was to determine the correlation between clinical severity and lung ultrasound profiles (no. of A, B and C profiles, and the total number of areas involved). Secondary objectives included assessment of the correlation between lung ultrasound profiles and clinical outcomes and development of a statistical model incorporating ultrasound and clinical parameters to allow prediction of COVID-19 related severity and outcomes.Findings: Between October 1, 2020, and January 31,2021, patients were screened for inclusion and total n=60 patients were evaluated and included in the final analysis. The most common abnormality seen were B lines, seen in at least one zone in n=53 (88.33%) of cases. A median of 9 (IQR: 5-12) zones of the 14 assessed had a B-profile. The total number of abnormal areas (zones with a B or C profile) correlated significantly with the PaO2/FiO2 ratio (ρ= -0.7232, p<0.0001) and SpO2/FiO2 ratio (ρ= -0.6866, p<0.0001), and differed significantly between mild and moderate vs severe cases (p=0.0026 mild vs moderate, p<0.0001 mild vs severe, p=0.0175 moderate vs severe). The total number of B lines were predictors of mortality (p=0.0188, OR 1.03, 95% CI 1.003-1.060). Statistical models that incorporated total number of B-lines, CRP and anticoagulation use could predict mortality (p=0.0124, pseudo R2=0.1740) with an AUC= 0.7682 (95% CI=0.6176-0.9188), and the total number of involved areas and LDH levels could distinguish severe disease from mild/moderate disease (p<0.0001, Pseudo R2=0.3822), AUC = 0.8743 (95% CI=0.7752-0.9733). A simplified cut off of ≥6 involved areas (of the 14 assessed) was 100% sensitive and 52% specific for differentiating severe disease from mild and moderate ones.Interpretation: In patients with COVID-19, increasing involvement of the lungs as assessed by ultrasonography correlates significantly with clinical severity and outcomes. These findings may be utilized in future prospective studies to validate the use of lung ultrasound to triage and prognosticate patients with COVID-19 infection.Funding Statement: No funding source was involved.Declaration of Interests: The authors have nothing to discloseEthics Approval Statement: The study was reviewed and cleared by the Institute Ethics Committee (IEC).

The Association Between Hypocalcemia and Outcome in COVID-19 Patients: a Retrospective Study (preprint)

Background: Calcium has been shown to have a vital role in the pathophysiology of SARS-CoV and MERS-CoV diseases but less is known about hypocalcemia in COVID-19 patients and its association with the disease severity and the final outcome. Therefore, this study was conducted with an aim to assess the clinical features in the COVID-19 patients having hypocalcemia and to observe its impact on COVID-19 disease severity and final outcome.Method: In this retrospective study, consecutive COVID-19 patients of all age groups were enrolled. Demographical, clinical and laboratory details were collected and analysed. On the basis of albumin-corrected calcium level patients were classified into normocalcemic (n=51) and hypocalcemic (n=110). Death was the primary outcome. Results: The mean age of hypocalcemic were significantly lower (p<0.05). A significantly higher number of normocalcemic patients had severe COVID-19 disease(92.73%, p<0.01), had comorbidities (82.73%, p<0.05) and required ventilator support(39.09%, p<0.01)compared to the hypocalcemic patients. The mortality rate was significantly higher (33.63%, p<0.05) in the hypocalcemic patients when compared with the normocalcemic patients (15.69%). Haemoglobin (p<0.01), hematocrit (p<0.01) and red cell count (p<0.01) were significantly lower with higher levels of absolute neutrophil count (<0.05) and neutrophil to lymphocyte ratio (p<0.01) in the hypocalcemic patients. Albumin-corrected calcium level had a significant positive correlation with haemoglobin level, haematocrit, red cell count, total protein, albumin and albumin to globulin ratio and a significant negative correlation with absolute neutrophil count and neutrophil to lymphocyte ratio.Conclusion: The disease severity, ventilator requirement and mortality were considerably higher in hypocalcemic COVID-19 patients. 

Clinico-pathological features in fatal Covid-19 Infection: A Preliminary Experience of a Tertiary Care Centre in North India using Post-Mortem Minimally Invasive Tissue Biopsies (preprint)

Background: The Covid-19 pandemic began in China in December 2019. India is the second most affected country, as of November 2020 with more than a 8.5million cases. Covid-19 infection primarily involves the lung with the severity of illness varying from influenza-like illness to acute respiratory distress syndrome. Other organs have also found to be variably affected. Studies evaluating the histopathological changes of Covid-19 are critical in providing a better understanding of the disease pathophysiology and guiding treatment. Minimally invasive biopsy techniques (MITS/B) provide an easy and suitable alternative to complete autopsies. In this prospective single-center study we present the histopathological examination of 37 patients who died with complications of Covid-19. Methods: This was an observational study conducted in the Intensive Care Unit of JPN Trauma Centre AIIMS. A total of 37 patients who died of Covid-19 were enrolled in the study. Post-mortem percutaneous biopsies were taken with the help of surface landmarking/ultrasonography guidance from lung, heart, liver, and kidneys; after obtaining ethical consent. The biopsy samples were then stained with haematoxylin and eosin stain. Immunohistochemistry (IHC) was performed using CD61 and CD163 in all lung cores. SARS-CoV-2 virus was detected using IHC with primary antibodies in selected samples. Details regarding demographics, clinical parameters, hospital course, treatment details, and laboratory investigations were also collected for clinical correlation. Results: A total of 37 patients underwent post-mortem minimally invasive tissue sampling. Mean age of the patients was 48.7years and 59.5% of them were males. Respiratory failure was the most common complication seen in 97.3%. Lung histopathology showed acute lung injury and diffuse alveolar damage in 78% of patients. Associated bronchopneumonia was seen in 37.5% of patients and scattered microthrombi were visualized in 21% of patients. Immunostaining with CD61 and CD163 highlighted megakaryocytes and increased macrophages in all samples. Immunopositivity for SARS-CoV-2 was observed in Type II pneumocytes. Acute tubular injury with epithelial vacuolization was seen in 46% of the renal biopsies but none of them showed evidence of microvascular thrombosis. 71% of the liver tissue cores showed evidence of Kupfer cell hyperplasia. 27.5% had evidence of submassive hepatic necrosis and 14% had features of acute on chronic liver failure. All the heart biopsies showed non-specific features such as hypertrophy with nucleomegaly with no evidence of myocardial necrosis in any of the samples. Conclusions The most common finding in this cohort is the diffuse alveolar damage with demonstration of SARS-CoV-2 protein in the acute phase of DAD. Microvascular thrombi were rarely identified in the lung, liver and kidney. Substantial hepatocyte necrosis, hepatocyte degeneration, Kupffer cell hypertrophy, micro, and macrovesicular steatosis unrelated to microvascular thrombi suggests that liver might be a primary target of Covid-19. This study highlights the importance of MITS/B in better understanding the pathological changes associated with Covid-19.

Poor Outcomes in Patients with Cirrhosis and COVID-19 (preprint)

Background and AimThere is a paucity of data on the clinical presentations and outcomes of Coronavirus disease 2019(COVID-19) in patients with underlying liver disease. We aimed to summarize the presentations and outcomes of COVID-19 positive patients and compare with historical controls.MethodsPatients with known chronic liver disease who presented with superimposed COVID- 19(n=28) between 22nd April and 22nd June 2020 were studied. Seventy-eight cirrhotic patients from historical controls were taken as comparison group.ResultsA total of 28 COVID patients- two without cirrhosis, one with compensated cirrhosis, sixteen with acute decompensation (AD), and nine with acute-on-chronic liver failure(ACLF) were included. The etiology of cirrhosis was alcohol(n=9), non-alcoholic fatty liver disease(n=2), viral(n=5), autoimmune hepatitis(n=4), and cryptogenic cirrhosis(n=6). The clinical presentations included complications of cirrhosis in 12(46.2%), respiratory symptoms in 3(11.5%) and combined complications of cirrhosis and respiratory symptoms in 11(42.3%) patients. The median hospital stay was 8(7-12) days. The mortality rate in COVID-19 patients was 42.3%(11/26), as compared to 23.1%(18/78) in the historical controls(p=0.077). All COVID-19 patients with ACLF(9/9) died compared to 53.3%(16/30) in ACLF of historical controls(p=0.015). Mortality rate was higher in COVID patients with compensated cirrhosis and AD as compared to historical controls 2/17(11.8%) vs 2/48(4.2%), though not statistically significant (p=0.278). Requirement of mechanical ventilation independently predicted mortality (hazard ratio, 13.68). Both non-cirrhotic patients presented with respiratory symptoms and recovered uneventfully.ConclusionCOVID-19 is associated with poor outcomes in patients with cirrhosis, with worst survival rates in ACLF. Mechanical ventilation is associated with a poor outcome.