Post COVID-19 sequelae: A prospective observational study from Northern India (preprint)

Background: Long COVID, or post-COVID-19 sequelae, is being seen in a growing number of patients reporting a constellation of symptoms, both pulmonary and extrapulmonary. Studies on COVID-19 recovered patients are scarce. Thus, there is a need to add granularity to our existing knowledge about the course and long-term effects of the infection. Aim: To describe the clinical details and risk factors of post-COVID sequelae in the North Indian population. Method: This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 to February 2021. Patients aged >18 years with a confirmed COVID-19 disease were recruited after at least two weeks of diagnosis and interviewed for any post-COVID-19 symptoms. Results: Of 1234 patients recruited, who were followed up for a median duration of 91 days (IQR: 45-181 days), 495 (40.11%) patients had symptoms. In 223 (18.1%) patients, the symptoms resolved within four weeks, 150 (12.1%) patients had symptoms till twelve weeks, and 122 (9.9%) patients had symptoms beyond twelve weeks of diagnosis of COVID-19. Most common long COVID-19 symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), disturbed sleep (1.4%), mood disturbances (0.48%) and anxiety (0.6%). The major determinants of developing post-COVID-19 symptoms in the patients were hypothyroidism and the severity of the disease. Conclusion: Most often, patients complain of myalgias, fatigue, dyspnoea, cough and disturbed sleep. Patients who are hypothyroid or have recovered from moderate to severe COVID-19 are at higher risk of developing post-COVID sequelae. Therefore, a multidisciplinary approach is required to diagnose and manage COVID-19 recovered 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.