Ultrastructural Changes in Autopsy Tissues of COVID-19 Patients.

INTRODUCTION: The COVID-19 pandemic resulted in substantial morbidity and mortality across the world. The prognosis was found to be poor in patients with co-morbidities such as diabetes, hypertension, interstitial lung disease, etc. Although biochemical studies were done in patient samples, no study has been reported from the Indian subcontinent about ultrastructural changes in the vital organs of COVID-19 patients. The present study was, therefore, conducted to understand the ultrastructural changes in the lung, liver, and brain of the deceased patients. METHODS: The present study was conducted on samples obtained from reverse transcription-polymerase chain reaction (RT-PCR)-positive patients who were admitted to a tertiary care hospital in Western India. Core needle biopsies were done in eight fatal cases of COVID-19. The samples were taken from the lungs, liver, and brain and subjected to light microscopy, immunohistochemistry (IHC), and transmission electron microscopy (TEM). Clinical details and biochemical findings were also collected.  Results: The study participants included seven males and one female. The presenting complaints included fever, breathlessness, and cough. Light microscopy revealed diffuse alveolar damage in the lungs. Further, a positive expression of SARS-CoV-2 nucleocapsid protein was observed in the pulmonary parenchyma of five patients. Also, the TEM microphotograph showed viral particles of size up to 80nm localized in alveolar epithelial cells. However, no viral particles were found in liver or brain samples. In the liver, macrovesicular steatosis and centrizonal congestion with loss of hepatocytes were observed in light microscopy. CONCLUSION:  This is the first study in the Indian population showing the in-situ presence of viral particles in core biopsies from fatal cases of COVID-19. As evident from the results, histology and ultrastructural changes in the lung correlated with the presence of viral particles. The study revealed a positive correlation between the damage in the lungs and the presence of viral particles.

Comparison of clinical characteristics and outcome in RT-PCR positive and false-negative RT-PCR for COVID-19: A Retrospective analysis.

Cases with SARS-CoV-2 RT-PCR negative pneumonia are an understudied group with uncertainty remaining regarding their treatment approach. We aimed to compare the clinical and radiological characteristics of RT-PCR positive and clinically diagnosed RT-PCR negative COVID-19. This was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age ≥18 years) with suspicion of COVID-19 with SARI (severe acute respiratory infections) who were subjected to RT-PCR testing (nasal/oropharyngeal swab) were included. Based on RTPCR results, patients were categorized and compared for demographic, clinical, and biochemical characteristics and outcomes. Out of 500 patients, 339 (67.8%) found RT-PCR positive. Except for the radiological findings, both groups differ in clinical presentation, disease severity (inflammatory markers), and outcome. RT-PCR-positive patients had raised ferritin, NLR (Neutrophil-Lymphocyte ratio), LDH, and high mortality compared to the swab-negative group. In-hospital mortality was also significantly high in RT-PCR positive group (HR=1.9, 95% CI=1.4-2.5, p=0.001). On multivariate analysis, NLR, ferritin, and d-dimer were the independent predictors of mortality in RT-PCR-positive (p=0.038, 0.054, and 0.023). At the same time, raised TLC (total leukocyte count) and procalcitonin were the risk factors for poor outcomes in RT-PCR-negative patients (p=0.041 and 0.038). We found significantly raised ferritin, NLR, and LDH levels and increased mortality in RT-PCR positive patients compared to RT-PCR negative. Incorporating clinical features, radiological, and biochemical parameters could be prudent while managing the RT-PCR-negative patients.

Use of rotational thromboelastometry to predict the outcome of COVID-19 patients: A retrospective observational study.

Background and Aims: The hypercoagulability occurring in COVID-19 patients is detected only by Rotational thromboelastometry (ROTEM). However, the benefit of performing ROTEM in the management of disease and predicting the outcome of COVID-19 patients is yet to be established. Material and Methods: The data of 23 critically ill and 11 stable COVID-19 adult patients were extracted from the hospital information system admitted between July and August 2020 and patient charts and analyzed retrospectively. The critically ill patients were divided as a survivor and non-survivor groups. The Intrinsic pathway part of ROTEM (INTEM) and Fibrinogen part of ROTEM (FIBTEM) were performed on day 0 for both critically ill and stable patients, and on day 10 for critically ill patients. The statistical package for social science (SPSS) version 26 was used for statistical analysis. Results: The median FIBTEM amplitude at 5 min (A5) and maximum clot firmness (MCF) were elevated in both stable and critically ill patients (24 vs 27 mm, P = 0.46 and 27.5 vs 40 mm, P = 0.011) with a significant difference in FIBTEM MCF. But there was no significant difference between number of survivors and non-survivors with FIBTEM MCF >25 at day 0 and day 10. Conclusion: The Hypercoagulability state as detected by ROTEM parameters at day 0 and day 10 had no association with the outcome (mortality) of critically ill COVID-19 patients. Hence it cannot be used as a prognostic test. The increasing age, comorbidities and D-dimer values were associated with a poor prognosis in COVID-19 patients.

Oxygen Cylinder Fire during the COVID-19 Pandemic.

The coronavirus disease-2019 (COVID-19) pandemic has resulted in the massive utilization of oxygen cylinders during the treatment of patients. This rapid turnover has necessitated their frequent replacements. Infection control measures have encouraged the use of alcohol-based sanitizers. Over-enthusiastic or inappropriate use of these solutions may increase the risk of fire. We report an unfortunate incident of accidental fire arising out from the integration of fuel, a source of ignition, and oxygen. We also discuss the proper practices to minimize such mishaps. How to cite this article: Paliwal B, Kothari N, Purohit A. Oxygen Cylinder Fire during the COVID-19 Pandemic. Indian J Crit Care Med 2022;26(8):974-975.

Emerging mucormycosis posing threat to community: Anesthetist's perspective in a tertiary care center.

Mucormycosis has become an ever-growing threat to human health, particularly after the COVID-19 pandemic. As the number of cases of mucormycosis increased, it put a burden on anesthesiologists. Here we describe the etiopathogenesis, clinical presentation, and anesthesia management of patients suffering from mucormycosis.

Evaluation of Liver Histopathological Findings of Coronavirus Disease 2019 by Minimally Invasive Autopsies.

AIM: The severe acute respiratory syndrome coronavirus 2 outbreak resulted in severe health impact with the loss of many lives across the world. Pulmonary parenchyma suffers the most from the brunt of the infection. However, evidence suggested a systemic involvement during the course of illness. Information on morphological changes of the liver is sparse in the literature. We aimed to evaluate the pathological findings in the liver by minimally invasive autopsies. METHODS: Postmortem core biopsies of the liver obtained from patients who succumbed to coronavirus disease 2019 disease were studied. Demographic findings, comorbidities, and relevant laboratory tests were collected. Detailed histopathological changes were assessed. RESULTS: Liver function tests were available in 40 cases, and it was deranged in 80% cases. A spectrum of histological changes was observed. Macrovesicular steatosis and nonspecific portal inflammation of mild degree were the common morphological changes. Features suggestive of vascular alteration were noted in more than half of the cases. These included increased portal vein branches, irregular luminal dilation, and herniation of portal veins into the periportal hepatocytes. In addition, we observed morphological changes attributed to terminal shock-related changes. CONCLUSION: The present study results highlight that liver parenchyma changes may be related to multiple pathogenic mechanisms. The presence of vascular alteration in portal tracts suggests derangement of hepatic vasculature related to systemic hypercoagulable state induced by the viral infection. It remains to be established if the histological changes are related to direct viral insult or to the systemic response caused by the viral attack.

Clinical features and mortality in COVID-19 SARI versus non COVID-19 SARI cases from Western Rajasthan, India.

BACKGROUND: In March 2020, the Indian Council of Medical Research (ICMR) issued guidelines that all patients presenting with severe acute respiratory infections (SARI) should be investigated for coronavirus disease 2019 (COVID-19). Following the same protocol, in our institute, all patients with SARI were transferred to the COVID-19 suspect intensive care unit (ICU) and investigated for COVID-19. METHODS: This study was planned to examine the demographical, clinical features, and outcomes of the first 500 suspected patients of COVID-19 with SARI admitted in the COVID-19 suspect ICU at a tertiary care center. Between March 7 and July 20, 2020, 500 patients were admitted to the COVID-19 suspect ICU. We analyzed the demographical, clinical features, and outcomes between COVID-19 positive and negative SARI cases. The records of all the patients were reviewed until July 31, 2020. RESULTS: Of the 500 suspected patients admitted to the hospital, 88 patients showed positive results for COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR) of the nasopharyngeal swabs. The mean age in the positive group was higher (55.31 ± 16.16 years) than in the negative group (40.46 ± 17.49 years) (P < 0.001). Forty-seven (53.4%) of these patients in the COVID-19 positive group and 217 (52.7%) from the negative group suffered from previously known comorbidities. The common symptoms included fever, cough, sore throat, and dyspnea. Eighty-five (20.6%) patients died in the COVID-19 negative group, and 30 (34.1%) died in the COVID-19 positive group (P = 0.006). Deaths among the COVID-19 positive group had a significantly higher age than deaths in the COVID-19 negative group (P < 0.001). Among the patients who died with positive COVID-19 status had substantially higher neutrophilia and lymphopenia (P < 0.001). X-ray chest abnormalities were almost three times more likely in COVID-19 deaths (P < 0.001). CONCLUSION: In the present article, 17.6% of SARI were due to COVID-19 infection with significantly higher mortality (34.1%) in COVID-19 positive patients with SARI. Although all patients presenting as SARI have considerable mortality rates, the COVID-19-associated SARI cases thus had an almost one-third risk of mortality.

Mucormycosis: A Case Series of Patients Admitted in Non-COVID-19 Intensive Care Unit of a Tertiary Care Center during the Second Wave.

Rhino-orbital-cerebral mucormycosis is an invasive fungal infection associated with mortality of 25-62%. There has been a surge in the number of cases during this second wave of coronavirus disease-2019 (COVID-19) in India. We report 10 cases of mucormycosis admitted to our adult intensive care unit. After reviewing the patient's information, we found that 60% of patients had received steroids, and most had uncontrolled blood sugar levels. Most patients received treatment with surgical debridement and antifungal, although the mortality rate was as high as 40%. We report two unique cases of renal and gastrointestinal mucormycosis as well. We concluded that poor glycemic control was the primary etiology behind the rise in the number of cases. Our report also stresses the importance of early surgical intervention and suggests further research comparing the efficacy of combination antifungal therapy versus single antifungal (amphotericin B) to help resource-limited settings in these times of drug crisis. How to cite this article: Yadav S, Sharma A, Kothari N, Bhatia PK, Goyal S, Goyal A. Mucormycosis: A Case Series of Patients Admitted in Non-COVID-19 Intensive Care Unit of a Tertiary Care Center during the Second Wave. Indian J Crit Care Med 2021;25(10):1193-1196.

Evaluation of Bone Marrow Findings of COVID-19 by Minimally Invasive Autopsies: A Single Tertiary Care Centre Experience from India.

The 2019 novel coronavirus (2019-nCoV) originated in Wuhan City of China. In India, first confirmed case of coronavirus disease (COVID-19) was reported on January 30, 2020 and India is presently hit by second wave of COVID-19. The aim of the present study was to evaluate bone marrow findings of COVID-19 by minimally invasive autopsies to aid in understanding pathophysiology of the disease. This prospective study was conducted at tertiary care centre of Western Rajasthan. After obtaining approval from Institute's ethics committee and consent from next of kins, minimally invasive autopsies were conducted in 37 COVID-19 deceased patients within an hour after the death. The tissue specimens were processed with standard biosafety measures. Electronic medical records were reviewed retrospectively and patients' clinical details and results of laboratory investigations were noted. In this prospective study, bone marrow biopsies were collected from 37 COVID-19 minimally invasive autopsies. Mean age of these cases was 61.8 years and male: female ratio was 2.36. Comorbidities were observed in 25 (67.5%) of all cases. Histopathological analysis revealed hypercellular, normocellular and hypocellular marrow in 5, 25 and 5 cases respectively (two biopsies were inadequate). There was marked interstitial prominence of histiocytes in 24 (68.5%) cases. Out of these, evidence of haemophagocytosis was observed in 14 (40%) cases, marked increase of haemosiderin laden macrophages in 20 (57.1%) cases. There was prominence of plasma cells in 28 (80%) cases. The present study attempted to fill the gap of dearth of literature from our country in COVID-19 autopsy studies by highlighting bone marrow findings. The data support the evidence of development of secondary haemophagocytic lymphocytosis in COVID-19 cases.

Clinical profile of bloodstream infections in COVID-19 patients: a retrospective cohort study.

BACKGROUND: Bloodstream infections (BSIs) are an emerging cause of significant morbidity and mortality in severe Coronavirus disease 2019 (COVID-19). We aimed to assess the prevalence, clinical profile and outcome of BSIs in critically ill COVID-19 patients. METHODS: This was a single-centre retrospective study conducted at a tertiary care hospital in Western India. All patients (age > 18 years) with reverse-transcription polymerase chain reaction (RT-PCR) confirmed COVID-19 admitted in the intensive care unit (ICU) were included. Hospital electronic records were searched for demographic data, time of bloodstream infection since admission, clinical profile, antimicrobial resistance pattern and clinical outcome of all patients who developed BSIs. RESULTS: Out of 750 patients admitted in COVID ICU, 8.5% developed secondary BSIs. All severe COVID-19 patients who developed BSIs succumbed to illness. A significant proportion of BSIs were Gram-negative pathogens (53/64, 82.8%). Acinetobacter baumannii was the commonest isolate, followed by Klebsiella pneumoniae (32.8% and 21.9%, respectively). Multidrug-resistance organisms (MDRO) were found in 57.8% of the cases. The majority of MDRO belonged to K. pneumoniae and Enterococcus groups. The proportion of Gram-negative bacteria resistant to carbapenems was 47.2% (25/53). On multivariate analysis, raised total leukocyte counts, mechanical ventilation and presence of comorbidities were significantly associated with the incidence of BSIs. CONCLUSION: We found a significant prevalence of Acinetobacter baumannii in COVID-19 associated BSIs. The presence of comorbidities raised leukocyte counts and mechanical ventilation should alarm clinicians for possible BSIs. The timely initiation of empirical antibiotics and rapid de-escalation is vital to improve the outcome. At the same time, strict compliance of infection control practices should be accomplished to reduce the occurrence of MDRO.

Endocrine Dysfunction among Patients with COVID-19: A Single-center Experience from a Tertiary Hospital in India.

OBJECTIVE: COVID-19 has emerged as a multi-system disease with the potential for endocrine dysfunction. We aimed to study the hormonal profile of hospitalized patients with COVID-19 at a tertiary care referral hospital at Jodhpur, India. DESIGN: A hospital-based clinical study of endocrine profile of COVID-19 patients conducted from 15th May to 30th June 2020 after ethical approval. MEASUREMENTS: Fasting blood samples for free thyroxine (T4), free tri-iodothyronine (T3), thyroid stimulating Hormone (TSH), serum prolactin; basal and 1 h post-intramuscular adrenocorticotropic hormone (ACTH) stimulated cortisol, interleukin-6 (IL-6), and high sensitivity C-reactive protein (hsCRP) were collected within 24 h of admission after written informed consent. All hormones and IL-6 were analyzed by chemiluminescent immunoassay. hsCRP was measured by immune-turbidimetric assay. RESULTS: Of 235 patients studied, 14% had severe disease and 5.5% died. Adrenal insufficiency was present in 14%, most of whom had mild disease. A robust adrenal response was observed in those with severe disease. Basal and post-ACTH serum cortisol were significantly increased in severe disease or those who died compared to those who were mild or asymptomatic. Basal and post-ACTH serum cortisol showed a significant positive correlation with hsCRP but not with IL-6. Low T3 and low T4 syndrome were documented in 25% and 5%, respectively. Serum TSH and FT3 levels declined significantly from asymptomatic to severe category. Hyperprolactinemia was found in 21 patients. hsCRP showed a rising trend with disease severity while IL-6 did not. CONCLUSIONS: Endocrine dysfunction in the form of adrenal insufficiency, low T3, and low TSH syndrome and hyperprolactinemia were common COVID-19 hospitalized patients.

Evaluation of Pathological Findings of COVID-19 by Minimally Invasive Autopsies: A Single Tertiary Care Center Experience from India.

Objectives The 2019 novel coronavirus (2019-nCoV) has spread across the globe with more than 6 lakh deaths. Clinical autopsies are important to understand the pathobiology of the disease. Materials and Methods Autopsy techniques have been modified to be minimally invasive autopsies in all COVID-19 positive cases, and tissue biopsies were sampled from lungs, liver, and bone marrow within an hour after death. Detailed histological analysis was performed in the sampled tissues, along with immunohistochemistry. Patients' clinical records were collected. Statistical Analysis Descriptive statistics were used to summarize data. Results Of the 21 cases studied, 76.2% patients were ≥ 60 years of age, 80.9% were males, and 85.7% had co-morbidities. Histopathological analysis revealed diffuse alveolar damage (including exudative and organizing phase) in 88.9% cases. Microthrombi were seen in 44.4% cases. Additional findings include viral cytopathic changes, metaplastic change in the epithelium, intra-alveolar hemorrhage, and pulmonary edema. Liver showed centrizonal congestion with hepatocytic loss, lobular inflammation, steatosis, Kupffer cell hypertrophy, and sinusoidal neutrophilic infiltration, while significant portal infiltrate and cholestasis were absent to minimal. Bone marrow revealed hemophagocytosis in 60% cases. Conclusion Incorporation of minimally invasive autopsies provides an effective method to study the pathological findings in COVID-19 deaths in resource-constrained settings. Presence of pulmonary microthrombi in a significant number of cases supports the vascular events, apart from the characteristic diffuse alveolar damage, as an important pathogenic mechanism for lung injury in COVID-19 infections. Histopathological findings in the liver and bone marrow suggest indirect insult to these organs, related to circulatory and/or hyperinflammatory response to viral infections.

Preparing for a COVID-19 pandemic: Redefining roles of multidisciplinary team in a large tertiary hospital in Rajasthan.

Through this manuscript, we would like to share our experience with building a COVID hospital, allocating duties, planning and managing supplies during COVID-19 pandemic. This manuscript is prepared by the Doctors of various specialties with vast experience involved in actual planning of the infrastructure and resources. This comprehensive manuscript will help teams to prepare and train, stockpile necessary equipment and prepare their staff to deal with current crisis if there is a surge in infected cases.