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.

Safe Practice of Flexible Bronchoscopy for Non-COVID-19 Indications during the SARS-CoV-2 Pandemic.

Background: Flexible bronchoscopy is an aerosol-generating procedure (AGP), which increases the risk of transmission of SARS-CoV-2 infection. We aimed to find COVID-19 symptoms among healthcare workers (HCWs) involved in flexible bronchoscopies for non-COVID-19 indications during the SARS-CoV-2 pandemic. Materials and Methods: The participants of this hospital-based single-center descriptive study were HCWs of our hospital involved in flexible bronchoscopies of patients with non-COVID-19 indications. These patients had no clinical features of COVID-19 and were tested negative for SARS-CoV-2 by the real-time polymerase chain reaction of nasopharyngeal and throat swabs before the procedure. The study outcome was the occurrence of COVID-19 in study participants after exposure to bronchoscopies. Results: Thirteen HCWs performed 81 bronchoscopies on 62 patients. Indications for bronchoscopies included malignancy (61.30%), suspected infections (19.35%), non-resolving pneumonia (6.45%), mucus plug removal (6.45%), central airway obstruction (4.84%), and hemoptysis (1.61%). The mean age of patients was 50.44 ± 15.00 years, and the majority was males (72.58%). Bronchoscopic procedures included 51 bronchoalveolar lavages, 32 endobronchial ultrasound- transbronchial needle aspiration (EBUS-TBNA), 26 endobronchial biopsies, 10 transbronchial lung biopsy (TBLB), 3 mucus plug removals, 2 conventional TBNA, and 2 radial EBUS-TBLB. Except for two HCWs who complained of transient throat irritation of non-infectious cause, none of the cases developed any clinical features suggestive of COVID-19. Conclusion: A dedicated bronchoscopy protocol helps in minimizing the risk of transmission of SARS-CoV-2 infection among HCWs involved in flexible bronchoscopies for non-COVID-19 indications during the SARS-CoV-2 pandemic.

Comparative Analysis of Serum Zinc, Copper and Magnesium Level and Their Relations in Association with Severity and Mortality in SARS-CoV-2 Patients.

The deficiencies of trace elements and infectious diseases often coexist and exhibit complex interactions. Several trace elements such as zinc (Zn), copper (Cu) and magnesium (Mg) have immunomodulatory functions and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of trace metals in association with severity and mortality in SARS-CoV-2 patients. A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate and severe) and outcome (discharged or deceased). Serum Zn, Mg and Cu levels were analysed by direct colourimetric method. Both serum Cu and Zn levels were significantly decreased in cases when compared to those in controls (p < 0.005 and p < 0.0001). Serum magnesium levels although not significant were found to be slightly decreased in controls. On comparing the trace elements between the deceased and discharged cases, a significant difference was found between serum copper and zinc levels, but for magnesium, both groups have similar levels. The receiver operating characteristic (ROC) curve results indicate that a serum Cu/Zn ratio along with the age of patient provides some reliable information on COVID-19 course and survival odds by yielding an AUC of 95.1% with a sensitivity of 93.8% and specificity of 89.8%. Therefore, we would like to emphasize that measuring the serum copper and zinc along with their ratio can be used as routine investigations for COVID-19 patients in proper identification and management of severe cases in upcoming new waves of COVID-19.

Predictors of mortality among hospitalized patients with COVID-19: A single-centre retrospective analysis.

Background: The severity of disease and mortality due to coronavirus disease (COVID-19) was found to be high among patients with concurrent medical illnesses. Serum biomarkers can be used to predict the course of COVID-19 pneumonia. Data from India are very scarce about predictors of mortality among COVID-19 patients. Methodology: In the present retrospective study of 65 RT-PCR confirmed COVID-19 patients, we retrieved data regarding clinical symptoms, laboratory parameters, and radiological grading of severity. Further, we also collected data about their hospital course, duration of stay, treatment, and outcome. Data analysis was done to compare the patient characteristics between survivor and non-survivor groups and to assess the predictors of mortality. Results: The mean age of the study population was 56.23 years (SD, 12.91) and most of them were males (63%); 81.5% of patients survived and were discharged, whereas 18.5% of patients succumbed to the disease. Univariate analysis across both groups showed that older age, diabetes mellitus, higher computed tomogram (CT) severity score, and raised levels of laboratory parameters viz, D-dimer, CPK-MB (creatine kinase), and lactate dehydrogenase (LDH) were associated with increased mortality among hospitalized patients. On multivariate analysis, elevated levels of serum D-dimer (odds ratio, 95% CI: 10.98, 1.13-106.62, p = 0.04) and LDH (odds ratio, 95% CI: 19.15, 3.28-111.87, p = 0.001) were independently associated with mortality. Conclusion: Older patients, diabetics, and patients with high CT severity scores at admission are at increased risk of death from COVID-19. Serum biomarkers such as D-dimer and LDH help in predicting mortality in COVID-19 patients.

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.

Pulmonary embolism and gastric bleed with disseminated mucormycosis - treading dangerous waters.

Mucormycosis is an opportunistic infection seen in immunocompromised patients or in surgical and trauma settings with Mucorales wound contamination. In immunocompetent people, disseminated mucormycosis is uncommon. To ensure survival, patients with mucormycosis require early diagnosis and aggressive treatment using a multi-modality approach. We present a case of disseminated mucormycosis in an immunocompetent patient who also had pulmonary embolism and gastrointestinal bleeding. A recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, identified retrospectively by a positive IgM against SARS-CoV-2, was the only risk factor present. This report emphasizes the increased risk of mucormycosis and thromboembolic complications following a recent SARS-CoV-2 infection, as well as its successful treatment with medical therapy alone.

Co-infections in Hospitalized COVID-19 Patients- A Prospective Observational Study.

INTRODUCTION: SARS -CoV-2 was first reported in Wuhan and declared a pandemic in March 2020. Co-infections during other pandemics have been associated with severe outcomes, but data are scarce regarding co-infections in COVID-19 patients. Our study evaluated co-infections prevalence and its impact on morbidity and mortality in hospitalized COVID -19 patients. METHODS: This prospective observational study included 100 patients admitted to a high-dependency unit at a tertiary care hospital in India. Prevalence of co-infections and clinical outcome-related data were analyzed in COVID-19 patients satisfying the inclusion criteria. RESULTS: 14% of patients had co-infections, out of which urinary tract infection was found in 9%. Patients with co-infections had a higher mortality rate (p<0.0004). Urinary co-infection emerged as an independent risk factor for mortality (p <0.001). CONCLUSION: Co-infections associated with COVID-19 infections are an essential risk factor for morbidity and mortality. Early identification and timely treatment of co-infections may help in improving clinical outcomes.

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.

Association of iron-related biomarkers with severity and mortality in COVID-19 patients.

BACKGROUND: Nutritional deficiency is associated with weaken immune system and increased susceptibility to infection. Among other nutrients, several trace elements have been shown to regulate immune responses. Iron is one of the most abundant trace elements present in our body, which is required in various biological processes. Iron has an immunomodulatory function and thus influence the susceptibility to the course and outcome of a variety of viral infections. So, this present study was aimed to study relations of different iron-related biomarkers in association to severity and mortality in SARS-CoV-2 patients. MATERIALS AND METHODS: A total of 150 individuals infected with COVID-19 and 50 healthy individuals were recruited. Cases were divided based on severity (mild, moderate, and severe) and outcome (discharged or deceased). Serum iron, TIBC, ferritin, transferrin, transferrin saturation levels were analyzed by the direct colourimetric method. RESULTS: In cases the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 29 µg/dL, 132.53 µg/dL, 106.3 mg/dL, 17.74 % and 702.9 ng/dL respectively. Similarly, in controls the median levels of serum iron, TIBC, transferrin, transferrin saturation and ferritin are 53 µg/dL, 391.88 µg/dL, 313.51 mg/dL, 12.81 % and 13.52 ng/dL respectively. On comparing the cases with the controls, a significant lower level of iron, TIBC, and transferrin were found in the cases along with the significant higher levels of ferritin and transferrin saturation. On comparing the Receiver operating characteristic (ROC) curves of Iron, Ferritin, Transferrin, Transferrin sat % and TIBC in relation to survival in COVID-19 patients it was found that iron, followed by transferrin and ferritin has the highest area under the curve (AUC) with 74 %, 63 % and 61 % respectively. Further, in pairwise analysis of ROC curve, a significant difference was found between the Iron-transferrin (p < 0.01), iron-TIBC (p < 0.001) and transferrin-ferritin (P < 0.01). The multiple regression model based on Iron and transferrin outperformed any other combination of variables via stepwise AIC selection with an AUC of 98.2 %. The cutoff point according to Youden's J index is characterized with a sensitivity of 98 % and a specificity of 96.8 %, indicating that iron along with transferrin can be a useful marker that may contribute to a better assessment of survival chances in COVID-19. CONCLUSION: Our study demonstrated a significantly decreased levels of iron, TIBC, & transferrin and a significantly increased levels of ferritin and transferrin saturation in COVID-19 patients when compared with controls. Further, Iron and transferrin were observed to be a good predictor of mortality in patients with COVID-19. From the above analysis we confirm that iron-related biomarkers play an important role in the development of oxidative stress and further lead to activation of the cytokine storm. So, continuous monitoring of these parameters could be helpful in the early detection of individuals developing the severe disease and can be used to decrease mortality in upcoming new waves of COVID-19.

Mortality and Its Predictors in COVID-19 Patients With Pre-existing Interstitial Lung Disease.

Background The data on the impact of coronavirus disease 2019 (COVID-19) on interstitial lung disease (ILD) is still limited. To the best of our knowledge, there has been no study from India to date to assess the impact of COVID-19 in patients with preexisting ILD. We undertook this study to assess the clinical outcome of ILD patients admitted to our hospital with COVID-19. Methods In this retrospective observational study, records of reverse transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 patients with preexisting ILD who were admitted to the hospital in the period from May 1, 2020, to April 30, 2021, were obtained from the hospital database. The clinical outcomes of the patients were recorded. Univariate analysis was performed to find relation between various predetermined risk factors for mortality and those with significant p values (p<0.05) were subjected to multiple logistic regression to determine independent risk factors. Results In our study of 28 patients, the overall mortality was 35.7%. On comparing the parameters associated with increased mortality, there was no effect of age, gender, comorbidities, type of ILD, CT thorax findings on diagnosis, use of corticosteroids and antifibrotics in the past, spirometric findings on mortality. On multivariate analysis, the significant parameters were interleukin 6 (IL-6), p=0.02, OR=1.020 (1.006-1.043) and D-dimer, p=0.04, OR=2.14 (5.55-1.14). Conclusion COVID-19 in patients with pre-existing ILD has a comparatively higher mortality. D-dimer and IL-6 are significant predictors of mortality in ILD patients infected with COVID-19.

Prevalence, Presentation and Outcome of Secondary Bloodstream Infections among COVID-19 Patients.

BACKGROUND: The higher mortality rate in COVID-19 patients is still a concern. Though some studies mention that elderly patients with co-morbidities are at higher risk of mortality, some others report uneventful outcomes in young patients even without co-morbidities. Secondary bacterial and fungal infections, especially with nosocomial pathogens are known to be associated with worse outcome in the ongoing pandemic as well as in the previous viral outbreaks. In such a scenario, the outcome of hospitalized COVID-19 patients can be improved by timely identification of secondary infections using appropriate biomarkers and by following appropriate infection control measures to prevent the spread of nosocomial pathogens. OBJECTIVE: The study aims to find out the prevalence of bloodstream infections (BSI) among hospitalized COVID-19 patients and to analyze their laboratory markers and outcome by comparing them with those without BSI. METHODS: In this descriptive cross-sectional study, the prevalence of secondary BSI was determined among the hospitalized COVID-19 patients by including 388 blood culture bottles collected from 293 patients, which were received in the microbiology lab within the study period. RESULTS: The overall prevalence of BSI in COVID-19 patients was 39.5% (116/293), out of which 35.5% (104/293) infections were bacterial, and 4.1% (12/293) were fungal, while 8.9% (26/293) patients grew contaminants, and 51.5% (151/293) were sterile. Common causative agents of secondary BSI were found to be MDR Klebsiella pneumoniae (10.9%) and Acinetobacter baumannii (8.8%) followed by Candida species (4.1%). Patients with co-morbidities like diabetes, hypertension and COPD were at higher risk of developing BSI with significantly higher levels of sepsis markers such as Creactive protein (CRP), procalcitonin, ferritin and Interleukin-6 (IL-6). The mortality rate was significantly higher (60.2%) in patients with BSI compared to the group of patients without BSI. CONCLUSION: Our findings suggest the necessity of early diagnosis of the secondary infections using appropriate biomarkers and following proper infection control measures to prevent the spread of the nosocomial infections and improve the outcome of hospitalized COVID-19 patients.

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.

New-onset hyperglycaemia and prolonged systemic corticosteroids therapy in mild COVID-19 patients as major risk factors for invasive mucormycosis: a preliminary study.

Background and Purpose: Rapid surge of invasive mucormycosis has surprised the Indian healthcare system amidst the coronavirus disease-19 (COVID-19) pandemic. Hence, there is an urgent need to find the risk factors for the sudden rise in cases of invasive mucormycosis among COVID-19 patients. This study aimed to find crucial risk factors for the sudden surge of invasive mucormycosis in India. Materials and Methods: This case-control study included 77 cases of COVID-19 associated mucormycosis (CAM) who matched the controls (45 controls) in terms of age , gender, and COVID-19 disease severity. The control group included subjects that matched controls without mucormycosis confirmed by reverse transcription-polymerase chain reaction at our tertiary care center during April-May 2021. Probable predisposing factors, such as duration of diabetes mellitus (DM), history of recent hospitalization, duration of hospital stay, mode of the received oxygen supplementation, and use of steroids, zinc, vitamin c, and any other specific drugs were collected and compared between the two groups. Moreover, the laboratory parameters, like glycated hemoglobin (HbA1c), highly sensitive C-reactive protein (hs-CRP), and erythrocyte sedimentation rate (ESR) were analyzed to find out the significant association with CAM. Results: DM (Odds ratio=7.7, 95% CI 3.30-18.12; P=<0.0001) and high glycated hemoglobin level (HbA1c>7.5 gm %) (odds ratio=6.2, 95% CI 1.4-26.7; P=0.014) were significant risk factors for the development of invasive mucormycosis among the COVID-19 cases. A higher number of mild COVID-19 cases developed CAM, compared to the moderate to severe cases (59.7% vs 40.3%). Use of systemic corticosteroids (odd ratio=5 with 95% CI 1.5-16.9; P=0.007) was found to be a risk factor for invasive mucormycosis only in mild COVID-19 cases. Use of oxygen, zinc, and vitamin C supplementation, and proprietary medicine did not lead to a significant risk of invasive mucormycosis in cases, compared to controls. Cases with invasive mucormycosis had a higher level of inflammatory markers (hs-CRP and ESR, P=<0.001 and 0.002, respectively), compared to the controls. Conclusion: Uncontrolled and new-onset DM and the use of systemic corticosteroids in mild cases were significantly associated with a higher risk of invasive mucormycosis in COVID-19 cases. There should be a strong recommendation against the use of systemic corticosteroids in mild COVID-19 cases.

Emotional distress among health professionals involved in care of inpatients with COVID-19: a survey based cross-sectional study.

INTRODUCTION: Health care workers (HCWs) are directly involved in processes linked with diagnosis, management, and assistance of coronavirus disease-19 (COVID-19) patients which could have direct implications on their physical and emotional health. Emotional aspects of working in an infectious pandemic situation is often neglected in favour of the more obvious physical ramifications. This single point assessment study aimed to explore the factors related to stress, anxiety and depression among HCWs consequent to working in a pandemic. MATERIAL AND METHODS: This was a cross-sectional study involving healthcare workers who were working in COVID-19 inpatient ward, COVID-19 screening area, suspect ward, suspect intensive care unit (ICU) and COVID-19 ICU across four hospitals in India. A web-based survey questionnaire was designed to elicit responses to daily challenges faced by HCWs. The questionnaire was regressed using machine-learning algorithm (Cat Boost) against the standardized Depression, Anxiety and Stress Scale - 21 (DASS 21) which was used to quantify emotional distress experienced by them. RESULTS: A total of 156 participants were included in this study. As per DASS-21 scoring, severe stress was seen in ∼17% of respondents. We could achieve an R² of 0.28 using our machine-learning model. The major factors responsible for stress were decreased time available for personal needs, increasing age, being posted out of core area of expertise, setting of COVID-19 care, increasing duty hours, increasing duty days, marital status and being a resident physician. CONCLUSIONS: Factors elicited in this study that are associated with stress in HCWs need to be addressed to provide wholesome emotional support to HCWs battling the pandemic. Targeted interventions may result in increased emotional resilience of the health-care system.

Oral Manifestations of COVID-19 Infection: An Analytical Cross-Sectional Study.

OBJECTIVES: The current COVID-19 pandemic has created a huge impact across the globe. Recent literature has reported the occurrence of varied oral lesions in COVID-19 patients in the form of sporadic case reports. This analytical cross-sectional study was carried out to gauge and understand the pattern of oral lesions in qualitative RT-PCR-confirmed COVID-19 patients. METHODS: A cross-sectional study involves a total of 500 qualitative RT-PCR confirmed, hospitalized COVID-19 patients who were meticulously scanned for any hard and soft tissue lesions developing concomitantly with the disease occurrence. RESULTS: This study included a total of 367 (73.4%) males and 133 (26.6%) female patients with a mean age of 53.46 ± 17.50 years. Almost 51.2% of patients presented with gustatory disturbance, 28% with xerostomia and 15.4% of patients were found to have oral findings like erythema, ulcers, depapillation of tongue. There was a statistically significant correlation between oral manifestations and disease severity (p ≤ 0.001). CONCLUSION: COVID-19 is found to effect oral health with greater probability in patients with severe diseases (SARI) which may be due to disease itself, immune response and lack of motivation for personal hygiene measures. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12663-021-01679-x.

D-dimer, disease severity, and deaths (3D-study) in patients with COVID-19: a systematic review and meta-analysis of 100 studies.

Hypercoagulability and the need for prioritizing coagulation markers for prognostic abilities have been highlighted in COVID-19. We aimed to quantify the associations of D-dimer with disease progression in patients with COVID-19. This systematic review and meta-analysis was registered with PROSPERO, CRD42020186661.We included 113 studies in our systematic review, of which 100 records (n = 38,310) with D-dimer data) were considered for meta-analysis. Across 68 unadjusted (n = 26,960) and 39 adjusted studies (n = 15,653) reporting initial D-dimer, a significant association was found in patients with higher D-dimer for the risk of overall disease progression (unadjusted odds ratio (uOR) 3.15; adjusted odds ratio (aOR) 1.64). The time-to-event outcomes were pooled across 19 unadjusted (n = 9743) and 21 adjusted studies (n = 13,287); a strong association was found in patients with higher D-dimers for the risk of overall disease progression (unadjusted hazard ratio (uHR) 1.41; adjusted hazard ratio (aHR) 1.10). The prognostic use of higher D-dimer was found to be promising for predicting overall disease progression (studies 68, area under curve 0.75) in COVID-19. Our study showed that higher D-dimer levels provide prognostic information useful for clinicians to early assess COVID-19 patients at risk for disease progression and mortality outcomes. This study, recommends rapid assessment of D-dimer for predicting adverse outcomes in COVID-19.

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.

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.

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.