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.

Changing Critical Care Patterns and Associated Outcomes in Mechanically Ventilated Severe COVID-19 Patients in Different Time Periods: An Explanatory Study from Central India.

Background: The outcomes in critical illness depend on disease severity, practice protocols, workload, and access to care. This study investigates the factors affecting outcomes in mechanically ventilated coronavirus disease-2019 acute respiratory distress syndrome (COVID-19 ARDS) patients admitted in a tertiary teaching hospital intensive care unit (ICU) in Central India with reference to different time periods in pandemic. This is one of the largest series of mechanically ventilated COVID-19 ARDS patients, globally. Methods: This retrospective cohort study classified the entire data into four time periods (Period 1: April 2020 to June 2020; Period 2: July 2020 to September 2020; Period 3: October 2020 to December 2020; and Period 4: January 2021 to April 2021). We performed a multivariable-adjusted analysis to evaluate predictors of mortality, adjusted for baseline-severity, sequential organ failure assessment (SOFA score) and time period. We applied mixed-effect binomial logistic regression to model fixed-effect variables with incremental complexity. Results: Among the 56 survivors (19.4%) out of 288 mechanically ventilated patients, there was an up-gradient of survival proportion (0, 18.2, 17.4, and 28.6%) in four time periods. Symptom-intubation interval (OR 1.16; 95% CI 1.03-1.31) and driving pressures (DPs) (OR 1.17; 95% CI 1.07-1.28) were significant predictors of mortality in the model having minimal AIC and BIC values. Patients aged above 60 years also had a larger effect, but statistically insignificant effect favoring mortality (OR 1.99; 95% CI 0.92-4.27). The most complex but less parsimonious model (with higher AIC/BIC) indicated the protective odds of high steroid on mortality (OR 0.59; 95% CI 0.59-0.82). Conclusion: The outcomes in mechanically ventilated COVID-19 ARDS patients are heterogeneous across time windows and may be affected by the complex interaction of baseline risk and critical care parameters. How to cite this article: Saigal S, Joshi A, Panda R, Goyal A, Kodamanchili S, Anand A, et al. Changing Critical Care Patterns and Associated Outcomes in Mechanically Ventilated Severe COVID-19 Patients in Different Time Periods: An Explanatory Study from Central India. Indian J Crit Care Med 2022;26(9):1022-1030.

Potential Association of Hypernatremia With Mortality in Patients With Acute Kidney Injury and COVID-19.

Background The outcome of acute kidney injury (AKI) in patients with COVID-19 and the factors associated with its outcome, including mortality, are understudied among the Indian population. Objective The objective of this study is to determine the outcome of AKI in a cohort of patients with COVID-19 admitted to medical wards and associated intensive care unit (ICU) and the factors associated with its outcome, including mortality. Method This is a retrospective study of patients with COVID-19 and AKI admitted to a tertiary care hospital. A total of 1765 patients were admitted to a hospital with COVID-19 between March 23, 2021, and June 30, 2021, during the second wave of the pandemic chiefly attributed to SARS-Co-V-2 lineage B.1.617. Patients with AKI for whom a nephrology call was sought for management (N=60) were included. Measurements carried out were the stage of AKI, co-morbidities, ICU admission, mechanical ventilation, lab parameters, and mortality. We classified AKI by comparing the highest to lowest recorded serum creatinine in hospital and staged AKI based on the Kidney Disease: Improving Global Outcomes (KDIGO) system. We further developed stepwise logistic regression models to find independent factors associated with mortality.  Results Out of the 1765 patients hospitalized with COVID-19, a total of 60 (3.4%) patients with AKI were referred to nephrology for management. The observed mortality in this cohort was 41/60 (68.3%). AKI stage 3 was observed to be the most common (78.3%). Based on a univariate analysis of association, age, chronic kidney disease, admission to ICU, the requirement for vasopressor and ventilation, lactate dehydrogenase (LDH) DH, liver function tests (LFT), hypernatremia, and leucocytosis were associated with the mortality of patients (p<0.05) with AKI and COVID-19 infection. Multivariate analysis using logistic regression led to the identification of hypernatremia (OR 5.24 {0.95-42.31}) and multiple co-morbidities (OR 2.59 {1.03-8.75}, p<0.07) as potential factors independently associated with mortality. Conclusion The study indicates the potential association of hypernatremia with mortality in AKI, along with the simultaneous presence of multiple co-morbidities with COVID-19. As the statistical power of the association is weak, we are claiming the association as potential only. It needs to be confirmed in other larger studies.

Predictors of Requirement of Inotrope Among Patients With Early Sepsis: Special Reference to Microcirculatory Parameters.

Introduction The management of septic shock and refractory septic shock is essential in preventing sepsis-related death. The handheld vital microscope is a new modality of investigation for sepsis for microcirculatory assessment. This study aimed to identify predictors of inotrope requirements among patients with early sepsis and impending septic shock with particular reference to sublingual microcirculation assessment parameters. Methodology We conducted an observational cross-sectional hospital-based study in central India. The formal sample size was calculated to be 52 patients using a convenient sampling technique. The study was initiated with ethics approval (IHEC-LOP/2019/ MD0090) with consent from the patients. We used the MicroScan (MicroVision Medical, Netherlands) Video Microscope System (No.16A00102) to obtain sidestream dark-field imaging along with the AVA 4.3C software (MicroVision Medical). Results Of 51 cases, 60.8% were women, and 39.2% were men, and the study population had a mean age of 41.0 ± 14.9 years. Patients were recruited from medical wards (64.7%) and emergency departments (35.3%). The most common site of infection was gastrointestinal (33.3%), followed by respiratory infections (25.5%) and genitourinary infections (11.8%). The quick sequential organ failure assessment score was 2.0 ± 0.1. Eight patients required inotropes, and six patients died. High respiratory rates and lactate levels were important predictors of inotrope requirements in patients with early sepsis. Sublingual microcirculatory parameters at baseline did not significantly affect the requirement of inotropes consequently. Conclusions Sublingual microscopy is a suggested tool for the management of sepsis. However, without clearly defined cut-off values, handheld vital microscopy could not predict fluid responsiveness among patients with early sepsis. Also, it would be difficult to incorporate this technology into regular practice without equipment upgrades and image acquisition software.

Clinico-Epidemio-Microbiological Exploratory Review Among COVID-19 Patients with Secondary Infection in Central India.

Purpose: Secondary infections (SI) in COVID-19 have been documented from 3.6% to 72% in various studies with mortality ranging from 8.1% to 57.6%. There is a gap in knowledge for clinico-epidemio-microbilogical association among COVID-19 patients with concomitant SI. Patients and Methods: This is a retrospective chart review, in central India. The study was undertaken for hospitalized adult patients during 1st June 2020 to 30th November 2020, with laboratory proven COVID-19 infection and secondary infection. Results: Out of the total 2338 number of patients, only 265 (11.3%) patients were investigated for microbiological identification of SI. Male gender was predominant (76.8%) and the mean age was 53.7 ± 17.8 years. Only 3.5% (82/2338) of patients were having microbiologically confirmed (bacterial or fungal) SI. The overall mortality was 50.9% (54/82) with a differential mortality of 88.8% (48/54) in high-priority areas and 21.4% (6/28) in low-priority areas. Blood was the most commonly investigated sample (56%) followed by urine (20.7%) and respiratory secretion (15.8%). A. baumanii complex (20/82, 24.3%) was the most common bacteria isolated followed by K. pneumonia (12/82, 14.6%) and E. coli (11/82, 13.4%). Candida spp. (20/82, 24.3%) was the most common fungal pathogen isolated. Sixty percent (12/20) of Acinetobacter spp. were carbapenam-resistant and 70.3% of Enterobacterales were carbapenam-resistant. Fluconazole resistant Candid a spp. was isolated only in 10% (2/20) of cases. Diabetes was the most common co-morbidity 54.8% (45/82) followed by hypertension (41.4%) and chronic heart disease (13.4%). The negative predictors of secondary infections are urinary catheterization, placement of central line and mechanical ventilation (invasive and non-invasive). Conclusion: There is an urgent need of better anti-microbial stewardship practices in India (institutional and extra institutional) for curtailment of secondary infection rates particularly among COVID-19 patients.

Adequate Antithrombin III Level Predicts Survival in Severe COVID-19 Pneumonia.

Critically ill patients with COVID-19 are at an increased thrombotic risk, hence thromboprophylaxis with heparin is considered mandatory. Antithrombin III (ATIII) is the most potent endogenous anticoagulant and is required for the clinical efficacy of heparin. Profound hypercoagulable and inflammatory state associated with COVID-19 can result in decreased ATIII levels and ineffective heparin treatment resulting in increased mortality. The present study evaluated ATIII levels in critically ill patients of COVID-19 and correlated them with other coagulation parameters and disease outcomes. A retrospective review of those critically ill COVID-19 patients was performed who were on a therapeutic dose of low molecular weight heparin (LMWH) and had serial measurements of ATIII, anti-factor Xa (antiFXa) assay and other routine coagulation parameters. A total of 27 critically ill COVID-19 patients were identified, out of these, 12 survived and 15 had disease-induced mortality. ATIII levels were found to be significantly lower in non-survivors on the third day of serial measurement along with worsening of other coagulation parameters. AntiFXa levels were found to be higher in non-survivors as compared to survivors. Further studies are required to establish ATIII as a prognostic marker and to determine the utility of monitoring antiFXa levels in COVID-19 patients on LMWH therapy.

Obstructive sleep apnea is highly prevalent in COVID19 related moderate to severe ARDS survivors: findings of level I polysomnography in a tertiary care hospital.

STUDY OBJECTIVES: Studies have found Obstructive Sleep Apnea (OSA) as a risk factor for increased risk for COVID19 Acute respiratory Distress Syndrome (ARDS); but most of the studies were done in already known patients of OSA. This study was done to find prevalence of OSA in patients with COVID-19 related acute respiratory distress syndrome. METHODOLOGY: A hospital based longitudinal study was conducted among COVID 19 Intensive Care Unit (ICU) survivors. All consecutive COVID19 with moderate to severe ARDS were evaluated for OSA by Level I Polysomnography (PSG) after 4-6 weeks of discharge. Prevalence of OSA and PSG variables {Total sleep time, Sleep efficiency, sleep stage percentage, Apnea Hypopnea Index (AHI), T90, nadir oxygen} was estimated. RESULTS: Out of 103 patients discharged from ICU during study period (October 2020 to 15 December 2020), 67 underwent Level I PSG. Mean Age was 52.6 ± 10.9 years and mean Body Mass Index was 27.5 ± 6.2 kg/m2. Total sleep time was 343.2 ± 86 min, sleep efficiency was 75.9 ± 14.2%. OSA (AHI ≥5) was seen in 65/67 patients and 49 patients had moderate to severe OSA (ie AHI ≥15). CONCLUSION: Moderate-severe OSA was highly prevalent (73%) in COVID19 moderate to severe ARDS survivors. Role of OSA in pathophysiology of COVID19 ARDS needs further evaluation.

Assessment of Obstructive Sleep Apnea in Association with Severity of COVID-19: A Prospective Observational Study.

INTRODUCTION: OSA has been postulated to be associated with mortality in COVID-19, but studies are lacking thereof. This study was done to estimate the prevalence of OSA in patients with COVID-19 using various screening questionnaires and to assess effect of OSA on outcome of disease. METHODOLOGY: In this prospective observational study, consecutive patients with RT-PCR confirmed COVID-19 were screened for OSA by different questionnaires (STOPBANG, Berlin Questionnaire, NoSAS, and Epworth Scale). Association between OSA, outcome (mortality) and requirement for respiratory support was assessed. RESULTS: In study of 213 patients; screening questionnaires for OSA [STOPBANG, Berlin Questionnaire (BQ), NoSAS] were more likely to be positive in patients who died compared to patients who survived. On binary logistic regression analysis, age ≥ 55 and STOPBANG score ≥ 5 were found to have small positive but independent effect on mortality even after adjusting for other variables. Proportion of patients who were classified as high risk for OSA by various OSA screening tools significantly increased with increasing respiratory support (p < 0.001 for STOPBANG, BQ, ESS and p = 0.004 for NoSAS). CONCLUSION: This is one of the first prospective studies of sequentially hospitalized patients with confirmed COVID-19 status who were screened for possible OSA could be an independent risk factor for poor outcome in patients with COVID-19.

Impact of COVID-19 epidemic curtailment strategies in selected Indian states: An analysis by reproduction number and doubling time with incidence modelling.

The Government of India in-network with the state governments has implemented the epidemic curtailment strategies inclusive of case-isolation, quarantine and lockdown in response to ongoing novel coronavirus (COVID-19) outbreak. In this manuscript, we attempt to estimate the impact of these steps across ten selected Indian states using crowd-sourced data. The trajectory of the outbreak was parameterized by the reproduction number (R0), doubling time, and growth rate. These parameters were estimated at two time-periods after the enforcement of the lockdown on 24th March 2020, i.e. 15 days into lockdown and 30 days into lockdown. The authors used a crowd sourced database which is available in the public domain. After preparing the data for analysis, R0 was estimated using maximum likelihood (ML) method which is based on the expectation minimum algorithm where the distribution probability of secondary cases is maximized using the serial interval discretization. The doubling time and growth rate were estimated by the natural log transformation of the exponential growth equation. The overall analysis shows decreasing trends in time-varying reproduction numbers (R(t)) and growth rate (with a few exceptions) and increasing trends in doubling time. The curtailment strategies employed by the Indian government seem to be effective in reducing the transmission parameters of the COVID-19 epidemic. The estimated R(t) are still above the threshold of 1, and the resultant absolute case numbers show an increase with time. Future curtailment and mitigation strategies thus may take into account these findings while formulating further course of action.