Factors Associated With Non-invasive Oxygen Therapy Failure in COVID-19 Pneumonia: A Single Center, Retrospective Study in a Tertiary Hospital in North India.

BACKGROUND: Non-invasive oxygen therapy (NIT) consists of high-flow nasal oxygen (HFNO) and continuous positive airway pressure (CPAP). NIT is routinely being used for the management of acute respiratory failure secondary to coronavirus disease-2019 (COVID-19) with variable outcomes. However, previously published studies show that NIT failure might delay endotracheal intubation and invasive mechanical ventilation and results in worse outcomes in patients with hypoxemic respiratory failure. Early prediction of failure of NIT, will help in early decision-making in initiating invasive mechanical ventilation. We retrospectively studied the predictors for NIT failure in patients with moderate to severe COVID-19. METHODS: Adult patients (>18 years) admitted to the intensive care unit (ICU) with moderate to severe COVID-19 ARDS and received NIT [HFNO and CPAP non-invasive ventilation (NIV)] were included in this study. Baseline clinical and laboratory data were collected retrospectively from the electronic hospital information system. NIT failure was defined as the need for invasive mechanical ventilation after the initiation of NIT in the ICU. Univariate and multivariate logistic regression analyses were used to find out the possible predictors of NIT failure. RESULTS: Out of 254 patients admitted to ICU, 127 patients were initiated NIT at admission to ICU. During the course of the ICU stay, 33 (26%) patients subsequently required invasive mechanical ventilation (NIT failure). Respiratory rate-oxygenation index (ROX index) of <2.97 at two hours and <3.63 at six hours of ICU admission predicted NIT failure in our cohort of patients with a high positive predictive value. CONCLUSION: Patient selection is crucial for successful NIT in COVID-19. Application of ROX index measured in the first six hours of ICU admission helps in the identification of patients at risk of NIT failure with moderate to severe COVID-19 ARDS.

Predictors of the Outcomes Following the Tocilizumab Treatment for Severe COVID-19

Background: Tocilizumab is used in severe COVID-19 yet has significant rates of treatment failure. Objectives: This retrospective study aimed to identify early predictors of the response to tocilizumab therapy. Methods: Biochemical and clinical characteristics of adult patients who received tocilizumab for severe COVID-19 pneumonia were retrospectively examined. A multivariable logistic regression model was constructed to identify factors that could predict the failure of tocilizumab therapy. A predictive nomogram was also created using the selected model. Results: Out of 101 eligible patients, 30 had treatment failure, and 71 survived on a 28-day follow-up. The partial pressure of oxygen to fraction of inspired oxygen ratio (PFR) on the day of tocilizumab administration (100 vs 80.5), lactate dehydrogenase (LDH;668 vs 507 U/L), neutrophil-to-lymphocyte ratio (NL ratio;24.7 vs 10), and creatine kinase myocardial band (CKMB;30.9 vs 22.7 U/L) were significantly different among the non-survivors and survivors, respectively. A logistic regression model was created, identifying LDH, NL ratio, pro-brain natriuretic peptide (ProBNP), and PFR on the day of tocilizumab administration as best predictors of mortality with an optimism-corrected area under the receiver operator characteristics (ROC) curve of 0.82. The model-implied odds ratios for mortality were 1.89 (95% CI 1.13-3.15) for every 100 U/L rise in serum LDH, 2.29 (95% CI 2.2-4.39) for every 10 unit rise in NL ratio, 1.23 (95% CI 0.95-1.58) for every 100 pg/ml increase in ProBNP, and 0.36 (95% CI 0.13-0.95) for every mmHg rise in PFR at intervention. Conclusion: This study identified NL ratio, LDH, CKMB, and PFR at intervention as important markers of risk of treatment failure following the tocilizumab therapy. A multivariable logistic regression model including LDH, NL ratio, ProBNP, and PFR at intervention best predicted the risk of mortality in patients with severe COVID-19 pneumonia treated with tocilizumab.

High-Dose Dexamethasone Versus Tocilizumab in Moderate to Severe COVID-19 Pneumonia: A Randomized Controlled Trial.

Background and objectives Recent randomized controlled trials (RCTs) have indicated potential therapeutic benefits with high-dose dexamethasone (HDD) or tocilizumab (TCZ) plus standard care in moderate to severe coronavirus disease 2019 (COVID-19) with acute respiratory distress syndrome (ARDS). No study has compared these two against each other. We aimed to compare the efficacy and safety of HDD against TCZ in moderate to severe COVID-ARDS. Methods Patients admitted with moderate to severe COVID-19 ARDS with clinical worsening within 48 hours of standard care were randomly assigned to receive either HDD or TCZ plus standard care. The primary outcome was ventilator-free days (VFDs) at 28 days. The main secondary outcomes were 28-day all-cause mortality and the incidence of adverse events. Our initial plan was to perform an interim analysis of the first 42 patients. Results VFDs were significantly lower in the HDD arm (median difference: 28 days; 95% confidence interval (CI): 19.35-36.65; Cohen's d = 1.14;p < 0.001). We stopped the trial at the first interim analysis due to high 28-day mortality in the HDD arm (relative risk (RR) of death: 6.5; p = 0.007; NNT (harm) = 1.91). The incidence of secondary infections was also significantly high in the HDD arm (RR: 5.5; p = 0.015; NNT (harm) = 2.33). Conclusions In our study population, HDD was associated with a very high rate of mortality and adverse events. We would not recommend HDD to mitigate the cytokine storm in moderate to severe COVID-19 ARDS. TCZ appears to be a much better and safer alternative.

Mortality Prediction of COVID-19 Patients at Intensive Care Unit Admission.

Background Coronavirus-2019 (COVID-19) patients admitted to the intensive care unit (ICU) have mortality rates between 30%-50%. Identifying patient factors associated with mortality can help identify critical patients early and treat them accordingly. Patients and methods In this retrospective study, the records of patients admitted to the COVID-19 ICU in a single tertiary care hospital from April 2020 to September 2020 were analysed. The clinical and laboratory parameters between patients who were discharged from the hospital (survival cohort) and those who died in the hospital (mortality cohort) were compared. A multivariate logistic regression model was constructed to identify parameters associated with mortality.  Results A total of 147 patients were included in the study. The age of the patients was 55 (45, 64), median (IQR), years. At admission, 23 (16%) patients were on mechanical ventilation and 73 (50%) were on non-invasive ventilation. Sixty patients (40%, 95% CI: 32.8 to 49.2%) had died. Patients who died had a higher Charlson comorbidity index (CCI): 3 (2, 4) vs. 2 (1, 3), p = 0.0019, and a higher admission sequential organ failure assessment (SOFA) score: 5 (4, 7) vs. 4 (3, 4), p < 0.001. Serum urea, serum creatinine, neutrophils on differential leukocyte count, neutrophil to lymphocyte ratio (N/L ratio), D-dimer, serum lactate dehydrogenase (LDH), and C-reactive protein were higher in the mortality cohort. The ratio of partial pressure of arterial oxygen to fraction of inspired oxygen, platelet count, lymphocytes on differential leukocyte count, and absolute lymphocyte count was lower in the mortality cohort. The parameters and cut-off values used for the multivariate logistic regression model included CCI > 2, SOFA score > 4, D-dimer > 1346 ng/mL, LDH > 514 U/L and N/L ratio > 27. The final model had an area under the curve of 0.876 (95% CI: 0.812 to 0.925), p < 0.001 with an accuracy of 78%. All five parameters were found to be independently associated with mortality.  Conclusions CCI, SOFA score, D-dimer, LDH, and N/L ratio are independently associated with mortality. A model incorporating the combination of these clinical and laboratory parameters at admission can predict COVID-19 ICU mortality with good accuracy.

Pulmonary Function, Mental and Physical Health in Recovered COVID-19 Patients Requiring Invasive Versus Non-invasive Oxygen Therapy: A Prospective Follow-Up Study Post-ICU Discharge.

Background Survivors of COVID-19 pneumonia may have residual lung injury and poor physical and mental health even after discharge. We hypothesized that COVID-19 severe acute respiratory distress syndrome (ARDS) patients needing mechanical ventilation may be at a greater risk of deterioration in pulmonary function, mental health, and quality of life (QOL). This study analyses the differences in pulmonary function, mental health, and QOL after recovery, in patients having received non-invasive oxygen therapy versus invasive mechanical ventilation during ICU stay. Methods Patients aged >18 years, who had completed 3 months post ICU discharge, with moderate to severe COVID-19 ARDS, were consecutively enrolled from May 1 to July 31, 2021. Patients were allocated into Group A - having required high flow nasal cannula (HFNC)/non-invasive ventilation (NIV) and Group B - having received invasive mechanical ventilation. Pulmonary function tests, 6-minute walk test (6-MWT), and health-related quality of life were compared. Results Of the 145 eligible patients, 31 were lost to follow-up and 21 died. Seventy-four patients were allocated into Groups A (57 patients) and B (17 patients). In Group A, abnormal forced expiratory volume in first second (FEV1), forced vital capacity (FVC), forced expiratory flow in mid-half of FVC (FEF25-75), and peak expiratory flow rate (PEFR) values were obtained in 27 (47.37%), 43 (75.44%), 11 (19.3%), and 25 (43.86%) patients, and in Group B, in 13 (76.47%), 17 (100%), 1 (5.88%), and 8 (47%) patients, respectively. No patient had abnormal FEV1/FVC. All Group B patients had a restrictive pattern in spirometry as compared to 77% in Group A. Group B had a lower arterial partial pressure of oxygen (PaO2) (p=0.0019), % predicted FVC (p<0.0001), % predicted FEV1 (p=0.001), and 6-MWT distance (p<0.001). The physical component score in the short-form survey 12 questionnaire was higher in group A, p<0.001, whereas the mental component score was comparable. Conclusions Patients requiring invasive mechanical ventilation (MV) have a greater risk of impaired pulmonary function and reduced QOL post-ICU discharge. This warrants a greater need for following these patients for better rehabilitation.

Coronavirus Disease (Covid-19) Associated Mucormycosis (CAM): Case Report and Systematic Review of Literature.

Severe coronavirus disease (COVID-19) is currently managed with systemic glucocorticoids. Opportunistic fungal infections are of concern in such patients. While COVID-19 associated pulmonary aspergillosis is increasingly recognized, mucormycosis is rare. We describe a case of probable pulmonary mucormycosis in a 55-year-old man with diabetes, end-stage kidney disease, and COVID-19. The index case was diagnosed with pulmonary mucormycosis 21 days following admission for severe COVID-19. He received 5 g of liposomal amphotericin B and was discharged after 54 days from the hospital. We also performed a systematic review of the literature and identified seven additional cases of COVID-19 associated mucormycosis (CAM). Of the eight cases included in our review, diabetes mellitus was the most common risk factor. Three subjects had no risk factor other than glucocorticoids for COVID-19. Mucormycosis usually developed 10-14 days after hospitalization. All except the index case died. In two subjects, CAM was diagnosed postmortem. Mucormycosis is an uncommon but serious infection that complicates the course of severe COVID-19. Subjects with diabetes mellitus and multiple risk factors may be at a higher risk for developing mucormycosis. Concurrent glucocorticoid therapy probably heightens the risk of mucormycosis. A high index of suspicion and aggressive management is required to improve outcomes.

High Prevalence of Hypocalcemia in Non-severe COVID-19 Patients: A Retrospective Case-Control Study.

Purpose: To compare serum total calcium and phosphate levels in patients with non-severe COVID-19 with age, sex, and serum 25-hydroxyvitamin D level matched healthy adult cohort. Methods: In this retrospective case-control study, medical records of patients (≥18 years) diagnosed as non-severe COVID-19 admitted at and discharged from our tertiary care institution during the period from April 10, 2020 and June 20, 2020 were retrieved. Baseline investigations, notably, serum calcium, phosphate, albumin, magnesium, 25-hydroxyvitamin D, and C-reactive protein (CRP), were performed at admission before any form of calcium or vitamin D supplementation were considered. The biochemical parameters were compared with age, sex, and 25-hydroxyvitamin D matched healthy adult controls (1:1 ratio) derived from the Chandigarh Urban Bone Epidemiological Study (CUBES). Results: After exclusion, 72 patients with non-severe COVID-19 (63 mild and 9 moderate disease) and an equal number of healthy controls were included in the final analysis. Age, sex, serum 25-hydroxyvitamin D, and albumin levels were matched between the 2 groups. Hypovitaminosis D and hypocalcemia were seen in 97 and 67% of the patients, respectively. The patients had lower serum calcium (P value <0.001) and phosphate (P = 0.007) compared with the controls. There was no statistically significant correlation between serum calcium and CRP. Conclusions: Hypocalcemia is highly prevalent even in COVID-19 patients with non-severe disease probably implying that hypocalcemia is intrinsic to the disease. Prospective studies with larger number of patients are required to prove this hypothesis and unravel the underlying pathophysiological mechanisms.