Requirement For Oxygen Support Research Articles

Association between baseline intact parathyroid hormone levels, COVID-19 severity, and long-term outcomes in patients undergoing hemodialysis: A multicenter retrospective study

The COVID-19 pandemic poses unique challenges for vulnerable populations, including patients undergoing maintenance hemodialysis (HD). This study explores the relationship between baseline intact parathyroid hormone (iPTH) levels and COVID-19 severity, post-acute hospitalization, and mortality rates in HD patients.
 Methods. A multicenter retrospective cohort study was conducted across multiple centers, encompassing 142 patients undergoing HD treatment in three regions of Ukraine. The study spanned from March 2020 to May 2022. Baseline iPTH levels, demographic characteristics, and relevant clinical indicators were systematically recorded. Key endpoints included the severity of COVID-19, post-acute hospitalization, and mortality rates.
 Results. Of the initially eligible 165 patients, 23 were excluded, resulting in a final cohort of 142 patients. During the acute phase of COVID-19, distinct patterns emerged in terms of hospitalization rates, oxygen support requirements, and mortality. Lower iPTH levels were significantly associated with severe COVID-19-associated pneumonia (p < 0.0001). A 20-month follow-up revealed a significant association between serum iPTH concentration <174 pg/mL and increased rates of post-acute COVID-19 hospitalization [HR 6.3 (95% CI 2.9; 13.7)] and all-cause mortality [HR 34.3 (95% CI 6.9; 74.5)].
 Conclusion. This multicenter retrospective study suggests potential links between baseline iPTH levels and COVID-19 outcomes in patients undergoing HD. Serum iPTH concentration ≤174 pg/mL was significantly associated with increased post-acute hospitalization and mortality rate in our patient cohort. The findings emphasize the need for further research to elucidate underlying mechanisms and establish the prognostic value of iPTH in this specific patient population.

Impact of human coronavirus infections on paediatric patients at a tertiary paediatric hospital: a retrospective study of the prepandemic era

Human coronaviruses (HCoVs) are important respiratory pathogens in humans and animals. Most HCoVs are emerging pathogens, with five known human pathogens identified in the last two decades. To examine the clinical course of HCoV infection in children to improve understanding of severity and outcomes. A retrospective review was undertaken of all encounters of children with known HCoV infection at a tertiary paediatric hospital from January 2015 to January 2018. Electronic medical records were reviewed for demographic data, HCoV type, viral co-pathogens, time to testing, need for hospitalization, requirement for higher-level care (HLC) including intensive care unit management and requirement for oxygen support, radiographic findings suggestive of lower respiratory tract (LRT) disease, and length of stay (LOS). In total, 450 encounters for 430 different patients were identified, with the majority (85%) being inpatient. OC43 was the most common HCoV. Younger patients (age <5 years) had higher probability of hospitalization [adjusted odds ratio (aOR) 2.2, 95% confidence interval (CI) 1.2-4.1], requirement for HLC (aOR 1.8, 95% CI 1.0-3.1) and presence of LRT findings on chest radiographs (aOR 1.7, 95% CI 1.01-2.9). Clinical outcomes did not differ between HCoV types, except LOS which was longer for 229E. Fifty-two (11%) encounters were detected after 3 days of hospitalization (median 25.5 days), suggesting possible nosocomial infection. HCoVs are important respiratory pathogens in the paediatric population, especially among patients aged <5 years who are at increased risk for severe disease. The role of HCoVs as hospital-acquired pathogens may be underappreciated.

A study on coagulation profile and clinical outcomes in hospitalized COVID-19 patients in a tertiary care hospital in South India

Introduction: Coagulation abnormalities are a common occurrence in patients with COVID-19, of particular significance is the relationship between D-dimer levels and clinical outcomes. A higher D-dimer level at admission is found to have a poor clinical outcome with increased severity of the disease and increased mortality. Aim and Objectives: To analyze the coagulation profile and its relation to the outcome of patients admitted with COVID-19 pneumonia in a tertiary care center in South India. Subjects and Methods: We conducted a prospective observational study looking at the admission D-dimer, prothrombin time (PT)/international normalized ratio (INR), and platelet levels in 102 admitted COVID-19 patients from February 2021 to January 2022. The relationship between these parameters on admission and the clinical outcome in the form of oxygen requirement, duration of stay, survival, and need for domiciliary oxygen was studied. Discussion and Results: Higher D-dimer levels at admission were associated with poor survival and longer duration of hospital stay with increased requirement of oxygen support. There was a significant correlation between the mean admission D-dimer level and the need for supplemental oxygen (P < 0.05) with patients having a higher D-dimer level at admission (D-dimer of moderate and severe categories: 0.62 ± 0.88 μg/mL and 2.46 ± 4.22 μg/mL, respectively) requiring a higher concentration of oxygen in the form of noninvasive ventilation/high-flow nasal cannula. Furthermore, PT, INR, and platelet count on admission were not useful in predicting the clinical course, oxygen requirement, and overall survival in the study population. Conclusion: Admission levels of D-Dimer can predict the clinical course and outcome of COVID-19 patients.

CLINICAL CHARACTERISTICS AND MORTALITY IN ADULTS 85 YEARS AND OLDER HOSPITALIZED WITH SARS-COV-2

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) places older adults at increased risk of hospitalization and mortality due to coronavirus disease 2019 (COVID-19). To date, research and regulatory data describe adults 65 years and older, with few reporting on characteristics specific to older adults 85 and older (“oldest-old”). A consecutive 12-month case series including 1,510 oldest-old patients hospitalized with SARS-CoV-2 is presented to describe clinical characteristics, Intensive Care Unit (ICU) utilization and in-hospital mortality from 26 urban, suburban and rural-serving hospitals in an integrated health system in Texas. Known predictors of poor prognosis in COVID-19 include older age, male sex, metabolic risk factors (dyslipidemia, obesity, diabetes) and respiratory failure requiring oxygen support. Compared with hospitalized patients &amp;lt; 85 years, oldest-old patients more often had 4+ chronic conditions (31% vs 12%, p&amp;lt; 0.0001), but less often had metabolic risk factors associated with increased risk for mechanical ventilation and mortality. Specifically, diabetes prevalence was similar between age groups (27% oldest-old vs 30%, NS), while obesity prevalence was lower (18% oldest-old vs 55%, p&amp;lt; 0.0001). Oxygen support requirements were largely similar to the general population, with 4 of 5 hospitalized patients requiring oxygenation support. Of 1,510 oldest-old patients hospitalized for SARS-CoV-2, 269 (18%) required admission to an ICU, 1,206 (80%) required oxygen support, and 1,221 (81%) survived. Following hospitalization, 78% required supportive care, including hospice (15%). Hospitalization characteristics across the lifespan suggest an accelerated and compounded need for ICU recovery and post-hospitalization rehabilitation attributed to the COVID-19 pandemic.

Detailed Analysis of the Impact of Clonal Hematopoiesis on the Risk of Severe COVID-19 Infection

Clonal hematopoiesis (CH) associated with aging has been highlighted because it correlates not only with leukemia development, but also with non-malignant conditions, such as cardiovascular diseases and a variety of infectious diseases. Of particular interest of recent years among these CH-associated diseases is COVID-19. To date, significant associations have been reported between COVID-19 and CH-related mutations (including single nucleotide variations and small insertions and deletions) or copy-number alterations (CNAs). However, the joint effect of both lesions has not been evaluated. To address this issue, we performed an integrated analysis of CH-related mutations and CNAs in 2,134 patients with COVID-19 infection. Gene mutations and CNAs were detected using targeted-capture sequencing of 23 CH-related genes and SNP-array-based copy-number analysis, respectively. Among COVID-19 patients, 37% had intermediate severe infections (defined by the requirement for oxygen support) and 29% had most severe infections (artificial respiration, and/or ICU hospitalization). In addition, we also examined 10,612 individuals without COVID-19 as negative controls. With a threshold of ≧20% clonal fractions, we identified gene mutations and CNAs in 8.1% and 1.3% of COVID-19 patients and in 4.9% and 0.7% of control subjects, respectively. Multiple lesions were detected in 1.8% (n=39) of COVID-19 patients, of which 20% were explained by cooccurring mutations and CNAs. Most frequent among these were mutations in DNMT3A, TET2, and ASXL1, and del(20q) in both COVID-19 and control groups, while PPM1D mutations were clearly overrepresented in COVID-19 patients compared with controls (0.80% vs. 0.26%). After age and sex were adjusted using multivariable logistic regression, the presence of CH was associated with intermediate/severe COVID-19 infections with an odds ratio (OR) of 1.73 [95%CI=1.42-2.11] compared with healthy controls. Associations of CH with mild or asymptomatic infections were less prominent (OR=1.36 [1.02-1.82]). Individual effects of mutations and CNAs on intermediate/most severe COVID-19 were similar in size (OR=1.77 [1.44-2.18] and 1.75 [1.04-2.95], respectively). However, when co-occurred, they conferred a higher risk of intermediate/most severe infections (OR=3.60 [1.51-8.51]), which is likely explained by an increased number of CH-related lesions because multiple alterations were more strongly associated with intermediate/most severe COVID-19 infections (OR=3.47 [2.19-5.50]) than a single alteration (OR=1.84 [1.49-2.28]), regardless of co-occurrence of gene mutations and CNAs. We further investigated the impact of individual genetic alterations and found that mutations in PPM1D and JAK2 were most strongly associated with intermediate/most severe COVID-19 infections (OR=3.36 [1.78-6.35] and 4.72 [1.95-11.4], respectively). By contrast, TET2 mutations had almost no impact on severe infections (OR=1.09 [0.70-1.70]). These findings suggest that the risk of severe infections was not uniform across different CH-related alterations, which should be further stratified based on the profiles of gene mutations and CNAs. In conclusion, our integrated analysis of gene mutations and CNAs in COVID-19 patients provided detailed information about the associations between CH and severe COVID-19 infections. These findings will enable better prognostic stratifications in COVID-19 patients based on the genetic profiles in CH. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The Burden of Residual SymptOms That Complicate the Life of Patients Who Have Suffered a new Coronavirus Infection (THROW study).

Aim To evaluate the prevalence of residual symptoms in patients hospitalized for novel coronavirus infection at 8 months after discharge and the severity of such symptoms depending on demographic characteristics, concurrent diseases, and specific features of the acute period of COVID-19.Material and methods This study included the patients who were managed for novel coronavirus infection in a COVID-19 hospital and provided their consent to participate in the study (98 patients). At 8 months after discharge from the hospital, a structured telephone interview was performed.Results Only 40 % of patients treated for COVID-19 did not have any complaints at 8 months after discharge from the hospital. The most frequent complaints in the long term were fatigue (30.5 %), weakness (28.4 %), shortness of breath (23.2 %), arthralgia (22.1 %), myalgia (17.9 %), and anosmia (15.8 %). The background of chronic diseases and obesity, percentage of lung damage according to CT data, and the requirement for oxygen support during the acute period in our sample were not related with the presence of symptoms in the long term. The presence and severity of symptoms during the long term were not determined by the clinical condition, volume of lung damage, or requirement for oxygen support but were related with the gender and severity of inflammation upon admission.Conclusion Independent predictors for persistence of symptoms in the patient sample with severe novel coronavirus infection during the long term included chest and joint pain during the stay in the hospital, female gender, and increased levels of C-reactive protein upon admission.

Prolonged ICU Stay in Severe and Critically-Ill COVID-19 Patients Who Received Convalescent Plasma Therapy.

Background Convalescent plasma administration in severe and critically-ill COVID-19 patients have been proven to not provide improvement in patients' outcome, yet it is still widely used in countries with limited resources due to its high availability and safety. This study aims to investigate its effects on ICU mortality, ICU length of stay (LoS), and improvement of oxygen support requirements. Methods Data of all severe and critically-ill patients in our COVID-19 ICU was collected retrospectively between May and November 2020. We dichotomized the variables and compared outcome data of 48 patients, who received convalescent plasma to 131 patients, receiving standard of care. Data were analyzed using multiple logistic regression to make prediction models of mortality, length of stay, and oxygen support device requirement. Result Overall mortality rate in our COVID-19 ICU was 55.3%, with a median overall length of stay of 8 (4–11) days. Less patients that received convalescent plasma presented with the need for mechanical ventilation on ICU admission (p < 0.001), but with comparable PaO2 to FiO2 (P/F) ratio (p=0.95). Factors that confounded mortality were obesity (aOR = 14.1; 95% CI (1.25, 166.7); p=0.032), mechanical ventilation (aOR = 333; 95% CI (4.5,1,000); p < 0.001), higher neutrophil-to-lymphocyte ratio (NLR) (aOR = 7.32; 95% CI (1.82, 29.4); p=0.005), and lower P/F ratio (aOR = 7.70; 95% CI (2.04, 29.4); p=0.003). ICU LoS was longer in patients, who had prior history of hypertension (aOR = 2.14; 95% CI (1.05, 4.35); p=0.036) and received convalescent plasma (aOR = 3.88; 95% CI (1.77, 8.05); p < 0.001). Deceased patients, who received convalescent plasma, stayed longer in the ICU with a mean length of stay of 12.87 ± 5.7 days versus 8.13 ± 4.8 days with a significant difference (U = 434; p < 0.000). The chance of improved oxygen support requirements was lower in obese patients (aOR = 9.18; 95%CI (2.0, 42.1); p < 0.004), mechanically ventilated patients (aOR = 13.15; 95% CI (3.75, 46.09); p < 0.001), patients with higher NLR (aOR = 2.5; 95% CI (1.07, 5.85); p=0.034), and lower P/F ratio (aOR = 2.76; 95% CI (1.1, 6.91); p=0.031). Conclusion The length of stay of patients in the convalescent plasma group was significantly longer than the control group. There was no effect of convalescent plasma in ICU mortality and no improvement was observed in terms of oxygen support requirements.

Outcomes of COVID-19 in Cancer Patients who Developed Acute Kidney Injury During Hospitalization in a Tertiary Care Hospital in India

Background: The development of acute kidney injury (AKI) in patients infected with COVID-19 has been observed to be associated with poor outcomes. Our study aimed to measure the outcomes of COVID-19 in cancer patients who developed AKI during hospitalization and the predictive baseline clinical and laboratory factors associated with the development of AKI. Materials and Methods: This retrospective cohort study was conducted at a COVID hospital that included only cancer patients with COVID-19 infection. Acute kidney injury (AKI) was defined according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria. The demographic, clinical, laboratory and outcomes data were collected from the hospital electronic database and abstracted from the case files. Results: Thirteen (12.8%) of the total 102 cancer patients developed AKI during hospitalization. Out of 13, 11 (84.6%) patients presented with hypoxemia during admission and required oxygen support. Breathlessness [Odds Ratio (OR) (95% CI): 5.8 (1.1-31.3)] or hypoxemia [OR 22.6 (2.6-194.5)] at the time of presentation and requirement of oxygen support [OR 7.5 (1.4-40.5)] were significantly associated with AKI after adjusting for age, gender, vaccination status and comorbidities. Median baseline values of inflammatory markers were significantly higher among those who developed AKI. Out of 102, 27 (26.5%) patients had in-hospital mortality. Mortality was high among those who developed AKI compared to those who didn’t develop AKI (92.3% vs 16.1%, p-value: &lt;0.001). Conclusions: The cancer patients infected by COVID-19 and who developed AKI were more vulnerable to poor outcomes in terms of in-hospital mortality. The patients with severe disease at presentation and higher levels of baseline inflammatory markers CRP, ferritin, and D-Dimer were more susceptible to the development of AKI and in turn, led to a higher risk of in-hospital mortality in these patients.

A Double-blind Multicenter Two-arm Randomized Placebo-controlled Phase-III Clinical Study to Evaluate the Effectiveness and Safety of Thymosin α1 as an Add-on Treatment to Existing Standard of Care Treatment in Moderate-to-severe COVID-19 Patients.

BackgroundFrom an epidemic outbreak, coronavirus disease-2019 (COVID-19) has quickly developed. Thymosin α1 (Tα1) has the ability to boost the T-cell numbers, support T-cell differentiation, maturation, and reduce cell apoptosis. In this study, we have investigated the efficacy and safety of Tα1 in moderate-to-severe COVID-19 patients.Patients and methodsIn this double-blind, multicenter, two-arm, randomized, placebo-controlled, phase III clinical study, patients were randomized to receive either Tα1 or placebo in combination with standard of care (SOC). The data on all-cause mortality, clinical progression/deterioration, duration of hospital/intensive care unit (ICU) stay, and safety data were collected. The patients were telephonically followed up on Day 28.ResultsA total of (n = 105) COVID-19 patients were included in the study, of which 40 and 65 were severe and moderate, respectively. Thymosin arm (11.1%) had a statistically lower death rate in comparison to the placebo arm (38.5%). A total of 67 adverse events were reported in 42 patients among 105 dosed patients during the study. Among them, 43 adverse events were of mild in nature, 16 adverse events were of moderate in nature, and 8 serious adverse events (death) occurred during the study.ConclusionThis study provides evidence that Tα1 can lower death rate in severe COVID-19 patients, reduce the load on hospitals by shortening the required number of days of hospitalization and help in abbreviating the requirement of oxygen support by positively impacting the recovery rate and time taken for recovery.How to cite this articleShetty A, Chandrakant NS, Darnule RA, Manjunath BG, Sathe P. A Double-blind Multicenter Two-arm Randomized Placebo-controlled Phase-III Clinical Study to Evaluate the Effectiveness and Safety of Thymosin α1 as an Add-on Treatment to Existing Standard of Care Treatment in Moderate-to-severe COVID-19 Patients. Indian J Crit Care Med 2022;26(8):913–919.

Assessing The Utility of D-Dimer Driven Anticoagulation Strategies In Severely Obese Patients With COVID-19

Funding AcknowledgementsType of funding sources: None.BackgroundMany studies to date have documented significant inflammatory vascular sequelae in association with COVID-19. Current guidelines suggest an initial strategy of therapeutic-dose anticoagulation to non-critically ill, hospitalized patients requiring low-flow oxygen and a concurrent D-dimer level above the upper limit of normal. However, the utility of D-dimer values in predicting thrombosis in severely obese patients are equivocal to poor, with prior evidence suggesting falsely elevated levels with greater BMI. Given the weight-based dosing of heparin, these patients may also be inadvertently at elevated risk for major bleeds.PurposeTo examine the utility of D-dimer levels in risk stratification and anticoagulation therapy in non-critically ill COVID-19 patients with severe obesity.MethodsIn this single-center, retrospective study, 32 severely obese patients (defined as BMI > 40) hospitalized with COVID-19 and requiring low flow oxygen delivery, without ICU level of care were analyzed. Clinical outcomes were compared between groups receiving therapeutic versus prophylactic doses of anticoagulation. All were treated with low molecular weight heparin (LMWH) per hospital protocol. The following data points were examined: length of hospitalization, mortality, anticoagulation therapy, initial d-dimer levels, thrombotic events, minor/major bleeds, and oxygen modality.ResultsIn total, 78% of patients initially presented with a D-dimer level above the upper limit of normal, with 53% of patients meeting criteria for therapeutic anticoagulation. However, there were no significant differences in incidence of thrombotic events, mean length of hospitalization or overall mortality. Furthermore, despite utilization of appropriate therapeutic anticoagulation, it did not reduce the overall use of oxygen support requirements, including high flow oxygen or non-invasive ventilation, when compared to individuals receiving prophylactic dosing.ConclusionThe clinical utility of D-dimer levels for guiding anticoagulation therapy in severely obese patients with COVID-19 may be limited. Here, we demonstrate that therapeutic dose approaches have nonsignificant differences in clinical outcomes when compared to prophylactic doses in this distinct population.

Maternal and perinatal outcomes of SARS-CoV-2 infection in unvaccinated pregnancies during Delta and Omicron waves.

ABSTRACTObjectiveThere is little evidence related to the effects of the Omicron severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variant on pregnancy outcomes, particularly in unvaccinated women. This study aimed to compare pregnancy outcomes of unvaccinated women infected with SARS‐CoV‐2 during the pre‐Delta, Delta and Omicron waves.MethodsThis was a retrospective cohort study conducted at two tertiary care facilities: Sancaktepe Training and Research Hospital, Istanbul, Turkey, and St George's University Hospitals NHS Foundation Trust, London, UK. Included were women who tested positive for SARS‐CoV‐2 by real‐time reverse‐transcription polymerase chain reaction (RT‐PCR) during pregnancy, between 1 April 2020 and 14 February 2022. The cohort was divided into three periods according to the date of their positive RT‐PCR test: (i) pre‐Delta (1 April 2020 to 8 June 2021 in Turkey, and 1 April 2020 to 31 July 2021 in the UK), (ii) Delta (9 June 2021 to 27 December 2021 in Turkey, and 1 August 2021 to 27 December 2021 in the UK) and (iii) Omicron (after 27 December 2021 in both Turkey and the UK). Baseline data collected included maternal age, parity, body mass index, gestational age at diagnosis and comorbidities. The primary outcome was the need for oxygen supplementation, classified as oxygen support via nasal cannula or breather mask, non‐invasive mechanical ventilation with continuous positive airway pressure (CPAP) or high‐flow oxygen, mechanical ventilation with intubation, or extracorporeal membrane oxygenation (ECMO). Inferences were made after balancing of confounders, using an evolutionary search algorithm. Selected confounders were maternal age, body mass index and gestational age at diagnosis of infection.ResultsDuring the study period, 1286 unvaccinated pregnant women with RT‐PCR‐proven SARS‐CoV‐2 infection were identified, comprising 870 cases during the pre‐Delta period, 339 during the Delta wave and 77 during the Omicron wave. In the confounder‐balanced cohort, infection during the Delta wave vs during the pre‐Delta period was associated with increased need for nasal oxygen support (risk ratio (RR), 2.53 (95% CI, 1.75–3.65); P < 0.001), CPAP or high‐flow oxygen (RR, 2.50 (95% CI, 1.37–4.56); P = 0.002), mechanical ventilation (RR, 4.20 (95% CI, 1.60–11.0); P = 0.003) and ECMO (RR, 11.0 (95% CI, 1.43–84.7); P = 0.021). The maternal mortality rate was 3.6‐fold higher during the Delta wave compared to the pre‐Delta period (5.3% vs 1.5%, P = 0.010). Infection during the Omicron wave was associated with a similar need for nasal oxygen support (RR, 0.62 (95% CI, 0.25–1.55); P = 0.251), CPAP or high‐flow oxygen (RR, 1.07 (95% CI, 0.36–3.12); P = 0.906) and mechanical ventilation (RR, 0.44 (95% CI, 0.06–3.45); P = 0.438) with that in the pre‐Delta period. The maternal mortality rate was similar during the Omicron wave and the pre‐Delta period (1.3% vs 1.3%, P = 0.999). The need for nasal oxygen support during the Omicron wave was significantly lower compared to the Delta wave (RR, 0.26 (95% CI, 0.11–0.64); P = 0.003). Perinatal outcomes were available for a subset of the confounder‐balanced cohort. Preterm birth before 34 weeks' gestation was significantly increased during the Delta wave compared with the pre‐Delta period (15.4% vs 4.9%, P < 0.001).ConclusionsAmong unvaccinated pregnant women, SARS‐CoV‐2 infection during the Delta wave, in comparison to the pre‐Delta period, was associated with increased requirement for oxygen support (including ECMO) and higher maternal mortality. Disease severity and pregnancy complications were similar between the Omicron wave and pre‐Delta period. SARS‐CoV‐2 infection of unvaccinated pregnant women carries considerable risks of morbidity and mortality regardless of variant, and vaccination remains key. Miscommunication of the risks of Omicron infection may impact adversely vaccination uptake among pregnant women, who are at increased risk of complications related to SARS‐CoV‐2. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Thromboprophylaxis in people hospitalized with COVID‐19: Assessing intermediate or standard doses in a retrospective cohort study

Background and ObjectivesCurrent clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID‐19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses. MethodsWe studied electronic health records from 50 091 adults hospitalized with COVID‐19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.5 mg, or heparin 5000 units twice or thrice per day) versus intermediate (enoxaparin 30 or 40 mg twice daily, or up to 1.2 mg/kg of body weight daily, heparin 7500 units thrice per day or heparin 10 000 units twice or thrice per day) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high‐flow nasal cannula, noninvasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HRs) with 95% confidence intervals (CIs) using adjusted time‐dependent Cox proportional hazards regression models. ResultsPeople whose first dose was high intensity were younger, more often obese, and had greater oxygen support requirements. Intermediate dose thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR, 3.39; 95% CI, 3.22‐3.57), severe disease (HR, 1.22; 95% CI, 1.17‐1.28), and death (HR, 1.37; 95% CI, 1.21‐1.55). Increased risks associated with intermediate‐dose thromboprophylaxis persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates. ConclusionsOur findings do not support routine use of intermediate‐dose thromboprophylaxis to prevent clinical worsening, severe disease, or death among adults hospitalized with COVID‐19.

Remdesivir for the treatment of patients hospitalized with COVID-19 receiving supplemental oxygen: a targeted literature review and meta-analysis

This network meta-analysis (NMA) assessed the efficacy of remdesivir in hospitalized patients with COVID-19 requiring supplemental oxygen. Randomized controlled trials of hospitalized patients with COVID-19, where patients were receiving supplemental oxygen at baseline and at least one arm received treatment with remdesivir, were identified. Outcomes included mortality, recovery, and no longer requiring supplemental oxygen. NMAs were performed for low-flow oxygen (LFO2); high-flow oxygen (HFO2), including NIV (non-invasive ventilation); or oxygen at any flow (AnyO2) at early (day 14/15) and late (day 28/29) time points. Six studies were included (N = 5245 patients) in the NMA. Remdesivir lowered early and late mortality among AnyO2 patients (risk ratio (RR) 0.52, 95% credible interval (CrI) 0.34–0.79; RR 0.81, 95%CrI 0.69–0.95) and LFO2 patients (RR 0.21, 95%CrI 0.09–0.46; RR 0.24, 95%CrI 0.11–0.48); no improvement was observed among HFO2 patients. Improved early and late recovery was observed among LFO2 patients (RR 1.22, 95%CrI 1.09–1.38; RR 1.17, 95%CrI 1.09–1.28). Remdesivir also lowered the requirement for oxygen support among all patient subgroups. Among hospitalized patients with COVID-19 requiring supplemental oxygen at baseline, use of remdesivir compared to best supportive care is likely to improve the risk of mortality, recovery and need for oxygen support in AnyO2 and LFO2 patients.

Abstract 395: Assessing Current Therapeutic Anticoagulation Strategies In Severely Obese Patients With Covid-19

Objective: To examine the utility of D-dimer levels in risk stratification and anticoagulation therapy in non-critically ill COVID-19 patients with severe obesity Background: Many studies to date have documented significant inflammatory vascular sequelae in association with COVID-19. Current guidelines suggest an initial strategy of therapeutic-dose anticoagulation to non-critically ill, hospitalized patients requiring low-flow oxygen and a concurrent D-dimer level above the upper limit of normal. However, the utility of D-dimer values in predicting thrombosis in severely obese patients are equivocal to poor, with prior evidence suggesting falsely elevated levels with greater BMI. Methods: In this single-center, retrospective study, 32 severely obese patients (defined as BMI &gt; 40) hospitalized with COVID-19 and requiring low flow oxygen without ICU level of care were analyzed. Clinical outcomes were compared between groups receiving therapeutic versus prophylactic doses of anticoagulation. All were treated with low molecular weight heparin (LMWH) per hospital protocol. The following data points were examined: length of hospitalization, mortality, anticoagulation therapy, initial d-dimer levels, thrombotic events, minor/major bleeds, and oxygen modality. Results: In total, 78% of patients initially presented with a D-dimer level above the upper limit of normal, with 53% of patients meeting criteria for therapeutic anticoagulation. However, there were no significant differences in incidence of thrombotic events, mean length of hospitalization or overall mortality. Furthermore, despite utilization of appropriate therapeutic anticoagulation, it did not reduce the overall use of oxygen support requirements, including high flow oxygen or non-invasive ventilation, when compared to individuals receiving prophylactic dosing. Conclusion: The utility of D-dimer levels in guiding anticoagulation therapy in severely obese patients with COVID-19 may be misleading.

IDF21-0123 Impact of Pre-existing Oral Antidiabetic Treatment on Clinical Outcomes of COVID-19: a Retrospective Study

Background: COVID-19 pandemic has affected vast population across the world. Several recent reports have indicated that diabetic patients are at a higher risk of developing a serious COVID. The inflammatory process associated with diabetes, as well as chronically elevated blood glucose levels, can result in a weakened immune response, which can exacerbate infections in diabetic patients. Because of the risk of lactic acidosis in the context of multi-organ dysfunction, including hepatic and renal failure, the majority of expert consensus to date has recommended avoiding metformin in COVID-19 patients with diabetes. On the other hand, several studies have shown that patients taking metformin can have a better outcome. As a result, further research is needed to determine the true impact of oral antidiabetic medication in diabetic COVID-19 patients. Aim: The aim of the study is to observe the effect of pre-existing oral antidiabetic therapy on COVID 19 clinical outcomes and to provide further information to help better clinical decisions pertaining to diabetes management during COVID 19. Method: The study enrolled 150 diabetic patients infected with COVID-19 from the duration of July 2020 to December 2020. 75 (metformin group) of these patients were on metformin therapy for their diabetes (alone or in combination with other medications). The remaining 75 patients (non-metformin group) were given one or more non-metformin antidiabetic drugs. A retrospective observational analysis was done for in-patient data gathered from medical records or the hospital information centre of Parul sevashram hospital, Vadodara, Gujarat, and clinical outcomes were recorded in a data collection form. The information gathered was examined and statistically analysed. Results: We found no significant difference in the age and gender of patients between the groups. There was no correlation observed between glycemic control (HbA1c level) and the severity of Covid-19. There was also a significant difference (odds ratio, 10.6, P=0.0003) observed among severity of the disease between the groups, Metformin 17 patients were found to be moderately ill as compared to non-metformin users (n=2, with moderate illness). There was no difference between Metformin or non metformin treated groups pertaining to their requirement of oxygen support (P = 1.00) as well as duration of hospital stay (P=0.78). However, there were few important differences found in the haematological parameters of the groups, such as lower platelet count (P=0.02), Serum creatinine level (P=0.0049), neutrophil count (P=0.001), HbA1C level (P=0.01), and fasting blood glucose level (P=0.05) were observed in the metformin treated patients. Use of methyl prednisolone demonstrated positive correlation with hyperglycemia when tested using multivariate analysis. No correlation between random blood sugar level and duration of hospital stay was found. Discussion: Our study concluded, contrary to the previous study, that there was a larger proportion of metformin-treated patients with greater severity as compared to non-metformin users. We also found a positive correlation between the use of methylprednisolone and the occurrence of hyperglycemia.

CORONAVIRUS DISEASE ASSOCIATED MUCORMYCOSIS FROM A TERTIARY CARE HOSPITAL

BACKGROUND: Coronavirus disease remains a health concern with recent rise of opportunistic infections especially mucormycosis in COVID-19 patients. Mucormycosis is well known to infect patients with diabetes mellitus, malignancy, chemotherapy, and other immunocompromised conditions. The treatment of COVID19 largely remains systemic steroids and other immunomodulators that add to the risk of invasive fungal infection. METHODOLOGY: We included patients who presented with diagnosed mucormycosis by culture in month May and June 2021 and who were previously treated for COVID-19 in last three months of presentation (recent COVID-19) or currently being treated for COVID19 (active COVID-19). Information regarding possible risk factors, like diabetes mellitus, steroid intake, hypertension, lung disease, ICU stay and requirement of oxygen support were collected .RESULTS Overall, 41 cases of mucormycosis in people with COVID-19 have been reported. Mucormycosis was predominantly seen in 30 males (73.17%). Pre-existing diabetes mellitus (DM) was present in 31 patients (75.6%) of cases. Corticosteroid intake for the treatment of COVID-19 was recorded in 28 patients (68.29%) of cases. Pre-existing lung disease was in 6 patient ( 14.63%), ICU stay due to COVID was in 7 patient (17.07%) , Pre-existing hypertension was in 12 patient (29.26 )and oxygen support at the time of COVID in 18 patient (43.9%) CONCLUSION: An unholy trinity of diabetes, rampant use of corticosteroid in a background of COVID-19 appears to increase mucormycosis. All efforts should be made to maintain optimal glucose and only judicious use of corticosteroids in patients with COVID-19.

Profile and outcome of COVID-19 patients treated at a secondary hospital in Central India during the second wave of the pandemic.

The second wave of the coronavirus disease 2019 (COVID-19) pandemic resulted in a significant rise in the number of infections and deaths as compared to the first wave. The published literature till now is limited to tertiary hospitals. We did this study to describe the demographic characteristics and outcomes of patients admitted to a secondary care hospital in central India during the second wave of the pandemic. This was a single-center, retrospective observational study conducted in a secondary hospital in central India. The data of patients with COVID-19 infection admitted between March 25 to May 25, 2021, were retrieved and analyzed. A total of 184 patients were included in the study. The mean age was 54.8 ± 14.5 years. Comorbidities included hypertension (40.2%), diabetes mellitus (29.9%), hypothyroidism (4.3%), and asthma (2.7%). The most common presenting complaints were cough (78.8%), breathlessness (61.4%), and fever (60.9%). The mean duration of symptoms was 5.4 ± 2.6 days. According to High-Resolution Computerised Tomography (HRCT) chest severity score, 29/181 (16%) patients had mild disease, 135/181 (74.5%) patients had moderate disease, and 17/181 (9.5%) patients had severe disease. The majority of the patients received remdesivir (90.2%) and 123 patients (66.8%) received corticosteroids. Half the patients (52.2%; n = 96) required intensive care unit admission, 79.3% (145 patients) required oxygen support, and 8.1% (15 patients) required non-invasive ventilator support. Our study from a secondary hospital setup showed that the second wave was very severe with a high requirement of oxygen support and intensive care monitoring.

Role of HRCT in Assessing Requirement of Oxygen for COVID-19 Patients: A Retrospective Study from Amalapuram, Andhra Pradesh, India

Introduction: Coronavirus Disease 2019 (COVID-19) infection has affected many countries in the world with its high rate of infectivity and created havoc with its mortality rate. A High Resolution Computed Tomography (HRCT) thorax scan is useful in detection and to assess the involvement of lung which is helpful to plan the management. Aim: To assess the oxygen requirement in COVID-19 patients based on the lung involvement using HRCT scan. Materials and Methods: A retrospective study was conducted from 1st May to 30th June 2021 in the Department of Radiodiagnosis, Konaseema Institute of Medical Sciences and Research Foundation, Amalapuram, Andhra Pradesh, India. HRCT thorax scans of 600 patients with COVID-19 infection were included. The patients were categorised based on their lung involvement into three groups (mild, moderate, severe) and then they were followed-up for the oxygen support that each patient received during their stay in hospital. Results: Among the 184 mild COVID-19 infection cases none required Bilevel Positive Airway Pressure (BiPAP)/ intubation. Sixty four out of 340 moderate COVID-19 infection cases required BiPAP and intubation and 28 out 76 severe COVID-19 infection cases required BiPAP and intubation. None in mild cases, 60 (17.6%) in moderate cases, and 32 (42.1%) in severe cases had mortality. The rate of oxygen support and risk of intubation increased as the score increases (p&lt;0.001). The Computed Tomography Severity Index (CTSI) also showed significant difference with the age and co-morbidities of the patients (p&lt;0.01). Conclusion: The HRCT is helpful in assessing the requirement of oxygen support in COVID-19 patients and to plan the management. There is increased non invasive and invasive ventilatory support along with increased morbidity and mortality as the score increases.

Remdesivir in Severe COVID-19 and Non-Invasive Ventilation: A Real-Life Experience.

Background: Antiviral treatment is a hot topic regarding therapy for COVID-19. Several antiviral drugs have been tested in the months since the pandemic began. Yet only Remdesivir obtained approval after first trials. The best time to administer Remdesivir is still a matter for discussion and this could also depend upon the severity of lung damage and the staging of the infection. Methods: We performed a real-life study of patients hospitalized forCOVID-19 and receiving non-invasive ventilation (NIV). In this single-center study, a 5 day course of Remdesivir was administered as compassionate use. Further therapeutic supports included antibiotics, low molecular weight heparin and steroids. Data collection included clinical signs and symptoms, gas exchange, laboratory markers of inflammation, and radiological findings. Major outcomes were de-escalation of oxygen-support requirements, clinical improvement defined by weaning from ventilation to oxygen therapy or discharge, and mortality. Adverse drug reactions were also recorded. All data were collected during hospitalization and during a 20-day follow up after treatment. Results: 51 patients were enrolled. A global clinical improvement was recorded in 22 patients (43%) at 12 days, and 36 (71%) at 20 days; in particular, at 12 days, 27 patients (53%) also had a de-escalation of oxygen-support class from a therapeutic point of view. Remdesivir use was associated with a lower hazard ratio for clinical improvement in the elderly (older than 70 years) and in subjects with more extensive lung involvement (total severity score at HRCT of more than 14). The 20-day mortality was 13%. Conclusions: Results demonstrated that Remdesivir is associated with an improvement in clinical, laboratory and radiological parameters in patients with severe COVID-19 and showed an overall mortality of 13%. We conclude that, in this cohort, Remdesivir was a beneficial add-on therapy for severe COVID-19, especially in adults with moderate lung involvement at HRCT.

JAK Inhibition with Ruxolitinib in Patients with COVID-19 and Severe Pneumonia: Multicenter Clinical Experience from a Compassionate Use Program in Italy.

Jak inhibitors are potent anti-inflammatory drugs that have the potential to dampen the hyperactive inflammatory response associated with severe COVID-19. We reviewed the clinical outcomes of 218 patients with COVID-19 hospitalized for severe pneumonia and treated with ruxolitinib through a compassionate use program. Data on the duration of treatment; outcomes at 4, 7, 14, and 28 days; oxygen support requirements; clinical status; and laboratory parameters were retrospectively collected. Overall, according to the physician evaluation, 66.5% of patients showed improvement at follow-up; of these, 83.5% showed improvement by day 7. Oxygen support status also showed improvement, and by day 7, 21.6% of patients were on ambient air, compared with 1.4% at baseline, which increased to 48.2% by day 28. Significant decreases in C-reactive protein and increases in the lymphocyte total count were already observed by day 4, which seemed to correlate with a positive outcome. At the end of the observation period, 87.2% of patients were alive. No unexpected safety findings were observed, and grade 3/4 adverse events were reported in 6.9% of patients.