Adult Coronavirus Disease 2019 Research Articles

Diagnostic and Prognostic Biomarkers of Coronavirus Disease 2019 in Children.

Predictors of early diagnosis and severe infection in children with coronavirus disease 2019 (COVID-19), which has killed more than 4 million people worldwide, have not been identified. However, some biomarkers, including cytokines and chemokines, are associated with the diagnosis, pathogenesis and severity of COVID-19 in adults. We examined whether such biomarkers can be used to predict the diagnosis and prognosis of COVID-19 in pediatric patients. Eighty-nine children were included in the study, comprising three patient groups of 69 patients (6 severe, 36 moderate and 27 mild) diagnosed with COVID-19 by real-time polymerase chain reaction observed for 2–216 months and clinical findings and 20 healthy children in the same age group. Hemogram, coagulation, inflammatory parameters and serum levels of 16 cytokines and chemokines were measured in blood samples and were analyzed and compared with clinical data. Interleukin 1-beta (IL-1β), interleukin-12 (IL-12) and interferon gamma-induced protein 10 (IP-10) levels were significantly higher in the COVID-19 patients (p = 0.035, p = 0.006 and p < 0.001). Additionally, D-dimer and IP-10 levels were higher in the severe group (p = 0.043 for D-dimer, area under the curve = 0.743, p = 0.027 for IP-10). Lymphocytes, C-reactive protein and procalcitonin levels were not diagnostic or prognostic factors in pediatric patients (p = 0.304, p = 0.144 and p = 0.67). Increased IL-1β, IL-12 and IP-10 levels in children with COVID-19 are indicators for early diagnosis, and D-dimer and IP-10 levels are predictive of disease severity. In children with COVID-19, these biomarkers can provide information on prognosis and enable early treatment.

Risk and Protective Factors for COVID-19 Morbidity, Severity, and Mortality.

The outbreak of the coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an evolving global health crisis. Currently, a number of risk factors have been identified to have a potential impact on increasing the morbidity of COVID-19 in adults, including old age, male sex, pre-existing comorbidities, and racial/ethnic disparities. In addition to these factors, changes in laboratory indices and pro-inflammatory cytokines, as well as possible complications, could indicate the progression of COVID-19 into a severe and critical stage. Children predominantly suffer from mild illnesses due to COVID-19. Similar to adults, the main risk factors in pediatric patients include age and pre-existing comorbidities. In contrast, supplementation with a healthy diet and sufficient nutrition, COVID-19 vaccination, and atopic conditions may act as protective factors against the infection of SARS-CoV-2. COVID-19 vaccination not only protects vulnerable individuals from SARS-CoV-2 infection, more importantly, it may also reduce the development of severe disease and death due to COVID-19. Currently used therapies for COVID-19 are off-label and empiric, and their impacts on the severity and mortality of COVID-19 are still unclear. The interaction between asthma and COVID-19 may be bidirectional and needs to be clarified in more studies. In this review, we highlight the clinical evidence supporting the rationale for the risk and protective factors for the morbidity, severity, and mortality of COVID-19.

A Retrospective Study on Experience of High-flow Nasal Cannula Oxygen in Critically Ill COVID-19 Adult Patients Admitted to Intensive Care Unit.

BackgroundThe use of high-flow nasal cannula (HFNC) in coronavirus disease-2019 (COVID-19) patients is debated due to its uncertain benefits and risks of aerosol dispersion. This retrospective study was aimed to assess the outcome of treatment with HFNC therapy in adult COVID-19 patients with acute hypoxemic respiratory failure (AHRF) admitted in intensive care units (ICU) and to assess the factors affecting outcome.Material and methodsWe retrieved electronic medical records of all COVID-19 patients who received HFNC for respiratory support after failure to maintain adequate oxygenation with conventional oxygen devices, between June 1 and August 31, 2020. The data retrieved were statistically analyzed.ResultsA total number of 558 COVID-19 patients were admitted to ICUs, out of which 139 patients were identified to be on HFNC and 85 met the inclusion criteria for the study. The success rate of 48.2% with HFNC was observed in these patients. The patients recorded to experience HFNC success were of young age and having higher baseline oxygen saturation compared to those who had its failure. The ROX indices post-initiation were observed to be significantly higher in the success group (p ≤0.001). Awake-prone positioning while receiving HFNC was followed by around more patients in the success group (p <0.001). On multivariate logistic regression analysis, baseline oxygen saturation, awake-prone positioning, and number of days on HFNC were found to be independently affected outcome with HFNC.ConclusionAlmost half of the cases of moderate-to-severe COVID-19 pneumonia can be managed successfully with HFNC, without the need of mechanical ventilation.How to cite this articleKerai S, Singh R, Saxena KN, Desai SD, Bhalotra AR. A Retrospective Study on Experience of High-flow Nasal Cannula Oxygen in Critically Ill COVID-19 Adult Patients Admitted to Intensive Care Unit. Indian J Crit Care Med 2022;26(1):62–66.

Associations of Nutritional Behavior and Gut Microbiota with the Risk of COVID-19 in Healthy Young Adults in Poland.

The numerous consequences of the coronavirus disease 2019 (COVID-19) pandemic in healthy young people and the lack of clarity as to the long-term disease outcomes have spurred the search for risk factors for SARS-CoV-2 infection. We aimed to evaluate the associations of nutritional behaviors, gut microbiota, and physical activity with the risk of COVID-19 in healthy young nonobese people. Data on body composition, anthropometric measurements, physical activity, dietary intake, and gut microbiota were obtained from 95 adults (mean age, 34.66 ± 5.76 years). A balanced diet rich in vegetables and fruit, including nuts, wholegrain cereal products, and legumes, covers the need for vitamins and minerals. Such a diet can be an effective measure to reduce the risk of COVID-19 in nonobese healthy physically active young people with normal immune function. People with balanced diet and an average daily consumption of >500 g of vegetables and fruit and >10 g of nuts had an 86% lower risk of COVID-19 compared with those whose diet was not balanced and who consumed lower amounts of these products. It is well documented that proper nutrition, physical activity, and maintenance of normal weight facilitate good health by ensuring optimal immune function. The beneficial effects of these interventions should be strongly emphasized during the COVID-19 pandemic.

Cardiac Manifestations in Patients with COVID-19: A Scoping Review.

Background:Coronavirus disease 2019 (COVID-19), commonly affects the lungs, but the involvement of other organs, particularly the heart, is highly prevalent as has been reported in several studies. The overall aim of this review was to provide an in-depth description of the available literature related to the cardiac system and COVID-19 infection. It focuses on type and the frequency of cardiac manifestations, clinical parameters and cardiac biomarkers that support the prognosis of COVID-19 patients, and the cardiac adverse events and outcomes related to pharmacotherapy.Methods:A scoping review was conducted searching Embase, PubMed, Epistomonikos, Medrxiv, BioRxiv databases, up to November 2020, for systematic reviews relevant to cardiac manifestations in adult COVID-19 patients. Relevant articles were screened and extracted to summarize key outcomes and findings.Results:A total of 63 systematic reviews met the inclusion criteria. The overall frequency of acute cardiac injury ranged from 15% to 33% in the reporting studies. The main cardiac complications were arrhythmias (3.1% to 6.9% in non-severe patients, 33.0% to 48.0% in severe disease), acute coronary syndromes (6% to 33% in severe disease), and myocarditis. Most studies found no association with the use of Renin-angiotensin-aldosterone system inhibitors (RAASI) with COVID-19 outcomes such as susceptibility to infection, hospitalization, severity, and mortality.Conclusion:This study provided an overview of the several cardiac complications associated with Covid-19. Cardiac injury, arrhythmias, myocarditis, cardiac failure, and acute coronary syndrome, are prevalent and clinically significant and associated with COVID-19 disease severity and mortality. Other studies are needed to clearly identify what is the part of viral heart infection and what is the part of cardiac injury secondary to acute respiratory failure and inflammation. In the therapeutic field, these systematic reviews gave heterogenous results. This underlines the importance of randomized trials to determine the right therapeutic approach.

Physiologically-based pharmacokinetic modeling of nafamostat to support dose selection for treatment of pediatric patients with COVID-19.

Pediatric patients with coronavirus disease 2019 (COVID-19) are increasing, and severe cases such as multisystem inflammatory syndrome are being reported. Nafamostat, a repurposing drug, is currently being explored for the treatment of COVID-19 in adults. However, the data supporting its exposure in pediatrics remains scarce. Physiologically-based pharmacokinetic (PBPK) modeling enables the prediction of drug exposure in pediatrics based on ontogeny of metabolic enzymes and age dependent anatomical and physiological changes. The study aimed to establish a PBPK model of nafamostat in adults, then scale the adult PBPK model to children for predicting pediatric exposures of nafamostat and an optimal weight-based nafamostat dose in pediatric population. The developed model adequately described adult exposure data in healthy volunteers following i.v. administration with three doses (10, 20, and 40 mg). Scaling adult PBPK models to five pediatric groups predicted that as age advances from neonate to adult, the exposure of nafamostat slightly increased from neonate to infant, steadily decreased from infant to child, and then increased from child to adult after the administration of 0.2 mg/kg/h for 14 days, a dosing regimen being conducted in a clinical trial for COVID-19. Based on the fold change of predicted area under the curve for the respective pediatric group over those of adults, weight-based dosages for each pediatric group may be suggested. The novel PBPK model described in this study may be useful to investigate nafamostat pharmacokinetics in a pediatric subgroup further.

Association between physical activity status and severity of COVID-19 in older adults.

The risk factors specific to the elderly population for severe coronavirus disease 2019 (COVID-19) caused by the Omicron variant of concern (VOC) are not yet clear. We performed an exploratory analysis using logistic regression to identify risk factors for severe COVID-19 illness among 4,868 older adults with a positive severe acute respiratory coronavirus 2 (SARS-CoV-2) test result who were admitted to a healthcare facility between 1 January 2022 and 16 May 2022. We then conducted one-to-one propensity score (PS) matching for three factors - dementia, admission from a long-term care facility and poor physical activity status - and used Fisher's exact test to compare the proportion of severe COVID-19 cases in the matched data. We also estimated the average treatment effect on treated (ATT) in each PS matching analysis. Of the 4,868 cases analysed, 1,380 were severe. Logistic regression analysis showed that age, male sex, cardiovascular disease, cerebrovascular disease, chronic lung disease, renal failure and/or dialysis, physician-diagnosed obesity, admission from a long-term care facility and poor physical activity status were risk factors for severe disease. Vaccination and dementia were identified as factors associated with non-severe illness. The ATT for dementia, admission from a long-term care facility and poor physical activity status was -0.04 (95% confidence interval -0.07 to -0.01), 0.09 (0.06 to 0.12) and 0.17 (0.14 to 0.19), respectively. Our results suggest that poor physical activity status and living in a long-term care facility have a substantial association with the risk of severe COVID-19 caused by the Omicron VOC, while dementia may be associated with non-severe illness.

Clinico-epidemiological profile and outcomes of adults with COVID-19: A hospital-based retrospective study in Kerala, India.

ABSTRACTIntroduction:The clinical and epidemiological presentations of patients with coronavirus disease 2019 (COVID-19) in India is still not well explored. We studied the epidemiological and clinical profile and outcomes of COVID-19 patients admitted to a tertiary care private hospital in Kerala, India.Methods:In this retrospective study, we analyzed data of 476 adult (≥18 years) COVID-19 patients admitted to a tertiary care hospital in Kerala from September 1, 2020 to March 31, 2021. The patients were categorized into mild, moderate, and severe cases and followed till discharge or death. Data were analyzed using Statistical Package for the Social Sciences (SPSS) version 23.0 with a significance set at P < 0.05.Results:The median age was 57 years (56% men). Mild, moderate, and severe cases accounted for 17%, 65%, and 18%, respectively. Around 75% had at least one comorbidity, and 51% had multiple comorbidities. The most common comorbidities were diabetes (45%), hypertension (44%), dyslipidemia (15%), and cardiac problems (12%). The elevated D-dimer values among patients in different categories were significantly different, with 74% in severe, 46% in moderate, and 19% in mild category patients. Serum ferritin, C-reactive protein, lactic acid dehydrogenase, and neutrophil to lymphocyte ratio values were significantly higher for severely ill patients. Thirty deaths (67% men) occurred during the study period, with a case fatality rate of 6.3%. Mortality mainly happened in the older age group (80%) and those with multimorbidity (90%).Conclusion:Age and multimorbidity are the major contributing factors for death in hospitalized COVID-19 patients. Generalization of the findings necessitates well-designed large-scale studies.

Uloga laboratorijskih biomarkera u dijagnostici i praćenju pacijenata sa COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a highly transmittable and heterogenic infection of the respiratory tract, characterized by a broad spectrum of clinical manifestations with a different degree of severity. Medical laboratories play an important role in early diagnosis and management of Coronavirus Disease 2019 (COVID-19) patients. Indeed, the results of several laboratory tests are essential for assessing the severity of the disease, selecting appropriate therapeutic procedures and monitoring treatment response. Routine laboratory testing in COVID-19 patients includes biomarkers of acute phase reaction, hematological and biochemical parameters that indicate tissue injury. The aim of this review paper is to describe the role of these biomarkers in the diagnostics and management of adult and pediatric COVID-19 patients.

The efficiency of high-flow nasal cannula for adult patients with coronavirus disease 19 in Jeddah, Saudi Arabia.

Early use of a high-flow nasal cannula (HFNC) provides positive outcomes for preventing the risk of intubation. However, the efficiency and usage of HFNC in the case of coronavirus disease 2019 (COVID-19) among adult patients with multiple risk factors remain debatable and require more investigation. The aim of this study was to determine the efficiency of HFNC in preventing the possible risk of intubation. This study was an observational cross-sectional study that was conducted at a selected hospital in Jeddah, Saudi Arabia, from July 2020 to August 2021. The data were collected from patients' medical records through the hospital health information system. Adult COVID-19 patients who used HFNC were included, while those who used bilevel positive airway pressure or continuous positive airway pressure without any trials of HFNC and neonatal or pediatric patients were excluded. The exposure of HFNC setting which included variables such as percentages of the fraction of inspired oxygen and the duration of using HFNC were measured to find the relation with respiratory rate oxygenation (ROX) index as a measurement of patient outcome. The data were analyzed by using the online calculator socscistatistics. com for prevalence statistics, and correlation tests of significance. Prevalence statistics were presented in mean, median, frequencies, and percentages. Statistical tests were used to measure correlations of key variables. P < 0.05 of ANOVA and t-tests was considered statistically significant. A total of 159 adult COVID-19 patients using HFNC were included, and most of these patients were male. The median age was 64 years. Most of patients were reported to have hypertension and diabetes mellitus. The majority (94.34%) of patients were successfully weaned from HFNC and shows effective intervention with a mean of 7.53 of ROX score. Appropriate implementation of HFNC might be a successful intervention for preventing the risk of intubation. According to the success rate of HFNC, which was considered a positive outcome, there might be a promising intervention for HFNC to prevent the risk of intubation and decrease the mortality rate.

White Blood Cells in COVID-19: A Study on Viral Induced Cytopathic Changes in the Peripheral Smear

Introduction: Laboratory parameters are crucial in diagnosis and prognosis of Coronavirus Disease 2019 (COVID-19). It would be of interest to explore morphological changes in infected White Blood Cells (WBCs). A detailed examination of peripheral smears may shed light on pathophysiology of infected cell lines and differentiate them from those in established viral infections like dengue and infectious mononucleosis. Aim: To study morphological changes of WBCs in peripheral smears of severe and non severe cases of COVID-19 patients. Materials and Methods: This cross-sectional study was conducted at a tertiary care centre, Dr. Chandramma Dayananda Sagar Institute of Medical Education and Research, Ramanagara, Karnataka, India, from April 2021 to August 2021 on 120 peripheral smears of adult COVID-19 positive cases. Abnormal morphological features were graded by counting 100 cells in each of neutrophils, lymphocytes and monocyte lineage. Changes were compared and analysed between severe and non severe groups using Statistical Package for Social Sciences (SPSS) software version 26.0. A p-value &lt;0.05 was considered as significant. Results: The study included total of 120 cases (59 severe and 61 non severe) with a mean age of 47 years. Male to female ratio in severe and non severe categories were 1:1.2 and 1:0.6, respectively. Severe category patients (n=59) were associated with statistically significant leucocytosis (p-value=0.04), absolute neutrophilia (p-value=0.03) and higher grades of morphological changes- abnormal nuclear morphology (p-value=0.002) and Pseudo-Pelger-Huët anomaly in neutrophils (p-value=0.029), plasmacytoid lymphocytes (p-value=0.03), cytoplasmic granularity and atypical lymphocytes (p-value=0.04). Monocytes showed large coalescent vacuoles and cytoplasmic granules (p-value=0.03). Though present in non severe category (n=61), they were proportionately of lesser grades. Conclusion: Viral cytopathic effects in WBC cell lines on peripheral smear had significant clinical implications on disease severity, undermining need for a comprehensive study of viral induced morphological changes in hospitalised COVID-19 patients.

Clinical Profile and Predictors of Mortality in Patients admitted with COVID-19 in a Tertiary Care Hospital

Hospitalization and survival rate in patients with coronavirus disease 2019 (COVID-19) is affected by pre-existing chronic medical conditions and the disease severity. The objectives of the study were to describe the baseline clinical profile, co-morbidities, disease severity and to assess the predictors of mortality in hospitalized adult patients with COVID-19 in a tertiary care hospital in Nepal. A cross-sectional study was conducted for two months on 168 adult COVID-19 patients admitted to Nobel Medical College Teaching Hospital Biratnagar. Demographics, comorbidities, disease severity, oxygen requirement, and treatment outcomes were studied. The mean age of the patients was 57.1 years and 56.5% were male. Out of 168, 16.7% and 10.1% of the participants had currently or in the past used alcohol or tobacco products respectively. Hypertension (28.6%) and chronic lung disease (16.1%) were the most common co-morbidities. The overall case-fatality rate was 17.9%, with 32.1% and 56.3% in the severe and critical COVID-19 subgroup respectively. The mortality rate for patients without co-morbidities was 2.4% which increased to 63.6% for those with three or more co-morbidities. Age, disease severity, and the number of co-morbidities were found to be associated with increased mortality (P&lt;0.05), whereas gender was not. The pre-existing chronic diseases and increased severity of the disease were associated with increased mortality in hospitalized COVID-19 adult patients.

Comparison of four different threshold values of shock index in predicting mortality of COVID-19 patients.

The object of this study was to examine the accuracy in pre-hospital shock index (SI) for predicting intensive care unit (ICU) requirement and 30-day mortality among from COVID-19 patients transported to the hospital by ambulance. All consecutive patients who were the age ≥18 years, transported to the emergency department (ED) by ambulance with a suspected or confirmed COVID-19 in the pre-hospital frame were included in the study. Four different cut-off points were compared (0.7, 0.8, 0.9, and 1.0) to examine the predictive performance of both the mortality and ICU requirement of the SI. The receiver operating characteristic (ROC) curve and the area under the curve (AUC) was employed to evaluate each cut-off value discriminatory for predicting 30-day mortality and ICU admission. The total of 364 patients was included in this study. The median age in the study population was 69 (55-80), of which 196 were men and 168 were women. AUC values for 30-day mortality outcome were calculated as 0.672, 0.674, 0.755, and 0.626, respectively, for threshold values of 0.7, 0.8, 0.9 and 1.0. ICU admission was more likely for the patients with pre-hospital SI> 0.9. Similarly, the mortality rate was higher in patients with pre-hospital SI> 0.9. Early triage of COVID-19 patients will ensure efficient use of healthcare resources. The SI could be a helpful, fast and powerful tool for predicting mortality status and ICU requirements of adult COVID-19 patients. It was concluded that the most useful threshold value for the shock index in predicting the prognosis of COVID-19 patients is 0.9.

Digestive system involvement and clinical outcomes among COVID-19 patients: A retrospective cohort study from Qatar.

BACKGROUNDCoronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus most commonly presents with respiratory symptoms. While gastrointestinal (GI) manifestations either at presentation or during hospitalization are also common, their impact on clinical outcomes is controversial. Some studies have described worse outcomes in COVID-19 patients with GI symptoms, while others have shown either no association or a protective effect. There is a need for consistent standards to describe GI symptoms in COVID-19 patients and to assess their effect on clinical outcomes, including mortality and disease severity.AIMTo investigate the prevalence of GI symptoms in hospitalized COVID-19 patients and their correlation with disease severity and clinical outcomes.METHODSWe retrospectively reviewed 601 consecutive adult COVID-19 patients requiring hospitalization between May 1-15, 2020. GI symptoms were recorded at admission and during hospitalization. Demographic, clinical, laboratory, and treatment data were retrieved. Clinical outcomes included all-cause mortality, disease severity at presentation, need for intensive care unit (ICU) admission, development of acute respiratory distress syndrome, and need for mechanical ventilation. Multivariate logistic regression model was used to identify independent predictors of the adverse outcomes. RESULTSThe prevalence of any GI symptom at admission was 27.1% and during hospitalization was 19.8%. The most common symptoms were nausea (98 patients), diarrhea (76 patients), vomiting (73 patients), and epigastric pain or discomfort (69 patients). There was no difference in the mortality between the two groups (6.21% vs 5.5%, P = 0.7). Patients with GI symptoms were more likely to have severe disease at presentation (33.13% vs 22.5%, P < 0.001) and prolonged hospital stay (15 d vs 14 d, P = 0.04). There was no difference in other clinical outcomes, including ICU admission, development of acute respiratory distress syndrome, or need for mechanical ventilation. Drugs associated with the development of GI symptoms during hospitalization were ribavirin (diarrhea 26.37% P < 0.001, anorexia 17.58%, P = 0.02), hydroxychloroquine (vomiting 28.52%, P = 0.009) and lopinavir/ritonavir (nausea 32.65% P = 0.049, vomiting 31.47% P = 0.004, and epigastric pain 12.65% P = 0.048). In the multivariate regression analysis, age > 65 years was associated with increased mortality risk [odds ratio (OR) 7.53, confidence interval (CI): 3.09-18.29, P < 0.001], ICU admission (OR: 1.79, CI: 1.13-2.83, P = 0.012), and need for mechanical ventilation (OR: 1.89, CI:1.94-2.99, P = 0.007). Hypertension was an independent risk factor for ICU admission (OR: 1.82, CI:1.17-2.84, P = 0.008) and need for mechanical ventilation (OR: 1.66, CI: 1.05-2.62, P = 0.028).CONCLUSIONPatients with GI symptoms are more likely to have severe disease at presentation; however, mortality and disease progression is not different between the two groups.

Relationship of chest computed tomography score with disease severity and laboratory values in children with COVID-19.

Although chest computed tomography (CT) score has been well evaluated in adult coronavirus disease (COVID-19), its use in paediatric cases is insufficiently studied. Our aim is to evaluate the relationship of chest CT score with disease severity and laboratory parameters. Seventy-six paediatric patients with confirmed COVID-19 and chest CT evaluation on admission have been included in this study. Chest CT score was calculated for each of the five lobes considering the extent of anatomical involvement, as follows: 0: 0%; 1: <5%; 2: 5%-25%; 3: 26%-50%; 4: 51%-75% and 5: >75%. The resulting total CT score was the sum of each individual lobar score; the range was between 0 and 25. Total chest CT score was found to be positively correlated with alanine aminotransferase and d-dimer, and negatively correlated with lymphocyte count. In receiver operating characteristic analysis, total chest CT score had area under the curve 0.99 (95% confidence interval, 0.98-1.00) at cut-off 2 with 95% sensitivity and 96% specificity for the severe disease. Furthermore, in-depth analysis of lobar CT scores showed a correlation between left upper lobe with lymphocyte count, left lower lobe with d-dimer, right middle and lower lobes with alanine aminotransferase and right upper lobe with leukocyte count. There is a significant relationship between chest CT score and COVID-19 severity and laboratory findings in children. This suggests that chest CT scores can be used to assess the severity of the disease and can play an important role in paediatric clinical practice.

Longitudinal Cytokine Profile in Patients With Mild to Critical COVID-19.

The cytokine release syndrome has been proposed as the driver of inflammation in coronavirus disease 2019 (COVID-19). However, studies on longitudinal cytokine profiles in patients across the whole severity spectrum of COVID-19 are lacking. In this prospective observational study on adult COVID-19 patients admitted to two Hong Kong public hospitals, cytokine profiling was performed on blood samples taken during early phase (within 7 days of symptom onset) and late phase (8 to 12 days of symptom onset). The primary objective was to evaluate the difference in early and late cytokine profiles among patient groups with different disease severity. The secondary objective was to assess the associations between cytokines and clinical endpoints in critically ill patients. A total of 40 adult patients (mild = 8, moderate = 15, severe/critical = 17) hospitalized with COVID-19 were included in this study. We found 22 cytokines which were correlated with disease severity, as proinflammatory Th1-related cytokines (interleukin (IL)-18, interferon-induced protein-10 (IP-10), monokine-induced by gamma interferon (MIG), and IL-10) and ARDS-associated cytokines (IL-6, monocyte chemoattractant protein-1 (MCP-1), interleukin-1 receptor antagonist (IL-1RA), and IL-8) were progressively elevated with increasing disease severity. Furthermore, 11 cytokines were consistently different in both early and late phases, including seven (growth-regulated oncogene-alpha (GRO-α), IL-1RA, IL-6, IL-8, IL-10, IP-10, and MIG) that increased and four (FGF-2, IL-5, macrophage-derived chemokine (MDC), and MIP-1α) that decreased from mild to severe/critical patients. IL-8, followed by IP-10 and MDC were the best performing early biomarkers to predict disease severity. Among critically ill patients, MCP-1 predicted the duration of mechanical ventilation, highest norepinephrine dose administered, and length of intensive care stay.

446. Prognostic Value of Absolute Lymphocyte Count for Disease Severity and Clinical Outcomes in Adult COVID-19 Inpatients

BackgroundLymphopenia has been reported as a relatively frequent finding in patients with coronavirus disease 2019 (COVID-19). This study aimed to assess the use of absolute lymphocyte count (ALC) as a prognostic biomarker for disease severity and clinical outcomes. MethodsA cohort of adult patients with COVID-19 admitted to Memorial Healthcare System, Hollywood, Florida from March 7, 2020 to January 18, 2021 was retrospectively analyzed. An absolute lymphocyte count (ALC) < 1.1 × 109/L was used as cutoff point to define lymphopenia. Correlations of ALC upon admission with age and serum levels of C-reactive protein, interleukin-6, lactate dehydrogenase, and creatinine were analyzed. Univariate and multivariate regression models were developed to assess the association of lymphopenia with the risk of ICU admission and clinical outcomes.Results4,485 hospitalized patients were included in the final analyses. Median age was 61 (interquartile range, 47-73) years and 2,311 (51.5%) were men. Lymphopenia was more frequent in patients admitted to the ICU compared to those that were not admitted to the ICU, with an odds ratio of 2.14 (95% confidence interval [CI], 1.78-2.56, p < .0001) (Figure 1). The actual value of the ALC was negatively correlated with age and serum levels of C-reactive protein, interleukin-6, lactate dehydrogenase, and creatinine (all p < 0.005). Patients with lymphopenia (n=2,409) compared to those without lymphopenia (n=2,076) had multivariable-adjusted odds ratios of 1.85 (95% CI, 1.53-2.24) for ICU admission, 2.08 (95% CI, 1.67-2.58) for intubation, 1.98 (95% CI, 1.31-3.00) for development of acute kidney failure, and 2.23 (95% CI, 1.79-2.79) for in-hospital mortality (Table 1). Analyses were adjusted for age, gender, race, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery disease, malignancy, obesity, and smoking. ConclusionLymphopenia in adult COVID -19 hospitalized patients was associated with increased risk of disease severity (as evidenced by need for ICU admission) and poor clinical outcomes. Absolute lymphocyte count may help with prognostication in individuals hospitalized with COVID-19.Disclosures All Authors: No reported disclosures

Estimation of Coronavirus Disease 2019 Hospitalization Costs From a Large Electronic Administrative Discharge Database, March 2020-July 2021.

BackgroundInformation on the costs of inpatient care for patients with coronavirus disease 2019 (COVID-19) is very limited. This study estimates the per-patient cost of inpatient care for adult COVID-19 patients seen at >800 US hospitals.MethodsPatients aged ≥18 years with ≥1 hospitalization during March 2020–July 2021 with a COVID-19 diagnosis code in a large electronic administrative discharge database were included. We used validated costs when reported; otherwise, costs were calculated using charges multiplied by cost-to-charge ratios. We estimated costs of inpatient care per patient overall and by severity indicator, age, sex, underlying medical conditions, and acute complications of COVID-19 using a generalized linear model with log link function and gamma distribution.ResultsThe overall cost among 654673 patients hospitalized with COVID-19 was $16.2 billion. Estimated per-patient hospitalization cost was $24 826. Among surviving patients, estimated per-patient cost was $13 090 without intensive care unit (ICU) admission or invasive mechanical ventilation (IMV), $21 222 with ICU admission alone, and $59 742 with IMV. Estimated per-patient cost among patients who died was $27 017. Adjusted cost differential was higher among patients with certain underlying conditions (eg, chronic kidney disease [$12 391], liver disease [$8878], cerebrovascular disease [$7267], and obesity [$5933]) and acute complications (eg, acute respiratory distress syndrome [$43 912], pneumothorax [$25 240], and intracranial hemorrhage [$22 280]).ConclusionsThe cost of inpatient care for COVID-19 patients was substantial through the first 17 months of the pandemic. These estimates can be used to inform policy makers and planners and cost-effectiveness analysis of public health interventions to alleviate the burden of COVID-19.

Comparing the clinical efficacy of COVID-19 vaccines: a systematic review and network meta-analysis

New Coronavirus Disease 2019 (COVID-19) vaccines are available to prevent the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. We compared the efficacy of new COVID-19 vaccines to prevent symptomatic and severe disease in the adult population and to prevent symptomatic COVID-19 among the elderly. Leading medical databases were searched until August 30, 2021. Published phase 3 randomized controlled trials (RCTs) evaluated efficacy of the vaccine to prevent symptomatic and sever COVID-19 in adults were included. Two reviewers independently evaluated the literature search results and independently extracted summary data. The risk of bias was evaluated using the Cochrane Risk of Bias Assessment Tool. We performed a network meta-analysis (NMA) according to PRISMA-NMA 2015 to pool indirect comparisons between different vaccines regarding their relative efficacy. The primary outcomes were the efficacy of the vaccine against symptomatic COVID-19 in adults (PROSPERO registration number: CRD42021235364). Above 200,000 adult participants from eight phase 3 RCTs were included in NMA, of whom 52% received the intervention (active COVID-19 vaccine). While each of nine vaccines was tested in the unique clinical trial as compared to control, based on indirect comparison, BNT162b2 and mRNA-1273 vaccines were ranked with the highest probability of efficacy against symptomatic COVID-19 (P-scores 0.952 and 0.843, respectively), followed by Gam-COVID-Vac (P-score 0.782), NVX-CoV23730 (P-score 0.700), CoronaVac (P-score 0.570), BN02 (P-score 0.428), WIV04 (P-score 0.327), and Ad26.COV2.S (P-score 0.198). No statistically significant difference was seen in the ability of the vaccines to prevent symptomatic disease in the elderly population. No vaccine was statistically significantly associated with a decreased risk for severe COVID-19 than other vaccines, although mRNA-1273 and Gam-COVID-Vac have the highest P-scores (0.899 and 0.816, respectively), indicating greater protection against severe disease than other vaccines. In our indirect comparison, the BNT162b2 and mRNA-1273 vaccines, which use mRNA technology, were associated with the highest efficacy to prevent symptomatic COVID-19 compared to other vaccines. This finding may have importance when deciding which vaccine to use, together with other important factors as availability of the vaccines, costs, logistics, side effects, and patient acceptability.

Abstract 9489: Echocardiographic Characteristics, Cardiovascular Factors, and Disease-Directed Therapy Do Not Explain Differences in Covid-19 Related Hispanic Outcomes

Introduction: Severe coronavirus disease 2019 (COVID-19) is associated with cardiovascular injury and disparate outcomes in different ethnic groups. However, the reason for this difference has not been elucidated. Methods: A retrospective cross-sectional study was done on adult COVID-19 patients at a single center from April 2020 to January 2021. Mortality, length of stay, mechanical ventilation use, and intensive care unit (ICU) status were compared across demographic groups, echocardiographic indices, and COVID-19-specific treatments. Results: One hundred fifty patients were included. In univariate analysis, elevated cardiac biomarkers, COVID-19 directed therapies, and elevated right-sided pressures were associated with higher mortality, mechanical ventilation use, length of stay, and ICU admission. Multivariable logistic regression predicted higher mortality for Hispanic ethnicity (odds ratio, OR, 6.7) even when adjusting for advanced age (OR 5.3), mechanical ventilation use (OR 18), and right ventricular systolic pressure (OR 1.1 per 1mmHg). There were no differences in underlying comorbidities, echocardiographic indices, cardiac biomarkers, or treatments between Hispanic and non-Hispanic patients. Conclusions: Despite being a younger cohort, Hispanic patients had a higher rate of mortality even when controlling for age, biomarkers, and echocardiographic indices. This suggests Hispanic ethnicity is an independent risk factor for mortality in COVID-19 infection, highlighting an important health inequity that warrants further investigation.