Species differences in plasma protein binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease inhibitor nirmatrelvir.

Plasma protein binding (PPB) studies on the SARS-CoV-2 main protease inhibitor nirmatrelvir revealed considerable species differences primarily in dog and rabbit, which prompted further investigations into the biochemical basis for these differences.The unbound fraction (fu) of nirmatrelvir in dog and rabbit plasma was concentration (2-200 µM)-dependent (dog fu,p 0.024-0.69, rabbit fu,p 0.010-0.82). Concentration (0.1-100 µM)-dependent binding in serum albumin (SA) (fu,SA 0.040-0.82) and alpha-1-acid glycoprotein (AAG) (fu,AAG 0.050-0.64) was observed in dogs. Nirmatrelvir showed minimal binding to rabbit SA (1-100 µM: fu,SA 0.70-0.79), while binding to rabbit AAG was concentration-dependent (0.1-100 µM: fu,AAG 0.024-0.66). In contrast, nirmatrelvir (2 µM) revealed minimal binding (fu,AAG 0.79-0.88) to AAG from rat and monkeys. Nirmatrelvir showed minimal-to-moderate binding to SA (1-100 µM; fu,SA 0.70-1.0) and AAG (0.1-100 µM; fu,AAG 0.48-0.58) from humans across tested concentrations.Nirmatrelvir molecular docking studies using published crystal structures and homology models of human and preclinical species SA and AAG were used to rationalise the species differences to plasma proteins. This suggested that species differences in PPB are primarily driven by molecular differences in albumin and AAG resulting in differences in binding affinity.

Clathrin-Mediated Albumin Clearance in Alveolar Epithelial Cells of Murine Precision-Cut Lung Slices.

A hallmark of acute respiratory distress syndrome (ARDS) is an accumulation of protein-rich alveolar edema that impairs gas exchange and leads to worse outcomes. Thus, understanding the mechanisms of alveolar albumin clearance is of high clinical relevance. Here, we investigated the mechanisms of the cellular albumin uptake in a three-dimensional culture of precision-cut lung slices (PCLS). We found that up to 60% of PCLS cells incorporated labeled albumin in a time- and concentration-dependent manner, whereas virtually no uptake of labeled dextran was observed. Of note, at a low temperature (4 °C), saturating albumin receptors with unlabeled albumin and an inhibition of clathrin-mediated endocytosis markedly decreased the endocytic uptake of the labeled protein, implicating a receptor-driven internalization process. Importantly, uptake rates of albumin were comparable in alveolar epithelial type I (ATI) and type II (ATII) cells, as assessed in PCLS from a SftpcCreERT2/+: tdTomatoflox/flox mouse strain (defined as EpCAM+CD31-CD45-tdTomatoSPC-T1α+ for ATI and EpCAM+CD31-CD45-tdTomatoSPC+T1α- for ATII cells). Once internalized, albumin was found in the early and recycling endosomes of the alveolar epithelium as well as in endothelial, mesenchymal, and hematopoietic cell populations, which might indicate transcytosis of the protein. In summary, we characterize albumin uptake in alveolar epithelial cells in the complex setting of PCLS. These findings may open new possibilities for pulmonary drug delivery that may improve the outcomes for patients with respiratory failure.

Investigation of inflammation, oxidative stress, and DNA damage in COVID-19 patients.

COVID-19 disease, which spreads worldwide, is a disease characterized by widespread inflammation and affects many organs, especially the lungs. The resulting inflammation can lead to reactive oxygen radicals, leading to oxidative DNA damage. The pneumonia severity of 95 hospitalized patients with positive RT-PCR test was determined and divided into three groups: mild, moderate, and severe/critical. Inflammation markers (neutrophil-lymphocyte ratio, serum reactive protein, procalcitonin, etc.) were determined, and IL-10 and IFN-γ measurements were analyzed using the enzyme-linked immunosorbent assay method. In evaluating oxidative damage, total thiol, native thiol, disulfide, and ischemia-modified albumin (IMA) levels were determined by measuring spectrophotometrically. The comet assay method's percentage of tail DNA obtained was used to determine oxidative DNA damage. As a result, when the mild and severe/critical groups were compared, we found that total thiol, native thiol, and disulfide levels decreased significantly in the severe/critical group due to the increase in inflammation markers and cytokine levels (p < 0.05). We could not detect any significance in IMA levels between the groups (p > 0.05). At the same time, we determined an increase in the tail DNA percent level, that is, DNA damage, due to the increased oxidative effect. As a result, we determined that inflammation and oxidative stress increased in patients with severe pneumonia, and there was DNA damage in these patients.

Effect of the COVID-19 pandemic on the oral health and nutritional status of Japanese older adults who underwent total hip or knee arthroplasty: A 3-year single-institution retrospective cohort study.

The coronavirus disease 2019 (COVID-19) pandemic affected the physical and mental health, socioeconomic status, and community behavior of people worldwide. The aim of this retrospective cohort study was to analyze the impact of the COVID-19 pandemic on the oral health and nutritional status of Japanese older adults based on the results of preoperative assessment in patients who underwent total hip or knee arthroplasty under general anesthesia. This study included older adults (≧65 years) who underwent total hip or knee arthroplasty in whom orthopantomography was performed for preoperative oral health assessment, during January 2019 to December 2021. Gender, age, number of family members living together, number of teeth, body mass index, and serum total protein and serum albumin levels were collected for analysis of this study. A total of 201 patients aged 65 to 89 years participated in the study. While the COVID-19 pandemic has had no impact on the oral health status, there has been a drop in serum albumin level from the results of multivariable-adjusted regression analysis considering age, gender, number of family members, and time. The COVID-19 pandemic has affected the serum albumin level of Japanese orthopedic patients aged 65 years or older.

Serum Albumin in Health and Disease: Esterase, Antioxidant, Transporting and Signaling Properties.

Being one of the main proteins in the human body and many animal species, albumin plays a decisive role in the transport of various ions-electrically neutral and charged molecules-and in maintaining the colloidal osmotic pressure of the blood. Albumin is able to bind to almost all known drugs, as well as many nutraceuticals and toxic substances, largely determining their pharmaco- and toxicokinetics. Albumin of humans and respective representatives in cattle and rodents have their own structural features that determine species differences in functional properties. However, albumin is not only passive, but also an active participant of pharmacokinetic and toxicokinetic processes, possessing a number of enzymatic activities. Numerous experiments have shown esterase or pseudoesterase activity of albumin towards a number of endogeneous and exogeneous esters. Due to the free thiol group of Cys34, albumin can serve as a trap for reactive oxygen and nitrogen species, thus participating in redox processes. Glycated albumin makes a significant contribution to the pathogenesis of diabetes and other diseases. The interaction of albumin with blood cells, blood vessels and tissue cells outside the vascular bed is of great importance. Interactions with endothelial glycocalyx and vascular endothelial cells largely determine the integrative role of albumin. This review considers the esterase, antioxidant, transporting and signaling properties of albumin, as well as its structural and functional modifications and their significance in the pathogenesis of certain diseases.

Erythrocytes increase endogenous sphingosine 1-phosphate levels as an adaptive response to SARS-CoV-2 infection.

Low plasma levels of the signaling lipid metabolite sphingosine 1-phosphate (S1P) are associated with disrupted endothelial cell (EC) barriers, lymphopenia and reduced responsivity to hypoxia. Total S1P levels were also reduced in 23 critically ill patients with coronavirus disease 2019 (COVID-19), and the two main S1P carriers, serum albumin (SA) and high-density lipoprotein (HDL) were dramatically low. Surprisingly, we observed a carrier-changing shift from SA to HDL, which probably prevented an even further drop in S1P levels. Furthermore, intracellular S1P levels in red blood cells (RBCs) were significantly increased in COVID-19 patients compared with healthy controls due to up-regulation of S1P producing sphingosine kinase 1 and down-regulation of S1P degrading lyase expression. Cell culture experiments supported increased sphingosine kinase activity and unchanged S1P release from RBC stores of COVID-19 patients. These observations suggest adaptive mechanisms for maintenance of the vasculature and immunity as well as prevention of tissue hypoxia in COVID-19 patients.

COVID-19 vulnerabilities are intensified by declining human serum albumin levels.

What is the topic of this review? Human serum albumin (HSA) a common factor in COVID-19 vulnerabilities. What advances does it highlight? Understanding of HSA capacity, and systemic vulnerabilities to COVID-19. Raising HSA in COVID-19 patients may alleviate systemic injury caused by diminished native HSA binding. A change in fluid therapy administration into the portal system of the liver is proposed to safely raise HSA levels. ABSTRACT: The specific nature of the vulnerabilities to COVID-19 are an intrinsic part of COVID-19 infection in many patients. This paper proposes that vulnerabilities to COVID-19 may be intensified by a decrease in human serum albumin (HSA) as a ligand carrier for nutrients. A mechanism for COVID-19 vulnerabilities is evident from consideration of ligand carriers such as HSA as intermediaries. We hypothesise that low levels of pool HSA binding, caused for whatever reason, affect the performance of albumin as a carrier protein reducing the availability of nutrients. Hypoalbuminaemia (low HSA) has been implicated as an indicator of COVID-19 and long-COVID-19. The levels of HSA directly affect the immune system and vulnerabilities to age, diabetes and obesity in COVID-19. Any slight reduction in available HSA has profound effects on ligand concentrations in the small capillaries where damage occurs in COVID-19. The clinical implication is that attempts should be made to return HSA to clinical levels to compensate for the additional ligands caused by infection (SARS-CoV-2 virions, antibodies and cellular breakdown products). Therapeutic albumin is usually given peripherally, and usual preparations are unbound to ligands, but we suggest that a clinical trial of HSA therapy via the hepatic portal vein should be considered.

Early enteral nutrition improves the outcome of critically ill patients with COVID-19: A retrospective study.

BACKGROUND AND OBJECTIVES: To evaluate the nutritional status of critically ill patients with COVID-19 and to determine which route of nutrition support is advantageous. METHODS AND STUDY DESIGN: This retrospective study was conducted in the ICU of a designated COVID-19 hospital. Patients were divided into an enteral nutrition (EN) group and parenteral nutrition (PN) group according to the initial route of nutrition support. NRS-2002 and NUTRIC were used to assess nutritional status. Blood nutritional markers such as albumin, total protein and hemoglobin were compared at baseline and seven days later. The primary endpoint was 28-day mortality. RESULTS: A total of 27 patients were enrolled in the study - 14 in the EN group and 13 in the PN group - and there were no significant demographic differences between groups. Most patients (96.3% NRS2002 score ≥5, 85.2% NUTRIC score ≥5) were at high nutritional risk. There was no significant difference in baseline albumin, total protein and hemoglobin levels between groups. After 7 days, albumin levels were significantly higher in the EN group than in the PN group (p=0.030). There was no significant difference in the other two indicators. The 28-day mortality was 50% in the EN group and 76.9% in the PN group. Kaplan-Meier survival analysis revealed significant differences between the groups (p=0.030). Cox proportional risk regression indicated that route of nutrition support was also an independent prognostic risk factor. CONCLUSIONS: The incidence of nutritional risk in critically ill patients with COVID-19 is very high. Early EN may be beneficial to patient outcomes.

Characteristics and mortality determinants of COVID-19 patients undergoing hemodialysis

Background/aim: The COVID-19 infection, which started in Wuhan City, China, in December 2019, turned into a pandemic in a very short time, affecting mainly the elderly and those with serious chronic illnesses. COVID-19 infections have been observed to have a high mortality rate, especially in patients undergoing maintenance hemodialysis. Materials and methods: Forty-two patients over 18 years of age who underwent a maintenance hemodialysis program at our unit, who tested positive for COVID-19 by PCR from nasopharyngeal swabs, and/or who were observed to have disease-related signs in their CTs were included in the study. Results: In this study, 23 of 42 patients receiving hemodialysis support in our clinic were included. The median age was 67 years old (min: 35; max: 91 years), and all of our patients had primary hypertension and other comorbidities. Their clinical evaluation showed that dry cough (47.8%) and shortness of breath (47.8%) were the most common symptoms. Fever was less pronounced (30.4%). The median time from the onset of symptoms to hospitalization was 1 day (min: 0; max:), and the time from hospitalization to death was 18 days (min: 1; max: 22). Transfer from the inpatient ward to the ICU took a median of 7 days (min: 1; max: 13). Among the 23 patients, 3 died during follow-up, and 20 were discharged with full recovery. Baseline ferritin, procalcitonin levels, and CRP/albumin rates were higher, and neutrophil/lymphocyte levels were lower in patients who eventually died. In these patients, despite being nonsignificant, there were more diabetic patients, and the D-dimer levels were higher than 1000 ugFEU/L. Conclusion: The COVID-19 infection is associated with increased mortality in chronic kidney diseases patients. Despite being nonsignificant, there was a trend towards increased mortality in patient with diabetes, D-dimer levels >1000 ugFEU/L, higher ferritin and prokalsitonin levels, an increased CRP/albumin ratio, and a lower neutrophil/lymphocyte ratio.

The role of the BUN/albumin ratio in predicting mortality in COVID-19 patients in the emergency department.

INTRODUCTION: Due to the high mortality and spread rates of coronavirus disease 2019 (COVID-19), there are currently serious challenges in emergency department management. As such, we investigated whether the blood urea nitrogen (BUN)/albumin ratio (BAR) predicts mortality in the COVID-19 patients in the emergency department. METHODS: A total of 602 COVID-19 patients who were brought to the emergency department within the period from March to September 2020 were included in the study. The BUN level, albumin level, BAR, age, gender, and in-hospital mortality status of the patients were recorded. The patients were grouped by in-hospital mortality. Statistical comparison was conducted between the groups. RESULTS: Of the patients who were included in the study, 312(51.8%) were male, and their median age was 63 years (49-73). There was in-hospital mortality in 96(15.9%) patients. The median BUN and BAR values of the patients in the non-survivor group were significantly higher than those in the survivor group (BUN: 24.76 [17.38-38.31] and 14.43 [10.84-20.42], respectively [p < 0.001]; BAR: 6.7 [4.7-10.1] and 3.4 [2.5-5.2], respectively [p < 0.001]). The mean albumin value in the non-survivor group was significantly lower than that in the survivor group (3.60 ± 0.58 and 4.13 ± 0.51, respectively; p < 0.001). The area-under-the-curve (AUC) and odds ratio values obtained by BAR to predict in-hospital COVID-19 mortality were higher than the values obtained by BUN and albumin (AUC of BAR, BUN, and albumin: 0.809, 0.771, and 0.765, respectively; odds ratio of BAR>3.9, BUN>16.05, and albumin<4.01: 10.448, 7.048, and 6.482, respectively). CONCLUSION: The BUN, albumin, and BAR levels were found to be reliable predictors of in-hospital mortality in COVID-19 patients, but BAR was found to be a more reliable predictor than the BUN and albumin levels.

Predicting the outcome of COVID-19 infection in kidney transplant recipients.

BACKGROUND: We aimed to present the demographic characteristics, clinical presentation, and outcomes of our multicenter cohort of adult KTx recipients with COVID-19. METHODS: We conducted a multicenter, retrospective study using data of patients hospitalized for COVID-19 collected from 34 centers in Turkey. Demographic characteristics, clinical findings, laboratory parameters (hemogram, CRP, AST, ALT, LDH, and ferritin) at admission and follow-up, and treatment strategies were reviewed. Predictors of poor clinical outcomes were analyzed. The primary outcomes were in-hospital mortality and the need for ICU admission. The secondary outcome was composite in-hospital mortality and/or ICU admission. RESULTS: One hundred nine patients (male/female: 63/46, mean age: 48.4 ± 12.4 years) were included in the study. Acute kidney injury (AKI) developed in 46 (42.2%) patients, and 4 (3.7%) of the patients required renal replacement therapy (RRT). A total of 22 (20.2%) patients were admitted in the ICU, and 19 (17.4%) patients required invasive mechanical ventilation. 14 (12.8%) of the patients died. Patients who were admitted in the ICU were significantly older (age over 60 years) (38.1% vs 14.9%, p = 0.016). 23 (21.1%) patients reached to composite outcome and these patients were significantly older (age over 60 years) (39.1% vs. 13.9%; p = 0.004), and had lower serum albumin (3.4 g/dl [2.9-3.8] vs. 3.8 g/dl [3.5-4.1], p = 0.002), higher serum ferritin (679 µg/L [184-2260] vs. 331 µg/L [128-839], p = 0.048), and lower lymphocyte counts (700/µl [460-950] vs. 860 /µl [545-1385], p = 0.018). Multivariable analysis identified presence of ischemic heart disease and initial serum creatinine levels as independent risk factors for mortality, whereas age over 60 years and initial serum creatinine levels were independently associated with ICU admission. On analysis for predicting secondary outcome, age above 60 and initial lymphocyte count were found to be independent variables in multivariable analysis. CONCLUSION: Over the age of 60, ischemic heart disease, lymphopenia, poor graft function were independent risk factors for severe COVID-19 in this patient group. Whereas presence of ischemic heart disease and poor graft function were independently associated with mortality.

Elevated glucose level leads to rapid COVID-19 progression and high fatality.

OBJECTIVES: We aimed to identify high-risk factors for disease progression and fatality for coronavirus disease 2019 (COVID-19) patients. METHODS: We enrolled 2433 COVID-19 patients and used LASSO regression and multivariable cause-specific Cox proportional hazard models to identify the risk factors for disease progression and fatality. RESULTS: The median time for progression from mild-to-moderate, moderate-to-severe, severe-to-critical, and critical-to-death were 3.0 (interquartile range: 1.8-5.5), 3.0 (1.0-7.0), 3.0 (1.0-8.0), and 6.5 (4.0-16.3) days, respectively. Among 1,758 mild or moderate patients at admission, 474 (27.0%) progressed to a severe or critical stage. Age above 60 years, elevated levels of blood glucose, respiratory rate, fever, chest tightness, c-reaction protein, lactate dehydrogenase, direct bilirubin, and low albumin and lymphocyte count were significant risk factors for progression. Of 675 severe or critical patients at admission, 41 (6.1%) died. Age above 74 years, elevated levels of blood glucose, fibrinogen and creatine kinase-MB, and low plateleta count were significant risk factors for fatality. Patients with elevated blood glucose level were 58% more likely to progress and 3.22 times more likely to die of COVID-19. CONCLUSIONS: Older age, elevated glucose level, and clinical indicators related to systemic inflammatory responses and multiple organ failures, predict both the disease progression and the fatality of COVID-19 patients.

Serum albumin concentrations are associated with disease severity and outcomes in coronavirus 19 disease (COVID-19): a systematic review and meta-analysis.

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is responsible for the most threatening pandemic in modern history. The aim of this systematic review and meta-analysis was to investigate the associations between serum albumin concentrations and COVID-19 disease severity and adverse outcomes. A systematic literature search was conducted in PubMed, from inception to October 30, 2020. Sixty-seven studies in 19,760 COVID-19 patients (6141 with severe disease or poor outcome) were selected for analysis. Pooled results showed that serum albumin concentrations were significantly lower in patients with severe disease or poor outcome (standard mean difference, SMD: - 0.99 g/L; 95% CI, - 1.11 to - 0.88, p < 0.001). In multivariate meta-regression analysis, age (t = - 2.13, p = 0.043), publication geographic area (t = 2.16, p = 0.040), white blood cell count (t = - 2.77, p = 0.008) and C-reactive protein (t = - 2.43, p = 0.019) were significant contributors of between-study variance. Therefore, lower serum albumin concentrations are significantly associated with disease severity and adverse outcomes in COVID-19 patients. The assessment of serum albumin concentrations might assist with early risk stratification and selection of appropriate care pathways in this group.

Identification of risk factors for in-hospital death of COVID - 19 pneumonia -- lessions from the early outbreak.

BACKGROUND: To examine the clinical characteristics and identify independent risk factors for in-hospital mortality of 2019 novel coronavirus (COVID-19) pneumonia. METHODS: A total of 156 patients diagnosed with COVID-19 pneumonia at the Central Hospital of Wuhan from January 29, 2020, to March 20, 2020, and 20 healthy individuals were enrolled in this single-centered retrospective study. The epidemiological parameters, clinical presentations, underlying diseases, laboratory test results, and disease outcomes were collected and analyzed. RESULTS: The median age of all enrolled patients was 66 years. At least one underlying disease was identified in 101 COVID-19 patients, with hypertension being the most common one, followed by cardiovascular disease and diabetes. The most common symptoms identified upon admission were fever, cough, dyspnea, and fatigue. Compared to survival cases, patients who died during hospitalization had higher plasma levels of D-dimer, creatinine, creatine kinase, lactate dehydrogenase, lactate, and lower percentage of lymphocytes (LYM [%]), platelet count and albumin levels. Most enrolled patients received antibiotics and anti-viral treatment. In addition, 60 patients received corticosteroids, and 51 received intravenous immunoglobulin infusion. Forty-four patients received noninvasive ventilation and 19 received invasive ventilation. Respiratory failure was the most frequently observed complication (106 [67.9%]), followed by sepsis (103 [66.0%]), acute respiratory distress syndrome (ARDS) (67 [42.9%]), and septic shock (50 [32.1%]). Multivariable regression suggested that advanced age (OR [odds ratio] = 1.098, 95% CI [confidence interval]: 1.006-1.199, P = 0.037), shorter duration from onset to admission (OR = 0.853, 95% CI: 0.750-0.969, P = 0.015) and elevated lactate level upon admission (OR = 2.689, 95% CI: 1.044-6.926, P = 0.040) were independent risk factors for in-hospital mortality for COVID-19 infection. Meanwhile, increased LYM (%) at admission (OR = 0.787, 95% CI: 0.686-0.903, P = 0.001) indicated a better prognosis. CONCLUSIONS: In this study, we discovered that age, duration from onset to admission, LYM (%), and lactate level upon admission were independent factors that affecting the in-hospital mortality rate.

Inflammatory and hematologic markers as predictors of severe outcomes in COVID-19 infection: A systematic review and meta-analysis.

BACKGROUND: Laboratory testing is commonly performed in patients with COVID-19. Each of the laboratory parameters has potential value for risk stratification and prediction of COVID-19 outcomes. This systematic review and meta-analysis aimed to evaluate the difference between these parameters in severe and nonsevere disease and to provide the optimal cutoff value for predicting severe disease. METHOD: We performed a systematic literature search through electronic databases. The variables of interest were serum procalcitonin, albumin, C-reactive protein (CRP), D-dimer, and lactate dehydrogenase (LDH) levels in each group of severity outcomes from COVID-19. RESULTS: There were a total of 4848 patients from 23 studies. Our meta-analysis suggest that patients with severe COVID-19 infections have higher procalcitonin, (mean difference 0.07; 95% CI 0.05-0.10; p < 0.00001), CRP (mean difference 36.88; 95% CI 29.10-44.65; p < 0.00001), D-Dimer (mean difference 0.43; 95% CI 0.31-0.56; p < 0.00001), and LDH (mean difference 102.79; 95% CI 79.10-126.49; p < 0.00001) but lower levels of albumin (mean difference -4.58; 95% CI -5.76 to -3.39; p < 0.00001) than those with nonsevere COVID-19 infections. The cutoff values for the parameters were 0.065 ng/mL for procalcitonin, 38.85 g/L for albumin, 33.55 mg/L for CRP, 0.635 µ/L for D-dimer, and 263.5 U/L for LDH, each with high sensitivity and specificity. CONCLUSION: This meta-analysis suggests elevated procalcitonin, CRP, D-dimer, and LDH and decreased albumin can be used for predicting severe outcomes in COVID-19.

Could serum albumin value and thrombocyte/lymphocyte ratio be an important prognostic factor in determining the severity of COVID 19?

Background and aim: Creating potential clinical markers for risk assessment in patients with COVID-19 continues to be an area of interest. In this study, we aimed to evaluate whether serum albumin level and thrombocyte/lymphocyte ratio are related to the severity of the disease. Materials and methods: The patients were divided into two groups according to the severity of disease. Demographic data, serum albumin value, lymphocyte count, TLO-1 values (thrombocyte/lymphocyte ratio-1), the highest thrombocyte count during hospitalization, TLO-2 (thrombocyte/lymphocyte ratio-2) values formed by the highest thrombocyte count, were recorded. Results: There was no statistically significant differences (P > 0.05) in terms of sex, thrombocyte count at the time of admission, and highest thrombocyte count during hospital follow-up. There were statistically significant differences in terms of age, comorbidity, lymphocyte value at the time of hospitalization, lymphocyte count during hospital follow-up, TLO 1, TLO 2, and serum albumin values between the groups. The ICU group were found to be older, had higher rates of comorbidity, lower lymphocyte values, higher TLO 1-2, and lower serum albumin levels (P < 0.05). Conclusion: TLO-2 ratio above 260 and lymphocyte level below 1 103 cells/µL, would be a predictor of further intensive care unit need.

Characteristics and Outcomes Based on Perceived Illness Severity in SARS-CoV-2.

OBJECTIVES: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) epidemic is characterized by a global sense of uncertainty, partly driven by the paucity of real-life clinical data. This study assessed whether admission patient characteristics were associated with need for intensive care unit (ICU) care. METHODS: The observational study included consecutive patients admitted to a large community teaching hospital with a diagnosis of SARS-CoV-2 between March 6, 2020 and March 31, 2020. Comparisons were made based on the need for ICU admission. RESULTS: A total of 156 patients were admitted, 42 of whom (26.9%) required ICU admission and 114 (73.1%) did not. No difference in age (61.9 years vs 60.5 years, P = 0.67), race/ethnicity, or comorbidities were noted, except that patients requiring ICU care had lower serum albumin levels and lymphocyte counts and higher liver function tests, white blood cell count, and absolute neutrophil count on admission. The average time from admission to death was similar (10 days in an ICU subset vs 9.2 days in a non-ICU subset, P = 0.78), yet patients necessitating ICU care had longer hospital lengths of stay (10.2 vs 5.1 days, P = 0.0002). At the time of data extraction, 15 patients in the ICU had died, 7 were discharged from the hospital, and 20 were still admitted while 5 patients died in the non-ICU cohort with 97 discharged and 12 patients admitted. CONCLUSIONS: This is the largest study assessing clinical differences based on the need for ICU admission in inpatients with SARS-CoV-2. It found few major differences in clinical variables between subsets. Among patients admitted to the ICU, outcomes were generally poor.

Factors Associated with a Positive Severe Acute Respiratory Syndrome Coronavirus 2 Testing in Suspected Cases Presenting with Pneumonia: A Retrospective Cohort Study in a Single Medical Center.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global emerging infectious disease. OBJECTIVES: To analyze the initial clinical characteristics of COVID-19 suspected and confirmed patients on admission in order to find out which kinds may be more likely to get positive nucleic acid testing results, and to explore the risk factors associated with all-cause death. METHODS: Medical records from 309 highly suspected cases with pneumonia were collected from February 13, 2020, to March 14, 2020, in a COVID-19-designated hospital of Wuhan. The majority of the clinical data were collected on the first day of hospital admission. RESULTS: Of 309 patients with median age 64 years (interquartile ranges [IQR], 53-72 years), 111 patients (35.9%) were confirmed by nucleic acid testing (median age 64 years, IQR: 56-71 years; 48 males). Of those 111 patients, 13 (11.7%) patients died. In multivariate analysis, factors associated with positive testing included fatigue (odds ratios [OR] = 3.14; 95% confidence interval [CI]: 1.88-5.24, p < 0.001), cough (OR = 0.55; 95% CI: 0.32-0.95, p = 0.032), no less than 1 comorbidity (OR = 1.77; 95% CI: 1.06-2.98, p = 0.030), and severe pneumonia (OR = 2.67; 95% CI: 1.20-5.97, p = 0.016). Furthermore, age, dyspnea, noneffective antibiotic treatment, white blood cell, lymphocyte, platelets, and organ dysfunction (e.g., higher lactate dehydrogenase) were significantly associated with all-cause in-hospital death in patients with COVID-19. CONCLUSION: Patients with severe forms of this disease were more likely to get positive results. Age and organ dysfunction were associated with a greater risk of death.

A biomarker based severity progression indicator for COVID-19: the Kuwait prognosis indicator score.

BACKGROUND: COVID-19 is a worldwide pandemic that is mild in most patients but can result in a pneumonia like illness with progression to acute respiratory distress syndrome and death. Predicting the disease severity at time of diagnosis can be helpful in prioritizing hospital admission and resources. METHODS: We prospectively recruited 1096 consecutive patients of whom 643 met the inclusion criterion with COVID-19 from Jaber Hospital, a COVID-19 facility in Kuwait, between 24 February and 20 April 2020. The primary endpoint of interest was disease severity defined algorithmically. Predefined risk variables were collected at the time of PCR based diagnosis of the infection. Prognostic model development used 5-fold cross-validated regularized logit regression. The model was externally validated against data from Wuhan, China. RESULTS: There were 643 patients with clinical course data of whom 94 developed severe COVID-19. In the final model, age, CRP, procalcitonin, lymphocyte percentage, monocyte percentages and serum albumin were independent predictors of a more severe illness course. The final prognostic model demonstrated good discrimination, and both discrimination and calibration were confirmed with an external dataset. CONCLUSION: We developed and validated a simple score calculated at time of diagnosis that can predict patients with severe COVID-19 disease reliably and that has been validated externally. The KPI score calculator is now available online at covidkscore.com.