Coronavirus Disease 2019 Adverse Outcomes Research Articles

COVID-19 mortality in 1984 Bhopal gas tragedy survivors: implications for chemically exposed populations.

Leakage of methyl isocyanate from the Union Carbide plant in Bhopal, India, killed thousands and left deleterious trans-generational effects. Gas-exposed populations experience higher rates of lung and metabolic diseases, and immune dysregulation, all associated with adverse outcomes in coronavirus disease 2019 (COVID-19). We used publicly available, official data from government sources to estimate COVID-19-associated crude mortality in populations with and without a history of gas exposure. Overall, there were 1240 deaths among patients hospitalized with known COVID-19 in Bhopal, of which 453 (36.53%) were in gas-exposed individuals, 726 (58.55%) were in gas-unexposed individuals and the exposure status of 61 (4.92%) individuals could not be determined. There were 351 and 375 deaths in gas-unexposed people in the first (April 2020-February 2021) and second (March 2021-July 2021) waves, respectively; in the gas-exposed population, there were 300 and 153 deaths in the two respective waves. The overall annualized crude mortality of COVID-19 was 3.84 (95% CI 3.41 to 4.33) times higher in the gas-exposed population at 83.6 (95% CI 76.1 to 91.7) per 100 000 compared with the gas-unexposed population, at 21.8 (95% CI 20.2 to 23.4) per 100,000. When stratified by age, compared with unexposed people, the gas-exposed individuals experienced 1.88 (95% CI 1.61 to 2.21) and 1.24 (95% CI 1.02 to 1.50) times the mortality rates in the age groups of 35-65 and >65 y, respectively. These findings indicate that gas-exposed individuals are likely to have a higher risk of severe COVID-19 and death and need to be specifically targeted and recognized for preventive and promotive efforts.

Physical fitness level and the risk of severe COVID-19: A systematic review.

To verify systematically the association between the status of physical fitness and the risk of severe Coronavirus disease 2019 (COVID-19). This systematic review is in accordance with the Preferred Reporting Items for Systematic Review and Meta Analyses (PRISMA) statement and the eligibility criteria followed the Population, Intervention, Comparison, Outcomes and Study (PICOS) recommendation. PubMed, Embase, SciELO and Cochrane electronic databases were searched. All studies that explored the relationship between the pattern of physical fitness and COVID-19 adverse outcomes (hospitalization, intensive care unit admission, intubation, or mortality), were selected. The quality of the studies was assessed by the specific scale of the Newcastle-Ottawa Scale. A total of seven observational studies were identified in this systematic review; 13​468 patients were included in one case-control study, two cohort studies, and four cross-sectional studies. All studies reported an inverse association between high physical fitness and severe COVID-19 (hospitalization, intensive care admission, or mortality). Only some studies reported comorbidities, especially obesity and cardiovascular disorders, but the results remained unchanged after controlling for comorbidities. The quality of the seven studies included was moderate according to the Newcastle-Ottawa Quality Assessment Scale. The methodological heterogeneity of the studies included did not allow a meta-analysis of the findings. In conclusion, higher physical fitness levels were associated with lower risk of hospitalization, intensive care admissions, and mortality rates among patients with COVID-19.

MicroRNA 205-5p and COVID-19 adverse outcomes: Potential molecular biomarker and regulator of the immune response.

Coronavirus disease 2019 (COVID-19) is an acute respiratory infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The uncontrolled systemic inflammatory response, resulting from the release of large amounts of pro-inflammatory cytokines, is the main mechanism behind severe acute respiratory syndrome and multiple organ failure, the two main causes of death in COVID-19. Epigenetic mechanisms, such as gene expression regulation by microRNAs (miRs), may be at the basis of the immunological changes associated with COVID-19. Therefore, the main objective of the study was to evaluate whether the expression of miRNAs upon hospital admission could predict the risk of fatal COVID-19. To evaluate the level of circulating miRNAs, we used serum samples of COVID-19 patients collected upon hospital admission. Screening of differentially expressed miRNAs in fatal COVID-19 was performed by miRNA-Seq and the validation of miRNAs by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The Mann-Whitney test and receiver operating characteristic (ROC) curve were used to validate the miRNAs, whose potential signaling pathways and biological processes were identified through an in silico approach. A cohort of 100 COVID-19 patients was included in this study. By comparing the circulating levels of miRs between survivors and patients who died due to complications of the infection, we found that the expression of miR-205-5p was increased in those who died during hospitalization, and the expression of both miR-205-5p (area under the curve [AUC] = 0.62, 95% confidence interval [CI] = 0.5-0.7, P = 0.03) and miR-206 (AUC = 0.62, 95% CI = 0.5-0.7, P = 0.03) was increased in those who lately evolved to severe forms of the disease (AUC = 0.70, 95% CI = 0.6-0.8, P = 0.002)."In silico" analysis revealed that miR-205-5p has the potential to enhance the activation of NLPR3 inflammasome and to inhibit vascular endothelial growth factor (VEGF) pathways. Impaired innate immune response against SARS-CoV-2 may be explained by epigenetic mechanisms, which could form early biomarkers of adverse outcomes.

COVID-19 Adverse Outcomes in Immunocompromised Patients

Background: Coronavirus disease 2019 (COVID-19) is a devastating viral pandemic infecting millions of people with a wide range of symptoms from fever to death. It has been suggested that immunocompromised patients are at a higher risk of severe disease, poor clinical outcomes, and mortality. However, these patients’ risk factors and COVID-19-related outcomes are not well characterized. Objectives: We evaluated the COVID-19-related outcomes among immunocompromised patients ranging from solid tumors, hematological malignancies, and HIV to autoimmune disease and transplant recipients who received immunosuppressive agents. We also aimed at finding risk factors related to mortality among immunocompromised patients with COVID-19. Methods: This cross-sectional study was conducted in Khansari Hospital, Iran between March and November 2021. We included immunocompromised patients with nasal swab positive SARS-CoV-2 polymerase chain reaction (PCR) results in the study. Patient outcomes, including hospitalization ward and the mortality rate, were assessed till three months after COVID-19 infection were evaluated in all patients. Moreover, the relation between risk factors and the rate of the mortality rate was analyzed in immunocompromised patients with COVID-19. Results: A total number of 74 immunocompromised patients with solid tumors, hematologic malignancies, autoimmune diseases, acquired immunodeficiencies, and solid-organ transplant recipients were included in the study. Results indicated that the male gender and ICU hospitalization significantly increase the mortality risk. Surprisingly, chemotherapy is associated with a lower risk of mortality. Conclusions: Identifying the risk factors can improve the decision-making on cancer patients’ management during the COVID-19 infection. A further large cohort of patients would be required to identify risk factors relating to poor clinical outcomes and mortality rates in immunocompromised patients with COVID-19.

Efficacy of serum apelin and galectin-3 as potential predictors of mortality in severe COVID-19 patients.

Apelin is a cardioprotective biomarker while galectin-3 is a pro-inflammatory and profibrotic biomarker. Endothelial dysfunction, hyperinflammation, and pulmonary fibrosis are key mechanisms that contribute to the development of adverse outcomes in Coronavirus disease 2019 (COVID-19)infection. This study aims to analyze the prognostic value of serum apelin and galectin-3 levels to early predict patients at high risk of mortality in patients hospitalized for severe COVID-19 pneumonia.The study included 78 severe COVID-19 patients and 40 healthy controls. The COVID-19 patients were divided into two groups, survivors and nonsurvivors, according to their in-hospital mortality status. Basic demographic and clinical data of all patients were collected, and blood samples were taken before treatment.In our study, serum apelin levels were determined to be significantly lower in both nonsurvivor and survivor COVID-19 patients compared to the control subjects (for both groups, p < 0.001). However, serum apelin levels were similar in survivor and nonsurvivor COVID-19 patients (p > 0.05). Serum galectin-3 levels were determined to be higher in a statistically significant way in nonsurvivors compared to survivors and controls (for both groups; p < 0.001). Additionally, serum galectin-3 levels were significantly higher in the survivor patients compared to the control subjects (p < 0.001). Positive correlations were observed between galectin-3 and age, ferritin, CK-MB and NT-proBNP variables (r = 0.32, p = 0.004; r = 0.24, p = 0.04; r = 0.24, p = 0.03; and r = 0.33, p = 0.003, respectively) while a negative correlation was observed between galectin-3 and albumin (r = -0.31, p = 0.006). Multiple logistic regression analysis revealed that galectin-3 was an independent predictor of mortality in COVID-19 patients (odds ratio [OR] = 2.272, 95% confidence interval [CI] = 1.106-4.667; p = 0.025). When the threshold value for galectin-3 was regarded as 2.8 ng/ml, it was discovered to predict mortality with 80% sensitivity and 57% specificity (area under the curve = 0.738, 95% CI = 0.611-0.866, p = 0.002).Galectin-3 might be a simple, useful, and prognostic biomarker that can be utilized to predict patients who are at high risk of mortality in severe COVID-19 patients.

Factors associated with improved outcome of inhaled corticosteroid use in COVID-19: A single institutional study.

Asthmatics seem less prone to adverse outcomes in coronavirus disease 2019 (COVID-19) and some data shows that inhaled corticosteroids (ICS) are protective. We gathered data on anecdotal ICS and outcomes of patients hospitalized with COVID-19, given there is literature supporting ICS may reduce risk of severe infection. In addition, we fill gaps in current literature evaluating Charlson Comorbidity Index (CCI) as a risk assessment tool for COVID-19. This was a single-center, retrospective study designed and conducted to identify factors associated intubation and inpatient mortality. A multivariate logistic regression model was fit to generate adjusted odds ratios (OR). Intubation was associated with male gender (OR, 2.815; 95% confidence interval [CI], 1.348-5.881; P = .006) and increasing body mass index (BMI) (OR, 1.053; 95% CI, 1.009-1.099; P = .019). Asthma was associated with lower odds for intubation (OR, 0.283; 95% CI, 0.108-0.74; P = .01). 80% of patients taking pre-hospital ICS were not intubated (n = 8). In-patient mortality was associated with male gender (OR, 2.44; 95% CI, 1.167-5.1; P = .018), older age (OR, 1.096; 95% CI, 1.052-1.142; P = <.001), and increasing BMI (OR, 1.079; 95% CI, 1.033-1.127; P = .001). Asthma was associated with lower in-patient mortality (OR, 0.221; 95% CI, 0.057-0.854; P = .029). CCI did not correlate with intubation (OR, 1.262; 95% CI, 0.923-1.724; P = .145) or inpatient mortality (OR, 0.896; 95% CI, 0.665-1.206; P = .468). Asthmatics hospitalized for COVID-19 had less adverse outcomes, and most patients taking pre-hospital ICS were not intubated. CCI score was not associated with intubation or inpatient mortality.

Reduction in Serum Magnesium Levels and Renal Function Are Associated with Increased Mortality in Obese COVID-19 Patients.

Several studies provide evidence that obesity is a significant risk factor for adverse outcomes in coronavirus disease 2019 (COVID-19). Altered renal function and disturbances in magnesium levels have been reported to play important pathophysiological roles in COVID-19. However, the relationship between obesity, renal function, circulating magnesium levels, and mortality in patients with COVID-19 remains unclear. In this retrospective cohort study, we characterized 390 hospitalized patients with COVID-19 that were categorized according to their body mass index (BMI). Patients were clinically characterized and biochemical parameters, renal function, and electrolyte markers measured upon admission. We found that in patients who died, BMI was associated with reduced estimated glomerular filtration rate (eGFR, Rho: −0.251, p = 0.001) and serum magnesium levels (Rho: −0.308, p < 0.0001). Multiple linear regression analyses showed that death was significantly associated with obesity (p = 0.001). The Cox model for obese patients showed that magnesium levels were associated with increased risk of death (hazard ratio: 0.213, 95% confidence interval: 0.077 to 0.586, p = 0.003). Thus, reduced renal function and lower magnesium levels were associated with increased mortality in obese COVID-19 patients. These results suggest that assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce mortality among obese COVID-19 patients.

Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor.

Of the patients infected with coronavirus disease 2019 (COVID-19), approximately 14–53% developed liver injury resulting in poor outcomes. Drug-induced liver injury (DILI) is the primary cause of liver injury in COVID-19 patients. In this study, we elucidated liver injury mechanism induced by drugs of pharmacologic treatments against SARS-CoV-2 (DPTS) using bioinformatics and systems biology. Totally, 1209 genes directly related to 216 DPTS (DPTSGs) were genes encoding pharmacokinetics and therapeutic targets of DPTS and enriched in the pathways related to drug metabolism of CYP450s, pregnane X receptor (PXR), and COVID-19 adverse outcome. A network, constructed by 110 candidate targets which were the shared part of DPTSGs and 445 DILI targets, identified 49 key targets and four Molecular Complex Detection clusters. Enrichment results revealed that the 4 clusters were related to inflammatory responses, CYP450s regulated by PXR, NRF2-regualted oxidative stress, and HLA-related adaptive immunity respectively. In cluster 1, IL6, IL1B, TNF, and CCL2 of the top ten key targets were enriched in COVID-19 adverse outcomes pathway, indicating the exacerbation of COVID-19 inflammation on DILI. PXR-CYP3A4 expression of cluster 2 caused DILI through inflammation-drug interaction and drug-drug interactions among pharmaco-immunomodulatory agents, including tocilizumab, glucocorticoids (dexamethasone, methylprednisolone, and hydrocortisone), and ritonavir. NRF2 of cluster 3 and HLA targets of cluster four promoted DILI, being related to ritonavir/glucocorticoids and clavulanate/vancomycin. This study showed the pivotal role of PXR associated with inflammation-drug and drug-drug interactions on DILI and highlighted the cautious clinical decision-making for pharmacotherapy to avoid DILI in the treatment of COVID-19 patients.

Prognostic Value of Mid-Region Proadrenomedullin and In Vitro Interferon Gamma Production for In-Hospital Mortality in Patients with COVID-19 Pneumonia and Respiratory Failure: An Observational Prospective Study.

Coagulopathy and immune dysregulation have been identified as important causes of adverse outcomes in coronavirus disease (COVID-19). Mid-region proadrenomedullin (MR-proADM) is associated with endothelial damage and has recently been proposed as a prognostic factor in COVID-19. In non-COVID-19 immunocompromised patients, low in vitro interferon gamma (IFNγ) production correlates with infection risk and mortality. This prospective, monocentric, observational study included adult patients consecutively admitted with radiologic evidence of COVID-19 pneumonia and respiratory failure. MR-proADM and in vitro IFNγ production were measured at T0 (day 1 from admission) and T1 (day 7 from enrollment). One hundred patients were enrolled. Thirty-six percent were females, median age 65 (Q1–Q3 54.5–75) years, and 58% had ≥1 comorbidity. Only 16 patients had received COVID-19 vaccination before hospitalization. At admission, the median PaO2:FiO2 ratio was 241 (157–309) mmHg. In-hospital mortality was 13%. MR-proADM levels differed significantly between deceased and survivors both at T0 (1.41 (1.12–1.77) nmol/L vs. 0.79 (0.63–1.03) nmol/L, p < 0.001) and T1 (1.67 (1.08–1.96) nmol/L vs. 0.66 (0.53–0.95) nmol/L, p < 0.001). In vitro IFNγ production at T0 and T1 did not vary between groups. When only the subset of non-vaccinated patients was considered, both biomarkers at T1 resulted significantly associated with in-hospital mortality. AUROC for MR-proADM at T0 to predict in-hospital mortality was 0.87 (95%CI 0.79–0.94), with the best cut-off point at 1.04 nmol/L (92% sensitivity, 75% specificity and 98% negative predictive value). In patients with COVID-19 pneumonia and different degrees of respiratory failure, MR-proADM at admission and during hospitalization resulted strongly associated with in-hospital mortality. Low in vitro IFNγ production after the first week of hospitalization was associated with mortality in non-vaccinated patients possibly identifying the subgroup characterized by a higher degree of immune suppression.

Association of COVID-19 severity with body mass index and underlying comorbid conditions-a hospital-based cross-sectional study

Background: To reduce the severity of the disease among COVID-19 patients with co-morbidities is the need of the hour. Obesity may contribute to adverse outcomes in coronavirus disease 2019 (COVID-19). This study aimed to find the association between the COVID-19 biomarker values and the underlying comorbid conditions and assess the severity of the disease according to the patients' body mass index (BMI).Methods: A single centre cross-sectional study was conducted in a tertiary hospital among 184 COVID-19 patients admitted for one month (June-July 2021).Results: The results show a statistically significant association between the COVID-19 severity and co-morbidity status of the patients, with diabetes mellitus being the most prevalent co-morbidity among the patients, followed by diabetes with hypertension. A statistically significant association was also seen between age and co-morbidity and biomarkers and co-morbidity.Conclusions: Obesity and other comorbid conditions like diabetes mellitus and hypertension should be given utmost importance during treatment among COVID-19 patients. Biomarker screening should be routinely done in patients with co-morbidities and obesity. Awareness among the COVID-19 patients regarding the comorbid conditions and BMI is the need of the hour.

The association between statin and COVID-19 adverse outcomes: national COVID-19 cohort in South Korea.

There currently exist limited and conflicting clinical data on the use of statins in coronavirus disease 2019 (COVID-19) patients. The aim of this paper was to compare hospitalized patients with COVID-19 who did and did not receive statins. We performed a population-based retrospective cohort study using South Korea's nationwide healthcare claim database. We identified consecutive patients hospitalized with COVID-19 and aged 40 years or older. Statin users were individuals with inpatient and outpatient prescription records of statins in the 240 days before cohort entry to capture patients who are chronic statin users and, therefore, receive statin prescriptions as infrequently as every 8 months. Our primary endpoint was a composite of all-cause death, intensive care unit (ICU) admission, mechanical ventilation use and cardiovascular outcomes [myocardial infarction (MI), transient cerebral ischemic attacks (TIA) or stroke]. We compared the risk of outcomes between statin users and non-users using logistic regression models after inverse probability of treatment weighting (IPTW) adjustment. Of 234,427 subjects in the database, 4,349 patients were hospitalized with COVID-19 and aged 40+ years. In total, 1,115 patients were statin users (mean age =65.9 years; 60% female), and 3,234 were non-users (mean age =58.3 years; 64% female). Pre-hospitalization statin use was not significantly associated with increased risk of the primary endpoint [IPTW odds ratio (OR) 0.82; 95% confidence interval (CI): 0.60-1.11]. Subgroup analysis showed a protective role of antecedent statin use for individuals with hypertension (IPTW OR 0.40; 95% CI: 0.23-0.69, P for interaction: 0.0087). Pre-hospitalization statin use is not detrimental and may be beneficial amongst hypertensive COVID-19 patients. Further investigation into statin is needed for more conclusive effects of statins for treatment of COVID-19.

333. Comparing COVID-19-related Morbidity and Mortality between Patients with and without Substance Use Disorder: A Retrospective Cohort Study

BackgroundEarly data suggest that people with substance use disorder (SUD) who develop coronavirus disease 2019 (COVID-19) have increased intubation and mortality rates when compared to those without SUD. Information on other COVID-19-related complications in this population is limited. We evaluated COVID-19 outcomes in patients with and without SUD.MethodsWe created a retrospective cohort of patients with COVID-19 admitted to an urban safety net hospital from 3/16/2020 to 4/8/2020. Inclusion criteria were admission with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and age greater than 18 years. SUD included alcohol use disorder or heavy alcohol use as defined by the National Institute on Alcohol Abuse and Alcoholism, use of cocaine, non-prescribed opioids or amphetamines. Primary outcome was inpatient mortality. Secondary outcomes were clinical complications (intubation, secondary infections, renal failure, venous thromboembolism, stroke, hepatitis, myocardial infarct, multisystem organ failure) and resource utilization (length of stay, intensive care unit [ICU] admission, ICU days, readmission). We used multivariable regression to assess factors associated with mortality and length of stay, and univariate analyses for other outcomes.ResultsOf 409 included patients, 70 (17.1%) had SUD. Those with SUD were more likely to be male and have pulmonary disease or hepatitis C. There were no differences in other comorbidities, mean age or race/ethnicity. After multivariable analysis, SUD was not associated with mortality (aOR 1.60; 95% CI, 0.60-3.81). Similarly baseline oxygenation defined as the ratio of oxygen saturation to fraction of inspired oxygen (aOR 1.57; 0.11-13.0) and administration of immunomodulatory therapy (tocilizumab, sarilumab or anakinra) (aOR 1.41; 0.65-3.01) did not affect mortality. In contrast, age (aOR 1.06; 1.03-1.09), sex (aOR 2.30; 1.04-5.47) and obstructive sleep apnea (aOR 4.07; 1.64-9.66) were associated with mortality. We did not find any associations with secondary outcomes.ConclusionOur findings suggest that substance use alone may not increase COVID-19 adverse outcomes. Future studies should evaluate these results in the current period of improved COVID-19 therapy.Disclosures All Authors: No reported disclosures

Immunopathology and Immunosenescence, the Immunological Key Words of Severe COVID-19. Is There a Role for Stem Cell Transplantation?

The outcomes of Coronavirus disease-2019 (COVID-19) vary depending on the age, health status and sex of an individual, ranging from asymptomatic to lethal. From an immunologic viewpoint, the final severe lung damage observed in COVID-19 should be caused by cytokine storm, driven mainly by interleukin-6 and other pro-inflammatory cytokines. However, which immunopathogenic status precedes this “cytokine storm” and why the male older population is more severely affected, are currently unanswered questions. The aging of the immune system, i.e., immunosenescence, closely associated with a low-grade inflammatory status called “inflammageing,” should play a key role. The remodeling of both innate and adaptive immune response observed with aging can partly explain the age gradient in severity and mortality of COVID-19. This review discusses how aging impacts the immune response to the virus, focusing on possible strategies to rejuvenate the immune system with stem cell-based therapies. Indeed, due to immunomodulatory and anti-inflammatory properties, multipotent mesenchymal stem cells (MSCs) are a worth-considering option against COVID-19 adverse outcomes.

Impact of COVID-19 on inflammatory bowel disease practice and perspectives for the future.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); since its first description in December 2019, it has rapidly spread to a global pandemic. Specific concerns have been raised concerning patients with inflammatory bowel diseases (IBD), which are chronic autoimmune inflammatory disorders of the gut that frequently require immunosuppressive and biological therapies to control their activity. Accumulating evidence has so far demonstrated that patients with IBD are not at increased risk of contracting severe acute respiratory syndrome coronavirus 2 infection. As for the general population, the identified risk factors for severe COVID-19 course among IBD patients have been established to be advanced age and the presence of comorbidities. Treatment with high-dose corticosteroids has also been associated with an increased risk of death in IBD patients with COVID-19. Information on COVID-19 is constantly evolving, with data growing at a rapid pace. This will guarantee better knowledge and stronger evidence to help physicians in the choice of the best therapeutic approach for each patient, concurrently controlling for the risk of IBD disease under treatment and the risk of COVID-19 adverse outcomes and balancing the two. Moreover, the impact of the enormous number of severe respiratory patients on healthcare systems and facilities has led to an unprecedented redeployment of healthcare resources, significantly impacting the care of patients with chronic diseases. In this newly changed environment, the primary aim is to avoid harm whilst still providing adequate management. Telemedicine has been applied and is strongly encouraged for patients without the necessity of infusion therapy and whose conditions are stable. The severe acute respiratory syndrome coronavirus 2 pandemic has already revolutionized the management of patients with chronic immune-mediated diseases such as IBD. Direct and indirect effects of the COVID-19 pandemic will be present for some time. This is the reason why continuous research, rapid solutions and constantly updated guidelines are of utmost importance. The aim of the present review is, therefore, to point out what has been learned so far as well as to pinpoint the unanswered questions and perspectives for the future.

Sex Differences in Association Between Anti-Hypertensive Medications and Risk of COVID-19 in Middle-Aged and OlderAdults.

BackgroundThere is ongoing debate about the associations between drug therapies targeting the renin–angiotensin–aldosterone system (RAAS) and adverse outcomes in coronavirus disease 2019 (COVID-19).ObjectiveThis study aims to examine the associations between using medications for the cardiovascular system and the risks associated with COVID-19 in middle-aged and older adults.MethodsA total of 77,221 participants (aged 50–86 years) from UK Biobank were tested for SARS-CoV-2 RNA. The medications included angiotensin-converting enzyme inhibitors (ACEI), angiotensin-receptor blockers (ARB), β-blockers, calcium channel blockers (CCB), statins, and aspirin. COVID-19 outcomes comprised a positive test result and severity of COVID-19 (defined as mild, hospitalization or death). We evaluated the risk among total participants and for sub-groups based on sex. Propensity score matching was performed 1:1 and logistic regression models were used.ResultsAmong the middle- and older aged participants, no significant associations between any class of medications and the likelihood of COVID-19 infection were observed. ACEI were associated with a higher mortality risk from COVID-19 (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.01–1.32) and CCB were associated with a lower hospitalization risk for COVID-19 (OR 0.87, 95% CI 0.79–0.96) among the male patients with COVID-19, while a lower mortality risk from COVID-19 (OR 0.67, 95% CI 0.47–0.96) was observed with ARB among the female patients with COVID-19.ConclusionsThe study suggested sex differences in the risk of death from COVID-19 with the use of ACEI and ARB among middle-aged and older adults. Sex differences in the risk of hospitalization for COVID-19 with the use of CCB was observed as well. It is of clinical importance that clinicians adopt different CVD treatment approaches for female and male patients with COVID-19.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40266-021-00886-y.

INR and COVID-19 severity and mortality: A systematic review with meta-analysis and meta-regression

ObjectivesD-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19. MethodsA literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468). ResultsThirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 ​% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 ​% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 ​% confidence interval, CI 0.42 to 0.77; p ​< ​0.001). There was extreme between-study heterogeneity (I2 ​= ​90.2 ​%; p ​< ​0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p ​= ​0.048) and D-dimer (p ​= ​0.001). ConclusionsProlonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes.

Admission Characteristics and Mortality Risk Among Patients Hospitalized with COVID-19.

Admission Characteristics and Mortality Risk Among Patients Hospitalized with COVID-19.

Radiographic Hepatic Steatosis Is Not Associated With Key Clinical Outcomes Among Patients Hospitalized With COVID-19.

BackgroundMetabolic syndrome increases adverse outcomes in coronavirus disease 2019 (COVID-19) infection. Hepatic steatosis may increase risk of COVID-19 severity. Current studies evaluating steatosis lack reliable definitions. We aimed to evaluate the association of radiographic hepatic steatosis and clinical outcomes of COVID-19 severity in a diverse cohort.MethodsWe retrospectively identified patients with COVID-19 infection admitted to two US academic hospitals. Outcomes were length of stay, intensive care unit use, mechanical ventilation, and in-hospital mortality. We used Mann-Whitney U-test for continuous measures and Chi-square or Fisher’s exact test for categorical measures. Multivariable linear and logistic regression analyses were used to adjust for confounders.ResultsOf the 319 patients, 14% had hepatic steatosis. There were no differences in length of stay (6 (4 - 16) vs. 9 (4 - 18) days, P = 0.6), intensive care unit (24% vs. 32%, P = 0.3), mechanical ventilation (28% vs. 38%, P = 0.32), or in-hospital mortality (7% vs. 17%, P = 0.12). After adjustment, there was no difference in length of stay (β: -14.37, 95% confidence interval (CI): -30.5 - 1.77, P = 0.08), intensive care unit (odds ratio (OR): 0.31, 95% CI: 0.03 - 1.09, P = 0.06), mechanical ventilation (OR: 0.13, 95% CI: 0.02 - 1.09, P = 0.06), or in-hospital mortality (OR: 0.27, 95% CI: 0.06 - 1.16, P = 0.08) among patients with hepatic steatosis.ConclusionRadiographic hepatic steatosis was not associated with worse outcomes among patients hospitalized with COVID-19.

Do Certain Biomarkers Predict Adverse Outcomes in Coronavirus Disease 2019?

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Given the rapid spread of the disease, the World Health Organization (WHO) declared the 2019 - 2020 coronavirus outbreak a Public Health Emergency of International Concern (PHEIC) on January 30, 2020, and a pandemic on March 11, 2020. There have been several reports of the limited resources including the lack of intensive care unit (ICU) beds and mechanical ventilators. Thus, biomarkers that predict ICU stay and mortality will be an important tool to appropriately allocate the limited resources. The aim of this review was to identify laboratory markers that can effectively predict the risk of severe infection and increased mortality in COVID-19 cases. We conducted a systematic review of existing literature in six databases to evaluate the predictive value of various biomarkers. We used the keywords “COVID-19”, “SARS-CoV-2”, “Novel corona virus pneumonia”, “Biomarkers”, “Adverse outcomes”, “Mortality”, etc. among many others to refine our search. Several biomarkers were identified to be associated with adverse outcomes in the above studies. These biomarkers can be used as a tool to identify patients at increased risk for adverse outcomes so that the need for aggressive critical care in such patients is met.

Chest radiography predictor of COVID-19 adverse outcomes. A lesson learnt from the first wave

AIMTo assess the role of a severity score based on chest radiography (CXR) in predicting the risk of adverse outcomes in coronavirus disease 2019 (COVID-19).MATERIALS AND METHODSOf the patients who presented to L. Sacco Hospital (Milan, Italy) between 21 February and 31 March 2020, patients with a laboratory confirmation of COVID-19 who also underwent a CXR were included in the study. To quantify the extent of lung involvement, each CXR image was given a score (Milan score), ranging from 0 to 24, depending on the presence of reticular pattern and/or ground-glass opacities and/or extensive consolidations in each of the 12 areas in which the lungs were divided. The score was calculated by an expert radiologist, blinded to laboratory tests. The ability of the Milan score to predict hospital admission and mortality, after adjusting for some variables (age; gender; comorbidities; time between symptoms onset and admission), using univariate and multivariate statistical analysis was investigated retrospectively.RESULTSAmong the 554 patients, 115 of which (21%) had a negative CXR, the in-hospital mortality was 16% (90/554). At univariate analysis, age, gender, and comorbidities were significant predictors of mortality and hospital admission. At multivariate analysis, adjusting for age and gender, the Milan score was an independent predictor of mortality and hospitalisation. In particular, patients with a Milan score ≥ 9 had a mortality risk five-times higher than those with a lower score. Other independent predictors of mortality were gender and age.CONCLUSIONSThe CXR Milan score was an independent predictive factor of both in-hospital mortality and hospital admission.