Characteristics and outcomes of an international cohort of 600 000 hospitalized patients with COVID-19.

BACKGROUND: We describe demographic features, treatments and clinical outcomes in the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) COVID-19 cohort, one of the world's largest international, standardized data sets concerning hospitalized patients. METHODS: The data set analysed includes COVID-19 patients hospitalized between January 2020 and January 2022 in 52 countries. We investigated how symptoms on admission, co-morbidities, risk factors and treatments varied by age, sex and other characteristics. We used Cox regression models to investigate associations between demographics, symptoms, co-morbidities and other factors with risk of death, admission to an intensive care unit (ICU) and invasive mechanical ventilation (IMV). RESULTS: Data were available for 689 572 patients with laboratory-confirmed (91.1%) or clinically diagnosed (8.9%) SARS-CoV-2 infection from 52 countries. Age [adjusted hazard ratio per 10 years 1.49 (95% CI 1.48, 1.49)] and male sex [1.23 (1.21, 1.24)] were associated with a higher risk of death. Rates of admission to an ICU and use of IMV increased with age up to age 60 years then dropped. Symptoms, co-morbidities and treatments varied by age and had varied associations with clinical outcomes. The case-fatality ratio varied by country partly due to differences in the clinical characteristics of recruited patients and was on average 21.5%. CONCLUSIONS: Age was the strongest determinant of risk of death, with a ∼30-fold difference between the oldest and youngest groups; each of the co-morbidities included was associated with up to an almost 2-fold increase in risk. Smoking and obesity were also associated with a higher risk of death. The size of our international database and the standardized data collection method make this study a comprehensive international description of COVID-19 clinical features. Our findings may inform strategies that involve prioritization of patients hospitalized with COVID-19 who have a higher risk of death.

Variation in COVID-19 disease severity at hospital admission over time and across hospitals: A multi-institution cohort of Michigan hospitals.

ABSTRACT: During the spring 2020 COVID-19 surge, hospitals in Southeast Michigan were overwhelmed, and hospital beds were limited. However, it is unknown whether threshold for hospital admission varied across hospitals or over time.Using a statewide registry, we performed a retrospective cohort study. We identified adult patients hospitalized with COVID-19 in Southeast Michigan (3/1/2020-6/1/2020). We classified disease severity on admission using the World Health Organization (WHO) ordinal scale. Our primary measure of interest was the proportion of patients admitted on room air. We also determined the proportion without acute organ dysfunction on admission or any point during hospitalization. We quantified variation across hospitals and over time by half-month epochs.Among 1315 hospitalizations across 22 hospitals, 57.3% (754/1,315) were admitted on room air, and 26.1% (343/1,315) remained on room air for the duration of hospitalization. Across hospitals, the proportion of COVID-19 hospitalizations admitted on room air varied from 32.3% to 80.0%. Across half-month epochs, the proportion ranged from 49.4% to 69.4% and nadired in early April 2020. Among patients admitted on room air, 75.1% (566/754) had no acute organ dysfunction on admission, and 35.3% (266/754) never developed acute organ dysfunction at any point during hospitalization; there was marked variation in both proportions across hospitals. In-hospital mortality was 13.7% for patients admitted on room air vs 26.3% for patients requiring nasal cannula oxygen.Among patients hospitalized with COVID-19 during the spring 2020 surge in Southeast Michigan, more than half were on room air and a third had no acute organ dysfunction upon admission, but experienced high rates of disease progression and in-hospital mortality.

Equitable Access to Liver Transplant: Bridging the Gaps in the Social Determinants of Health.

The COVID-19 pandemic and social justice movement have highlighted the impact of social determinants of health (SDOH) and structural racism in the United States on both access to care and patient outcomes. With the evaluation for liver transplantation being a highly subjective process, there are multiple ways for SDOH to place vulnerable patients at a disadvantage. This policy corner focuses on three different methods to reverse the deleterious effects of SDOH-identify and reduce implicit bias, expand and optimize telemedicine, and improve community outreach.

The prevalence and impact of pre-existing sleep disorder diagnoses and objective sleep parameters in patients hospitalized for COVID-19.

STUDY OBJECTIVES: Obstructive sleep apnea and other sleep disorders overlap with comorbidities associated with poor outcomes related to severe acute respiratory syndrome coronavirus 2 infection. However, the prevalence of obstructive sleep apnea among patients hospitalized for COVID-19 and relationship to outcomes is poorly characterized, and the relevance of other sleep disorders remains unknown. The objective of this study was to identify the prevalence of pre-existing sleep disorders and association with outcomes related to severe COVID-19 illness. METHODS: Patients with severe acute respiratory syndrome coronavirus 2 infection admitted to the University of Michigan Hospital System were included. Electronic medical records were queried for sleep disorders diagnostic codes. Data were extracted from polysomnography and home sleep testing in a subgroup with previous diagnostic testing at our center. Logistic regression was used to examine the association of sleep disorders with mechanical ventilation requirement, treatment with vasopressors, and death and Cox proportional hazards regression for time to discharge. RESULTS: Among n = 572 adult patients hospitalized for COVID-19, 113 (19.8%) patients had obstructive sleep apnea, 4 patients had central sleep apnea (0.7%), 5 had hypoventilation (0.9%), 63 had insomnia (11.0%), and 22 had restless legs syndrome or periodic limb movements disorder (3.9%). After adjusting for age, sex, body mass index, and race, no significant relationship was apparent between sleep disorders diagnoses or indices of sleep-disordered breathing severity and outcomes. CONCLUSIONS: This is the first study to determine the prevalence of obstructive sleep apnea and other sleep disorders in a well-characterized cohort of patients hospitalized for COVID-19. Once hospitalized, a significant contribution of sleep disorders to outcomes was not identified. Therefore, future evaluations should focus on earlier outcomes, such as infection or clinical manifestations after exposure to severe acute respiratory syndrome coronavirus 2.

COVID-19 Outcomes Among Solid Organ Transplant Recipients: A Case-control Study.

BACKGROUND: Solid organ transplant (SOT) recipients are considered to be "vulnerable" to COVID-19 infection due to immunosuppression. To date, there are no studies that compared the disease severity of COVID-19 in SOT recipients with nontransplant patients. METHODS: In this case-control study, we compared the outcomes of COVID-19 between SOT recipients and their matched nontransplant controls. The cases were all adult SOT recipients (N = 41) from our academic health center who were diagnosed with COVID-19 between March 10, 2020 and May 15, 2020 using positive reverse transcriptase polymerase chain reaction for SARS-CoV2. The controls (N = 121) were matched on age (±5 y), race, and admission status (hospital or outpatient). The primary outcome was death and secondary outcomes were severe disease, intubation and renal replacement therapy (RRT). RESULTS: Median age of SOT recipients (9 heart, 3 lung, 16 kidney, 8 liver, and 5 dual organ) was 60 y, 80% were male and 67% were Black. Severe disease adjusted risk of death was similar in both the groups (hazard ratio = 0.84 [0.32-2.20]). Severity of COVID-19 and intubation were similar, but the RRT use was higher in SOT (odds ratio = 5.32 [1.26, 22.42]) compared to non-SOT COVID-19 patients. Among SOT recipients, COVID-19-related treatment with hydroxychloroquine (HCQ) was associated with 10-fold higher hazard of death compared to without HCQ (hazard ratio = 10.62 [1.24-91.09]). CONCLUSIONS: Although African Americans constituted one-tenth of all SOT in our center, they represented two-thirds of COVID-19 cases. Despite high RRT use in SOT recipients, the severe disease and short-term death were similar in both groups. HCQ for the treatment of COVID-19 among SOT recipients was associated with high mortality and therefore, its role as a treatment modality requires further scrutiny.

Hepatic Steatosis Is Associated with Increased Disease Severity and Liver Injury in Coronavirus Disease-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is a global pandemic. Obesity has been associated with increased disease severity in COVID-19, and obesity is strongly associated with hepatic steatosis (HS). However, how HS alters the natural history of COVID-19 is not well characterized, especially in Western populations. AIMS: To characterize the impact of HS on disease severity and liver injury in COVID-19. METHODS: We examined the association between HS and disease severity in a single-center cohort study of hospitalized COVID-19 patients at Michigan Medicine. HS was defined by either hepatic steatosis index > 36 (for Asians) or > 39 (for non-Asians) or liver imaging demonstrating steatosis > 30 days before onset of COVID-19. The primary predictor was HS. The primary outcomes were severity of cardiopulmonary disease, transaminitis, jaundice, and portal hypertensive complications. RESULTS: In a cohort of 342 patients, metabolic disease was highly prevalent including nearly 90% overweight. HS was associated with increased transaminitis and need for intubation, dialysis, and vasopressors. There was no association between HS and jaundice or portal hypertensive complications. In a sensitivity analysis including only patients with liver imaging > 30 days before onset of COVID-19, imaging evidence of hepatic steatosis remained associated with disease severity and risk of transaminitis. CONCLUSIONS: HS was associated with increased disease severity and transaminitis in COVID-19. HS may be relevant in predicting risk of complications related to COVID-19.

Tocilizumab for Treatment of Mechanically Ventilated Patients With COVID-19.

BACKGROUND: Severe coronavirus disease 2019 (COVID-19) can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is an approved treatment. METHODS: We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability postintubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared with tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability of treatment weighting (IPTW). RESULTS: 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range, 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean: 55 vs 60 years), less likely to have chronic pulmonary disease (10% vs 28%), and had lower D-dimer values at time of intubation (median: 2.4 vs 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death (HR, .55; 95% CI, .33-.90) and improved status on the ordinal outcome scale [OR per 1-level increase, .58; .36-.94). Although tocilizumab was associated with an increased proportion of patients with superinfections (54% vs 26%; P < .001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection (22% vs 15%; P = .42). Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS: In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.