Risk factors for severe COVID-19 in the young-before and after ICU admission.

BACKGROUND: Factors associated with severe COVID-19 and death among young adults are not fully understood, including differences between the sexes. The aim of this study was to identify factors associated with severe COVID-19 requiring intensive care and 90-day mortality among women and men below 50 years of age. METHODS: A register-based study using data from mandatory national registers, where patients with severe COVID-19 admitted to the ICU with need for mechanical ventilation (cases) between March 2020 and June 2021 were matched regarding age, sex, and district of residence with 10 population-based controls. Both the study population and the controls were divided into groups based on age (< 50 years, 50-64, and ≥ 65 years) and sex. Multivariate logistic regression models including socioeconomic factors were used to calculate odds ratios (OR) with 95% confidence intervals (CIs) for associations between severe COVID-19 in the population to compare the magnitude of the risk associations for co-morbidities in the different age categories, and subsequently factors associated with 90-day mortality among patients admitted to ICU. RESULTS: In total, 4921 cases and 49,210 controls (median age 63 years, 71% men) were included. The co-morbidities with the strongest associations with severe COVID-19 for the young population compared to older patients were chronic kidney disease (OR 6.80 [3.61-12.83]), type 2 diabetes (OR 6.31 [4.48-8.88]), hypertension (OR 5.09 [3.79-6.84]), rheumatoid arthritis (OR 4.76 [2.29-9.89]), obesity (OR 3.76 [2.88-4.92]), heart failure (OR 3.06 [1.36-6.89]), and asthma (OR 3.04 [2.22-4.16]). When comparing women vs. men < 50 years of age, stronger associations were seen for women regarding type 2 diabetes (OR 11.25 [6.00-21.08] vs OR 4.97 [3.25-7.60]) and hypertension (OR 8.76 [5.10-15.01] vs OR 4.09 [2.86-5.86]). The factors associated with 90-day mortality in the young were previous venous thromboembolism (OR 5.50 [2.13-14.22]), chronic kidney disease (OR 4.40 [1.64-11.78]) and type 2 diabetes (OR 2.71 [1.39-5.29]). These associations with 90-day mortality were foremost driven by the female population. CONCLUSION: Chronic kidney failure, type 2 diabetes, hypertension, rheumatoid arthritis, obesity, heart failure, and asthma were the strongest risk factors associated with severe COVID-19 requiring ICU-care in individuals < 50 years compared to the older population. However, after ICU admission, previous thromboembolism, chronic kidney failure, and type 2 diabetes were associated with increased 90-day mortality. The risk associations for co-morbidities were generally stronger among younger individuals compared to older and in women compared to men.

Association Between CKD, Obesity, Cardiometabolic Risk Factors, and Severe COVID-19 Outcomes.

Introduction: Chronic kidney disease (CKD) is a risk factor for acquiring severe COVID-19, but underlying mechanisms are unknown. We aimed to study the risk associated with CKD for severe COVID-19 outcomes in relation to body mass index (BMI) and diabetes because they are common risk factors for both CKD and severe COVID-19. Methods: This nationwide case-control study with data from mandatory national registries included 4684 patients (cases) admitted to the intensive care units (ICUs) requiring mechanical ventilation and 46,840 population-based controls matched by age, sex, and district of residency. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for associations between severe COVID-19 and exposures with adjustment for confounders, in subgroups by BMI, and matched by type 2 diabetes. Results: The median age was 64 years, and 27.7% were female. CKD was observed in 5.4% of the cases and 1.5% of the controls, whereas 1.9% and 0.3% had end-stage CKD, respectively. CKD was associated with severe COVID-19 (OR, 2.20 [95% CI, 1.85-2.62]), continuous renal replacement therapy (CRRT) in ICU (OR, 7.36 [95% CI, 5.39-10.05]), and death any time after ICU admission (OR, 2.51 [95% CI, 1.96-3.22]). The risk associated with CKD for severe COVID-19 did not differ significantly by weight but was higher in those without diabetes (OR, 2.76 [95% CI, 2.15-3.55]) than in those with diabetes (OR, 1.88 [95% CI, 1.37-2.59]). Conclusion: CKD, especially end-stage CKD, is an important risk factor for severe COVID-19 and death after ICU admission also in patients with normal BMI and without type 2 diabetes.

Immigrant background and socioeconomic status are associated with severe COVID-19 requiring intensive care.

To determine whether immigrant background and socioeconomic status were associated with increased risk to develop severe Coronavirus disease 2019 (COVID-19) requiring mechanical ventilation at the intensive care unit and to study their effects on 90-day mortality. Nationwide case-control study with personal-level data from the Swedish Intensive Care register linked with socioeconomic data from Statistics Sweden and comorbidity data from the national patient register. For each case of COVID-19 treated with mechanical ventilation at the intensive care unit (outcome), 10 population controls were matched for age, sex and area of residence. Logistic and Cox regression were used to study the association between the exposure (immigrant background, income and educational level) and 90-day mortality. In total, 4 921 cases and 49 210 controls were matched. In the adjusted model, the risk of severe COVID-19 was highest in individuals born in Asia (Odds ratio [OR] = 2.44, 95% confidence interval [CI] = 2.20-2.69), South America (OR = 2.34, 95% CI = 1.82-2.98) and Africa (OR = 2.11, 95% CI = 1.76-2.50). Post-secondary education was associated with a lower risk of severe COVID-19 (OR = 0.75, CI = 0.69-0.82) as was the highest (vs. lowest) income quintile (OR = 0.87, CI = 0.77-0.97). In the fully adjusted Cox-regression analysis birth region of Africa (OR 1.38, CI = 1.03-1.86) and high income (OR 0.75, CI 0.63-0.89) were associated with 90-day mortality. Immigrant background, educational level and income were independently associated with acquiring severe COVID-19 with need for mechanical ventilation.

Avoiding Routine Oxygen Therapy in Patients With Myocardial Infarction Saves Significant Expenditure for the Health Care System-Insights From the Randomized DETO2X-AMI Trial.

Background: Myocardial infarction (MI) occurs frequently and requires considerable health care resources. It is important to ensure that the treatments which are provided are both clinically effective and economically justifiable. Based on recent new evidence, routine oxygen therapy is no longer recommended in MI patients without hypoxemia. By using data from a nationwide randomized clinical trial, we estimated oxygen therapy related cost savings in this important clinical setting. Methods: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial randomized 6,629 patients from 35 hospitals across Sweden to oxygen at 6 L/min for 6-12 h or ambient air. Costs for drug and medical supplies, and labor were calculated per patient, for the whole study population, and for the total annual care episodes for MI in Sweden (N = 16,100) with 10 million inhabitants. Results: Per patient, costs were estimated to 36 USD, summing up to a total cost of 119,832 USD for the whole study population allocated to oxygen treatment. Applied to the annual care episodes for MI in Sweden, costs sum up to between 514,060 and 604,777 USD. In the trial, 62 (2%) patients assigned to oxygen and 254 (8%) patients assigned to ambient air developed hypoxemia. A threshold analysis suggested that up to a cut-off of 624 USD spent for hypoxemia treatment related costs per patient, avoiding routine oxygen therapy remains cost saving. Conclusions: Avoiding routine oxygen therapy in patients with suspected or confirmed MI without hypoxemia at baseline saves significant expenditure for the health care system both with regards to medical and human resources. Clinical Trial Registration: ClinicalTrials.gov, identifier: NCT01787110.

Association between cardiometabolic disease and severe COVID-19: a nationwide case-control study of patients requiring invasive mechanical ventilation.

AIMS: The risks associated with diabetes, obesity and hypertension for severe COVID-19 may be confounded and differ by sociodemographic background. We assessed the risks associated with cardiometabolic factors for severe COVID-19 when accounting for socioeconomic factors and in subgroups by age, sex and region of birth. METHODS AND RESULTS: In this nationwide case-control study, 1.086 patients admitted to intensive care with COVID-19 requiring mechanical ventilation (cases), and 10.860 population-based controls matched for age, sex and district of residency were included from mandatory national registries. ORs with 95% CIs for associations between severe COVID-19 and exposures with adjustment for confounders were estimated using logistic regression. The median age was 62 years (IQR 52-70), and 3003 (24.9%) were women. Type 2 diabetes (OR, 2.3 (95% CI 1.9 to 2.7)), hypertension (OR, 1.7 (95% CI 1.5 to 2.0)), obesity (OR, 3.1 (95% CI 2.4 to 4.0)) and chronic kidney disease (OR, 2.5 (95% CI 1.7 to 3.7)) were all associated with severe COVID-19. In the younger subgroup (below 57 years), ORs were significantly higher for all cardiometabolic risk factors. The risk associated with type 2 diabetes was higher in women (p=0.001) and in patients with a region of birth outside European Union(EU) (p=0.004). CONCLUSION: Diabetes, obesity and hypertension were all independently associated with severe COVID-19 with stronger associations in the younger population. Type 2 diabetes implied a greater risk among women and in non-EU immigrants. These findings, originating from high-quality Swedish registries, may be important to direct preventive measures such as vaccination to susceptible patient groups. TRIAL REGISTRATION NUMBER: Clinicaltrial.gov (NCT04426084).

Stimulating the Resolution of Inflammation Through Omega-3 Polyunsaturated Fatty Acids in COVID-19: Rationale for the COVID-Omega-F Trial.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). SARS-CoV-2 triggers an immune response with local inflammation in the lung, which may extend to a systemic hyperinflammatory reaction. Excessive inflammation has been reported in severe cases with respiratory failure and cardiovascular complications. In addition to the release of cytokines, referred to as cytokine release syndrome or "cytokine storm," increased pro-inflammatory lipid mediators derived from the omega-6 polyunsaturated fatty acid (PUFA) arachidonic acid may cause an "eicosanoid storm," which contributes to the uncontrolled systemic inflammation. Specialized pro-resolving mediators, which are derived from omega-3 PUFA, limit inflammatory reactions by an active process called resolution of inflammation. Here, the rationale for omega-3 PUFA supplementation in COVID-19 patients is presented along with a brief overview of the study protocol for the trial "Resolving Inflammatory Storm in COVID-19 Patients by Omega-3 Polyunsaturated Fatty Acids - A single-blind, randomized, placebo-controlled feasibility study" (COVID-Omega-F). EudraCT: 2020-002293-28; clinicaltrials.gov: NCT04647604.