Association of Cardiovascular Medications with Adverse Outcomes in a Matched Analysis of a National Cohort of Patients with COVID-19

BACKGROUND The use of statins, angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs), and anticoagulants may be associated with fewer adverse outcomes in COVID-19 patients. METHODS Nested within a cohort of 800,913 patients diagnosed with COVID-19 between 4/1/20 and 6/24/21 from the Optum COVID-19 database, three case-control studies were conducted. Cases—defined as persons who: a) were hospitalized within 30 days of COVID-19 diagnosis (n=88,405);b) were admitted to the intensive care unit [ICU]/received mechanical ventilation during COVID-19 hospitalization (n=22,147);c) died during COVID-19 hospitalization (n=2,300)—were matched 1:1 using demographic/clinical factors with controls randomly selected from a pool of patients who did not experience the case definition/event. Medication use was based on prescription ≤90 days before COVID-19 diagnosis. RESULTS Statin use was associated with decreased risk of hospitalization (adjusted odds ratio [aOR], 0.72;95% CI, 0.69, 0.75) and ICU admission/mechanical ventilation (aOR, 0.90;95% CI, 0.84, 0.97). ACEI/ARB use was associated with decreased risk of hospitalization (aOR, 0.67;95% CI, 0.65, 0.70), ICU admission/mechanical ventilation (aOR, 0.92;95% CI, 0.86, 0.99) and death (aOR, 0.60;95% CI, 0.47, 0.78). Anticoagulant use was associated with decreased risk of hospitalization (aOR, 0.94;95% CI, 0.89, 0.99) and death (aOR, 0.56;95% CI, 0.41, 0.77). Interaction effects—in the model predicting hospitalization—were statistically significant for: statins and ACEI/ARBs (p<.0001), statins and anticoagulants (p=.003), ACEI/ARBs and anticoagulants (p<.0001). An interaction effect—in the model predicting ventilator use/ICU—was statistically significant for statins and ACEI/ARBs (p=.002). CONCLUSIONS Statins, ACEI/ARBs, and anticoagulants were associated with decreased risks of the adverse outcomes under study. These findings may provide clinically relevant information regarding potential treatment for patients with COVID-19.

Single-center investigation on central-line-associated bloodstream infections and blood-culture contamination during the early months of the coronavirus disease 2019 (COVID-19) pandemic.

In this retrospective cohort study, we assessed central-line-associated bloodstream infections (CLABSIs) and blood-culture contamination frequency during the first pandemic wave. Coronavirus disease 2019 (COVID-19) was significantly associated with CLABSI and blood-culture contamination. In the COVID-19 cohort, malignancy was associated with CLABSI. Black race, end-stage renal disease, and obesity were associated with blood-culture contamination.

Association of testosterone therapy with disease progression in older males with COVID-19.

IMPORTANCE: Low testosterone levels in males have been linked with increase in proinflammatory cytokines-a primary culprit in COVID-19 disease progression-and with adverse COVID-19 outcomes. To date, however, no published studies have assessed the effect of testosterone therapy on COVID-19 outcomes in older men. OBJECTIVE: To examine whether testosterone therapy reduced disease progression in older men diagnosed with COVID-19. DESIGN, SETTING, AND PARTICIPANTS: Nested within a national cohort of older (aged ≥50 years) male patients diagnosed with COVID-19 between January 1, 2020 and July 1, 2021 from the Optum electronic health record COVID-19 database, two matched case-control studies of COVID-19 outcomes were conducted. Cases-defined, respectively, as persons who (a) were hospitalized ≤30 days after COVID-19 diagnosis (n = 33,380), and (b) were admitted to the intensive care unit or received mechanical ventilation during their COVID-19 hospitalization (n = 10,273)-were matched 1:1 with controls based on demographic and clinical factors. EXPOSURES: Testosterone therapy was defined based on receipt of prescription at ≤60, ≤90, or ≤120 days before COVID-19 diagnosis. MAIN OUTCOMES AND MEASURES: Adjusted odds ratios (ORs) for the risk of hospitalization within 30 days of COVID-19 diagnosis and intensive care unit admission/mechanical ventilation during COVID-19 hospitalization. RESULTS: The use of testosterone therapy was not associated with decreased odds of hospitalization (≤60 days: OR = 0.92, 95% confidence interval [CI] = 0.70-1.20; ≤90 days: OR = 0.87, 95% CI = 0.68-1.13; ≤120 days: OR = 0.97, 95% CI = 0.72-1.32) or intensive care unit admission/mechanical ventilation (≤60 days: OR = 0.67, 95% CI = 0.37-1.23; ≤90 days: OR = 0.63, 95% CI = 0.36-0.11; ≤120 days: OR = 0.58, 95% CI = 0.29-1.19). CONCLUSIONS AND RELEVANCE: This study showed that testosterone therapy was not associated with decreased risks of COVID-19 adverse outcomes. These findings may provide clinically relevant information regarding testosterone treatment in older men with COVID-19 and other respiratory viral infections with similar pathogenesis.

COVID-19 Infection and Incidence of Myocarditis: A Multi-Site Population-Based Propensity Score-Matched Analysis.

Background Cardiovascular complications from COVID-19 include myocarditis, acute myocardial infarction, heart failure, and others. Population-level data is lacking about the relationship between COVID-19 and cardiovascular complications; therefore, we conducted a study to examine the incidence of myocarditis, acute myocardial infarction (AMI), heart failure (HF) after COVID-19 infection. Methods Retrospective cohort study using de-identified data from 50 health systems across the United States. Cohort groups were created using patients ≥18 who were admitted to hospitals for respiratory illness with COVID-19 in 2020 and respiratory illness without COVID-19 for 2020 and 2019. There were 107,699 patients with COVID-19, 77,499 patients with respiratory illness in 2020, and 112,898 patients in 2019. The COVID-19 group was matched to each respiratory illness group by propensity score. Patients with prior specific cardiovascular events such as myocarditis, AMI, HF were excluded. The primary outcome was myocarditis, and secondary outcomes were AMI and HF. Results In the COVID-19 group, 79 (0.12%) patients had new-onset myocarditis compared to 29 (0.04%) patients in the non-COVID-19 control (Pneumonia/flu) group Odd's Ratio (OR), (OR 2.73, CI 95%, 1.78-4.18). In the COVID-19 group, 1512 patients developed HF compared to 2,659 patients in the non-COVID-19 group (OR 0.49, CI 95%, 0.46-0.52). 1125 patients in COVID-19 group had AMI compared to 1243 patients in non-COVID-19 group (OR 0.87, CI 95%, 0.80-0.94). Conclusion COVID-19 was associated with a 2-3-fold higher risk of myocarditis. Unexpectedly, lower rates of HF diagnosis reflect challenges faced due to the severity of lung disease leading to obscuring physical exam findings required for HF diagnosis and early mortality before a diagnosis of HF was made.

Incidence of venous thrombotic events and events of special interest in a retrospective cohort of commercially insured US patients.

OBJECTIVE: To estimate the US incidence of thrombotic events and related rare diagnoses. DESIGN: Claims-based retrospective cohort study of incidence. SETTING: US commercial health insurance administrative claims database. PARTICIPANTS: Adults 25-64 years of age between 2015 and 2019 with a minimum of 12 consecutive thrombosis-free months of continuous enrolment beginning 2014 were selected. MAIN OUTCOMES: Age (10-year intervals) and sex stratum-specific incidence rates per 100 000 person-years were determined for venous thromboembolism (VTE), cerebral venous thrombosis (CVT) and other major venous thrombotic events, and events of special interest, including immune thrombocytopenic purpura (ITP), haemolytic-uremic syndrome (HUS) and heparin-induced thrombocytopenia (HIT). RESULTS: Of 13 249 229 enrollees (half female/male), incidence of venous thromboembolic events (deep vein thrombosis (DVT), pulmonary embolism (PE), CVT or other major venous thrombotic conditions) was 247.89 per 100 000 person-years (95% CI: 245.96 to 249.84). Incidence of VTE was 213.79 with ICD codes alone (95% CI: 211.99 to 215.59) and 129.34 (95% CI: 127.95 to 130.75) when also requiring a filled anticoagulation prescription or an inferior vena cava (IVC) filter. Incidence was 6.37 for CVT (95% CI: 6.07 to 6.69), 26.06 for ITP (95% CI: 25.44 to 26.78), 0.94 for HUS (95% CI: 0.82 to 1.06) and 4.82 for HIT (95% CI: 4.56 to 5.10). The co-occurrence of CVT with either ITP or HIT (diagnoses within 14 days of one another) was 0.090 (95% CI: 0.06 to 0.13). Incidence tended to increase with age and was higher for women under 55. Incidence for CVT, HUS and CVT with ITP or HIT was higher for women in all age groups. Incidence of PE and CVT increased significantly over the 5-year period, while DVT rates decreased. CONCLUSIONS: These results are the first US estimates for the incidence of thrombotic and rare events of interest in a large, commercially insured US population. Findings provide a critically important reference for determining excess morbidity associated with COVID-19 and more generally for vaccine pharmacovigilance.

Outcomes of Patients with COPD Hospitalized for Coronavirus Disease 2019.

RATIONALE: There is controversy concerning the association of chronic obstructive pulmonary disease (COPD) as an independent risk factor for mortality in patients hospitalized with Coronavirus Disease 2019 (COVID-19). We hypothesize that patients with COPD hospitalized for COVID-19 have increased mortality risk. OBJECTIVE: To assess whether COPD increased the risk of mortality among patients hospitalized for COVID-19. METHODS: We conducted a retrospective cohort analysis of patients with COVID-19 between February 10, 2020, and November 10, 2020, and hospitalized within 14 days of diagnosis. Electronic health records from U.S. facilities (Optum COVID-19 data) were used. RESULTS: In our cohort of 31,526 patients, 3030 (9.6%) died during hospitalization. Mortality in patients with COPD was higher than that of patients without COPD, 14.02% and 8.8%, respectively. Univariate (odds ratio [OR] 1.68; 95% confidence interval [CI] 1.54 to 1.84) and multivariate (OR 1.33; 95% CI 1.18 to 1.50) analysis showed that patients with COPD had greater odds of death due to COVID-19 than patients without COPD. We found significant interactions between COPD and sex and COPD and age. Specifically, the increased mortality risk associated with COPD was observed among female (OR 1.62; 95% CI 1.36 to 1.95) but not male patients (OR 1.14; 95% CI 0.97 to 1.34); and in patients aged 40 to 64 (OR 1.42; 95% CI 1.07 to 1.90) and 65 to 79 (OR 1.48; 95% CI 1.23 to 1.78) years. CONCLUSIONS: COPD is an independent risk factor for death in adults aged 40 to 79 years hospitalized with COVID-19 infection.

The impact of long-term opioid use on the risk and severity of COVID-19.

Based on evidence of the immunosuppressive effects of chronic opioids, long-term users of prescription and illicit opioids comprise an unrecognized but growing population of Americans with compromised immune function and respiratory depression who may be at high risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 19 (COVID-19)-related hospitalization, prolonged ICU stay, adverse events, and death. This perspective is of broad clinical and public health importance because the US has the highest population of long-term users of prescription opioids, a sequel of a decade-long practice of opioid overprescribing in the US. For long-term opioid users who are hospitalized for COVID-19, clinicians face clinical challenges arising from the suppressive effects of opioids on the respiratory and immune functions, as well as the potential for adverse drug-drug interaction when opioids have to be continued in long-term users. More research is needed to further understand the association of long-term opioid use and susceptibility to COVID-19 and other emerging infections.

The Impact of Substance Use Disorder on COVID-19 Outcomes.

OBJECTIVE: The goal of this study was to examine the impact of substance use disorder on the risk of hospitalization, complications, and mortality among adult patients diagnosed as having COVID-19. METHODS: The authors conducted a propensity score (PS)-matched double-cohort study (N=5,562 in each cohort) with data from the TriNetX Research Network database to identify 54,529 adult patients (≥18 years) diagnosed as having COVID-19 between February 20 and June 30, 2020. RESULTS: Primary analysis (PS matched on demographic characteristics and presence of diabetes and obesity) showed that substance use disorder was associated with an increased risk of hospitalization (odds ratio [OR]=1.84, 95% confidence interval [CI]=1.69-2.01), ventilator use (OR=1.45, 95% CI=1.22-1.72), and mortality (OR=1.30, 95% CI=1.08-1.56). CONCLUSIONS: The findings suggest that COVID-19 patients with substance use disorders are at increased risk for adverse outcomes. The attenuation of ORs in the model that matched for chronic respiratory and cardiovascular diseases associated with substance abuse suggests that the observed risks may be partially mediated by these conditions.

Sex Hormones and Novel Corona Virus Infectious Disease (COVID-19).

Given the rapid spread of the coronavirus disease 2019 (COVID-19) pandemic and its overwhelming effect on health care systems and the global economy, innovative therapeutic strategies are urgently needed. The proposed primary culprit of COVID-19 is the intense inflammatory response-an augmented immune response and cytokine storm-severely damaging the lung tissue and rendering some patients' conditions severe enough to require assisted ventilation. Sex differences in the response to inflammation have been documented and can be attributed, at least in part, to sex steroid hormones. Moreover, age-associated decreases in sex steroid hormones, namely, estrogen and testosterone, may mediate proinflammatory increases in older adults that could increase their risk of COVID-19 adverse outcomes. Sex hormones can mitigate the inflammation response and might provide promising therapeutic potential for patients with COVID-19. In this article, we explore the possible anti-inflammatory effects of estrogen and testosterone and the anabolic effect of testosterone, with particular attention to the potential therapeutic role of hormone replacement therapy in older men and women with COVID-19.