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.

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.

Trends in the Use of Benzodiazepines, Z-Hypnotics, and Serotonergic Drugs Among US Women and Men Before and During the COVID-19 Pandemic.

Importance: The ongoing COVID-19 pandemic and associated mitigation measures have disrupted access to psychiatric medications, particularly for women. Objective: To assess the sex differences in trends in the prescribing of benzodiazepines, Z-hypnotics and serotonergic (selective serotonin reuptake inhibitors [SSRIs] and serotonin and norepinephrine reuptake inhibitors [SNRIs]), which are commonly prescribed for anxiety, insomnia, and depression. Design, Setting, and Participants: This cohort study used data from Clinformatics Data Mart, one of the largest commercial health insurance databases in the US. Enrollees 18 years or older were required to have complete enrollment in a given month during our study period, January 1, 2018, to March 31, 2021, to be included for that month. Main Outcomes and Measures: Prescription of a benzodiazepine, Z-hypnotic, or SSRI or SNRI. For each month, the percentage of patients with benzodiazepine, Z-hypnotic, or SSRI or SNRI prescriptions by sex was calculated. Results: The records of 17 255 033 adults (mean [SD] age, 51.7 [19.5] years; 51.3% female) were examined in 2018, 17 340 731 adults (mean [SD] age, 52.5 [19.7] years; 51.6% female) in 2019, 16 916 910 adults (mean [SD] age, 53.7 [19.8] years; 51.9% female) in 2020, and 15 135 998 adults (mean [SD] age, 56.2 [19.8] years; 52.5% female) in 2021. Compared with men, women had a higher rate of prescriptions for all 3 drugs classes and had larger changes in prescription rates over time. Benzodiazepine prescribing decreased from January 2018 (women: 5.61%; 95% CI, 5.60%-5.63%; men: 3.03%; 95% CI, 3.02%-3.04%) to March 2021 (women: 4.91%; 95% CI, 4.90%-4.93%; men: 2.66%; 95% CI, 2.65%-2.67%), except for a slight increase in April 2020 among women. Z-hypnotic prescribing increased from January 2020 for women (1.39%; 95% CI, 1.38%-1.40%) and February 2020 for men (0.97%; 95% CI, 0.96%-0.98%) to October 2020 (women: 1.46%; 95% CI, 1.46%-1.47%; men: 1.00%; 95% CI, 0.99%-1.01%). Prescribing of SSRIs and SNRIs increased from January 2018 (women: 12.77%; 95% CI; 12.75%-12.80%; men: 5.56%; 95% CI, 5.44%-5.58%) to April 2020 for men (6.73%; 95% CI, 6.71%-6.75%) and October 2020 for women (15.18%; 95% CI, 15.16%-15.21%). Conclusions and Relevance: In this cohort study, coinciding with the COVID-19 pandemic onset was an increase in Z-hypnotic as well as SSRI and SNRI prescriptions in both men and women along with an increase in benzodiazepine prescriptions in women, findings that suggest a substantial mental health impact of COVID-19-associated mitigation measures.

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.