IMPORTANCE It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.OBJECTIVE To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSTo examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.EXPOSURES ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. MAIN OUTCOMES AND MEASURESIn the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. RESULTSIn the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age-and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). CONCLUSIONS AND RELEVANCEPrior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.

Abstract Background and objectives Male sex has been associated with severe Coronavirus disease 2019 (Covid-19) infection. We examined the association between male sex and severe Covid-19 infection and if an increased risk remains after adjustment for age and comorbidities. Methods Nationwide register-based follow-up study of Covid-19 patients in Denmark until May 16, 2020. Average risk ratio comparing 30-day composite outcome of all-cause death, severe Covid-19 diagnosis or intensive care unit (ICU) admission for men versus women standardized to the age and comorbidity distribution of all patients were derived from multivariable Cox regression. Included covariates were age, hypertension, diagnoses including obesity, alcohol, sleep apnea, diabetes, chronic obstructive pulmonary disease, previous myocardial infarction (MI), ischemic heart disease (IHD), heart failure (HF), atrial fibrillation (AF), stroke, peripheral artery disease, cancer, liver-, rheumatic-, and chronic kidney disease (CKD). Results Of 4,842 Covid-19 patients, 2,281 (47.1%) were men. Median age was 57 [25%-75% 43-73] for men versus 52 [38-71] for women (P<0.001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P<0.001) as well as AF, stroke and HF (all P=0.01) were more often seen in men, and so was CKD (P=0.03). Obesity diagnosis (P<0.001) were more often seen in women. Other comorbidity differences were insignificant (P>0.05). The fully adjusted average risk ratio was 1.63 [95% CI 1.44-1.84]. Conclusions Men with Covid-19 infection have >50% higher risk of all-cause death, severe Covid-19 infection, or ICU admission than women. The excess risk was not explained by age and comorbidities.

Background: Streptococci frequently cause infective endocarditis (IE), yet the prevalence of IE in patients with bloodstream infections (BSIs) caused by different streptococcal species is unknown. We aimed to investigate the prevalence of IE at species level in patients with streptococcal BSIs. Methods: We investigated all patients with streptococcal BSIs, from 2008 to 2017, in the Capital Region of Denmark. Data were crosslinked with Danish nationwide registries for identification of concomitant hospitalization with IE. In a multivariable logistic regression analysis, we investigated the risk of IE according to streptococcal species adjusted for age, sex, ≥3 positive blood culture bottles, native valve disease, prosthetic valve, previous IE, and cardiac device. Results: Among 6506 cases with streptococcal BSIs (mean age 68.1 years [SD 16.2], 52.8% men) the IE prevalence was 7.1% (95% CI, 6.5–7.8). The lowest IE prevalence was found with Streptococcus pneumoniae ( S pneumoniae ) 1.2% (0.8–1.6) and Spyogenes 1.9% (0.9–3.3). An intermediary IE prevalence was found with Sanginosus 4.8% (3.0–7.3), Ssalivarius 5.8% (2.9–10.1), and Sagalactiae 9.1% (6.6–12.1). The highest IE prevalence was found with Smitis/oralis 19.4% (15.6–23.5), Sgallolyticus (formerly Sbovis ) 30.2% (24.3–36.7), Ssanguinis 34.6% (26.6–43.3), Sgordonii 44.2% (34.0–54.8), and Smutans 47.9% (33.3–62.8). In multivariable analysis using S pneumoniae as reference, all species except S pyogenes were associated with significantly higher IE risk, with the highest risk found with S gallolyticus odds ratio (OR) 31.0 (18.8–51.1), S mitis/oralis OR 31.6 (19.8–50.5), S sanguinis OR 59.1 (32.6–107), S gordonii OR 80.8 (43.9–149), and S mutans OR 81.3 (37.6–176). Conclusions: The prevalence of IE in streptococcal BSIs is species dependent with S mutans, S gordonii, S sanguinis, S gallolyticus , and S mitis/oralis having the highest IE prevalence and the highest associated IE risk after adjusting for IE risk factors.