Lung Ultrasound Findings Associated With COVID-19 ARDS, ICU Admission, and All-Cause Mortality.

BACKGROUND: As lung ultrasound (LUS) has emerged as a diagnostic tool in patients with COVID-19, we sought to investigate the association between LUS findings and the composite in-hospital outcome of ARDS incidence, ICU admission, and all-cause mortality. METHODS: In this prospective, multi-center, observational study, adults with laboratory-confirmed SARS-CoV-2 infection were enrolled from non-ICU in-patient units. Subjects underwent an LUS evaluating a total of 8 zones. Images were analyzed off-line, blinded to clinical variables and outcomes. A LUS score was developed to integrate LUS findings: ≥ 3 B-lines corresponded to a score of 1, confluent B-lines to a score of 2, and subpleural or lobar consolidation to a score of 3. The total LUS score ranged from 0-24 per subject. RESULTS: Among 215 enrolled subjects, 168 with LUS data and no current signs of ARDS or ICU admission (mean age 59 y, 56% male) were included. One hundred thirty-six (81%) subjects had pathologic LUS findings in ≥ 1 zone (≥ 3 B-lines, confluent B-lines, or consolidations). Markers of disease severity at baseline were higher in subjects with the composite outcome (n = 31, 18%), including higher median C-reactive protein (90 mg/L vs 55, P < .001) and procalcitonin levels (0.35 µg/L vs 0.13, P = .033) and higher supplemental oxygen requirements (median 4 L/min vs 2, P = .001). However, LUS findings and score did not differ significantly between subjects with the composite outcome and those without, and were not associated with outcomes in unadjusted and adjusted logistic regression analyses. CONCLUSIONS: Pathologic findings on LUS were common a median of 3 d after admission in this cohort of non-ICU hospitalized subjects with COVID-19 and did not differ among subjects who experienced the composite outcome of incident ARDS, ICU admission, and all-cause mortality compared to subjects who did not. These findings should be confirmed in future investigations. The study is registered at Clinicaltrials.gov (NCT04377035).

Impact of Nationwide COVID-19 Lockdowns on the Implantation Rate of Cardiac Implantable Electronic Devices.

AIM: The COVID-19 pandemic resulted in a significant decrease in the number of hospital admissions for severe emergent cardiovascular diseases during lockdowns worldwide. This study aimed to determine the impact of both the first and the second Danish nationwide lockdown on the implantation rate of cardiac implantable electronic devices (CIEDs). METHODS: We retrospectively analysed the number of CIED implantations performed in Denmark and stratified them into 3-week intervals. RESULTS: The total number of de novo CIED implantations decreased during the first lockdown by 15.5% and during the second by 5.1%. Comparing each 3-week interval using rate ratios, a significant decrease in the daily rates of the total number of de novo and replacement CIEDs (0.82, 95% CI [0.70, 0.96]), de novo CIEDs only (0.82, 95% CI [0.69, 0.98]), and non-acute pacemaker implantations (0.80, 95% CI [0.63, 0.99]) was observed during the first interval of the first lockdown. During the second lockdown (third interval), a significant decrease was seen in the daily rates of de novo CIEDs (0.73, 95% CI [0.55, 0.97]), and of pacemakers in total during both the second (0.78, 95% CI [0.62, 0.97]) and the third (0.60, 95% CI [0.42, 0.85]) intervals. Additionally, the daily rates of acute pacemaker implantation decreased during the second interval (0.47, 95% CI [0.27, 0.79]) and of non-acute implantation during the third interval (0.57, 95% CI [0.38, 0.84]). A significant increase was observed in the number of replacement procedures during the first interval of the second lockdown (1.70, 95% CI [1.04, 2.85]). CONCLUSIONS: Our study found only modest changes in CIED implantations in Denmark during two national lockdowns.

All-cause mortality among Danish nursing home residents before and during the COVID-19 pandemic: a nationwide cohort study.

A substantial part of mortality during the COVID-19-pandemic occurred among nursing home residents which caused alarm in many countries. We investigate nursing home mortality in relation to the expected mortality prior to the pandemic. This nationwide register-based study included all 135,501 Danish nursing home residents between 2015 until October 6, 2021. All-cause mortality rates were calculated using a standardization method on sex and age distribution of 2020. Survival probability and lifetime lost for 180 days was calculated using Kaplan Meier estimates. Of 3,587 COVID-19 related deaths, 1137 (32%) occurred among nursing home residents. The yearly all-cause mortality rates per 100,000 person-years in 2015, 2016, and 2017 were 35,301 (95% CI: 34,671-35,943), 34,801 (95% CI: 34,180-35,432), and 35,708 (95% CI: 35,085-36,343), respectively. Slightly elevated mortality rates per 100,000 person-years were seen in 2018, 2019, 2020, and 2021 of 38,268 (95% CI: 37,620-38,929), 36,956 (95% CI: 36,323-37,600), 37,475 (95% CI: 36,838-38,122), and 38,536 (95% CI: 37,798-39,287), respectively. For SARS-CoV-2-infected nursing home residents, lifetime lost difference was 42 days (95% CI: 38-46) in 2020 versus non-infected in 2018. Among vaccinated in 2021, lifetime lost difference was 25 days (95% CI: 18-32) for SARS-CoV-2-infected versus non-infected. Even though a high proportion of COVID-19 fatalities took place in nursing homes and SARS-CoV-2-infection increased the risk of individual death, the annual mortality was only slightly elevated. For future epidemics or pandemics reporting numbers of fatal cases in relation to expected mortality is critical.

Cardiac Characteristics of the First Two Waves of COVID-19 in Denmark and the Prognostic Value of Echocardiography: The ECHOVID-19 Study.

INTRODUCTION: COVID-19 has spread globally in waves, and Danish treatment guidelines have been updated following the first wave. We sought to investigate whether the prognostic values of echocardiographic parameters changed with updates in treatment guidelines and the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, 20E (EU1) and Alpha (B.1.1.7), and further to compare cardiac parameters between patients from the first and second wave. METHODS: A total of 305 patients hospitalised with COVID-19 were prospectively included, 215 and 90 during the first and second wave, respectively. Treatment in the study was defined as treatment with remdesivir, dexamethasone, or both. Patients were assumed to be infected with the dominant SARS-CoV-2 variant at the time of their hospitalisation. RESULTS: Mean age for the first vs. second wave was 68.7±13.6 vs. 69.7±15.8 years and 55% vs. 62% were male. Left ventricular (LV) systolic and diastolic function was worse in patients hospitalised during the second wave (LV ejection fraction (LVEF) for first vs. second wave = 58.5±8.1% vs. 52.4±10.6%, p<0.001) and global longitudinal strain (GLS) = 16.4±4.3% vs. 14.2±4.3%, p<0.001). In univariable cox regressions, reduced LVEF (HR=1.07 per 1% decrease, p=0.002), GLS (HR=1.21 per 1% decrease, p<0.001), and TAPSE (HR=1.18 per 1mm decrease, p<0.001) were associated with covid-related mortality, but only GLS remained significant in fully adjusted analysis (HR=1.14, p=0.02). CONCLUSION: Reduced GLS was associated with covid-related mortality independently of wave, treatment, and SARS-CoV-2 variant. LV function was significantly impaired in patients hospitalised during the second wave.

Myocardial Work in Patients Hospitalized With COVID-19: Relation to Biomarkers, COVID-19 Severity, and All-Cause Mortality.

Background COVID-19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID-19. We hypothesized that GWI was associated with disease severity and all-cause death in patients with COVID-19. Methods and Results In a multicenter study of patients admitted with COVID-19 (n=305), 249 underwent pressure-strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT-proBNP [N-terminal pro-B-type natriuretic peptide]), disease severity (oxygen requirement and CRP [C-reactive protein]), and all-cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT-proBNP was observed, with increasing NT-proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100-mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow-up (median, 58 days). In multivariable Cox regression, GWI was associated with all-cause death (hazard ratio, 1.08 [95% CI, 1.01-1.15], per 100-mm Hg% decrease), but did not increase C-statistics when added to clinical parameters. Conclusions In patients admitted with COVID-19, our findings indicate that NT-proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all-cause death, but did not provide prognostic information beyond readily available clinical parameters. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035.

Feasibility of randomizing Danish citizens aged 65-79 years to high-dose quadrivalent influenza vaccine vs. standard-dose quadrivalent influenza vaccine in a pragmatic registry-based setting: rationale and design of the DANFLU-1 Trial.

BACKGROUND: High-dose influenza vaccines provide better protection against influenza infection than standard-dose in persons aged 65 years and above; however, in most countries, high-dose vaccines are not widely implemented. Assessing the relative effectiveness of high-dose compared to standard-dose vaccines on hospitalizations and mortality would enable more robust public health and cost-effectiveness estimates. This study aims to investigate the feasibility of conducting a pragmatic randomized clinical trial in Denmark comparing high-dose to standard-dose vaccines utilizing existing vaccination infrastructure and the Danish nationwide health registries for data collection. METHODS: The DANFLU-1 trial (NCT05048589) is a pragmatic, open-label, active-controlled randomized trial randomizing Danish citizens aged 65-79 years to either high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine. The study utilizes the infrastructure of a private vaccination provider (Danske Lægers Vaccinations Service) for recruitment, inclusion, randomization, and vaccination. All collection of baseline and follow-up data including safety monitoring is performed centrally by the Department of Cardiology at Herlev and Gentofte Hospital, Copenhagen, Denmark using the Danish nationwide health registries. The study aims to include 40,000 participants during the 2021/2022 influenza season. The primary endpoints address feasibility and include the number of participants enrolled, randomization balance, and representativeness compared to the Danish general population. Relative vaccine effectiveness will also be assessed, however, this feasibility study is not powered for clinical outcomes and may be affected by the COVID-19 pandemic. DISCUSSION: The DANFLU-1 study is investigating the feasibility of conducting a large-scale pragmatic clinical trial in Denmark utilizing existing infrastructure and the Danish nationwide registries. This will provide valuable insight, especially for potential future fully powered vaccine trials, but also for trials wishing to investigate other interventions. TRIAL REGISTRATION: Clinicaltrials.gov : NCT05048589 , registered September 17, 2021.

Feasibility of randomizing Danish citizens aged 65–79 years to high-dose quadrivalent influenza vaccine vs. standard-dose quadrivalent influenza vaccine in a pragmatic registry-based setting: rationale and design of the DANFLU-1 Trial

Background High-dose influenza vaccines provide better protection against influenza infection than standard-dose in persons aged 65 years and above;however, in most countries, high-dose vaccines are not widely implemented. Assessing the relative effectiveness of high-dose compared to standard-dose vaccines on hospitalizations and mortality would enable more robust public health and cost-effectiveness estimates. This study aims to investigate the feasibility of conducting a pragmatic randomized clinical trial in Denmark comparing high-dose to standard-dose vaccines utilizing existing vaccination infrastructure and the Danish nationwide health registries for data collection. Methods The DANFLU-1 trial (NCT05048589) is a pragmatic, open-label, active-controlled randomized trial randomizing Danish citizens aged 65–79 years to either high-dose quadrivalent influenza vaccine or standard-dose quadrivalent influenza vaccine. The study utilizes the infrastructure of a private vaccination provider (Danske Lægers Vaccinations Service) for recruitment, inclusion, randomization, and vaccination. All collection of baseline and follow-up data including safety monitoring is performed centrally by the Department of Cardiology at Herlev and Gentofte Hospital, Copenhagen, Denmark using the Danish nationwide health registries. The study aims to include 40,000 participants during the 2021/2022 influenza season. The primary endpoints address feasibility and include the number of participants enrolled, randomization balance, and representativeness compared to the Danish general population. Relative vaccine effectiveness will also be assessed, however, this feasibility study is not powered for clinical outcomes and may be affected by the COVID-19 pandemic. Discussion The DANFLU-1 study is investigating the feasibility of conducting a large-scale pragmatic clinical trial in Denmark utilizing existing infrastructure and the Danish nationwide registries. This will provide valuable insight, especially for potential future fully powered vaccine trials, but also for trials wishing to investigate other interventions. Trial registration Clinicaltrials.gov: NCT05048589, registered September 17, 2021.

Prognostic implications of serial high-sensitivity cardiac troponin testing among patients with COVID-19: A Danish nationwide registry-based cohort study.

Background: Although troponin elevation is associated with worse outcomes among patients with coronavirus disease 2019 (COVID-19), prognostic implications of serial troponin testing are lacking. We investigated the association between serial troponin measurements and adverse COVID-19 outcomes. Methods: Using Danish registries, we identified COVID-19 patients with a high-sensitivity troponin measurement followed by a second measurement within 1-24 h. All measurements during follow-up were also utilized in subsequent time-varying analyses. We assessed all-cause mortality associated with the absence/presence of myocardial injury (≥1 troponin measurement >99th percentile upper reference limit) and absence/presence of dynamic troponin changes (>20% relative change if first measurement elevated, >50% relative change if first measurement normal). Results: Of 346 included COVID-19 patients, 56% had myocardial injury. Overall, 20% had dynamic troponin changes. In multivariable Cox regression models, myocardial injury was associated with all-cause mortality (HR = 2.56, 95%CI = 1.46-4.51), as were dynamic troponin changes (HR = 1.66, 95%CI = 1.04-2.64). We observed a low incidence of myocardial infarction (4%) and invasive coronary procedures (4%) among patients with myocardial injury. Conclusions: Myocardial injury and dynamic troponin changes determined using serial high-sensitivity troponin testing were associated with poor prognosis among patients with COVID-19. The risk of developing myocardial infarction requiring invasive management during COVID-19 hospitalization was low.

SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study.

OBJECTIVE: To investigate the association between SARS-CoV-2 vaccination and myocarditis or myopericarditis. DESIGN: Population based cohort study. SETTING: Denmark. PARTICIPANTS: 4 931 775 individuals aged 12 years or older, followed from 1 October 2020 to 5 October 2021. MAIN OUTCOME MEASURES: The primary outcome, myocarditis or myopericarditis, was defined as a combination of a hospital diagnosis of myocarditis or pericarditis, increased troponin levels, and a hospital stay lasting more than 24 hours. Follow-up time before vaccination was compared with follow-up time 0-28 days from the day of vaccination for both first and second doses, using Cox proportional hazards regression with age as an underlying timescale to estimate hazard ratios adjusted for sex, comorbidities, and other potential confounders. RESULTS: During follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male. Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination. Among 498 814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis or myopericarditis within 28 days from vaccination date (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)). Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 5.24 (2.47 to 11.12) and the absolute rate was 5.7 (3.3 to 9.3) per 100 000 vaccinated individuals within 28 days of vaccination. CONCLUSIONS: Vaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years, while BNT162b2 vaccination was only associated with a significantly increased risk among women. However, the absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups. The benefits of SARS-CoV-2 mRNA vaccination should be taken into account when interpreting these findings. Larger multinational studies are needed to further investigate the risks of myocarditis or myopericarditis after vaccination within smaller subgroups.

Glycated haemoglobin levels among 3295 hospitalized COVID-19 patients, with and without diabetes, and risk of severe infection, admission to an intensive care unit and all-cause mortality.

AIM: To determine the risk of adverse outcomes across the spectrum of glycated haemoglobin (HbA1c) levels among hospitalized COVID-19 patients with and without diabetes. MATERIALS AND METHODS: Danish nationwide registries were used to study the association between HbA1c levels and 30-day risk of all-cause mortality and the composite of severe COVID-19 infection, intensive care unit (ICU) admission and all-cause mortality. The study population comprised patients hospitalized with COVID-19 (3 March 2020 to 31 December 2020) with a positive polymerase chain reaction (PCR) test and an available HbA1c ≤ 6 months before the first positive PCR test. All patients had at least 30 days of follow-up. Among patients with diabetes, HbA1c was categorized as <48 mmol/mol, 48 to 53 mmol/mol, 54 to 58 mmol/mol, 59 to 64 mmol/mol (reference) and >64 mmol/mol. Among patients without diabetes, HbA1c was stratified into <31 mmol/mol, 31 to 36 mmol/mol (reference), 37 to 41 mmol/mol and 42 to 47 mmol/mol. Thirty-day standardized absolute risks and standardized absolute risk differences are reported. RESULTS: We identified 3295 hospitalized COVID-19 patients with an available HbA1c (56.2% male, median age 73.9 years), of whom 35.8% had diabetes. The median HbA1c was 54 and 37 mmol/mol among patients with and without diabetes, respectively. Among patients with diabetes, the standardized absolute risk difference of the composite outcome was higher with HbA1c < 48 mmol/mol (12.0% [95% confidence interval {CI} 3.3% to 20.8%]) and HbA1c > 64 mmol/mol (15.1% [95% CI 6.2% to 24.0%]), compared with HbA1c 59 to 64 mmol/mol (reference). Among patients without diabetes, the standardized absolute risk difference of the composite outcome was greater with HbA1c < 31 mmol/mol (8.5% [95% CI 0.5% to 16.5%]) and HbA1c 42 to 47 mmol/mol (6.7% [95% CI 1.3% to 12.1%]), compared with HbA1c 31 to 36 mmol/mol (reference). CONCLUSIONS: Patients with COVID-19 and HbA1c < 48 mmol/mol or HbA1c > 64 mmol/mol had a higher associated risk of the composite outcome. Similarly, among patients without diabetes, varying HbA1c levels were associated with higher risk of the composite outcome.

Recovery of cardiac function following COVID-19 - ECHOVID-19: a prospective longitudinal cohort study.

AIMS: The degree of cardiovascular sequelae following COVID-19 remains unknown. The aim of this study was to investigate whether cardiac function recovers following COVID-19. METHODS AND RESULTS: A consecutive sample of patients hospitalized with COVID-19 was prospectively included in this longitudinal study. All patients underwent an echocardiographic examination during hospitalization and 2 months later. All participants were successfully matched 1:1 with COVID-19-free controls by age and sex. A total of 91 patients were included (mean age 63 ± 12 years, 59% male). A median of 77 days (interquartile range: 72-92) passed between the two examinations. Right ventricular (RV) function improved following resolution of COVID-19: tricuspid annular plane systolic excursion (TAPSE) (2.28 ± 0.40 cm vs. 2.11 ± 0.38 cm, P < 0.001) and RV longitudinal strain (RVLS) (25.3 ± 5.5% vs. 19.9 ± 5.8%, P < 0.001). In contrast, left ventricular (LV) systolic function assessed by global longitudinal strain (GLS) did not significantly improve (17.4 ± 2.9% vs. 17.6 ± 3.3%, P = 0.6). N-terminal pro-B-type natriuretic peptide decreased between the two examinations [177.6 (80.3-408.0) ng/L vs. 11.7 (5.7-24.0) ng/L, P < 0.001]. None of the participants had elevated troponins at follow-up compared to 18 (27.7%) during hospitalization. Recovered COVID-19 patients had significantly lower GLS (17.4 ± 2.9% vs. 18.8 ± 2.9%, P < 0.001 and adjusted P = 0.004), TAPSE (2.28 ± 0.40 cm vs. 2.67 ± 0.44 cm, P < 0.001 and adjusted P < 0.001), and RVLS (25.3 ± 5.5% vs. 26.6 ± 5.8%, P = 0.50 and adjusted P < 0.001) compared to matched controls. CONCLUSION: Acute COVID-19 affected negatively RV function and cardiac biomarkers but recovered following resolution of COVID-19. In contrast, the observed reduced LV function during acute COVID-19 did not improve post-COVID-19. Compared to the matched controls, both LV and RV function remained impaired.

Nationwide cardiovascular disease admission rates during a second COVID-19 lockdown.

Societal lockdowns during the first wave of the coronavirus disease 2019 pandemic were associated with decreased admission rates for acute cardiovascular conditions worldwide. In this nationwide Danish study of the first five weeks of a second pandemic lockdown, incidence of new-onset heart failure and atrial fibrillation remained stable, but there was a significant drop in new-onset ischemic heart disease and ischemic stroke during the fourth week of lockdown, which normalized promptly. The observed drops were lower compared to the first Danish lockdown in March 2020; thus, our data suggest that declines in acute cardiovascular disease admission rates during future lockdowns are avoidable.

Lung ultrasound findings in hospitalized COVID-19 patients in relation to venous thromboembolic events: the ECHOVID-19 study.

PURPOSE: Several studies have reported thromboembolic events to be common in severe COVID-19 cases. We sought to investigate the relationship between lung ultrasound (LUS) findings in hospitalized COVID-19 patients and the development of venous thromboembolic events (VTE). METHODS: A total of 203 adults were included from a COVID-19 ward in this prospective multi-center study (mean age 68.6 years, 56.7% men). All patients underwent 8-zone LUS, and all ultrasound images were analyzed off-line blinded. Several LUS findings were investigated (total number of B-lines, B-line score, and LUS-scores). RESULTS: Median time from admission to LUS examination was 4 days (IQR: 2, 8). The median number of B-lines was 12 (IQR: 8, 18), and 44 (21.7%) had a positive B-line score. During hospitalization, 17 patients developed VTE (4 deep-vein thrombosis, 15 pulmonary embolism), 12 following and 5 prior to LUS. In fully adjusted multivariable Cox models (excluding participants with VTE prior to LUS), all LUS parameters were significantly associated with VTE (total number of B-lines: HR = 1.14, 95% CI (1.03, 1.26) per 1 B-line increase), positive B-line score: HR = 9.79, 95% CI (1.87, 51.35), and LUS-score: HR = 1.51, 95% CI (1.10, 2.07), per 1-point increase). The B-line score and LUS-score remained significantly associated with VTE in sensitivity analyses. CONCLUSION: In hospitalized COVID-19 patients, pathological LUS findings were common, and the total number of B-lines, B-line score, and LUS-score were all associated with VTE. These findings indicate that the LUS examination may be useful in risk stratification and the clinical management of COVID-19. These findings should be considered hypothesis generating. GOV ID: NCT04377035.

Severe mental illness is associated with increased mortality and severe course of COVID-19.

OBJECTIVE: Psychiatric disorders have been associated with unfavourable outcome following respiratory infections. Whether this also applies to coronavirus disease 2019 (COVID-19) has been scarcely investigated. METHODS: Using the Danish administrative databases, we identified all patients with a positive real-time reverse transcription-polymerase chain reaction test for COVID-19 in Denmark up to and including 2 January 2021. Multivariable cox regression was used to calculate 30-day absolute risk and average risk ratio (ARR) for the composite end point of death from any cause and severe COVID-19 associated with psychiatric disorders, defined using both hospital diagnoses and redemption of psychotropic drugs. RESULTS: We included 144,321 patients with COVID-19. Compared with patients without psychiatric disorders, the standardized ARR of the composite outcome was significantly increased for patients with severe mental illness including schizophrenia spectrum disorders 2.43 (95% confidence interval [CI], 1.79-3.07), bipolar disorder 2.11 (95% CI, 1.25-2.97), unipolar depression 1.70 (95% CI, 1.38-2.02), and for patients who redeemed psychotropic drugs 1.70 (95% CI, 1.48-1.92). No association was found for patients with other psychiatric disorders 1.13 (95% CI, 0.86-1.38). Similar results were seen with the outcomes of death or severe COVID-19. Among the different psychiatric subgroups, patients with schizophrenia spectrum disorders had the highest 30-day absolute risk for the composite outcome 3.1% (95% CI, 2.3-3.9%), death 1.2% (95% CI, 0.4-2.0%) and severe COVID-19 2.7% (95% CI, 1.9-3.6%). CONCLUSION: Schizophrenia spectrum disorders, bipolar disorder, unipolar depression and psychotropic drug redemption are associated with unfavourable outcomes in patients with COVID-19.