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Background: Large randomized controlled trials (RCT) have shown that COVID-19 vaccines are effective at preventing severe COVID-19. However, the RCT's are not powered to detect rare adverse events. It has been reported that the new mRNA based COVID-19 vaccines may increase the risk of thromboembolic and ischemic events. Likewise, thromboembolic and ischemic events are also known complications to infection with SARS-CoV-19. Currently, less is known about the risk-reward relationship of receiving an mRNA-based COVID-19 vaccine versus contracting COVID-19 infection with respect to thromboembolic and ischemic outcomes. Purpose: To compare the risk of thromboembolic and ischemic events following COVID-19 vaccination to the risk following infection with SARS-CoV-19. Methods: The study period was from March 2020 to August 2021. All individuals were >18 years old. The population was stratified into two different groups. The vaccinated group consisted of recipients of the first dose of either Moderna (mRNA-1273, n=488,220) or Pfizer-BioNTech (BNT162b2 mRNA, n=3,186,164) vaccines. Individuals who had previously tested positive for SARS-CoV-19 were excluded. The other group consisted of individuals who had tested positive for SARS-CoV-19 in the same period who had not yet received their first vaccination dose (n=233,926). The exposure period for both groups was set to 28 days following vaccination/testing positive for SARS-CoV-19 (Figure 1). Patient level data were obtained on all included individuals using nationwide registries. Primary outcomes were acute myocardial infarction (AMI), ischemic stroke, pulmonary embolism (PE), and deep venous thrombosis (DVT). Odds ratios were obtained from logistic regression models with the vaccinated group acting as reference. Multivariable models were adjusted for demographics and comorbidities. Results: In the vaccinated group, mean age was 53±19 years and 50.3% were female. In the group of participants testing positive for SARS-CoV-19, mean age was 42.1±17.4 years and 50.2% were female. In total, 773 suffered a stroke, 472 suffered a PE, 500 suffered an AMI, and 484 suffered a DVT during the 28-day exposure period. We observed an increased absolute risk of all outcomes for participants testing positive for SARS-CoV-19 as compared to participants being vaccinated (stroke: 0.049% vs 0.019%, p<0.001), (PE: 0.91% vs 0.0072%, p<0.001), (AMI: 0.021 vs 0.013, p=0.0004), and (DVT: 0.037% vs 0.011%, p<0.001). In multivariable models, participants testing positive for SARS-CoV-19 had a significantly increased risk of all outcomes compared to participants being vaccinated: (stroke: OR: 4.0, 95% CI: [2.9–5.6], p<0.001), (PE: OR: 38.6 95% CI: [30.3–48.5], p<0.001), (AMI: OR: 3.3, 95% CI: [2.1–5.00], p<0.001), and (DVT: OR: 5.3, 95% CI: [3.8–7.5], p<0.001) (Figure 2). Conclusion: The risks of thromboembolic and ischemic events were substantially higher after SARS-CoV-19 infection than after vaccination in the Danish population. Funding Acknowledgement: Type of funding sources: Public hospital(s). Main funding source(s): Gentofte University HospitalFigure 1Figure 2
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Background: The studies investigating the safety and efficacy of the SARS-COV2 mRNA vaccines only included a limited number of heart failure patients and no separate analyses were performed regarding the safety of the vaccines in this patient population. Purpose: The aims of this study were to investigate the risk of worsening heart failure and all-cause mortality associated with the SARS-COV-2 mRNA vaccines in a nationwide cohort of patients with heart failure. Methods: Using the Danish nationwide registries, two cohorts were constructed;1) all prevalent heart failure patients in 2019 and 2) all prevalent heart failure patients in 2021 who were vaccinated with either of the two mRNA vaccines (BNT162B2 or mRNA-1273). The patients in the two cohorts were matched 1:1 using exact exposure matching on age, sex, and duration of heart failure (intervals). For patients in the 2021 cohort, the index date was defined as the date of the patients' second vaccination. Patients in the 2019 cohort were assigned the index day and month of their 1:1 match in the 2021 cohort, but used the pre-vaccination index year 2019. The primary outcomes were worsening heart failure and all-cause mortality and secondary outcomes were myocarditis and venous thromboembolism. Standardized risks were estimated based on outcome-specific Cox regression analyses, and all models were standardized to age, sex, duration of heart failure, use of SGLT2 inhibitors or Entresto, ischemic heart disease, cancer, diabetes, atrial fibrillation, and admission with heart failure <90 days before index. Results: The total study population comprised 101,786 patients, with 50,893 patients in each cohort. The median age of the study population was 74 (interquartile range (IQR);66,81), and duration of heart failure was 4.1 (IQR: 2.0,6.7) years. The standardized risk of all-cause mortality within 90 days was 2.2% (95% CI: 2.1% to 2.4%) in the 2021 cohort and 2.6% (95% CI: 2.4% to 2.7%) in the 2019 cohort, showing a significantly lower risk difference for all-cause mortality in 2021 versus 2019 (risk difference: −0.3% (95% CI: −0.5% to −0.1%)) Figure 1)). The standardized risk of worsening heart failure within 90 days was 1.1% (95% CI: −1.0% to 1.2%) in the 2021 cohort and 1.1% (95% CI: 1.0% to 1.2%) in the 2019 cohort showing no significant difference in the risk of worsening heart failure between the two cohorts (risk difference: 0% (95% CI: −0.1% to 0.1%)). No significant differences were found for venous thromboembolism or myocarditis. Conclusion: This study showed that the SARS-COV2 mRNA vaccines were not associated with an increased risk of worsening heart failure, venous thromboembolism or myocarditis, but was associated with a decreased risk of all-cause mortality. Our study may suggest that these vaccines are safe in heart failure patients. Funding Acknowledgement: Type of funding sources: Foundation. Main funding source(s): The Danish Heart FoundationLæge Sofus Carl Emil Friis og hustrus legatFigure 1
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Background: Patients with rheumatoid arthritis (RA) may have impaired immu-nogenicity to COVID-19 vaccines. Objectives: To investigate the incidence of COVID-19 infection and hospitalisation in unvaccinated and vaccinated patients with RA compared with matched individuals;and secondarily in patients with RA according to DMARD treatment. Methods: Danish nationwide matched cohort study from January to October 2021. Patients with RA were identifed in DANBIO and matched 1:20 with individuals from the general population on age, sex, and vaccination status (month and exact type of vaccination). Primary and secondary outcomes were COVID-19 hospitalisation (Danish National Patient Register) and positive SARS-CoV2 PCR test (Danish COVID-19 Surveillance Register), respectively. Stratifed by vaccination status, incidence rates (IRs) per 1000 person years (PY) and comor-bidity-adjusted hazard ratios (aHRs) in cause-specifc Cox models were calculated with 95% confdence intervals. Using the Aalen-Johansen estimator, the cumulative incidence of COVID-19 hospitalisations was visualised according to RA and vaccine exposure status. Results: Regardless of vaccination status, patients with RA had increased incidence of COVID-19 hospitalisation compared to matched individuals (Table 1). However, the absolute risk was 0.20% for unvaccinated patients at 60 days and 0.08% for comparators, whereas it remained below 0.05% at 180 days of follow-up in both groups when fully vaccinated (Figure 1). Increased SARS-CoV2 infection rates were seen only among unvacci-nated patients with RA (Table 1). Unadjusted analyses showed increased incidence of COVID-19 hospitalisation among rituximab-treated compared with conventional DMARD treated: unvaccinated HR 4.71 (1.98 to 11.18) and vaccinated HR 11.69 (2.07 to 66.06). However, the proportions of patients with previous cancer and treated with prednisolone were higher among the rituximab treated. Conclusion: The incidence of COVID-19 hospitalisation was increased for both unvaccinated and vaccinated patients with RA compared with controls. Importantly, the parallel decreasing risk for patients with RA suggests a comparable relative beneft of vaccination. Less favourable outcomes among rituximab-treated warrant that this drug should be considered with extra care.
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Background: Patients with small vessel vasculitis (SVV) and large vessel vas-culitis (LVV, including giant cell arteritis (GCA)) are considered at higher risk of infections compared to the general population, owing to their underlying condition and the use of immunosuppressive drugs. Thus, the risk of COVID-19 infection and related outcomes during the global pandemic is of immediate concern to rheumatologists worldwide. Objectives: To estimate the incidence of COVID-19 hospitalisation in patients with vasculitis, and to evaluate the impact of glucocorticoid treatment on the outcome between March 2020 and February 2021. Methods: With use of the Danish nationwide registers, a cohort of patients with LVV and SVV, respectively, and general population controls (GPCs) matched on age and gender was established. Hazard ratios (HR) for COVID-19 hospitalisation was estimated. National COVID-19 surveillance data was used to calculate the odds ratio (OR) of having had a positive SARS-CoV2 PCR test. Lastly, a nested case-control design and conditional logistic regression was used to estimate the impact of glucocorticoids on the risk of hospitalisation. Results: Patients with SVV (n=1090) had an increased incidence of COVID-19 hospitalisation compared with GPCs (comorbidity-adjusted HR 2·73;95% CI 1·64-4·55), whereas no increased risk was seen in patients with LVV. Patients with vasculitis had similar likelihoods of having had a positive PCR test as GPCs. Glucocorticoids did not increase the HR of hospitalisation among patients with LVV or SVV. Conclusion: Patients with SVV were more likely to be admitted with COVID-19 than the GPCs. The impact of glucocorticoid treatment on the risk of hospitalisation needs further investigation.
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OBJECTIVES: This study aimed to explore return to work after COVID-19 and how disease severity affects this. STUDY DESIGN: This is a Nationwide Danish registry-based cohort study using a retrospective follow-up design. METHODS: Patients with a first-time positive SARS-CoV-2 polymerase chain reaction test between 1 January 2020 and 30 May 2020, including 18-64 years old, 30-day survivors, and available to the workforce at the time of the first positive test were included. Admission types (i.e. no admission, admission to non-intensive care unit [ICU] department and admission to ICU) and return to work was investigated using Cox regression standardised to the age, sex, comorbidity and education-level distribution of all included subjects with estimates at 3 months from positive test displayed. RESULTS: Among the 7466 patients included in the study, 81.9% (6119/7466) and 98.4% (7344/7466) returned to work within 4 weeks and 6 months, respectively, with 1.5% (109/7466) not returning. Of the patients admitted, 72.1% (627/870) and 92.6% (805/870) returned 1 month and 6 months after admission to the hospital, with 6.6% (58/870) not returning within 6 months. Of patients admitted to the ICU, 36% (9/25) did not return within 6 months. Patients with an admission had a lower chance of return to work 3 months from positive test (relative risk [RR] 0.95, 95% confidence interval [CI] 0.94-0.96), with the lowest chance in patients admitted to an ICU department (RR 0.54, 95% CI 0.35-0.72). Female sex, older age, and comorbidity were associated with a lower chance of returning to work. CONCLUSION: Hospitalised patients with COVID-19 infection have a lower chance of returning to work with potential implications for postinfection follow-up and rehabilitation.
Subject(s)
COVID-19 , Adolescent , Adult , Aged , Cohort Studies , Denmark/epidemiology , Female , Humans , Infant , Intensive Care Units , Middle Aged , Registries , Retrospective Studies , Return to Work , SARS-CoV-2 , Young AdultABSTRACT
BACKGROUND: The significance of chronic kidney disease on susceptibility to COVID-19 and subsequent outcomes remains unaddressed. OBJECTIVE: To investigate the association of estimated glomerular filtration rate (eGFR) on risk of contracting COVID-19 and subsequent adverse outcomes. METHODS: Rates of hospital-diagnosed COVID-19 were compared across strata of eGFR based on conditional logistic regression using a nested case-control framework with 1:4 matching of patients diagnosed with COVID-19 with controls from the Danish general population on age, gender, diabetes and hypertension. Risk of subsequent severe COVID-19 or death was assessed in a cohort study with comparisons across strata of eGFR based on adjusted Cox regression models with G-computation of results to determine 60-day risk standardized to the distribution of risk factors in the sample. RESULTS: Estimated glomerular filtration rate was inversely associated with rate of hospital-diagnosed COVID-19: eGFR 61-90 mL/min/1.73m2 HR 1.13 (95% CI 1.03-1.25), P = 0.011; eGFR 46-60 mL/min/1.73m2 HR 1.26 (95% CI 1.06-1.50), P = 0.008; eGFR 31-45 mL/min/1.73m2 HR 1.68 (95% CI 1.34-2.11), P < 0.001; and eGFR ≤ 30 mL/min/1.73m2 3.33 (95% CI 2.50-4.42), P < 0.001 (eGFR > 90 mL/min/1.73m2 as reference), and renal impairment was associated with progressive increase in standardized 60-day risk of death or severe COVID-19; eGFR > 90 mL/min/1.73m2 13.9% (95% CI 9.7-15.0); eGFR 90-61 mL/min/1.73m2 16.1% (95% CI 14.5-17.7); eGFR 46-60 mL/min/1.73m2 17.8% (95% CI 14.7-21.2); eGFR 31-45 mL/min/1.73m2 22.6% (95% CI 18.2-26.2); and eGFR ≤ 30 mL/min/1.73m2 23.6% (95% CI 18.1-29.1). CONCLUSIONS: Renal insufficiency was associated with progressive increase in both rate of hospital-diagnosed COVID-19 and subsequent risk of adverse outcomes. Results underscore a possible vulnerability associated with impaired renal function in relation to COVID-19.
Subject(s)
COVID-19/epidemiology , Disease Susceptibility , Renal Insufficiency, Chronic/complications , Adult , Aged , Case-Control Studies , Denmark/epidemiology , Female , Glomerular Filtration Rate , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/virology , Renal Insufficiency, Chronic/epidemiology , Retrospective Studies , Risk Factors , SARS-CoV-2ABSTRACT
AIMS: The hospitalization of patients with MI has decreased during global lockdown due to the COVID-19 pandemic. Whether this decrease is associated with more severe MI, e.g. MI-CS, is unknown. We aimed to examine the association of Corona virus disease (COVID-19) pandemic and incidence of acute myocardial infarction with cardiogenic shock (MI-CS). METHODS: On March 11, 2020, the Danish government announced national lock-down. Using Danish nationwide registries, we identified patients hospitalized with MI-CS. Incidence rates (IR) and incidence rate ratios (IRR) were used to compare MI-CS before and after March 11 in 2015-2019 and in 2020. RESULTS: We identified 11,769 patients with MI of whom 696 (5.9%) had cardiogenic shock in 2015-2019. In 2020, 2132 MI patients were identified of whom 119 had cardiogenic shock (5.6%). The IR per 100,000 person years before March 11 in 2015-2019 was 9.2 (95% CI: 8.3-10.2) and after 8.9 (95% CI: 8.0-9.9). In 2020, the IR was 7.5 (95% CI: 5.8-9.7) before March 11 and 7.7 (95% CI: 6.0-9.9) after. The IRRs comparing the 2020-period with the 2015-2019 period before and after March 11 (lockdown) were 0.81 (95% CI: 0.59-1.12) and 0.87 (95% CI: 0.57-1.32), respectively. The IRR comparing the 2020-period during and before lockdown was 1.02 (95% CI: 0.74-1.41). No difference in 7-day mortality or in-hospital management was observed between study periods. CONCLUSION: We could not identify a significant association of the national lockdown on the incidence of MI-CS, along with similar in-hospital management and mortality in patients with MI-CS.