Potential contributors to increased pulmonary embolism hospitalizations during the Covid-19 pandemic

Background After the first Covid-19 infection wave, a constant increase of pulmonary embolism (PE) hospitalizations not linked with active PCR-confirmed Covid-19 has been observed but potential contributors to this observation are unclear. Therefore, we analyzed associations between changes in PE hospitalizations and (1) the incidence of non-Covid-19 pneumonia, (2) the use of computed tomography pulmonary angiography (CTPA), (3) volume depletion and (4) preceding Covid-19 infection numbers in Germany. Methods Claims data of Helios hospitals in Germany were used and consecutive cases with a hospital admission between May 6 and December 15, 2020 (PE surplus period) were analyzed and compared to corresponding periods covering the same weeks in 2016–2019 (control period). We analyzed the number of PE cases in the target period with multivariable Poisson general linear mixed models (GLMM) including (a) cohorts of 2020 versus 2016– 2019, (b) the number of cases with pneumonia, (c) CTPA, and (d) volume depletion and adjusted for age and sex. In order to associate the daily number of PE cases in 2020 with the number of preceding SARS-CoV-2 infections in Germany, we calculated the average number of daily infections (divided by 10,000) occurring 14 up to 90 days with increasing window sizes before PE cases and modelled the data with Poisson regression. Results There were 2,404 PE hospitalizations between May 6 and December 15, 2020 as opposed to 2,112 – 2,236 (total 8,717) in the corresponding 2016 – 2019 control periods. (crude rate ratio [CRR] 1.10, 95% CI 1.05 – 1.15, P <0.01). Using multivariable Poisson GLMM adjusted for age, sex and volume depletion, PE cases were significantly associated with the number of cases with pneumonia (CRR 1.09, 95 % CI 1.07−1.10, P <0.01), and with CTPA (CRR 1.10, 95 % CI 1.09−1.10, P <0.01). The increase of PE cases in 2020 compared with the control period remained significant (CRR 1.07, 95 % CI 1.02−1.12, P <0.01) when controlling for those factors. In the 2020 cohort, number of preceding average daily Covid-19 infections were associated with increased PE case incidence in all investigated windows, i.e. including preceding infections from 14 to 90 days. The best model (log likelihood −576) was with a window size of 4 days, i.e. average Covid-19 infections 14 – 17 days before PE hospitalization had a risk of 1.20 (95 % CI 1.12– 1.29, P <0.01). Conclusions There is an increase in PE cases since early May 2020 compared to corresponding periods in 2016 – 2019. This surplus was significant even when controlling for changes in potential modulators such as demographics, volume depletion, non-Covid-19 pneumonia, CTPA use and preceding Covid-19 infections. Future studies are needed (1) to investigate a potential causal link for increased risk of delayed PE with preceding SARS-CoV-2 infection, and (2) to define optimal screening for SARS-CoV-2 in patients presenting with pneumonia and PE.