Risk of Cardiovascular Events after Covid-19: a double-cohort study
Authors: Tereshchenko Larisa G. , Bishop Adam , Fisher-Campbell Nora , Levene Jacqueline , Morris Craig C. , Patel Hetal , Beeson Erynn , Blank Jessica A. , Bradner JG N. , Coblens Michelle , Corpron Jacob W. , Davison Jenna M. , Denny Kathleen , Earp Mary S. , Florea Simeon , Freeman Howard , Fuson Olivia , Guillot Florian , Haq Kazi , Hyde Jessica , Khader Ayesha , Kolseth Clinton , Kim Morris , Krol Olivia , Lin Lisa , Litwin Liat , Malik Aneeq , Mitchell Evan , Mohapatra Aman , Mullen Cassandra , Nix Chad D , Oyeyemi Ayodele , Rutlen Christine , Corley-Stampke Lisa , Tam Ashley , Van Buren Inga , Wallace Jessica , Khan Akram 
Published: December 2021

Objective

To determine absolute and relative risks of either symptomatic or asymptomatic SARS-CoV-2 infection for late cardiovascular events and all-cause mortality.

Methods

We conducted a retrospective double-cohort study of patients with either symptomatic or asymptomatic SARS-CoV-2 infection [COVID-19(+) cohort] and its documented absence [COVID-19(-) cohort]. The study investigators drew a simple random sample of records from all Oregon Health & Science University (OHSU) Healthcare patients (N=65,585) with available COVID-19 test results, performed 03.01.2020 - 09.13.2020. Exclusion criteria were age < 18y and no established OHSU care. The primary outcome was a composite of cardiovascular morbidity and mortality. All-cause mortality was the secondary outcome.

Results

The study population included 1355 patients (mean age 48.7±20.5 y; 770(57%) female, 977(72%) white non-Hispanic; 1072(79%) insured; 563(42%) with cardiovascular disease (CVD) history). During a median 6 months at risk, the primary composite outcome was observed in 38/319 (12%) COVID-19(+) and 65/1036 (6%) COVID-19(-) patients (p=0.001). In Cox regression adjusted for demographics, health insurance, and reason for COVID-19 testing, SARS-CoV-2 infection was associated with the risk of the primary composite outcome (HR 1.71; 95%CI 1.06-2.78; p=0.029). Inverse-probability-weighted estimation, conditioned for 31 covariates, showed that for every COVID-19(+) patient, the average time to all-cause death was 65.5 days less than when all these patients were COVID-19(-): average treatment effect on the treated -65.5 (95%CI -125.4 to -5.61) days; p=0.032.

Conclusions

Either symptomatic or asymptomatic SARS-CoV-2 infection is associated with increased risk of late cardiovascular outcomes and has causal effect on all-cause mortality in a late post-COVID-19 period.

ClinicalTrials.gov Identifier: NCT04555187

Key messages

What is already known about this subject

Acute, symptomatic COVID-19 can cause acute cardiovascular manifestations.

Post-acute or “long” COVID-19 can be a debilitating disease following acute infection with a heterogenous presentation.

What might this study add?

Either symptomatic or asymptomatic SARS-CoV-2 infection is associated with increased risk of late cardiovascular outcomes.

Either symptomatic or asymptomatic SARS-CoV-2 infection has causal effect on all-cause mortality in a late post-COVID-19 period.

How might this impact on clinical practice?

As we begin to care for more survivors of COVID-19, we will need to better understand not only how to care for their acute symptoms and complications following infection, but also recognize future cardiovascular risk and mitigate such risk with appropriate screening and preventative measures.