Risks and burdens of incident dyslipidaemia in long COVID: a cohort study

Abstract

Background: Non-clinical evidence and a few human studies with short follow-ups suggest increased risk of dyslipidaemia in the post-acute phase of COVID-19 (ie, >30 days after SARS-CoV-2 infection). However, detailed large-scale controlled studies with longer follow-ups and in-depth assessment of the risks and burdens of incident dyslipidaemia in the post-acute phase of COVID-19 are not yet available. We, therefore, aimed to examine the risks and 1-year burdens of incident dyslipidaemia in the post-acute phase of COVID-19 among people who survive the first 30 days of SARS-CoV-2 infection.

Methods: In this cohort study, we used the national health-care databases of the US Department of Veterans Affairs to build a cohort of 51 919 participants who had a positive COVID-19 test and survived the first 30 days of infection between March 1, 2020, and Jan 15, 2021; a non-infected contemporary control group (n=2 647 654) that enrolled patients between March 1, 2020, and Jan 15, 2021; and a historical control group (n=2 539 941) that enrolled patients between March 1, 2018, and Jan 15, 2019. Control groups had no evidence of SARS-CoV-2 infection, and participants in all three cohorts were free of dyslipidaemia before cohort enrolment. We then used inverse probability weighting using predefined and algorithmically-selected high dimensional variables to estimate the risks and 1-year burdens of incident dyslipidaemia, lipid-lowering medications use, and a composite of these outcomes. We reported two measures of risk: hazard ratios (HRs) and burden per 1000 people at 12 months. Additionally, we estimated the risks and burdens of incident dyslipidaemia outcomes in mutually exclusive groups based on the care setting of the acute infection (ie, participants who were non-hospitalised, hospitalised, or admitted to intensive care during the acute phase of SARS-CoV-2 infection).

Findings: In the post-acute phase of the SARS-CoV-2 infection, compared with the non-infected contemporary control group, those in the COVID-19 group had higher risks and burdens of incident dyslipidaemia, including total cholesterol greater than 200 mg/dL (hazard ratio [HR] 1·26, 95% CI 1·22-1·29; burden 22·46, 95% CI 19·14-25·87 per 1000 people at 1 year), triglycerides greater than 150 mg/dL (1·27, 1·23-1·31; 22·03, 18·85-25·30), LDL cholesterol greater than 130 mg/dL (1·24, 1·20-1·29; 18·00, 14·98-21·11), and HDL cholesterol lower than 40 mg/dL (1·20, 1·16-1·25; 15·58, 12·52-18·73). The risk and burden of a composite of these abnormal lipid laboratory outcomes were 1·24 (95% CI 1·21-1·27) and 39·19 (95% CI 34·71-43·73), respectively. There was also increased risk and burden of incident lipid-lowering medications use (HR 1·54, 95% CI 1·48-1·61; burden 25·50, 95% CI 22·61-28·50). A composite of any dyslipidaemia outcome (laboratory abnormality or lipid-lowering medications use) yielded an HR of 1·31 (95% CI 1·28-1·34) and a burden of 54·03 (95% CI 49·21-58·92). The risks and burdens of these post-acute outcomes increased in a graded fashion corresponding to the severity of the acute phase of COVID-19 infection (ie, whether patients were non-hospitalised, hospitalised, or admitted to intensive care). The results were consistent in analyses comparing the COVID-19 group to the non-infected historical control group.

Interpretation: Our findings suggest increased risks and 1-year burdens of incident dyslipidaemia and incident lipid-lowering medications use in the post-acute phase of COVID-19 infection. Post-acute care for those with COVID-19 should involve attention to dyslipidaemia as a potential post-acute sequela of SARS-CoV-2 infection.

Funding: US Department of Veterans Affairs.

Figure 1

Risks and 1-year burdens of incident post-acute COVID-19 dyslipidaemia outcomes compared with the contemporary control cohort Outcomes were ascertained 30 days after the COVID-19-positive test until the end of follow-up. Adjusted HRs and 95% CIs are presented. The length of the bar represents the excess burden per 1000 people at 1 year and associated 95% CIs are also shown.

Figure 2

Subgroup analyses of the risks of incident post-acute COVID-19 composite dyslipidaemia outcomes compared with the contemporary control cohort Composite outcomes consisted of lipid laboratory abnormalities (total cholesterol >200 mg/dL, triglycerides >150 mg/dL, LDL >130 mg/dL, and HDL <40 mg/dL), lipid-lowering medication prescription (statins, bile acid resins, and fibrates), and any dyslipidaemia outcome (incident occurrence of any dyslipidaemia outcome studied). Outcomes were ascertained 30 days after the COVID-19 positive test until the end of follow-up. Adjusted hazard ratios and 95% CIs are presented.

Figure 3

Risks and 1-year burdens of incident post-acute COVID-19 dyslipidaemia outcomes compared with the contemporary control cohort by care setting of the acute infection Risks and burdens were assessed at 1 year in mutually exclusive groups comprising non-hospitalised individuals with COVID-19, individuals hospitalised for COVID-19, and individuals admitted to intensive care for COVID-19 during the acute phase (first 30 days) of COVID-19. Outcomes were ascertained 30 days after the COVID-19-positive test until the end of follow-up. The contemporary control cohort served as the reference category. Within the COVID-19 cohort, there were those who were non-hospitalised, hospitalised, and admitted to intensive care. Adjusted hazard ratios and 95% CIs are presented. The length of the bar represents the excess burden per 1000 people at 1 year and related 95% CIs are also presented.