Association of Lipid Levels With COVID-19 Infection, Disease Severity and Mortality: A Systematic Review and Meta-Analysis

Abstract

BackgroundCoronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to severe illness. Cholesterol in the host cell plasma membrane plays an important role in the SARS-CoV-2 virus entry into cells. Serum lipids, especially low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), are in constant interaction with the lipid rafts in the host cell membranes and can modify the interaction of virus with host cells and the resultant disease severity. Recent studies on serum lipid levels and COVID-19 disease severity lack consistency.ObjectivesOur systematic review and meta-analysis compared the serum levels of total cholesterol (TC), LDL-C, HDL-C, and triglycerides (TG) between (1) COVID-19 patients vs. healthy controls; (2) severe vs. non-severe COVID-19 disease; (3) deceased vs. surviving COVID-19 patients.MethodsPRISMA guidelines were followed. We included peer-reviewed articles on observational (case-control and cohort) studies from PubMed and Embase published from the database inception until September 1, 2021. We used random-effects meta-analysis for pooled mean-differences (pMD) in lipid levels (mg/dL) for the above groups.ResultsAmong 441 articles identified, 29 articles (26 retrospective and 3 prospective cohorts), with an aggregate of 256,721 participants, were included. COVID-19 patients had lower TC (pMD-14.9, 95%CI-21.6 to −8.3) and HDL-C (pMD-6.9, 95%CI −10.2 to −3.7) levels (mg/dL). Severe COVID-19 patients had lower TC (pMD-10.4, 95%CI −18.7 to −2.2), LDL-C (pMD-4.4, 95%CI −8.4 to −0.42), and HDL-C (pMD-4.4, 95%CI −6.9 to −1.8) at admission compared to patients with non-severe disease. Deceased patients had lower TC (pMD-14.9, 95%CI −21.6 to −8.3), LDL-C (pMD-10.6, 95%CI −16.5 to −4.6) and HDL-C (pMD-2.5, 95%CI −3.9 to −1.0) at admission. TG levels did not differ based on COVID-19 severity or mortality. No publication bias was noted.ConclusionWe demonstrated lower lipid levels in patients with COVID-19 infection and an association with disease severity and mortality. Their potential role in COVID-19 pathogenesis and their utility as prognostic factors require further investigation.

HDL cholesterol levels and susceptibility to COVID-19

“…On the contrary, recent evidence suggests that low serum levels of LDL-C, HDL-C, and total cholesterol (TC) at hospital admission are associated with severe disease and mortality in COVID-19. 7,8 However, these associations were based on measurements made during hospital admission and suffer from the possibility of reverse causality due to the acute inflammatory response in COVID-19. Additionally, clinical data on the impact of past HDL-C and LDL-C levels on the risk and outcome of infectious diseases remain inconsistent.…”

“…5,6 On the contrary, recent evidence suggests that low serum levels of LDL-C, HDL-C, and total cholesterol (TC) at hospital admission are associated with severe disease and mortality in COVID-19. 7,8 However, these associations were based on measurements made during hospital admission and suffer from the possibility of reverse causality due to the acute inflammatory response in COVID-19. 9 Among the various serum lipoprotein fractions, preclinical evidence suggests that HDL-C is an important modulator of inflammation, 10,11 with potential mechanisms including interference with viral fusion, reduction in the rate of bacterial complications, and neutralization of exaggerated immune responses.…”

High-throughput mass spectrometry maps the sepsis plasma proteome and differences in response

“…Further work is needed to establish the mechanisms driving SPC and whether they are reflective of treatable traits. Animal and human studies, for example, already highlight lipoproteins as potential therapeutic targets in sepsis (Tanaka et al, 2020) and COVID-19 (Chidambaram et al, 2022). Additional work is also required to determine the maximally informative biomarkers appropriate for point of care testing, and whether these can be applied in combination with other 'omic platforms and currently available clinical or laboratory variables to better stratify patients.…”

A unique dysregulation pattern of lipid metabolism and immune responses in patients with omicron SARS-CoV-2 recurrence

“…Some recent studies have reported that patients with diverse infections, such as Epstein–Barr virus, cytomegalovirus and tuberculosis, had lower levels of lipoproteins in comparison with non-infected individuals. 1–3 In the research by Vignesh et al , 4 lower lipid was also observed in COVID-19 patients compared to uninfected controls. Consistent with these reports, our research revealed the reduced lipoprotein pattern in Omi-Rec patients and highlights the important role of lipid metabolism in SARS-CoV-2 shedding.…”