Low HDL-c levels at admission are associated with greater severity and worse clinical outcomes in patients with COVID-19 disease.

Background and aims: HDL particles may act to buffer host cells from excessive inflammatory mediators. The aim of this study is to investigate if the lipid profile provides a prognostic biomarker for COVID-19 outcomes. Methods: This was a prospective study of the characteristics of 125 adult COVID-19 patients with a lipid profile performed on the day of admission analyzed with regard to clinical outcomes. Results: Seventy-seven patients (61.2%) were men, with a mean age of 66.3 (15.6) years. 54.1% had bilateral pneumonia. The all-cause mortality rate during hospitalization was 20.8%. We found a direct association between more severe disease assessed by the WHO classification, admission to the ICU and death with more pronounced lymphopenia, higher levels of CRP, ferritin (p < 0.001), D-dímer and lactate dehydrogenase (LDH) all statistically significant. Lower leves of HDL-c and LDL-c were also associated with a worse WHO classification, ICU admission, and death,. HDL-c levels were inversely correlated with inflammatory markers CRP (r = -0.333; p < 0.001), ferritin (r = -0.354; p < 0.001), D-dímer (r = -0.214; p < 0.001), LDH (r = -0.209; p < 0.001. LDL-c levels were significantly associated with CRP (r = -0.320; p < 0.001) and LDH (r = -0.269; p < 0.001). ROC curves showed that HDL [AUC = 0.737(0.586-0.887), p = 0.005] and lymphocytes [AUC = 0.672(0.497-0.847], p < 0.043] had the best prognostic accuracy to predict death. In a multivariate analysis, HDL-c (ß = -0.146(0.770-0.971), p = 0.014) and urea (ß = 0.029(1.003-1.057), p = 0.027) predicted mortality. Conclusion: Hypolipidemia including HDL levels at admission identifies patients with a higher risk of death and worse clinical manifestations who may require more intensive care.

Plasma Apolipoprotein Concentrations Are Highly Altered in Severe Intensive Care Unit COVID-19 Patients: Preliminary Results from the LIPICOR Cohort Study.

SARS-CoV-2 infection goes beyond acute pneumonia, as it also impacts lipid metabolism. Decreased HDL-C and LDL-C levels have been reported in patients with COVID-19. The lipid profile is a less robust biochemical marker than apolipoproteins, components of lipoproteins. However, the association of apolipoprotein levels during COVID-19 is not well described and understood. The objective of our study is to measure plasma levels of 14 apolipoproteins in patients with COVID-19 and to evaluate the relationships between apolipoprotein levels, severity factors and patient outcomes. From November to March 2021, 44 patients were recruited on admission to the intensive care unit because of COVID-19. Fourteen apolipoproteins and LCAT were measured by LC-MS/MS in plasma of 44 COVID-19 patients on admission to the ICU and 44 healthy control subjects. Absolute apolipoprotein concentrations were compared between COVID-19 patients and controls. Plasma apolipoproteins (Apo) A (I, II, IV), C(I, II), D, H, J and M and LCAT were lower in COVID-19 patients, whereas Apo E was higher. COVID-19 severity factors such as PaO2/FiO2 ratio, SO-FA score and CRP were correlated with certain apolipoproteins. Lower Apo B100 and LCAT levels were observed in non-survivors of COVID-19 versus survivors. To conclude, in this study, lipid and apolipoprotein profiles are altered in COVID-19 patients. Low Apo B100 and LCAT levels may be predictive of non-survival in COVID-19 patients.

Autoimmune Reaction Associated With Long COVID Syndrome and Cardiovascular Disease: A Genetic Case Report.

A 35-year-old woman with history of cardiovascular disease presented with shortness of breath, lightheadedness, fatigue, chest pain, and premature ventricular contractions 3 weeks after her second COVID-19 vaccine. Symptoms subsided following catheter ablation and ibuprofen except for chest pain and fatigue, which persisted following ablation and subsequent SARS-CoV-2 infection. The case suggests causal associations between COVID-19 vaccine/infection and recurrence of cardiovascular disease, including long-COVID-like symptoms. (Level of Difficulty: Advanced.).

Seasonal variations and the influence of COVID-19 pandemic on hemoglobin A1c, glycoalbumin, and low-density lipoprotein cholesterol.

Aim: The purpose of the study was to investigate seasonal variations in HbA1c, GA and LDL-C and to examine the effects of the COVID-19 pandemic on these variations and on glycemic and lipid control themselves in patients with type 2 diabetes. Patients and methods: The subjects were outpatients with type 2 diabetes who had received standard treatment for glycemic control for more than 3 years. Data for patients who visited our hospital from January 2021 to March 2021 were retrospectively investigated based on electronic medical records. Results: HbA1c showed seasonal variation (high in winter-spring and low in summer-autumn), and this was similar during the COVID-19 pandemic. However, the mean HbA1c over 1 year was significantly elevated during the COVID-19 pandemic (7.53 ± 1.02% in 2020) compared with the previous 2 years: (7.34 ± 0.91 in 2018, 7.39 ± 0.93 in 2019; 2020 vs. 2018; 0.19%, P < 0.001; 2020 vs. 2019; 0.14%, P = 0.0013) and the difference was larger in winter. GA showed no apparent seasonal variation, but mean GA during the COVID-19 pandemic was elevated compared with earlier years (2020 vs. 2018, P < 0.001; 2020 vs. 2019, P < 0.001). LDL-C did not show apparent seasonal variation and was unaffected by COVID-19 pandemic. Conclusion: The COVID-19 pandemic influenced mean HbA1c and GA levels over 1 year, but did not affect seasonal variations, while LDL-C was not affected by COVID-19. Observation of these levels over a longer period is warranted to determine the longer-term influence of the COVID-19 pandemic.

Effect of COVID-19 on lipid profile parameters and its correlation with acute phase reactants: A single-center retrospective analysis.

Background and objective: The development and correlation of dyslipidemia is unknown in COVID-19. This investigation was performed to assess the pathological alterations in lipid profile and their association in COVID-19. Methods: This was a retrospective study performed on real-world patients to assess serum levels of LDL-C, HDL, TG, TC on COVID-19 patients (mild: 319; moderate: 391; critical: 357). Age- and gender-matched controls who had their lipid profiles in the same period were included as the control group. Results: LDL-C, HDL, TG, and TC levels were significantly lower in COVID-19 patients when compared with the control group (P < 0.001, 0.047, 0.045, <0.001, respectively). All parameters decreased gradually with COVID-19 disease severity (LDL-C: median (IQR), mild: 98 (91,134); moderate: 97 (81,113); critical: 68 (68,83); HDL: mild: 45 (37,50); moderate: 46 (41,50); critical: 40 (37,46); TG: mild: 186 (150,245); moderate: 156 (109,198); critical: 111 (98,154); TC: mild: 224 (212,238); moderate: 212 (203,213); critical: 154 (125,187)). Logistic regression demonstrated lipid profile as predictor of severity of COVID-19 disease. Conclusion: Hypolipidemia develops in increasing frequency with severe COVID-19 disease. It inversely correlates with levels of acute-phase reactants, indicating SARS-COV-2 as the causative agent for alteration in lipid and thyroid levels.

Lipid profile changes in patients with COVID-19 referred to medical centers in Kermanshah, Iran; a case-control study.

OBJECTIVE: To evaluate blood lipid profiles in patients with coronavirus disease 2019 (COVID-19), and to explore the association with disease severity. METHODS: This case-control study included patients with COVID-19, referred to two medical centers in Kermanshah, Iran (between July 2020 and December 2020), and healthy controls. Lipid profiles were evaluated in patients who were grouped according to severe (intensive care unit [ICU]), or less severe (outpatient), forms of COVID-19, and in healthy controls, and were compared among the three groups. RESULTS: A total of 132 participants were included, comprising ICU (n = 49), outpatient (n = 48) and control (n = 35) groups. Mean cholesterol levels were lower in the patient groups than in controls; high-density lipoprotein cholesterol (HDL-C) levels were higher in the ICU group versus outpatients, and low-density lipoprotein cholesterol (LDL-C) levels were lower in the ICU group versus outpatients. The frequency of diabetes and hypertension was higher in the ICU group than in the outpatient group. Furthermore, LDL-C level was associated with disease severity (odds ratio 0.966, 95% confidence interval 0.944, 0.989). CONCLUSION: Lipid profiles differ between severe and less severe forms of COVID-19. LDL-C level may be a useful indicator of COVID-19 severity.

Possible mechanisms of cholesterol elevation aggravating COVID-19.

Importance: Despite the availability of a vaccine against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), humans will have to live with this virus and the after-effects of the coronavirus disease 2019 (COVID-19) infection for a long time. Cholesterol plays an important role in the infection and prognosis of SARS-CoV-2, and the study of its mechanism is of great significance not only for the treatment of COVID-19 but also for research on generic antiviral drugs. Observations: Cholesterol promotes the development of atherosclerosis by activating NLR family pyrin domain containing 3 (NLRP3), and the resulting inflammatory environment indirectly contributes to COVID-19 infection and subsequent deterioration. In in vitro studies, membrane cholesterol increased the number of viral entry sites on the host cell membrane and the number of angiotensin-converting enzyme 2 (ACE2) receptors in the membrane fusion site. Previous studies have shown that the fusion protein of the virus interacts with cholesterol, and the spike protein of SARS-CoV-2 also requires cholesterol to enter the host cells. Cholesterol in blood interacts with the spike protein to promote the entry of spike cells, wherein the scavenger receptor class B type 1 (SR-B1) plays an important role. Because of the cardiovascular protective effects of lipid-lowering therapy and the additional anti-inflammatory effects of lipid-lowering drugs, it is currently recommended to continue lipid-lowering therapy for patients with COVID-19, but the safety of extremely low LDL-C is questionable. Conclusions and Relevance: Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death from COVID-19, which are mediated by NLRP3 and atherosclerotic plaques, respectively. Cholesterol present in the host cell membrane, virus, and blood may also directly participate in the virus cell entry process, but the specific mechanism still needs further study. Patients with COVID-19 are recommended to continue lipid-lowering therapy.

U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis.

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12-4.68; p = 0.023) and 2.02 (1.04-3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81-3.40 mmol/L (108.6-131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07-6.37; p = 0.035) and 2.36 (1.09-5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.

Follow-up study on serum cholesterol profiles and potential sequelae in recovered COVID-19 patients.

BACKGROUND: COVID-19 patients develop hypolipidemia. However, it is unknown whether lipid levels have improved and there are potential sequlae in recovered patients. OBJECTIVE: In this follow-up study, we evaluated serum lipidemia and various physiopathological laboratory values in recovered patients. METHODS: A 3-6 month follow-up study was performed between June 15 and September 3, 2020, to examine serum levels of laboratory values in 107 discharged COVID-19 patients (mild = 59; severe/critical = 48; diagnoses on admission). Sixty-one patients had a revisit chest CT scan. A Wilcoxon signed-rank test was used to analyze changes in laboratory values at admission and follow-up. RESULTS: LDL-c and HDL-c levels were significantly higher at follow-up than at admission in severe/critical cases (p <  0.05). LDL-c levels were significantly higher at follow-up than at admission in mild cases (p <  0.05). Coagulation and liver functional values were significantly improved at follow-up than at admission for patients (p <  0.05). Increases in HDL-c significantly correlated with increases in numbers of white blood cells (p <  0.001) during patients' recovery. With exclusion of the subjects taking traditional Chinese medicines or cholesterol-lowering drugs, LDL-c and HDL-c levels were significantly increased at follow-up than at admission in severe/critical cases (p <  0.05). Residue lesions were observed in CT images in 72% (44 of 61) of follow-up patients. CONCLUSIONS: Improvements of LDL-c, HDL-c, liver functions, and incomplete resolution of lung lesions were observed at 3-6 month follow-up for recovered patients, indicating that a long-term recovery process could be required and the development of sequelae such as pulmonary fibrosis could be expected in some patients.