Changes in lipid metabolism in patients with severe COVID-19

Background: Dyslipidemia plays an important role in the pathogenesis and evolution of critical illness, but limited information exists regarding the lipid metabolism of severe coronavirus disease 2019 (COVID-19) patients. The aim of this study was to investigate role of dyslipidemia in patients with severe COVID-19 Methods: We retrospectively reviewed 216 severe COVID-19 patients with clari�ed outcomes (discharged or deceased), admitted to the West Court of Union Hospital in Wuhan, China, between February 1 and March 31, 2020. The dynamic changes of lipid pro�les and their relationships with disease severity and clinical outcomes were analyzed. Results: A total of 216 severe COVID-19 patients, including 24 non-survivors and 192 survivors, were included in the �nal analyses. The levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (Apo-AI) on admission were signi�cantly lower in non-survivors compared to survivors. During hospitalization, low-density lipoprotein cholesterol (LDL-C), total cholesterol(TC), HDL-C and Apo-AI were shown an increasing trend in survivors, but maintained lower levels or shown downward trend in non-survivors. The serum levels of HDL-C and Apo-AI were inversely correlated with C-reactive protein (CRP), length of hospital stay of survivors and disease severity. The receiver operating characteristic (ROC) curve analysis identi�ed a CRP/ HDL-C ratio cut-off value of 62.54 as the predictor for in-hospital mortality (AUC=0.823, Sensitivity=83.3%, Speci�city=70.8%). Logistic regression analysis demonstrated that hypertension, neutrophils-to-lymphocytes ratio(NLR), platelet count and high CRP/ HDL-C ratio (>62.54) were independent factors to predict in-hospital mortality. Conclusions: The results demonstrated that dyslipidemia was associated with the in�ammatory response, disease severity and poor prognosis of COVID-19. High CRP/ HDL-C ratio may serve as an independently potential predictor for hospital mortality among patients


Background
In December 2019, a novel pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, China, and the disease caused by SARS-CoV-2 has been named as the coronavirus disease-2019 (COVID-19) by the World Health Organization(WHO).On March 11, 2020, the World Health Organization (WHO) declared that COVID-19 has evolved into a global pandemic, with a signi cant impact on the global economy and life security.Until July 15, 2020, the WHO announced that the overall number of con rmed cases of COVID-19 was 12,964,809 worldwide, with 570,288 deaths [1].Among a total of 72 314 case of COVID-19 reported by the Chinese Center for Disease Control and Prevention, most patients were classi ed as mild (81%),14% were severe and 5% were critical, and the overall case-fatality rate was 49.0% among critical cases [2].Although most of mild patients had asymptomatic and/or mild clinical symptoms and good prognosis, some of severe COVID-19 patients, especially those patients with old age and several preexisting comorbidities, could develop to severe illnesses including acute respiratory distress syndrome, septic shock, multiple organ failure or even death in a short period of time [3,4].Therefore, it is meaningful to determine effective indicators to predict the disease severity and clinical outcome, and help to reduce the mortality of severe and critical patients with COVID-19.
Dyslipidemia play an important role in the pathogenesis and evolution of atherosclerosis, and they are always at the forefront of medical research.However, it is not widely known that lipids are an integral part of the pulmonary innate and adaptive immune responses to various pulmonary diseases, including in uenza pneumonia, asthma, acute lung injury (ALI), chronic obstructive pulmonary disease, and other lung disorders [5,6].In addition, high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (Apo-AI), low-density lipoprotein cholesterol (LDL-C) and other lipid parameters showed signi cant changes during pulmonary infection and in ammation [7].HDL display pleiotropic characteristics, including lipopolysaccharide (LPS) and lipoteichoic acid (LTA) neutralization, anti-in ammatory, anti-thrombotic, anti-oxidative, anti-apoptotic and endotheliocyte protective effects [8,9].Clinical data demonstrate that HDL concentration decrease rapidly during sepsis, and there is a signi cant correlation between the low level of HDL and the poor prognosis of sepsis [10].Experimental studies have also manifested that injection of reconstituted HDL (rHDL) or HDL mimetic peptide can reduce the mortality of sepsis animal models [11][12][13].Apo-AI is the major protein component of HDL, and it has anti-in ammatory properties.The decrease of Apo -AI level was reported to be closely associated with poor prognosis in multiple disease states, such as infective endocarditis, systemic in ammatory response syndrome, acute pancreatitis, and sepsis [14][15][16].Furthermore, administration of Apo-AI mimetic peptides or overexpression of Apo-AI could reduce LPS-or in uenza virus-induced lung in ammatory damage [17,18].Therefore, changes of lipid metabolism in patients under in ammatory conditions was related to adverse clinical outcomes.During the course of COVID-19, SARS-CoV-2 could induce excessive and uncontrolled cytokine storm in severe and critical patients with COVID-19, which was associated with the disease severity and prognosis of the disease [19].Thus, elevated cytokines may change lipid pro le of patients with COVID-19.
Recently, studies have found that levels of LDL-C and TC in COVID-19 patients are decreased [20,21].Nevertheless, these studies largely focused on the levels of total cholesterol(TC), triglycerides (TG), HDL cholesterol(HDL-C) and LDL cholesterol(LDL-C).Little is known about lipoprotein and apolipoprotein levels and the dynamic change of lipid.More importantly, whether these changes and lipid pro les at admission can help to predict the clinical outcome of the COVID-19 patients remains unclear.C-reactive protein (CRP) is a common in ammatory marker, which increases in most patients with COVID-19 and is closely related to the severity of the disease [22].And HDL and Apo-AI display pleiotropic properties including anti-oxidant and anti-in ammatory functions [9].Therefore, the ratio of CRP/HDL-C or CRP/ Apo-AI may re ect the balance between pro-in ammatory and anti-in ammatory process.In this retrospective study, we aim to evaluate whether dysregulation of lipid pro les, new markers (CRP/HDL-C and CRP/ Apo-AI) and the dynamic changes in lipid pro les serve as prognostic indicator in patients with severe COVID-19.[23].Patients with severe COVID-19 met any of the following criteria: respiratory rate ≥ 30 breaths per minute; nger of oxygen saturation ≤ 93% at rest; PaO2 / FiO2 ≤ 300 mmHg.We excluded patients who received parenteral nutrition containing lipids at the time of blood sampling, patients who were immunocompromised, patients with a known severe hepatic dysfunction, patients with familial or genetic disorders of lipid metabolism, and patients without lipid pro les detection on admission.By the time of March 31, 2020, a total of 216 severe COVID-19 patients with the clari ed clinical outcome (died or recovered) were recruited in this study, and a ow diagram is showed in Fig. 1.

Study design and participants
The study was approved by the Ethics Committee of Union Hospital of Huazhong University of Science and Technology and ethics board of Xiangya Hospital, Central South University (No. 202003049).Written informed consent was waived by the Ethics Commission of the designated hospital due to the emerging infectious diseases.

Data Collection
The clinical records and laboratory data of each patient was obtained from the electronic medical system.A group of experienced respiratory clinicians reviewed and re ned the data.The demographic data, comorbidities, clinical symptoms and signs and clinical outcomes (death or recovery) were extracted from their electronic medical records.Laboratory results on admission, including blood routine, liver function, kidney function, coagulation function, C-reactive protein, were collected and evaluated.The dynamic changes of lipid and apolipoprotein levels for severe COVID-19 patients during hospitalization (day 1, n = 216), day 5-7 (n = 121) and day 15-17 (n = 130) were collected as well.All laboratory data were tested in the same laboratory with the same standard.Furthermore, disease severity was also evaluated by the National Early Warning Score 2[24] (NEWS 2) and Sequential Organ Failure Assessment ( SOFA) score.

Statistical analysis
Categorical variables were presented as numbers (percentages, %), and compared by Chi-square test or Fisher's exact test.Continuous variables with normal distribution were shown as mean ± standard deviation and compared with the Student t test, otherwise, continuous variables with skewed distribution were presented with medians [interquartile range (IQR)], and compared withMann-Whitney U test.Correlations between variables were analyzed with Spearman's coe cients.Receiver operating characteristic (ROC) curve analyses were performed to determine the cutoff values, sensitivity, and speci city of potential mediators (Apo-AI, HDL-C, CRP/ HDL-C ratio and CRP/ Apo-AI ratio) for predicting in-hospital mortality.Meanwhile, the best Youden index (sensitivity + speci city − 1) was obtained to calculate appropriate cut-off point of potential mediators (CRP/ HDL-C ratio and CRP/ Apo-AI ratio) to predict in-hospital death.In addition, risk factors were evaluated by univariate analysis, and variables with statistical signi cance in univariate analysis were selected in the multivariate analysis by using a multiple logistic stepwise regression to calculate independent risk factors to predict in-hospital mortality.For all analyses, P < 0.05 (two-tailed) was considered statistically signi cant.Graphpad Prism 8.0 (Graphpad Software, La Jolla,CA, USA) and SPSS 22.0 softwares (SPSS Inc., Chicago, IL, USA) were used for statistical graphs and analyses.

Demographics and baseline clinical characteristics of severe COVID-19 patients
A total of 216 severe COVID-19 patients were included in the nal analysis based on the selection criteria(Fig.1).The demographics and baseline clinical characteristics of severe COVID-19 patients are summarized in Table 1.Twenty-four patients died during hospitalization and 192 were discharged from hospital.The mean age of the 216 patients was 61.3 years, and 139(64.4%)weremen.Hypertension is the most common comorbidity, followed by diabetes, coronary heart disease, chronic obstructive lung disease and malignancy.Compared with the survivor group, the non-survivor had higher prevalence of hypertension (66.7% vs 41.7%, P = 0.02).The respiration rate and temperature were signi cantly higher in non-survivors compared to survivors.However, there was no signi cant difference between the two groups in high respiratory rate(> 24 breaths per min) and fever (temperature ≥ 37.3 °C).Compared with the survivors, the non-survivors had greater disease severity as evidenced by higher SOFA score and NEWS 2 score(P 0.0001), accompanied with signi cantly higher white blood cell and neutrophil count, NLR, CRP, procalcitonin, lactate dehydrogenase, total bilirubin, urea nitrogen, hypersensitive troponin I and D-dimer, and lower lymphocyte, albumin and platelet count compared to survivors (Table 2).Lipid pro les were analyzed on admission (day 1), on day 5-7 and day 15-17 after admission (Fig. 2).On admission, the serum levels of high-density lipoprotein cholesterol (HDL-C) and apolipoprotein AI (Apo-AI) were signi cantly lower in non-survivors, whereas there was no difference in total cholesterol(TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), Apo-B and lipoprotein A (LP-A) (Table 2).Furthermore, HDL-C and Apo-AI levels were signi cantly lower in non-survivors at all time points (Fig. 2).The LDL-C and TC concentration was signi cantly lower in non-survivors on day 5-7 (p < 0.05) and day 15-17(p < 0.001).During day 1 to day 15-17, low-density lipoprotein cholesterol (LDL-C), total cholesterol(TC), HDL-C and Apo-AI were shown an increasing trend in survivors, but maintained lower levels or shown downward trend in non-survivors(Fig.2).
Relationship between lipid pro les and CRP levels, disease severity The levels of HDL-C and Apo-AI were signi cantly higher in survivors, while the levels of C-reactive protein were higher in non-survivors(P 0.0001)(Table 1).Both HDL and Apo-AI were inversely correlated with SOFA score, NEWS2 score, length of hospital stay of survivors and CRP level (Table 3).Of these, Apo-AI had the strongest inverse correlation with length of stay of survivors (R= -0.562, p < 0.001) and CRP (R= -0.570, p < 0.001).The ratios ( CRP/HDL-C or CRP/ Apo-AI) may serve as new markers to re ect the balance between pro-in ammatory and anti-in ammatory factors.Surprisingly, the ratios of CRP/HDL-C and CRP/ Apo-AI were signi cantly higher in non-survivors(Table 2).Additionally, CRP/HDL-C and CRP/ Apo-AI had the strongest negative correlation with SOFA score, length of hospital stay of survivors and CRP(Table 3).

CRP/ HDL-C ratio may serve as a new marker to predict adverse clinical outcome
In order to evaluate the prognostic value and determine the best cut-off of CRP/ HDL-C ratio for predicting in-hospital mortality among COVID-19 patients, receiver operation characteristic (ROC) curves were performed (Fig. 3).The area under the ROC curve (AUC) was 0.295(95% CI:0.196-0.394,P= 0.001) for Apo-AI, 0.328(95% CI:0.224-0.431,P= 0.006) for HDL-C, 0.823(95% CI:0.737-0.910,P 0.0001) for CRP/ HDL-C ratio, 0.811(95% CI:0.726-0.895,P 0.0001) for CRP/ Apo-AI ratio(Table 3).The best cut-off points of CRP/ HDL-C ratio for predicting in-hospital mortality was 62.543 with the best Youden index, the sensitivity of 83.3%, the speci city of 70.8% and the accuracy of 72.2%(Fig.3).Similarly, the best cut-off points of CRP/Apo-AI ratio was 84.264 for predicting in-hospital death, with the sensitivity for 75.0%, the speci city for 75.0% and the accuracy for 75.0%.Then, we de ned the high CRP/ HDL-C ratio( 62.543) and the high CRP/ Apo-AI ratio( 84.264).
In univariate analysis, we exclude the variables that are calculated from other variables to prevent the occurrence of collinearity, such as disease severity scores, or those variables of the same type with different indicators and strong correlation [16].Finally, parameters including hypertension, respiration rate, temperature, platelet count, NLR, lactate dehydrogenase, total bilirubin, albumin, urea nitrogen, creatine kinase, D-dimer, procalcitonin, high CRP/ HDL-C ratio( 62.543) and high CRP/ Apo-AI ratio( 84.264) were entered into the multivariate logistic regression model.In the nal model, hypertension, NLR, platelet count and high CRP/ HDL-C ratio were independent factors to predict in-hospital mortality (Table 5).The clinical characteristics and outcomes of patients were divided into two groups by low and high CRP/ HDL-C ratio (high CRP/ HDL-C ratio 62.543 and low CRP/ HDL-C ratio 62.543, Table 6) according to the cut-off value calculated by the ROC curve (Figure .3).The rate of hospital mortality, the proportion of COVID-19 with critical subtype, SOFA score and NEWS2 score were signi cantly higher in high CRP/ HDL-C ratio group than in the group with a low CRP/ HDL-C ratio.Moreover, patients in high CRP/ HDL-C ratio group were older with more men, accompanied with higher levels of white blood cell count, neutrophil, lymphocyte, NLR, aspartate aminotransferase, lactate dehydrogenase, total bilirubin, albumin, urea nitrogen, hypersensitive troponin I, C-reactive protein, D-dimer, prothrombin time, international normalized ratio and procalcitonin than the patients in low CRP/ HDL-C ratio group (Table 6).

Discussion
In this study, we found the dyslipidemia in patients with severe COVID-19, and demonstrated that low levels of HDL-C and Apo-AI at admission were signi cantly associated with high levels of CRP, prolonged hospital stay, increased disease severity.Additionally, the analysis of the longitudinal changes of lipid pro les showed that non-survival COVID-19 patients persistent had hypolipidemia including TC, HDL-C, LDL-C, Apo-AI than the survival patients during the early period of hospitalization.Furthermore, hypertension, NLR, platelet count and high CRP/ HDL-C ratio ( 62.543) could serve as independent factors to predict in-hospital mortality, especially, higher CRP/ HDL-C ratio was closely associated with increased hospital mortality.
Acute in ammation caused by viral infection may result in dyslipidemia in patients, and the lipid metabolism is known to play an important role in host immune response.Clinical observations have displayed that patients with acute Epstein-Barr virus(EBV) infection had lower levels of Apo-AI, HDL-C, TC, Apo B, LDL-C and LP-A compared with their controls [25].Another study showed that cytomegalovirus(CMV) infection was associated with lower HDL-C in normal-weight females [26].
Compared with other febrile patients, dengue-positive patients had lower HDL-C and LDL-C levels [27].In addition, SARS patients had lower levels of Apo-AI compared to their normal controls from the results of plasma proteomics [28].Similarly, our study showed that non-survivors with severe COVID-19 showed lower HDL-C and Apo-AI concentrations at admission compared to those survivors.Additionally, the analysis of longitudinal changes of lipid pro les demonstrated that LDL-C, HDL-C, TC and Apo-AI remained persistent at low levels, or even further gradually decreased during disease progression in nonsurvivors, while in survivors, although initially decreased, aforementioned lipid pro les were shown to increase steadily during recovery.Several possible hypotheses might explain the dynamic changes during the course of COVID-19.Firstly, Liver plays an critical role in lipid metabolism, and liver dysfunction caused by SARS-CoV2 infection or potential drugs will affect lipid synthesis.It was reported that 14%-53% of patients with COVID-19 had hepatic dysfunction, especially in those severe and critical patients [29].Therefore, the synthesis of apolipoproteins and lipoproteins would be affected by hepatic dysfunction of patients with severe COVID-19.Secondly, acute in ammation caused by SARS-CoV-2 might alter lipid metabolism as well.Severe and critical patients with COVID-19 were commonly accompanied with largely excessive release of proin ammatory cytokines, such as IL-1, IL-6, IL-12, IFN -γ and TNF-α, as the disease progressed over time and gradually got worse [30].It was shown that tumor necrosis TNF-α, IL-1β, and IL-6 could decrease synthesis and/or secretion of apolipoproteins in hepatic cell lines in dose-dependent way [31].
Additionally, severe in ammatory response could also cause capillary leakage, thus resulting in the leakage of lipoproteins and apolipoproteins particles from intravascular to extravascular compartment [32].In our study, we found that HDL-C and Apo-AI were closely associated with in ammatory marker of CRP, which might partially explain the hypolipidemia was associated with in ammatory response in severe COVID-19 patients.Finally, a very recent study has showed that a rare missense variant in cholesteryl ester transfer protein gene (CETP, rs1800777-A) that was associated with marked reduction in HDL-C levels and adverse clinical outcome during sepsis [33].COVID-19 patients who carry the A allele may have lower HDL level and worse prognosis compared with non-carriers [33].Therefore, the genetic variation of CETP gene is a key regulator of HDL-C levels and clinical prognosis during sepsis.At present, the genetic variation of CETP gene in patients with COVID-19 has not been reported, and it may be a promising research direction in the treatment and evaluation of prognosis among patients with COVID-19.
Since COVID-19 is a global pandemic with a high mortality rate, it will be helpful to determine several early markers to predict the disease severity and prognosis of COVID-19.Previous studies showed that low levels of Apo-AI and HDL-C have been used as prognostic biomarkers in patients with pneumonia, sepsis and other infections.An observational study indicated that a low level of Apo-AI was an indicator for poor prognosis in cirrhotic patients with severe sepsis [16].Similarly, gradually-declined HDL-C level from day 1 to day 7 after admission could serve as a poor prognostic indicator among patients with severe community-acquired pneumonia [34].Consistently, our data suggested that both HDL-C and Apo-AI levels were inversely correlated with disease severity scored (SOFA score and NEWS2 score), length of stay of survivors and in ammatory marker of CRP in patients with severe COVID-19.Additionally, our data also reported the low power of HDL-C and Apo-AI levels at admission to predict the in-hospital mortality.HDL and Apo-AI display pleiotropic properties including antioxidant and anti-in ammatory functions [9].CRP is a common in ammatory marker.Thus, the ratio of HDL and its major protein, Apo-AI, display pleiotropic protective functions, which include anti-infectious, anti-in ammatory, anti-oxidative, anti-thrombotic and Anti-diabetic properties [9].An increasing number of evidences showed that HDL, particularly its major protein, Apo-AI, played protective effects in a variety of lung disease, including ALI, ARDS, chronic obstructive pulmonary disease(COPD), asthma, pulmonary brosis and viral pneumonia[6].However, there are no clinical and experimental studies on the protective effect of HDL and Apo-AI in COVID-19.In severe and critical COVID-19 patients, clinical outcome can be signi cantly worsened by excessive release of pro-in ammatory cytokines [30].HDL and Apo-AI may help in preventing in ammatory injury and improving the clinical outcome with anti-in ammatory and antioxidative properties.Then, a systematic review and meta-analysis showed that bacterial co-infection occurred in 7% of hospitalized COVID-19 patients and 14% of ICU patients, and the bacterial co-infection would lead to a higher mortality of COVID-19 [37].Studies showed that HDL was capable to bind and neutralize Gram-negative LPS and Gram-positive lipoteichoic acid (LTA), thus reducing LTA and LPSinduced in ammatory injury [38,39], thus providing the conception that HDL-based therapies might be promising in severe COVID-19 patients with bacterial co-infection.Diabetes was a common comorbidity in patients with COVID-19, and associated with greater disease severity and higher mortality of COVID-19 [40], especially in those population with poorly-controlled glycemia [41].Several experimental studies have demonstrated that HDL particles displayed anti-diabetic properties by improving insulin sensitivity and β cell insulin secretion [9,42,43].The evidence suggested that HDL or Apo-AI might improve glycemic control and promote a better prognosis in severe COVID-19 patients.Although no clinical and experimental studies were conducted to determine the role of HDL and Apo-AI-based therapy in COVID-19, it would be a promising direction in searching novel treatment for severe patients with COVID-19.
Our study was subject to a few limitations that should not go unnoticed.Firstly, this study was a retrospective study with a relatively small sample size, large cohort study would be required to further con rm our conclusion.Secondly, asymptomatic patients and those with mild symptoms were not be enrolled, thus the conclusions drew by the study might not be applicable to asymptomatic and mild patients.Thirdly, a large number of factors could affect the lipid metabolism in COVID-19, the speci c mechanism about the dyslipidemia could not be concluded, and would be required further powerful investigation.

Conclusion
In conclusion, our study demonstrated that dyslipidemia was associated with the in ammatory response, disease severity and poor prognosis of COVID-19.High CRP/ HDL-C ratio may serve as an independently   Figure 3 This was a retrospective, single-center, observational study among patients with severe COVID-19 who was admitted to the West Court of Union Hospital of Huazhong University of Science and Technology during the management by national medical team from February 1 to March 31, 2020.All the participants were diagnosed with COVID-19 based on the WHO interim guidance.Classi cation of clinical types of COVID-19 were based on Diagnosis and Treatment Protocol for Novel Coronavirus Pneumonia (Trial Version 7) published by National Health Commission & National Administration of Traditional Chinese Medicine of China Abbreviations COVID-19, coronavirus disease 2019 ;NLR, neutrophils-to-lymphocytes ratio; TC, total cholesterol; TG, triglycerides; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; Apo-AI, apolipoprotein AI; Apo-B, apolipoprotein B; LP-A, lipoprotein A; CRP,C-reactive protein; MAP, mean arterial pressure; NEWS 2 score, National Early Warning Score 2 score ; SOFA score ,Sequential Organ Failure Assessment score ;IQR, interquartile range; AUC, area under the ROC curve ;SE, standard error.

Figure 1 Flow
Figure 1

Figure 2 Presentation
Figure 2

Table 1
Baseline Characteristics of Patients with severe COVID-19 Data are presented as mean ± standard deviation (SD), medians (IQR) and n (%).P values were calculated by Student t test, Mann-Whitney U test, Chi-square test or Fisher's exact test, as appropriate.P values indicate differences between non-survivors and survivors.Abbreviations : IQR, interquartile range; MAP, mean arterial pressure; NEWS 2 score, National Early Warning Score 2 score ; SOFA score ,Sequential Organ Failure Assessment score.

Table 2
Laboratory ndings of patients with different outcomes Lipid Levels In Patients With Severe Covid-19

Table 3
Correlation between the lipid levels, CRP, length of hospital stay of survivors and the disease severity scores

Table 4 ROC
Curve of HDL-C, APO-AI, CRP/ HDL-C ratio and CRP/ Apo-AI ratio to predict in-hospital mortality.

Table 5
Logistic regression of the nal model.
a CRP/ HDL-C ratio higher than 62.543.

Table 6
Patients' demographic data and baseline clinical characteristics grouped according to CRP/ HDL-C ratio.Data are presented as mean ± standard deviation (SD), medians (IQR) and n (%).P values were calculated by Student t test, Mann-Whitney U test, Chi-square test or Fisher's exact test, as appropriate.P values indicate differences between high CRP/ HDL-C ratio group and low CRP/ HDL-C ratio group.Abbreviations : NLR,neutrophils-to-lymphocytes ratio; HDL-C, high-density lipoprotein cholesterol; CRP,C-reactive protein; NEWS 2 score, National Early Warning Score 2 score ; SOFA score ,Sequential Organ Failure Assessment score.
a CRP/ HDL-C ratio higher than 62.543 b CRP/ HDL-C ratio lower than 62.543 [19,35]s usually have an imbalance between anti-in ammatory and pro-in ammatory processes.Clinical and experimental studies have shown that patients with severe COVID-19 may exhibit features of systemic hyper-in ammation and in ammatory cytokine storm, which releases proin ammatory cytokines excessively and uncontrollably including IL-6 and TNF-α[19,35].And clinical reports showed that anti-in ammation therapies (such as glucocorticoids, immunosuppressants and in ammatory cytokines antagonists), which may help in preventing further injury in severe and critical COVID-19 patients, is an effective treatment to improve the clinical outcome[36].Similarly, we found that the ratios of CRP/HDL-C and CRP/Apo-AI were signi cantly higher in survival COVID-19 patients compared to those non-survivors, and these ratios had strong negative correlation with SOFA score, length of stay of survivors and CRP.Moreover, high CRP/ HDL-C ratio ( 62.543) was proved to be independent factor to predict in-hospital mortality among patients with severe COVID-19.Based on these ndings, high CRP/ HDL-C ratio not only shows the imbalance of in ammation in patients with severe COVID-19, but also correlate with deteriorating disease severity and worsening prognosis, and might be serve as a potential indicator for poor outcome among COVID-19.
CRP/HDL-C or CRP/ Apo-AI may re ect the balance between pro-in ammatory and anti-in ammatory factors.It is noteworthy that severe COVID-19