This observational study first revealed the blood lipids status of adult COVID-19 patients, found that low HDL-C was associated with poor outcomes of adult COVID-19 patients, and provided a basis for HDL-C to predict COVID-19 prognosis and even become a potential therapeutic target for COVID-19.
In this study, HDL-C levels of adult COVID-19 patients were lower than normal at admission, which was similar to previous researches. Several studies showed infected patients, especially those with sepsis, always had a significant drop in HDL levels [10, 12, 15, 20, 21, 22], but the reason for the decline in HDL level remained unexplained. However, several hypotheses are considered to be possible, including a decrease in HDL synthesis, overconsumption or redistribution of HDL particles from intravascular to the extravascular space [10, 23].
Previous studies also showed septic patients with low HDL-C level showed higher mortality and other adverse clinical outcomes [15, 22]. Several studies have found significant increases in mortality in sepsis patients with an HDL level below 25 mg/dl (0.65 mmol/L) [16, 20], so we compared the clinical characteristics and prognosis of COVID-19 patients with an HDL level above and below 25 mg/dl (0.65 mmol/L). In this study, patients with low HDL-C level showed higher proportion of severe events, while further regression analysis also revealed that low HDL-C was an independent risk factor for severe events in COVID-19. Therefore, HDL-C may play a protective role in COVID-19, while COVID-19 patients with reduced HDL-C need to be given timely monitoring and treatment as soon as possible to improve the outcomes.
Excessive inflammation is one of the important features of COVID-19 patients, especially in severe and died patients [24, 25, 26, 27], usually manifested by a marked increase in inflammatory factors, such as CRP and interleukins [3, 28]. HDL-C is believed to have an inhibitory effect on inflammation [29, 30, 31]. In this study, patients with low HDL-C showed a higher level of CRP, which suggested that HDL-C may inhibit the inflammatory response and thus play a protective role in COVID-19 patients.
The protective effect of HDL-C in bacterial infection is relatively definite. Numerous studies have found that HDL-C can bind and neutralize the biological toxicity of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) [32, 33, 34]. In different experimental septic models, infusion of reconstituted HDL reduced inflammation, decreased bacterial count, attenuated organ injury and improved survival [10, 35, 36], which greatly encouraged the application of HDL in sepsis treatment in the future. However, the role of HDL-C in viral infection remains unclear. We found in this study that HDL-C decreased in COVID-19 patients, and HDL-C level was negatively correlated with severity of illness, which suggests that HDL-C may be a potential therapeutic target for COVID-19, but the specific mechanism is still unclear, and further research is still needed.
Our study has some limitations. First, we cannot obtain the basic HDL-C data before symptom onset, so it is uncertain whether the decrease in HDL-C level occurred after infection with SAR-CoV-2. Second, previous studies showed that HDLs decrease significantly in the early stage of sepsis, but the time from the symptom onset to the detection of HDLs is different, which may cause some bias in the analysis of the relationship between HDLs and COVID-19. Third, we have not got the HDL-C data on the recovery period, and the correlation between the dynamic changes of HDL-C and the outcome of COVID-19 may be more valuable.