Correlating circulating adipokine levels with COVID-19 severity

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A new study in the International Journal of Obesity determines whether plasma adipokine levels were associated with coronavirus disease 2019 (COVID-19)-related systemic inflammation, severity, and clinical parameters in mild, severe, and critically ill COVID-19 patients.

Study: Circulating adipokine levels and COVID-19 severity in hospitalized patients. Image Credit: Near D Krasaesom / Shutterstock.com

Study: Circulating adipokine levels and COVID-19 severity in hospitalized patients. Image Credit: Near D Krasaesom / Shutterstock.com

Obesity and COVID-19

Obesity is a crucial risk factor for intensive care unit (ICU) admission and high mortality due to COVID-19.

Previous studies indicate that more than 70% of people admitted to the ICU due to COVID-19 are obese or overweight. This suggests that dysfunctional or excess adipose tissue can regulate pulmonary and systemic inflammatory responses against infection, leading to lung injury and respiratory failure.

In addition to excessive adipose tissue accumulation, obese people also exhibit a dysregulated secretion of inflammatory cytokines and adipokines by adipose tissues. This affects the metabolism of organs and tissue and precipitates a chronic inflammatory state. This chronic inflammatory state worsens COVID-19-associated immunopathology, thus making obese patients susceptible to severe organ injury.

Some studies have reported an increase in plasma leptin in COVID-19 patients who were admitted to the ICU. In contrast, others have observed a decrease in leptin levels in severe COVID-19 patients compared to moderate and mild patients.

About the study

The current study involved 186 severe COVID-19 patients and 71 critical COVID-19 patients. All study participants were recruited during three inclusion periods, the first of which was between March 6, 2020, and April 3, 2020, whereas the second and third waves were between April 24, 2020, to June 6, 2020, and September 28, 2020, to December 3, 2020, respectively.

Patients were categorized based on their hospitalization requirements. To this end, mild referred to patients who did not require hospitalization, whereas severe represented those hospitalized in the general ward, and critical indicated ICU admission.

Nasopharyngeal or oropharyngeal swabs were used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were treated according to the local COVID-19 protocol.

Demographic data and serum samples were collected from 30 individuals participating in the COVID-19 HOME study to compare severe and critically ill patients. In addition, clinical data and plasma samples were collected from 40 critically ill non-COVID-19 patients who were admitted to the ICU between April 24, 2020, and June 6, 2020. Plasma samples were also obtained from 101 healthy controls.

Multi-analyte profiling of plasma adipokines, including visfatin, resistin, adiponectin, and leptin, and inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and IL-10, was performed on both COVID-19 and control samples.

Study findings

The median age of the critical patients was 66 years, most of whom were male. The body mass index (BMI) of both severe and critical COVID-19 patients was similar. However, critical patients were more likely to experience thromboembolic events, liver dysfunction, and acute kidney injury than severe COVID-19 patients.

The median hospital stay was 17 days for critical patients and five days for severe patients. The length of ICU stay was longer for critical COVID-19 patients as compared to critical non-COVID patients.

Similar leptin levels between critical COVID-19 and non-COVID patients were observed. However, no association between COVID-19 severity and leptin levels was identified.

Plasma leptin levels were higher in severe COVID-19 patients with similarly high BMIs than in critical COVID-19 patients. Adiponectin levels were reduced to similar levels in severe and critical COVID-19 patients and non-COVID critical patients compared to healthy controls and mild patients.

The adiponectin to leptin (Adpn/Lep) ratio was also reduced in both non-COVID critical and hospitalized COVID-19 patients compared to healthy controls and mild patients. In addition, higher resistin levels were observed in severe and critical COVID-19 patients and non-COVID critical patients.

Visfatin levels were higher in critical COVID-19 patients as compared to severe patients. IL-10, TNF-α, and IL-6 levels were highest among severe and critical COVID-19 patients. Comparable levels were also observed in non-COVID-critical patients.

The TNF-α/IL-10 ratio was reduced in severe and critical COVID-19 patients and non-COVID critical patients.

IL-6 positively correlated with resistin, visfatin, and adiponectin levels, whereas it was negatively correlated with plasma leptin levels in severe patients. TNFα and IL-10 also positively correlated with visfatin and resistin levels in severe patients. 

In critical patients, most correlations were lost, as IL-6 negatively correlated with leptin levels, while TNF-α and IL-10 were positively correlated with resistin. Resistin, leptin, and IL-6 plasma levels correlated with the fraction of inspired oxygen (FiO2) in severe patients. Resistin levels are also correlated with ICU and duration of hospital stay in critical patients.

The mortality rate of COVID-19 patients was 43.7%. Critical COVID-19 non-survivors were often older than non-survivors. However, the plasma levels of all adipokines were similar between both the survivors and non-survivors.

Moreover, 100% of critical and 85% of severe COVID-19 patients admitted during the second wave received corticosteroids compared to 9% of patients admitted during the first wave. In addition, one patient in the first wave and two in the second wave received tocilizumab in combination with corticosteroids.

The age, comorbidities, percentage of males, and BMI of patients admitted to the ward and ICU was similar during the first and second waves. The duration of ICU and hospital stay were also similar for both severe and critical patients during the first and second waves.

Higher plasma leptin levels were observed in critical and severe COVID-19 patients during the second wave compared to the first wave. A 55% reduction in IL-6 levels was observed in critical COVID-19 patients during the second wave compared to the first; however, this was not reported for severe COVID-19 patients.

Conclusions

The current study demonstrates an association between plasma adipokine levels and COVID-19 hospitalization; however, no association was observed regarding mortality. Further studies are needed to determine the impact of altered adipokine secretion, respiratory failure, and lung injury in COVID-19 patients.

Limitations

The current study has several limitations. First, the study did not include abdominal computed tomography (CT) scans and hip-to-waist ratio, which might help accurately determine the amount of visceral body fat.

A second limitation was that all samples were plasma, except serum samples from mild patients. Finally, firm conclusions could not be drawn from the study, as many samples had below detection limits of visfatin.

Journal reference:

  • Flikweert, A. W., Kobold, A. C. M., van der Sar-van der Brugge, S., et al. (2022). Circulating adipokine levels and COVID-19 severity in hospitalized patients. International Journal of Obesity. doi:10.1038/s41366-022-01246-5.



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