This study shows for the first time that Adpn/Lep had an excellent discriminatory accuracy for the presence of Covid-19 pneumonia in lean people. Adpn/Lep is a ratio that was initially proposed as a marker of adipose tissue dysfunction, increased cardio-metabolic risk (21,23) and low-grade inflammation (24). Obesity (12,18), insulin resistance (15), and inflammation (25-27) are associated with a decrease of adiponectin and an increase of circulating leptin. Consistent with this, Adpn/Lep decreases with the increasing number of metabolic risk factors (23) and it is negatively correlated with CRP levels and systemic inflammation (24). For these reasons, it has been suggested that Adpn/Lep might discriminate between the patients that are “metabolically healthy” and those that are “metabolically unhealthy” (23).
Frühbeck et al. have recently proposed that Adpn/Lep should have a value >1 in normal conditions, corresponding to a low cardio-metabolic risk, while values between >0.5 and <1 should correspond to a moderate risk, and values <0.5 should correspond to a high cardio-metabolic risk (28). Interestingly, in this work by Frühbeck et al., lean subjects (mean BMI of 22), with mean arterial blood pressure of 123/71 mmHg, mean glycemia of 91 mg/dL, and lipids levels within reference targets, had a mean value of Adpn/Lep of 2.83 ± 2.16 (28). In line with these findings, in our study, 2.23 was the optimal cutoff value discriminating between lean patients that were in good health and those with Covid-19 pneumonia, allowing to identify correctly 88% of the patients with a sensitivity of 90% and a specificity of 83%. In other words, a high value of Adpn/Lep is consistent with a state of good health in lean patients and it could rule out any low-grade or acute systemic inflammation, including the state triggered by SARS-Cov2 infection.
Our study shows that the Adpn/Lep could be used not only to identify patients with adipose tissue dysfunction and high cardio-metabolic risk, but also to rule out the presence of acute inflammatory diseases, such as Covid-19 pneumonia. The issue that remains to be solved is the heterogeneity of methods to measure Adpn/Lep, mostly due to the variety of methods available to measure adiponectin (16,17). Adiponectin can be measured with different techniques, such as radioimmunoassays, enzyme-linked immunosorbent assays, chemiluminescent immunoassays and immunoturbidimetric methods, in both manual or fully automated ways (17). Consequently, a standardization of adiponectin assays, as well as a clear definition of normal and pathological reference ranges is still lacking (16).
It can be speculated that the decrease of Adpn/Lep, which is seen in obese patients and patients with Covid-19 pneumonia, might contribute to development of severe form of disease, due to the anti-inflammatory actions of adiponectin and the pro-inflammatory effects of leptin. Several studies demonstrate that obesity is a risk factor for developing a severe form of Covid-19 pneumonia (1), requiring intensive care unit admission, intubation and mechanical ventilation (3,29-31). Last year we demonstrated that also other antropometric indexes, such as neck circumference, might predict the need of mechanical ventilation support (32). Consistent with the literature, in this study, we found that BMI – as well as age - was independently associated with the need of non-invasive mechanical ventilation (NIMV), the days of NIMV, and the days of hospitalization. Nevertheless, we did not find any significant association between the levels of circulating adipokines and these outcomes, possibly due to the small number of patients.
The limitations of this study include the small number of patients recruited, as well as the measurement of the adipokines with manual enzyme-linked immunosorbent assays. On the other hand, it has to be taken into account that even in our small cohort, Adpn/Lep had an excellent discriminatory accuracy in identifying Covid-19 pneumonia in lean subjects.
In conclusion, our data indicate that patients with Covid-19 pneumonia had higher levels of leptin, and lower Adpn/Lep. Leptin had an acceptable discriminatory accuracy for Covid-19 pneumonia in patients with BMI >30, while Adpn/Lep had an excellent discriminatory accuracy for Covid-19 pneumonia in patients with BMI <25, with a cutoff of 2.23. Our data indicate that high Adpn/Lep (>2.23) in lean patients is consistent with a state of good health, which decreases in case of inflammatory states, ranging from adipose tissue dysfunction with low-grade inflammation to Covid-19 pneumonia.