This is for our readers that treat patients in the ICU.
Findings from a study published in the Journal of Endocrinological Investigation suggest an association between testosterone deficiency and high risk of acute hypoxemic respiratory failure at admission, need of oxygen support and mortality during hospital stay in adult males with coronavirus disease 2019 (COVID-19).
The study involved 221 males patients, with a median age of 70.5 years and median body mass index of 27.2 kg/m2, hospitalised for COVID-19 at the IRCCS Humanitas Research Hospital, Rozzano-Milan, Italy, between November 1, 2020 and January 31, 2021. Overall, normal testosterone serum levels (> 12 nmol/L; Group III) were found in 7.7% of the study population (n = 17), whereas frankly low testosterone levels were detected in 176 (79.6%) patients (< 8 nmol/L; Group I) and borderline testosterone serum levels were observed in 28 (12.7%) patients (8–12 nmol/L; Group II).
Patients in Group I were significantly older (P = 0.001) and had higher number of comorbidities (P = 0.001), higher serum levels of interleukin (IL)-6 levels (P = 0.001), C-reactive protein (CRP) (P < 0.001), ferritin (P = 0.012) and lactate dehydrogenase (LDH) (P < 0.001) compared with patients in Group III. Moreover, patients in Group I showed lower arterial partial pressure oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio (P = 0.001) and serum levels of free-triiodothyronine (fT3) (P = 0.041) in comparison with patients in Group III.
On the other hand, patients in Group II had significantly lower IL-6 (P = 0.001), LDH (P = 0.018) and higher PaO2/FiO2 ratio (P = 0.044) than those in Group I, while no significant between-group differences was observed in CRP (P = 0.107) and ferritin (P = 0.869) values. Patients in Group II also had significantly higher serum CRP (P = 0.005), LDH (P = 0.04) and ferritin (P = 0.009) in comparison with those in Group III, whereas the difference in PaO2/FiO2 ratio (P = 0.128) was not significant.
At study entry, 115 patients (52.0%) fulfilled the criteria for acute hypoxemic respiratory failure. The prevalence of acute hypoxemic respiratory failure was significantly higher in patients of Group I as compared with both Group II (P = 0.009) and Group III (P < 0.001), while no significant difference was observed between patients in Groups II and III (P = 0.488).
Further, 134 patients (60.6%) required oxygen support (99 with high-flow nasal or mask oxygen; 33 with continuous positive airways pressure and 2 with invasive ventilation) during hospital stay. The prevalence of patients requiring ventilation (either invasive or non-invasive) was significantly higher in Group I compared to either Group II or III (P < 0.001 for both comparisons), while no significant difference was observed between the latter two groups (P = 0.756). Meanwhile, 39 patients (17.6%) died during their hospital stay, all but one were from Group I (P < 0.009 vs Group II and III).
In the multivariable regression analyses, low testosterone values maintained significant associations with acute respiratory insufficiency (odds ratio [OR] 0.85, 95% confidence interval [CI] 0.79–0.94; P < 0.001) and in-hospital mortality (OR 0.80, 95% CI 0.69–0.95; P = 0.009), independent of age, comorbidities, thyroid function and inflammation.
“The prevalence of hypogonadism is increased within specific populations, including patients with diabetes, metabolic syndrome, obesity, cardiovascular disease, chronic obstructive pulmonary disease, renal disease and cancer. Consistently, a high burden of comorbidities was observed in our low testosterone population, with more than 50% of subjects with low testosterone values having 2 or more comorbidities. Moreover, up to 50% of the population was found to have low T3 syndrome, which is an established predictor of higher mortality among COVID-19 hospitalised subjects. However, when the potential clinical impact of low testosterone values was evaluated, we found that low testosterone serum levels were associated with unfavourable COVID-19 outcomes, independently of comorbidities burden, thyroid status and inflammation markers,” wrote W Vena, IRCCS Humanitas Research Hospital, Milan, Italy, and colleagues.
“This retrospective cohort adds consistent evidence to previous reports about the role of low circulating [testosterone] levels as a marker of higher risk of severe outcomes among COVID-19 male patients,” the authors noted. “In view of the pandemic dimensions of COVID-19, prospective studies are needed to evaluate gonadal function in subjects recovering from illness and its relationship with long-term consequences of the disease on general health status.”