ABSTRACT
PURPOSE: While SARS-CoV-2 infection appears not to be clinically evident in the testes, indirect inflammatory effects and fever may impair testicular function. To date, few long-term data of semen parameters impairment after recovery and comprehensive andrological evaluation of recovered patients has been published. The purpose of this study was to investigate whether SARS-CoV-2 infection affect male reproductive health. METHODS: Eighty patients were recruited three months after COVID-19 recovery. They performed physical examination, testicular ultrasound, semen analysis, sperm DNA integrity evaluation (TUNEL), anti-sperm antibodies (ASA) testing, sex hormone profile evaluation (Total testosterone, LH, FSH). In addition, all patients were administered International Index of Erectile Function questionnaire (IIEF-15). Sperm parameters were compared with two age-matched healthy pre-COVID-19 control groups of normozoospermic (CTR1) and primary infertile (CTR2) subjects. RESULTS: Median values of semen parameters from recovered SARS-CoV-2 subjects were within WHO 2010 fifth percentile. Mean percentage of sperm DNA fragmentation (%SDF) was 14.1 ± 7.0%. Gelatin Agglutination Test (GAT) was positive in 3.9% of blood serum samples, but no positive semen plasma sample was found. Only five subjects (6.2%) had total testosterone levels below the laboratory reference range. Mean bilateral testicular volume was 31.5 ± 9.6 ml. Erectile dysfunction was detected in 30% of subjects. CONCLUSION: Our data remark that COVID-19 does not seem to cause direct damage to the testicular function, while indirect damage appears to be transient. It is possible to counsel infertile couples to postpone the research of parenthood or ART procedures around three months after recovery from the infection.
ABSTRACT
Background: Severe Coronavirus disease 2019 (COVID-19) has been associated with a dysregulated cytokine production, lymphocyte and monocyte exhaustion, and immunothrombotic complications that reduce gas exchange in the lungs and contribute to multiorgan failure. Aim(s): The objective of this study was to characterize the interplay between platelets and the dysregulated immune phenotype that drives disease severity. Method(s): To achieve this goal, we performed a high-throughput flow cytometric profiling of the phenotype and interactions of platelets circulating in the blood of Sars-COV2-positive subjects upon hospitalization. Patients were stratified into non-ICU (n = 35) and critically ill ICU (n = 25) patients and compared to sex-and age-matched Sars-COV2-negative patients (n = 15) and healthy volunteers (n = 20). All participants gave written informed consent. The study was approved by the Ethics Committee of our institution. Result(s): Platelets from ICU patients had dysfunctional mitochondria and a non-adhesive phenotype. Displayed significantly less glycoprotein (GP)Ibalpha and GPVI on the surface and failed to present active integrin alphaIIbbeta3 and P-selectin on the plasma membrane in response to exogenous stimuli. Platelet hypo-responsiveness positively correlated with the Horowitz index (PaO2/FiO2 ratio), a measure of lung function, and with the D-dimer concentration, a surrogate marker of ongoing thrombosis. Exposure of platelets from healthy volunteers to acute hypoxic conditions (1% O2) recapitulated this phenotype in vitro. Despite the low adhesiveness, platelets of ICU patients bound avidly to innate immune cells. Interactions with monocytes and NK cells increased with severity, even though these leukocytes subpopulations were reduced in the circulation of ICU patients. Platelet-T cell aggregates were doubled in non-ICU patients compared to controls but were not detectable among the ICU patients. Conclusion(s): In summary, platelets from COVID-19 patients who have reduced lung function present features of metabolic and functional exhaustion and bind primarily innate but not adaptive immune cells, thus promoting the dysregulated immune response that drives COVID19 severity.
ABSTRACT
Background : COVID-19 imposes a high burden of morbidity and mortality worldwide;since the beginning of this pandemic, several sex-related differences have been described in the pathogenesis and clinical course of the disease. Although the identification of biomarkers to stratify the severity of the disease is recognized as pivotal to identify patients with a higher risk of clinical deterioration, few studies investigated sex-related differences in the performance of these biomarkers. Aims : To evaluate sex differences in the serum concentrations of biomarkers of platelet activation and vascular inflammation in patients with COVID-19. Methods : We performed a retrospective, preliminary analysis of a single center study which is recruiting patients with COVID-19 at different stages of severity. Vascular inflammation and platelet activation markers were measured in batch in serum samples collected from the venous circulation by multiplex bead-based flow cytometry assay. Results : Among 74 COVID-19 patients (median age: 69 years;65% males;55% with clinically-diagnosed severe disease), data on individual biomarkers were available for 69 individuals (36% females). No significant differences were observed for age between males and females. Compared to SARS-Cov2-negative subjects, the serum concentration of soluble CD40L (sCD40L), Plasminogen Activator Inhibitor 1, Matrix Metalloproteinase-9, Myeloid-Related Protein 8/14, Myeloperoxidase, Osteopontin in SARS-Cov2-positive subjects increased significantly in relation to disease severity. Among these, men, compared to women, showed higher levels of sCD40L, an X-linked marker of platelet activation, (Median: 17892 pg/ml [Interquartile Range, IQR: 11197-34520] vs. 11225 pg/ml [IQR: 5625-22644], P = 0.019) and osteopontin, a sialoprotein implicated in estrogen-stimulated endothelial repair (Median: 151184 pg/ml [IQR: 82739-200141] vs. 74219 pg/ml [31602-144440], P = 0.011). Conclusions : In this preliminary analysis, we found that potentially relevant sex-based differences may exists in the levels of thromboinflammatory biomarkers which are currently investigated for the prognostic stratification of COVID-19 patients. Pre-specified analysis disaggregated by sex are needed to take into account differences in the performance of these biomarkers.