Microbiology and immune mechanisms associated with male infertility.

Up to 50% of infertility is caused by the male side. Varicocele, orchitis, prostatitis, oligospermia, asthenospermia, and azoospermia are common causes of impaired male reproductive function and male infertility. In recent years, more and more studies have shown that microorganisms play an increasingly important role in the occurrence of these diseases. This review will discuss the microbiological changes associated with male infertility from the perspective of etiology, and how microorganisms affect the normal function of the male reproductive system through immune mechanisms. Linking male infertility with microbiome and immunomics can help us recognize the immune response under different disease states, providing more targeted immune target therapy for these diseases, and even the possibility of combined immunotherapy and microbial therapy for male infertility.

Prognostic Value of Serum/Plasma Neurofilament Light Chain for COVID-19 Associated Mortality (preprint)

Given the continued spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), early predictors of coronavirus disease 19 (COVID-19) mortality might improve patients outcomes. Increased levels of circulating neurofilament light chain (NfL), a biomarker of neuro-axonal injury, have been observed in patients with severe COVID-19. We investigated whether NfL provides non-redundant clinical value to previously identified predictors of COVID-19 mortality. We measured serum or plasma NfL concentrations in a blinded fashion in 3 cohorts totaling 338 COVID-19 patients. In cohort 1, we found significantly elevated NfL levels only in critically ill COVID-19 patients compared to healthy controls. Longitudinal cohort 2 data showed that NfL is elevated late in the course of the disease, following two other prognostic markers of COVID-19: decrease in absolute lymphocyte count (ALC) and increase in lactate dehydrogenase (LDH). Significant correlations between LDH and ALC abnormalities and subsequent rise of NfL implicate multi-organ failure as a likely cause of neuronal injury at the later stages of COVID-19. Addition of NfL to age and gender in cohort 1 significantly improved the accuracy of mortality prediction and these improvements were validated in cohorts 2 and 3. In conclusion, although substantial increase in serum/plasma NfL reproducibly enhances COVID-19 mortality prediction, NfL has clinically meaningful prognostic value only close to death, which may be too late to alter medical management. When combined with other prognostic biomarkers, rising longitudinal NfL measurements triggered by LDH and ALC abnormalities would identify patients at risk of COVID-19 associated mortality who might still benefit from escalated care.

SARS-CoV-2 RNA Shedding in Semen and Oligozoospermia of Patient with Severe Coronavirus Disease 11 Weeks after Infection.

We report severe acute respiratory syndrome coronavirus 2 in semen by using quantitative reverse transcription PCR during the late convalescent phase. Virus was associated with adequate humoral and cell-mediated responses, suggesting possible seeding of the immune-privileged testes. We provide longitudinal semen quality data for 6 other men, including 3 who had oligozoospermia.

Persistent Male Genital Tract Inflammation and Semen Impairment: A Long-Term Effect of SARS-Cov-2 Infection (preprint)

Background: Recent reports evidenced an impairment of semen parameters in men affected by coronavirus disease 2019 (COVID-19). In particular, our group previously reported that 1 over 4 COVID-19 healed men were found to be crypto- / azoo-spermic. Moreover, most patients had elevated IL-8 semen levels at sperm analysis. The aim of our study was to assess semen parameters and inflammation by evaluating a panel of sperm cytokine levels (IL-1, IL-4, IL-6, IL-8, IL-17, INF gamma, TNF-alpha) on average 1 month after the second SARS-CoV-2 negative nasopharyngeal swab and 3 months later. Methods: : Ten men who showed normozoospermia (n=3), oligozoospermia (n=3) or crypto/azoospermia (n=4) 1 month after healing from COVID-19 in our previous study, were re-called and re-evaluated 3 months after the first semen analysis. Semen parameters were evaluated according to WHO manual and seminal plasma cytokine levels by an ELISA method. Results: : At 3-months follow-up, 8 men showed an overall increase of semen parameters compared to levels assessed after 1 month. In particular, of the 4 crypto-/azoo-spermic men 1 month after healing, 2 resulted oligozoospermic, 1 normozoospermic and only 1 remained azoospermic. Two of the 3 oligozoospermic men turned normozoozpermic. Semen cytokine levels were remarkably high one month after healing and remained elevated after 3 months, with the exception of IL-6. Conclusions: : This is the first longitudinal, prospective study comparing semen parameters and semen inflammatory markers one and three months after recovering from COVID-19. Our data indicate an overall tendency to an improvement of semen parameters although a genital tract inflammatory condition appears to persist at least 3 months after COVID-19 recovery. This condition could have an impact on male fertility requiring a careful follow up of these patients.

The effect of COVID-19 on spermatogenesis (preprint)

Background : The viral pandemic of the coronavirus disease 2019 (COVID-19) has become a serious worldwide public health emergency, evolving exponentially. While the main organ targeted in this disease is the lungs, other vital organs may be implicated. The main host receptor of the SARS-CoV-2 is angiotensin converting enzyme 2 (ACE2), a major component of the renin-angiotensin-aldosterone system (RAAS). The ACE2 is also involved in testicular male regulation of steroidogenesis and spermatogenesis. A recent report published in JAMA Network revealed that in an analysis 38 semen samples from COVID‐19 patients pcr +ve. As the SARS-CoV-2 may have the potential to infect the testis via ACE2 and adversely affect male reproductive system. From this point the purpose of this study is how covid-19 affect spermatogenesis. methods: Aim: how covid-19 affect spermatogenesis. Design and setting of the study: a100 patients had been enrolled in the study by a criteria suggesting good semen analysis. two sets of semen analysis done, the first after 72days of first positive swab for covid-19 to show changes in semen analysis from normal values in the cycle of spermatogenesis during infection, the other sample after 72 days from the first sample to show if the changes regress to normal and to compare it with the first sample. Results: a total number 100 patients first sample show 2% of patients oligospermia, 36% of patients teratospermia . the second sample show 4% of patients teratospermia . by comparing the two samples there is a significant increase in sperm concentration with mean concentration in the first sample 96.49 million /ml , mean concentration in the second sample 104.67 million /ml , a significant increase in motility (A+B) with mean percentage of 44% in the first sample and 46% in the second sample , a highly significant increase in the normal forms of sperms with mean percentage of 23.4 % in the first sample and 30.55 % in the second sample .Conclusions: covid-19 affect spermatogenesis in the form of reversible teratospermia, reversable decrease sperm count but within normal level, reversable decrease in the sperm motility but also within normal level.

The Inflammatory Markers of Multisystem Inflammatory Syndrome in children (MIS-C) and Adolescents During the COVID-19 Pandemic: A Meta-Analysis (preprint)

As per the indicated need in literature, we conducted a systematic review and meta-analysis to characterize inflammatory markers of MIS-C patients with COVID-19, Kawasaki disease (KD), and coronary artery abnormalities. We searched nine databases for studies on inflammatory markers of MIS-C. After quality check, data were pooled using a fixed- or random-effects model. Inflammatory markers included white blood cell count (WBC) or leukocytes, absolute lymphocyte count (ALC), absolute neutrophil count (ANC), platelet count (PLT), C-reactive protein (CRP), procalcitonin (PCT), ferritin, D-dimer, lactate dehydrogenase (LDH), fibrinogen and erythrocyte sedimentation rate (ESR) for comparisons by severity and age. Twenty studies with 2,990 participants yielded 684 MIS-C patients. Compared to non-severe COVID-19 patients, MIS-C patients had lower ALC and higher ANC, CRP and D-dimer levels. Compared to severe COVID-19 patients, MIS-C patients had lower LDH and PLT counts and higher ESR levels. Compared to KD patients, MIS-C patients had lower ALC and PLT, and higher CRP and ferritin levels. Severe MIS-C patients had higher levels of WBC, CRP, D-dimer and ferritin. For MIS-C, younger children had lower CRP and ferritin levels than medium-aged/older children. Measurement of inflammatory markers might assist clinicians in accurate evaluation and diagnosis of MIS-C and the associated disorders.