Quantitative Proteomics of COVID-19 Recovered Patients Identifies Long-Term Changes in Sperm Proteins Leading to Cellular Stress in Spermatozoa

Abstract:

Following an initial recovery, COVID-19 survivors struggle with a spectrum of persistent medical complications, including fatigue, breathlessness, weight loss, hair loss, and attention deficits. Additionally, there is growing evidence of adverse effects of COVID-19 on the male reproductive system. This investigation seeks to understand the long-term ramifications on male fertility by examining hormonal profiles, semen parameters, and sperm proteome of recovered COVID-19 patients compared to controls.

The serum hormone profiles between the two groups showed minimal variations except for prolactin, cortisol, and testosterone levels. Testosterone levels were slightly lower, while prolactin and cortisol were elevated in COVID-19 cases compared to controls.

Though semen parameters exhibited no significant disparities between the COVID-19 and control groups, quantitative proteomics analysis revealed changes in sperm proteins. It identified 190 differentially expressed proteins, of which 161 were upregulated and 29 downregulated in COVID-19 cases.

Western blotting analysis validated the differential expression of serpin B4 and calpain 2. Bioinformatics analysis signifies cellular stress in the spermatozoa of COVID-19 recovered patients and thus, SOD and MDA levels in semen were measured. MDA levels were found to be significantly elevated, indicating lipid peroxidation in COVID-19 samples.

While the effects of COVID-19 on semen parameters may exhibit a potential for reversal within a short duration, the alterations it inflicts on sperm proteome are persisting consequences on male fertility. This study paves the path for further research and emphasizes the significance of comprehending the complex molecular processes underlying the long-term consequences of COVID-19 on male reproductive health.

Source: Chopra P, Tomar AK, Thapliyal A, Ranjan P, Datta SK, Yadav S. Quantitative Proteomics of COVID-19 Recovered Patients Identifies Long-Term Changes in Sperm Proteins Leading to Cellular Stress in Spermatozoa. Reprod Sci. 2024 Apr 24. doi: 10.1007/s43032-024-01560-5. Epub ahead of print. PMID: 38658489. https://pubmed.ncbi.nlm.nih.gov/38658489/

Identifying, synthesising and appraising existing evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic review

Abstract

Objectives: To identify, synthesise and appraise evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and pregnancy.

Design: Mixed-methods systematic review, using convergent segregated design.

Data sources: MEDLINE, EMBASE, Scopus, PsycINFO, CINAHL, MedRxiv, PROSPERO and grey literature sources through 6 August 2023.

Eligibility criteria: We included original research studies, expert opinion and grey literature reporting on ME/CFS and pregnancy/post partum (up to 2 years), risk of pregnancy outcomes with ME/CFS or experiences during pregnancy for mother, partner or health and social care professionals following ME/CFS during pregnancy, all where the evidence was relevant to a confirmed ME/CFS diagnosis prior to pregnancy.

Data extraction and synthesis: Three independent reviewers completed all screening, data extraction and quality assessment. Risk of bias was assessed using the mixed-methods appraisal tool V.2018. Qualitative and quantitative literature was analysed separately using thematic and descriptive syntheses. Findings were integrated through configuration.

Results: Searches identified 3675 articles, 16 met the inclusion criteria: 4 quantitative (1 grey), 11 qualitative (9 grey) and 1 grey mixed-methods study. Of the four quantitative studies that reported on ME/CFS severity during pregnancy, two suggested pregnancy negatively impacted on ME/CFS, one found most women had no change in ME/CFS symptoms and one found ME/CFS improved; this difference in symptom severity across studies was supported by the qualitative evidence. The qualitative literature also highlighted the importance of individualised care throughout pregnancy and birth, and the need for additional support during family planning, pregnancy and with childcare. Only one quantitative study reported on pregnancy outcomes, finding decreased vaginal births and higher rates of spontaneous abortions and developmental and learning delays associated with pregnancies in those with ME/CFS.

Conclusions: Current evidence on ME/CFS in pregnancy is limited and findings inconclusive. More high-quality research is urgently needed to support the development of evidence-based guidelines on ME/CFS and pregnancy.

Source: Slack E, Pears KA, Rankin J, Newton JL, Pearce M. Identifying, synthesising and appraising existing evidence relating to myalgic encephalomyelitis/chronic fatigue syndrome and pregnancy: a mixed-methods systematic review. BMJ Open. 2023 Oct 5;13(10):e070366. doi: 10.1136/bmjopen-2022-070366. PMID: 37798026. https://bmjopen.bmj.com/content/13/10/e070366 (Full text)

Approaches towards menstrual cycle disorder therapy in reproductive-aged women with long COVID

Abstract:

Background. The mirror of a female’s reproductive health is the menstrual cycle. The SARS-CoV-2 pandemic itself acts as a significant stressor. This leads to women’s overall health and life quality disturbance. Moreover, patients struggle with long COVID effects, which is a prolongation of symptoms after recovery. Due to the expression of angiotensin-converting enzyme type 2 receptors in the intestinal mucosa and inflammation, the gastrointestinal (GI) tract is also triggered by the virus.

Objectives. To assess the efficacy of the chosen treatment approach in women with changes in premenstrual syndrome and cyclicity due to long COVID with or without GI symptoms.

Material and methods. A single-centre longitudinal interventional study was organized. Were studied data from the conducted tests (progesterone level, ultrasound follicle scan, etc.) and surveys. Then the effectiveness of the suggested treatment with the use of oral and vaginal forms of progesterone was evaluated. The study was held in the Kyiv City Center of Reproductive and Perinatal Medicine (Ukraine) from January to June 2021.

Results. On average 78% patients without GI symptoms experienced relief after 3 months and 89% patients after 6 months of suggested treatment. 71% patients with GI symptoms experienced improvement after 3 and 87% of them after 6 months. The vaginal progesterone had better results compared to oral form. Averagely 6–8% experienced side effects (nausea, hypotension, less compliance) due to progesterone intake. The vaginal micronised progesterone also presented better results than oral with fewer side effects compared to the total number of participants.

Conclusions. The proposed approach has shown particular correction of the menstrual cycle disturbances in women with long COVID. Vaginal micronized progesterone offers more promising outcomes in patients with GI symptoms and disrupted absorption, compared to the oral form.
Further investigation is required for a more reasonable conclusion.

Source: Kaminskyi, V., Serbeniuk, A., & Kumpanenko, Y. (2023). Approaches towards menstrual cycle disorder therapy in reproductive-aged women with long COVID. REPRODUCTIVE ENDOCRINOLOGY, (68), 44–47. https://doi.org/10.18370/2309-4117.2023.68.44-47 http://reproduct-endo.com/article/view/284093

The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study

Abstract:

Background: SARS-CoV-2 may affect the male reproductive system as it uses angiotensin-converting enzyme [ACE]2, which is expressed in testicular tissue, as an entry point into the cell. Few studies have evaluated the long-term effects of mild COVID-19 on testicular function, and INSL3 levels have not previously been assessed during acute SARS-CoV-2 infection.

Objectives: To assess the impact of acute SARS-CoV-2 infection on testicular function including INSL3 and the presence of SARS-CoV-2 RNA in semen in non-hospitalised men with mild COVID-19.

Materials and methods: This longitudinal study included 36 non-hospitalised SARS-CoV-2-positive men (median age 29 years). Inclusion was within seven days following a positive SARS-CoV-2 RT-PCR test. Reproductive hormone levels, semen parameters, and the presence of SARS-CoV-2 RNA in oropharyngeal and semen samples were assessed during acute SARS-CoV-2 infection (baseline) and at three- and six-month follow-up. Wilcoxon matched-pair signed-rank (two samples) test was used to assess time-related alterations in reproductive hormone levels and semen parameters.

Results: Lower plasma testosterone [T] (total and calculated free [c-fT]) and higher LH concentrations were observed during acute SARS-CoV-2 infection (baseline) compared to three- and six-month follow-up. Consequently, ratios of c-fT/LH were lower at baseline compared to three- and six-month follow-up (P < 0.001 and P = 0.003, respectively). Concomitantly, lower INSL3 concentrations were observed at baseline compared to three-month follow-up (P = 0.01). The total number of motile spermatozoa was also lower at baseline compared to six-month follow-up (P = 0.02). The alterations were detected irrespective of whether the men had experienced SARS-CoV-2-related fever episodes or not. No SARS-CoV-2 RNA was detected in semen at any time point.

Discussion and conclusion: This study showed a reduction in testicular function, which was for the first time confirmed by INSL3, in men mildly affected by SARS-CoV-2 infection. The risk of transmission of SARS-CoV-2 RNA via semen seems to be low. Febrile episodes may impact testicular function, but a direct effect of SARS-CoV-2 cannot be excluded. This article is protected by copyright. All rights reserved.

Source: Lauritsen MP, Kristensen TL, Bo Hansen C, Schneider UV, Talbot AL, Skytte AB, Petersen JH, Johannsen TH, Zedeler A, Albrethsen J, Juul A, Priskorn L, Jørgensen N, Westh H, Freiesleben NC, Nielsen HS. The impact of acute SARS-CoV-2 on testicular function including insulin-like factor 3 [INSL3] in men with mild COVID-19: A longitudinal study. Andrology. 2023 Jul 8. doi: 10.1111/andr.13494. Epub ahead of print. PMID: 37421657. https://pubmed.ncbi.nlm.nih.gov/37421657/