Semen Proteomics of COVID-19 Convalescent Men Reveals Disruption of Key Biological Pathways Relevant to Male Reproductive Function

Ghosh, Susmita; Parikh, Swapneil; Nissa, Mehar Un; Acharjee, Arup; Singh, Avinash; Patwa, Dhruv; Makwana, Prashant; Athalye, Arundhati S.; Barpanda, Abhilash; Laloraya, Malini; Srivastava, Sanjeeva; Parikh, Firuza R.

doi:10.1021/acsomega.1c06551

Cited by 24 publications

(28 citation statements)

References 66 publications

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“…Besides, the association of CST3 with S100A9 also indicates a correlation between monocyte-mediated inflammatory response and HRCT score, which supports our previous findings. We also found a strong association between HRCT score and PSAP, a gene involved in antigen presentation and male fertility, both are perturbed in severe COVID-19 patients (47,48).…”

Section: Distinct Immune Response Signatures As Revealed By Similarit...supporting

confidence: 54%

Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals

et al. 2022

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IntroductionDespite numerous efforts to describe COVID-19's immunological landscape, there is still a gap in our understanding of the virus's infections after-effects, especially in the recovered patients. This would be important to understand as we now have huge number of global populations infected by the SARS-CoV-2 as well as variables inclusive of VOCs, reinfections, and vaccination breakthroughs. Furthermore, single-cell transcriptome alone is often insufficient to understand the complex human host immune landscape underlying differential disease severity and clinical outcome.MethodsBy combining single-cell multi-omics (Whole Transcriptome Analysis plus Antibody-seq) and machine learning-based analysis, we aim to better understand the functional aspects of cellular and immunological heterogeneity in the COVID-19 positive, recovered and the healthy individuals.ResultsBased on single-cell transcriptome and surface marker study of 163,197 cells (124,726 cells after data QC) from the 33 individuals (healthy=4, COVID-19 positive=16, and COVID-19 recovered=13), we observed a reduced MHC Class-I-mediated antigen presentation and dysregulated MHC Class-II-mediated antigen presentation in the COVID-19 patients, with restoration of the process in the recovered individuals. B-cell maturation process was also impaired in the positive and the recovered individuals. Importantly, we discovered that a subset of the naive T-cells from the healthy individuals were absent from the recovered individuals, suggesting a post-infection inflammatory stage. Both COVID-19 positive patients and the recovered individuals exhibited a CD40-CD40LG-mediated inflammatory response in the monocytes and T-cell subsets. T-cells, NK-cells, and monocyte-mediated elevation of immunological, stress and antiviral responses were also seen in the COVID-19 positive and the recovered individuals, along with an abnormal T-cell activation, inflammatory response, and faster cellular transition of T cell subtypes in the COVID-19 patients. Importantly, above immune findings were used for a Bayesian network model, which significantly revealed FOS, CXCL8, IL1β, CST3, PSAP, CD45 and CD74 as COVID-19 severity predictors.DiscussionIn conclusion, COVID-19 recovered individuals exhibited a hyper-activated inflammatory response with the loss of B cell maturation, suggesting an impeded post-infection stage, necessitating further research to delineate the dynamic immune response associated with the COVID-19. To our knowledge this is first multi-omic study trying to understand the differential and dynamic immune response underlying the sample subtypes.

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Section: Distinct Immune Response Signatures As Revealed By Similarit...supporting

confidence: 54%

Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals

et al. 2022

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“…Return to normal sperm morphology values is observed with increasing time after recovery ( Guo et al , 2021a ; Donders et al , 2022 ; Hu et al , 2022 ). Emerging evidence showed that key biological pathways relevant to male reproductive function are disrupted in COVID-19 convalescent men ( Ghosh et al , 2022 ).…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2, fertility and assisted reproduction

Ata

Vermeulen

Mocanu

et al. 2022

Human Reproduction Update

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BACKGROUND In 2020, SARS-CoV-2 and the COVID-19 pandemic had a huge impact on the access to and provision of ART treatments. Gradually, knowledge of the virus and its transmission has become available, allowing ART activities to resume. Still, questions on the impact of the virus on human gametes and fertility remain. OBJECTIVE AND RATIONALE This article summarizes published data, aiming to clarify the impact of SARS-CoV-2 and the COVID-19 disease on human fertility and assisted reproduction, as well as the impact of vaccination, and from this, provide answers to questions that are relevant for people contemplating pregnancy and for health care professionals. SEARCH METHODS PUBMED/MEDLINE and the WHO COVID-19 database were searched from inception to 5 October 2022 with search terms focusing on ‘SARS-CoV-2’ and gametes, embryos, reproductive function, fertility and ART. Non-English studies and papers published prior to 2020 were excluded, as well as reviews and non-peer reviewed publications. Full papers were assessed for relevance and quality, where feasible. OUTCOMES From the 148 papers included, the following observations were made. The SARS-CoV-2-binding proteins, angiotensin-converting enzyme 2 (ACE2) and type II transmembrane serine protease (TMPRSS2), are expressed in the testis, but co-expression remains to be proven. There is some evidence of SARS-CoV-2 RNA in the ejaculate of COVID-19 patients with severe disease, but not in those with mild/moderate disease. SARS-CoV-2 infection can impair spermatogenesis, but this seems to resolve after one spermatogenic cycle. Testosterone levels seem to be lower during and after COVID-19, but long-term data are lacking; disease severity may be associated with testosterone levels. COVID-19 cannot be considered a sexually transmitted disease. There is no co-expression of ACE2 and TMPRSS2 in the myometrium, uterus, ovaries or fallopian tubes. Oocytes seem to have the receptors and protease machinery to be susceptible to SARS-CoV-2 infection; however, viral RNA in oocytes has not been detected so far. Women contemplating pregnancy following COVID-19 may benefit from screening for thyroid dysfunction. There is a possible (transient) impact of COVID-19 on menstrual patterns. Embryos, and particularly late blastocysts, seem to have the machinery to be susceptible to SARS-CoV-2 infection. Most studies have not reported a significant impact of COVID-19 on ovarian reserve, ovarian function or follicular fluid parameters. Previous asymptomatic or mild SARS-CoV-2 infection in females does not seem to negatively affect laboratory and clinical outcomes of ART. There are no data on the minimum required interval, if any, between COVID-19 recovery and ART. There is no evidence of a negative effect of SARS-CoV-2 vaccination on semen parameters or spermatogenesis, ovarian function, ovarian reserve or folliculogenesis. A transient effect on the menstrual cycle has been documented. Despite concerns, cross reactivity between anti-SARS-CoV-2 spike protein antibodies and Syncytin-1, an essential protein in human implantation, is absent. There is no influence of mRNA SARS-CoV-2 vaccine on patients’ performance during their immediate subsequent ART cycle. Pregnancy rates post-vaccination are similar to those in unvaccinated patients. WIDER IMPLICATIONS This review highlights existing knowledge on the impact of SARS-CoV-2 infection or COVID-19 on fertility and assisted reproduction, but also identifies gaps and offers suggestions for future research. The knowledge presented should help to provide evidence-based advice for practitioners and couples contemplating pregnancy alike, facilitating informed decision-making in an environment of significant emotional turmoil.

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“…While most published studies analyzed in this research area have focused on the following specimen types: blood samples, including serum [11][12][13][14][15][16][17][18][19][20][21] , plasma 12,13,[22][23][24][25][26][27][28][29][30][31][32] , and peripheral blood mononuclear cells (PBMC) 33,34 , there are also studies analyzing FFPE tissue 35,36 , urine [37][38][39][40][41] , fecal 42 , sputum 23 , extracellular vesicle 43,44 , cerebrospinal fluid 21 , semen 45 , colostrum 46 , colostrum 47 and nasopharynx swabs samples 48 . All these studies have provided proteomic snapshots of different aspects of tissues from COVID-19 patients.…”

Section: Introductionmentioning

confidence: 99%

COVIDpro: Database for mining protein dysregulation in patients with COVID-19

Zhang

Luna

Tan

et al. 2022

Preprint

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Background: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) still has limited treatment options partially due to our incomplete understanding of the molecular dysregulations of the COVID-19 patients. We aimed to generate a repository and data analysis tools to examine the modulated proteins underlying COVID-19 patients for the discovery of potential therapeutic targets and diagnostic biomarkers. Methods: We built a web server containing proteomic expression data from COVID-19 patients with a toolset for user-friendly data analysis and visualization. The web resource covers expert-curated proteomic data from COVID-19 patients published before May 2022. The data were collected from ProteomeXchange and from select publications via PubMed searches and aggregated into a comprehensive dataset. Protein expression by disease subgroups across projects was compared by examining differentially expressed proteins. We also visualize differentially expressed pathways and proteins. Moreover, circulating proteins that differentiated severe cases were nominated as predictive biomarkers. Findings: We built and maintain a web server COVIDpro (https://www.guomics.com/covidPro/) containing proteomics data generated by 41 original studies from 32 hospitals worldwide, with data from 3077 patients covering 19 types of clinical specimens, the majority from plasma and sera. 53 protein expression matrices were collected, for a total of 5434 samples and 14,403 unique proteins. Our analyses showed that the lipopolysaccharide-binding protein, as identified in the majority of the studies, was highly expressed in the blood samples of patients with severe disease. A panel of significantly dysregulated proteins was identified to separate patients with severe disease from non-severe disease. Classification of severe disease based on these proteomic signatures on five test sets reached a mean AUC of 0.87 and ACC of 0.80. Interpretation: COVIDpro is an online database with an integrated analysis toolkit. It is a unique and valuable resource for testing hypotheses and identifying proteins or pathways that could be targeted by new treatments of COVID-19 patients.

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Semen Proteomics of COVID-19 Convalescent Men Reveals Disruption of Key Biological Pathways Relevant to Male Reproductive Function

Cited by 24 publications

References 66 publications

Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals

Single-cell multiomics revealed the dynamics of antigen presentation, immune response and T cell activation in the COVID-19 positive and recovered individuals

SARS-CoV-2, fertility and assisted reproduction

COVIDpro: Database for mining protein dysregulation in patients with COVID-19

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