Prospective two‐arm study of the testicular function in patients with COVID‐19

Enikeev, Dmitry; Taratkin, Mark; Morozov, Andrey; Petov, Vladislav; Korolev, Dmitry; Shpikina, Anastasia; Spivak, Leonid; Kharlamova, S. A.; Shchedrina, I S; Mestnikov, Oleg; Fiev, D.; Ганжа, Т. М.; Geladze, Marina; Mambetova, A. Zh.; Коган, Е. А.; Zharkov, N.V.; Demyashkin, Grigory; Shariat, Shahrokh F.; Глыбочко, П. В.

doi:10.1111/andr.13159

Cited by 37 publications

(46 citation statements)

References 28 publications

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“…Leydig cells, which produce testosterone, are known targets of SARS-CoV-2 35,37,77 . The decrease in testosterone correlates with disease severity 76,78 . The direct infection of the testicles observed in the NHP studies presented here are consistent with the MGT pathology reported in men [35][36][37][38][39][40] .…”

Section: Discussionmentioning

confidence: 99%

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An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Madden

Thomas

Blair

et al. 2022

Preprint

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Because of the recognized systemic nature of SARS-CoV-2 infection, a non-invasive and unbiased method is needed to clarify its spatiotemporal dynamics in vivo after transmission. We recently developed a probe based on the anti-SARS-CoV-2 spike antibody CR3022 to study SARS-CoV-2 pathogenesis in vivo. Herein, we describe its use in immunoPET to investigate SARS-CoV-2 infection of rhesus macaques. Using PET/CT imaging of macaques at different times post-SARS-CoV-2 inoculation, we demonstrate that the 64Cu-labelled CR3022-F(ab′)2 probe targeting the spike protein of SARS-CoV-2 can be used to study the dynamics of infection within the respiratory tract and uncover novel sites of infection. Differences in lung pathology between infection with the WA1 isolate and the delta variant were readily observed using immunoPET and corroborated CT lung pathology. The ability of the probe to illuminate lung-associated pathology demonstrates its specificity and function to detect infection in PET scan. The 64Cu-CR3022-probe also demonstrated dynamic changes occurring between 1- and 2-weeks post-infection. Remarkably, a robust signal was seen in the male genital tract (MGT) of all three animals studied. Infection of the MGT was validated by immunofluorescence imaging of infected cells in the testicular and penile tissue and severe pathology was observed in the testes of one animal at 2-weeks post-infection. The results presented here underscore the utility of using immunoPET to study the dynamics of SARS-CoV-2 infection to understand its pathogenicity and discover new anatomical sites of viral replication. We provide direct evidence for SARS-CoV-2 infection of the MGT in rhesus macaques revealing the possible pathologic outcomes of viral replication at these sites.

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Section: Discussionmentioning

confidence: 99%

“…Leydig cells, which produce testosterone, are known targets of SARS-CoV-2 35, 37, 77 . The decrease in testosterone correlates with disease severity 76, 78 . This susceptibility of the MGT to infection with SARS-CoV-2 may be consideration in the of higher mortality associated with COVID-19 in men compared to women.…”

Section: Discussionmentioning

confidence: 99%

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Madden

Thomas

Blair

et al. 2022

Preprint

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“…Although more evidence is needed as to whether the virus can directly infect the testis, it is reasonable to suggest that SARS-CoV2 could invade Sertoli cells, destroy the blood-testis barrier, and cause testicular inflammation. 5 Our IHC and IF results revealed high expression of ACE2 and TMPRSS2 in kidney specimens of adults and fetuses; however, cellular co-localization of them could only be detected in fetal but not adult specimens (Figure S1G and Figure 2E).…”

mentioning

confidence: 72%

“…Although more evidence is needed as to whether the virus can directly infect the testis, it is reasonable to suggest that SARS‐CoV2 could invade Sertoli cells, destroy the blood‐testis barrier, and cause testicular inflammation. 5 …”

mentioning

confidence: 99%

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Profiling of host entry factors in adults and fetuses for severe acute respiratory syndrome coronavirus‐2 infection indicates its developmental regulation

Wang

Zhang

et al. 2022

Clinical & Translational Med

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Dear Editor,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is imposing the ongoing coronavirus disease 2019 pandemic. Despite numerous studies on the pathology of SARS-CoV-2 infection, we addressed the following three questions. (1) COVID-19 manifests in respiratory, digestive, heart, cerebral, and urogenital tissues; however, there is heterogeneity regarding the virus loads and pathology among these organ systems within the same patient.(2) On one end of the COVID-19 patient spectrum, fetuses would only display liver and renal injury due to possible maternal-fetal vertical SARS-CoV-2 transmission in the third trimester of pregnancy. On the other end of the spectrum, adults are more susceptible to COVID-19 and elderly patients are more prone to develop severe symptoms. Although multiple mechanisms might account for the observed discrepancies, differential expression of key entry-related factors that mediate direct SARS-CoV-2 infection could be one underlying these two questions. 1,2 However, no study has systematically assessed the expression levels of virus entry-related factors in fetuses and adults. (3) Angiotensin-converting enzyme 2 (ACE2), the receptor mediating SARS-CoV-2 infection, and transmembrane serine protease 2 (TMPRSS2), the protease priming SARS-CoV-2 infection, is expressed in multiple cell types distributed across multiple tissues and organs; are their developmental relationships among the SARS-CoV-2 tropic cell types?To answer the first two questions, we profiled and compared the expression patterns of ACE2, TMPRSS2 and neuropilin-1 (NRP1) at both protein and messenger RNA (mRNA) levels across the whole human body tissues. NRP1 can mediate SARS-CoV-2 infection in a furin-dependent manner when ACE2 expression is low or even in its absence if viral load is high, which might contribute to increased tropic cell types. 3 For their protein expression patterns, we performed immunohistochemistry (IHC) This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

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Association of SARS-CoV-2 Infection During Controlled Ovarian Stimulation With Oocyte- and Embryo-Related Outcomes

Fen

et al. 2023

JAMA Netw Open

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ImportanceSARS-CoV-2 infection has had significant effects on the health of people worldwide. Whether SARS-CoV-2 infection during controlled ovarian stimulation (COS) is associated with laboratory outcomes in assisted reproductive technology remains unclear.ObjectiveTo investigate the association between SARS-CoV-2 infection during COS with oocyte- and embryo-related outcomes.Design, Setting, and ParticipantsA multicenter cohort study was conducted of couples undergoing assisted reproductive technology treatments in 7 reproductive centers in 4 provinces in China from October 1, 2022, to December 31, 2022. All couples received nucleic acid testing for SARS-CoV-2 during COS. The SARS-CoV-2–positive group included couples in which either partner was infected with SARS-CoV-2. The SARS-CoV-2–negative group comprised couples without infection.ExposureIn the SARS-CoV-2–positive group, either partner was infected with SARS-CoV-2 during COS, defined as a positive test result for the SARS-CoV-2 antigen.Main Outcomes and MeasuresPrimary outcomes were the available embryo and blastocyst and top-quality embryo and blastocyst rates. Secondary outcomes were the number of oocytes retrieved, the mature oocyte rate, normal fertilization (2 pronuclei observed on day 1 after insemination [2PN]), oocyte degeneration, 2PN cleavage, and blastocyst formation rates.ResultsA total of 585 heterosexual couples with infertility participated in the study (median [IQR] age for female partners, 33 [30-37] years), with 135 couples in the SARS-CoV-2–positive group and 450 in the SARS-CoV-2–negative group. The characteristics of the groups were similar. The SARS-CoV-2–positive group had a significantly lower top-quality embryo rate (odds ratio [OR], 0.83; 95% CI, 0.71-0.96), top-quality blastocyst rate (OR, 0.59; 95% CI, 0.45-0.77), available blastocyst rate (OR, 0.70; 95% CI, 0.59-0.82), and blastocyst formation rate (OR, 0.61; 95% CI, 0.52-0.71) than the SARS-CoV-2–negative group. Analysis of the associations of infection by sex showed that the female positive group had impaired oocyte and embryo quality regarding mature oocyte rate, 2PN cleavage rate, top-quality embryo rate, blastocyst formation rate, available blastocyst rate, and top-quality blastocyst rate compared with the SARS-CoV-2–negative group. Compared with the SARS-CoV-2–negative group, the male positive group and the group of couples with both positive partners had significantly decreased available blastocyst rate, top-quality blastocyst rate, and blastocyst formation rate compared with the SARS-CoV-2 negative group.Conclusions and RelevanceIn this cohort study, SARS-CoV-2 infection during COS was negatively associated with embryo and blastocyst quality. Reproductive physicians should be more attentive to patients with SARS-CoV-2 infection during COS and should give couples who have been infected adequate counseling.

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Prospective two‐arm study of the testicular function in patients with COVID‐19

Cited by 37 publications

References 28 publications

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

An immunoPET probe to SARS-CoV-2 reveals early infection of the male genital tract in rhesus macaques

Profiling of host entry factors in adults and fetuses for severe acute respiratory syndrome coronavirus‐2 infection indicates its developmental regulation

Association of SARS-CoV-2 Infection During Controlled Ovarian Stimulation With Oocyte- and Embryo-Related Outcomes

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