COVID-19 disrupts the blood–testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins

Peirouvi, Tahmineh; Aliaghaei, Abbas; Farsani, Bahram Eslami; Ziaeipour, Sanaz; Ebrahimi, Vahid; Forozesh, Mehdi; Ghadipasha, Masoud; Mahmoudiasl, Gholam-Reza; Aryan, Arefeh; Moghimi, Negin; Abdi, Shabnam; Raoofi, Amir; Godaneh, Mohammadhossein Kargar; Abdollahifar, Mohammad‐Amin

doi:10.1007/s00011-021-01497-4

Cited by 42 publications

(36 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…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] . The infection of the MGT may be a common outcome in SARS-CoV-2 infection.…”

Section: Discussionsupporting

confidence: 90%

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 90%

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

View full text Add to dashboard Cite

show abstract

“…Besides, implantation loss in female mice caused by intraperitoneal injection of lipopolysaccharide (LPS) indicates that inflammation changes can impair the inflammatory state of the uterus during the implantation window (Moustafa et al, 2019). In male mice, the SARS-CoV-2 infection could disrupt the blood-testis barrier through the induction of inflammatory cytokines and disruption of junctional protein rather than directly invading the target cells (Peirouvi et al, 2021). It means that the cytokine storm caused by SARS-CoV-2 infection could impair the peripheral organs and result in an interstitial inflammation.…”

Section: Discussionmentioning

confidence: 99%

Delayed Antiviral Immune Responses in Severe Acute Respiratory Syndrome Coronavirus Infected Pregnant Mice

Zhu

Wang

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

Sex differences in immune responses had been reported to correlate with different symptoms and mortality in the disease course of coronavirus disease 2019 (COVID-19). However, whether severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection interferes with females’ fertility and causes different symptoms among pregnant and non-pregnant females remains unknown. Here, we examined the differences in viral loads, SARS-CoV-2-specific antibody titers, proinflammatory cytokines, and levels of T cell activation after SARS-CoV-2 sub-lethal infection between pregnant and non-pregnant human Angiotensin-Converting Enzyme II (ACE2) transgenic mouse models. Both mice showed elevated levels of viral loads in the lung at 4 days post-infection (dpi). However, viral loads in the pregnant group remained elevated at 7 dpi while decreased in the non-pregnant group. Consistent with viral loads, increased production of proinflammatory cytokines was detected from the pregnant group, and the IgM or SARS-CoV-2-specific IgG antibody in serum of pregnant mice featured delayed elevation compared with non-pregnant mice. Moreover, by accessing kinetics of activation marker expression of peripheral T cells after infection, a lower level of CD8+ T cell activation was observed in pregnant mice, further demonstrating the difference of immune-response between pregnant and non-pregnant mice. Although vertical transmission did not occur as SARS-CoV-2 RNA was absent in the uterus and fetus from the infected pregnant mice, a lower pregnancy rate was observed when the mice were infected before embryo implantation after mating, indicating that SARS-CoV-2 infection may interfere with mice’s fertility at a specific time window. In summary, pregnant mice bear a weaker ability to eliminate the SARS-CoV-2 virus than non-pregnant mice, which was correlated with lower levels of antibody production and T cell activation.

show abstract

“…Increased levels of autoantibodies against testis-related proteins suggest their role in affecting male reproductive system, and thus declining male fertility in COVID-19. Although several investigations have found that COVID-19 patients have altered seminal parameters and decreased reproductive hormone levels 53 , histological or functional abnormalities in male genital system 54 , damaged blood-testis barrier 55 , and impaired spermatogenesis 56 , the cause of this comorbidity has not yet been investigated, and remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Auto-Immunoproteomics Analysis of COVID-19 ICU Patients Revealed Increased Levels of Autoantibodies Related to Male Reproductive System

Schmidt

Abdesselem

Suhre

et al. 2022

Preprint

View full text Add to dashboard Cite

The role of autoantibodies in coronavirus disease (COVID-19) complications is not yet fully understood. The current investigation screened two independent cohorts of 97 COVID-19 patients (Discovery (Disc) cohort from Qatar (n = 49) and Replication (Rep) cohort from New York (n = 48)) utilizing high-throughput KoRectly Expressed (KREX) immunome protein-array technology. Autoantibody responses to 57 proteins were significantly altered in the COVID-19 Disc cohort compared to healthy controls (P ≤ 0.05). The Rep cohort had altered autoantibody responses against 26 proteins compared to non-COVID-19 ICU patients that served as controls. Both cohorts showed substantial similarities (r2 = 0.73) and exhibited higher autoantibodies responses to numerous transcription factors, immunomodulatory proteins, and human disease markers. Analysis of the combined cohorts revealed elevated autoantibody responses against SPANXN4, STK25, ATF4, PRKD2, and CHMP3 proteins in COVID-19 patients. KREX analysis of the specific IgG autoantibody responses indicates that the targeted host proteins are supposedly increased in COVID-19 patients. The autoantigen-autoantibody response was cross-validated for SPANXN4 and STK25 proteins using Uniprot BLASTP and sequence alignment tools. SPANXN4 is essential for spermiogenesis and male fertility, which may predict a potential role for this protein in COVID-19 associated male reproductive tract complications and warrants further research.

show abstract

COVID-19 disrupts the blood–testis barrier through the induction of inflammatory cytokines and disruption of junctional proteins

Cited by 42 publications

References 38 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

Delayed Antiviral Immune Responses in Severe Acute Respiratory Syndrome Coronavirus Infected Pregnant Mice

Auto-Immunoproteomics Analysis of COVID-19 ICU Patients Revealed Increased Levels of Autoantibodies Related to Male Reproductive System

Contact Info

Product

Resources

About