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1.
J Med Virol ; 93(12): 6671-6685, 2021 12.
Article in English | MEDLINE | ID: covidwho-1544318

ABSTRACT

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of syndromes involving multiple organ systems and is primarily mediated by viral spike (S) glycoprotein through the receptor-binding domain (RBD) and numerous cellular proteins including ACE2, transmembrane serine protease 2 (TMPRSS2), kidney injury molecule-1 (Kim-1), and neuropilin-1 (NRP-1). In this study, we examined the entry tropism of SARS-CoV-2 and SARS-CoV using S protein-based pseudoviruses to infect 22 cell lines and 3 types of primary cells isolated from respiratory, urinary, digestive, reproductive, and immune systems. At least one cell line or type of primary cell from each organ system was infected by both pseudoviruses. Infection by pseudoviruses is effectively blocked by S1, RBD, and ACE2 recombinant proteins, and more weakly by Kim-1 and NRP-1 recombinant proteins. Furthermore, cells with robust SARS-CoV-2 pseudovirus infection had strong expression of either ACE2 or Kim-1 and NRP-1 proteins. ACE2 glycosylation appeared to be critical for the infections of both viruses as there was a positive correlation between infectivity of either SARS-CoV-2 or SARS-CoV pseudovirus with the level of glycosylated ACE2 (gly-ACE2). These results reveal that SARS-CoV-2 cell entry could be mediated by either an ACE2-dependent or -independent mechanism, thus providing a likely molecular basis for its broad tropism for a wide variety of cell types.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Gastrointestinal Tract/virology , Genitalia/virology , Hepatitis A Virus Cellular Receptor 1/metabolism , Immune System/virology , Neuropilin-1/metabolism , Respiratory System/virology , SARS-CoV-2/physiology , Serine Endopeptidases/metabolism , Virus Internalization , Blotting, Western , COVID-19/metabolism , COVID-19/virology , Cell Line , Cells, Cultured , Fluorescent Antibody Technique , Gastrointestinal Tract/cytology , Genitalia/cytology , Humans , Immune System/cytology , Respiratory System/cytology
2.
Rheumatol Int ; 41(11): 1885-1894, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1375632

ABSTRACT

The SARS-CoV-2 virus is known to mediate attack via ACE-2 Receptor, thus having adverse effects on cardiovascular, respiratory, digestive and reproductive systems, the latter being an area of emerging concern, due to the associated impact on fertility, with potential for an outsized effect on population distribution and socioeconomic road map in subsequent years. This narrative review aims to put forth the current evidence of effect of SARS-CoV-2 on human fertility from a multipronged immunologic, haematologic, and gynaecologic perspective; highlighting the areas of contradiction and potential future measures. A literature search was conducted through the MEDLINE and SCOPUS databases to identify articles on the subject in English. Relevant information was extracted from around 300 articles for this review. The existing data give non-conclusive evidence about the impact of SARS-CoV-2 infection on fertility; however, a greater impact on male fertility as compared to females merits further exploration. However, reproduction and fertility is a key concern and considering the pandemic is prolonged, natural conception or ART require extra precautions.


Subject(s)
Autoimmunity , COVID-19/complications , Fertility , Genitalia/virology , Angiotensin-Converting Enzyme 2 , COVID-19/epidemiology , Female , Humans , Male , Pandemics , Pregnancy , SARS-CoV-2
3.
J Med Virol ; 93(12): 6671-6685, 2021 12.
Article in English | MEDLINE | ID: covidwho-1330343

ABSTRACT

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of syndromes involving multiple organ systems and is primarily mediated by viral spike (S) glycoprotein through the receptor-binding domain (RBD) and numerous cellular proteins including ACE2, transmembrane serine protease 2 (TMPRSS2), kidney injury molecule-1 (Kim-1), and neuropilin-1 (NRP-1). In this study, we examined the entry tropism of SARS-CoV-2 and SARS-CoV using S protein-based pseudoviruses to infect 22 cell lines and 3 types of primary cells isolated from respiratory, urinary, digestive, reproductive, and immune systems. At least one cell line or type of primary cell from each organ system was infected by both pseudoviruses. Infection by pseudoviruses is effectively blocked by S1, RBD, and ACE2 recombinant proteins, and more weakly by Kim-1 and NRP-1 recombinant proteins. Furthermore, cells with robust SARS-CoV-2 pseudovirus infection had strong expression of either ACE2 or Kim-1 and NRP-1 proteins. ACE2 glycosylation appeared to be critical for the infections of both viruses as there was a positive correlation between infectivity of either SARS-CoV-2 or SARS-CoV pseudovirus with the level of glycosylated ACE2 (gly-ACE2). These results reveal that SARS-CoV-2 cell entry could be mediated by either an ACE2-dependent or -independent mechanism, thus providing a likely molecular basis for its broad tropism for a wide variety of cell types.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Gastrointestinal Tract/virology , Genitalia/virology , Hepatitis A Virus Cellular Receptor 1/metabolism , Immune System/virology , Neuropilin-1/metabolism , Respiratory System/virology , SARS-CoV-2/physiology , Serine Endopeptidases/metabolism , Virus Internalization , Blotting, Western , COVID-19/metabolism , COVID-19/virology , Cell Line , Cells, Cultured , Fluorescent Antibody Technique , Gastrointestinal Tract/cytology , Genitalia/cytology , Humans , Immune System/cytology , Respiratory System/cytology
4.
Hong Kong Med J ; 27(2): 118-126, 2021 04.
Article in English | MEDLINE | ID: covidwho-1187156

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs the angiotensin-converting enzyme 2 (ACE2) receptor in the renin-angiotensin system for viral entry. The ACE2 receptor is present in both female and male reproductive systems, and reports of multi-organ involvement have led to uncertainty regarding its effects on the reproductive system and fertility. We review the existing literature regarding the function of ACE2 and the renin-angiotensin system in the female and male reproductive systems to postulate the possible implications of SARS-CoV-2 regarding fertility. Because of the presence of ACE2 in the ovaries, SARS-CoV-2 infection may disrupt ovarian function and hence oocyte quality. Higher expression of ACE2 in the endometrium with age and during the secretory phase raises concern about increased susceptibility to infection during periods of high ACE2 expression. The possibility of vertical transmission and the presence of ACE2 in the placenta and during pregnancy are also discussed. The presence of SARS-CoV-2 RNA in semen is controversial, but impaired semen quality has been found in men with moderate coronavirus disease 2019 infection. Evidence of orchitis and hormonal changes seen in male coronavirus disease 2019 infection may lead to infertility. The implications of these effects on assisted reproductive technology (ART) outcomes are also explored. The ART guidelines from different fertility societies for the management of patients treated with ART are provided. The importance of prioritising 'time-sensitive' patients for ART, counselling patients about the uncertainty and risks of ART, and pregnancy during the pandemic is discussed. Recommendations are also provided for infection control and safe regulation of ART centres and laboratories.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19 , Fertility/physiology , Genitalia , SARS-CoV-2 , COVID-19/complications , COVID-19/epidemiology , COVID-19/virology , Female , Genitalia/metabolism , Genitalia/virology , Humans , Male , Pregnancy , Risk Assessment , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity
5.
Syst Biol Reprod Med ; 67(1): 3-23, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-1132358

ABSTRACT

The COVID-19 pandemic has led to a worldwide health emergency that has impacted 188 countries at last count. The rapid community transmission and relatively high mortality rates with COVID-19 in modern times are relatively unique features of this flu pandemic and have resulted in an unparalleled global health crisis. SARS-CoV-2, being a respiratory virus, mainly affects the lungs, but is capable of infecting other vital organs, such as brain, heart and kidney. Emerging evidence suggests that the virus also targets male and female reproductive organs that express its main receptor ACE2, although it is as yet unclear if this has any implications for human fertility. Furthermore, professional bodies have recommended discontinuing fertility services during the pandemic such that reproductive services have also been affected. Although increased safety measures have helped to mitigate the propagation of COVID-19 in a number of countries, it seems that there is no predictable timeline to containment of the virus, a goal likely to remain elusive until an effective vaccine becomes available  and widely distributed across the globe. In parallel, research on reproduction has been postponed for obvious reasons, while diagnostic tests that detect the virus or antibodies against it are of vital importance to support public health policies, such as social distancing and our obligation to wear masks in public spaces. This review aims to provide an overview of critical research and ethics issues that have been continuously emerging in the field of reproductive medicine as the COVID-19 pandemic tragically unfolds.Abbreviations: ACE2: angiotensin- converting enzyme 2; ART: Assisted reproductive technology; ASRM: American Society for Reproductive Medicine; CCR9: C-C Motif Chemokine Receptor 9; CDC: Centers for Disease Control and Prevention; COVID-19: Coronavirus disease 2019; Ct: Cycle threshold; CXCR6: C-X-C Motif Chemokine Receptor 6; ELISA: enzyme-linked immunosorbent assay; ESHRE: European Society of Human Reproduction and Embryology; ET: Embryo transfer; FSH: Follicle Stimulating Hormone; FFPE: formalin fixed paraffin embedded; FYCO1: FYVE And Coiled-Coil Domain Autophagy Adaptor 1; IFFS: International Federation of Fertility Societies; IUI: Intrauterine insemination; IVF: In vitro fertilization; LH: Luteinizing Hormone; LZTFL1: Leucine Zipper Transcription Factor Like 1; MAR: medically assisted reproduction services; MERS: Middle East Respiratory syndrome; NGS: Next Generation Sequencing; ORF: Open Reading Frame; PPE: personal protective equipment; RE: RNA Element; REDa: RNA Element Discovery algorithm; RT-PCR: Reverse=trascriptase transcriptase-polymerase chain reaction; SARS: Severe acute respiratory syndrome; SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; SLC6A20: Solute Carrier Family 6 Member 20; SMS: Single Molecule Sequencing; T: Testosterone; TMPRSS2: transmembrane serine protease 2; WHO: World Health Organization; XCR1: X-C Motif Chemokine Receptor.


Subject(s)
COVID-19 , Fertility , Host-Pathogen Interactions , Reproduction , SARS-CoV-2/physiology , Animals , Biomedical Research , COVID-19 Testing , Genitalia/virology , Humans , Reproductive Medicine/ethics , Reproductive Techniques, Assisted , Spermatogenesis
6.
Stem Cell Res ; 52: 102189, 2021 04.
Article in English | MEDLINE | ID: covidwho-1062597

ABSTRACT

Since the emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in December 2019, it has rapidly spread across many countries and it has become a crucial global health concern. Furthermore, SARS-CoV-2 infection not only effect on respiratory system, but on reproductive system of human. However, there has been not any review described the transmission paths and effects of SARS-CoV-2 infection on human reproductive system, systematically. In order to describe the transmission paths of SARS-CoV-2, effect on the male/female reproductive system of SARS-CoV-2 and some successful prevention measures. We would like to review effect of SARS-CoV-2 on reproductive system. To conclude, SARS-CoV-2 infection might damage to male reproductive system via ACE2 receptor mediating and male patients were reportedly slightly more affected than women by SARS-CoV-2 infections.


Subject(s)
COVID-19/complications , Genitalia/virology , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/metabolism , Female , Genital Diseases, Female/virology , Genital Diseases, Male/virology , Global Health , Humans , Infant, Newborn , Infectious Disease Transmission, Vertical , Male , Ovary/virology , Pregnancy , Semen/virology , Sex Factors , Testis/virology , Uterus/virology
7.
JBRA Assist Reprod ; 25(2): 310-313, 2021 04 27.
Article in English | MEDLINE | ID: covidwho-1052536

ABSTRACT

The COVID-19 pandemic is an unexpected worldwide situation, and all countries have implemented their own policies to curb the spread of the virus. The pathophysiology of COVID-19 has opened numerous hypotheses of functional alterations in different physiological aspects. The direct impact of SARS-CoV-2 on the urogenital organs of males and females is still to be assessed. Nevertheless, based on biological similarities between SARS-CoV and SARS-CoV-2, several hypotheses have been proposed. In this study, we will discuss the possible mechanism of action, and potential effects on the male/female reproductive system and fertility.


Subject(s)
COVID-19 , Fertility , Reproduction , SARS-CoV-2 , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/metabolism , Genitalia/immunology , Genitalia/metabolism , Genitalia/virology , Humans , Serine Endopeptidases/immunology , Serine Endopeptidases/metabolism
8.
J Chin Med Assoc ; 83(10): 895-897, 2020 10.
Article in English | MEDLINE | ID: covidwho-990893

ABSTRACT

An outbreak of pneumonia associated with coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, China, in December 2019, and has been spread worldwide rapidly now. Over 5.3-million confirmed cases and 340,000 disease-associated deaths have been found till May 25, 2020. The potential pathophysiology for SARS-CoV-2 to affect the target is via the receptor, angiotensin-converting enzyme 2 (ACE2). ACE2 can be found in the respiratory, cardiovascular, gastrointestinal tract, urinary tract, and reproductive organs such as human ovaries and Leydig cells in the testis. This receptor plays a dominant role in the fertility function. Considering the crucial roles of testicular cells of the male reproductive system, increasing numbers of studies focus on the effects of SARS-CoV-2 on the testis. In this literature, we reviewed several studies to evaluate the relevance between SARS-CoV-2, ACE receptor, and female and male reproductive system and found that the risk of being attacked by SARS-CoV-2 is higher in males than in females. Since men infected with SARS-CoV-2 virus may have the risk of impaired reproductive performance, such as the orchitis and an elevated of luteinizing hormone (LH), and additionally, SARS-CoV-2 virus may be found in semen, although the latter is still debated, all suggest that we should pay much attention to sexual transmitted disease and male fertility after recovering from COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Genitalia/virology , Pneumonia, Viral/complications , Angiotensin-Converting Enzyme 2 , COVID-19 , Female , Fertility , Humans , Male , Pandemics , Peptidyl-Dipeptidase A/physiology , SARS-CoV-2 , Sex Characteristics
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