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1.
Int J Mol Sci ; 23(13)2022 Jun 28.
Article in English | MEDLINE | ID: covidwho-1934125

ABSTRACT

This Special Issue is intended to provide up-to-date information on reproduction, including the reproduction of germ cells and reproductive organs (ovary, testis, and uterus) [...].


Subject(s)
Reproduction , Testis , Female , Germ Cells , Humans , Male , Ovary , Uterus
2.
Genet Med ; 24(8): 1653-1663, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1819495

ABSTRACT

PURPOSE: Emerging evidence suggest that infection-dependent hyperactivation of complement system (CS) may worsen COVID-19 outcome. We investigated the role of predicted high impact rare variants - referred as qualifying variants (QVs) - of CS genes in predisposing asymptomatic COVID-19 in elderly individuals, known to be more susceptible to severe disease. METHODS: Exploiting exome sequencing data and 56 CS genes, we performed a gene-based collapsing test between 164 asymptomatic subjects (aged ≥60 years) and 56,885 European individuals from the Genome Aggregation Database. We replicated this test comparing the same asymptomatic individuals with 147 hospitalized patients with COVID-19. RESULTS: We found an enrichment of QVs in 3 genes (MASP1, COLEC11, and COLEC10), which belong to the lectin pathway, in the asymptomatic cohort. Analyses of complement activity in serum showed decreased activity of lectin pathway in asymptomatic individuals with QVs. Finally, we found allelic variants associated with asymptomatic COVID-19 phenotype and with a decreased expression of MASP1, COLEC11, and COLEC10 in lung tissue. CONCLUSION: This study suggests that genetic rare variants can protect from severe COVID-19 by mitigating the activity of lectin pathway and prothrombin. The genetic data obtained through ES of 786 asymptomatic and 147 hospitalized individuals are publicly available at http://espocovid.ceinge.unina.it/.


Subject(s)
COVID-19 , Aged , COVID-19/genetics , Collectins/genetics , Collectins/metabolism , Germ Cells , Humans , Lectins/genetics , SARS-CoV-2 , Whole Exome Sequencing
3.
mBio ; 13(3): e0358021, 2022 06 28.
Article in English | MEDLINE | ID: covidwho-1807332

ABSTRACT

Structural characterization of infection- and vaccination-elicited antibodies in complex with antigen provides insight into the evolutionary arms race between the host and the pathogen and informs rational vaccine immunogen design. We isolated a germ line-encoded monoclonal antibody (mAb) from plasmablasts activated upon mRNA vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and determined its structure in complex with the spike glycoprotein by electron cryomicroscopy (cryo-EM). We show that the mAb engages a previously uncharacterized neutralizing epitope on the spike N-terminal domain (NTD). The high-resolution structure reveals details of the intermolecular interactions and shows that the mAb inserts its heavy complementarity-determining region 3 (HCDR3) loop into a hydrophobic NTD cavity previously shown to bind a heme metabolite, biliverdin. We demonstrate direct competition with biliverdin and that, because of the conserved nature of the epitope, the mAb maintains binding to viral variants B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and B.1.1.529 (omicron). Our study describes a novel conserved epitope on the NTD that is readily targeted by vaccine-induced antibody responses. IMPORTANCE We report the first structure of a vaccine-induced antibody to SARS-CoV-2 spike isolated from plasmablasts 7 days after vaccination. The genetic sequence of the antibody PVI.V6-14 suggests that it is completely unmutated, meaning that this type of B cell did not undergo somatic hypermutation or affinity maturation; this cell was likely already present in the donor and was activated by the vaccine. This is, to our knowledge, also the first structure of an unmutated antibody in complex with its cognate antigen. PVI.V6-14 binds a novel, conserved epitope on the N-terminal domain (NTD) and neutralizes the original viral strain. PVI.V6-14 also binds the newly emerged variants B.1.1.7 (alpha), B.1.351 (beta), B.1.617.2 (delta), and B.1.1.529 (omicron). Given that this antibody was likely already present in the donor prior to vaccination, we believe that this antibody class could potentially "keep up" with the new variants, should they continue to emerge, by undergoing somatic hypermutation and affinity maturation.


Subject(s)
COVID-19 Vaccines , COVID-19 , Epitopes , Spike Glycoprotein, Coronavirus , Antibodies, Monoclonal , Antibodies, Neutralizing/chemistry , Antibodies, Viral/chemistry , Biliverdine , COVID-19/prevention & control , COVID-19 Vaccines/immunology , Germ Cells/metabolism , Humans , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/immunology
5.
Gynecol Obstet Fertil Senol ; 50(2): 173-181, 2022 02.
Article in French | MEDLINE | ID: covidwho-1450113

ABSTRACT

The current pandemic context raises questions about COVID-19 consequences on Assisted Reproduction Technology (ART). Indeed, according to the first Biomedicine Agency recommendations, ART centers suspended their activities in March 2020 during the first wave of Covid-19. However, SARS-CoV-2 direct and indirect effects on gametes, fertility, pregnancy and neonatal health are still debated. The aim of this review is to assess the available data on this subject, to inform patients in care and adapt daily practice. Most recent studies are based on the effects of the infectious syndrome, on hormonal factors as well as on the expression of viral entry proteins (ACE2 and TMPRSS2) in cells involved in gametogenesis, to assess the impact of COVID-19. So far, no effect on female gametes was highlighted. More studies are needed to confirm this hypothesis. Mother to children transmission couldn't be proven, yet neonatal infection remains possible. However, men are more susceptible to be infected by SARS-CoV-2, to be symptomatic, and spermatogenesis is likely to be affected. Presence of the virus in semen is infrequently reported, but all of these parameters should be taken into account in ART.


Subject(s)
COVID-19 , SARS-CoV-2 , Female , Fertility , Germ Cells , Humans , Male , Pregnancy , Spermatogenesis , Technology
6.
Front Immunol ; 12: 653489, 2021.
Article in English | MEDLINE | ID: covidwho-1150694

ABSTRACT

The ongoing COVID-19 pandemic caused by the novel coronavirus, SARS-CoV-2 has affected all aspects of human society with a special focus on healthcare. Although older patients with preexisting chronic illnesses are more prone to develop severe complications, younger, healthy individuals might also exhibit serious manifestations. Previous studies directed to detect genetic susceptibility factors for earlier epidemics have provided evidence of certain protective variations. Following SARS-CoV-2 exposure, viral entry into cells followed by recognition and response by the innate immunity are key determinants of COVID-19 development. In the present review our aim was to conduct a thorough review of the literature on the role of single nucleotide polymorphisms (SNPs) as key agents affecting the viral entry of SARS-CoV-2 and innate immunity. Several SNPs within the scope of our approach were found to alter susceptibility to various bacterial and viral infections. Additionally, a multitude of studies confirmed genetic associations between the analyzed genes and autoimmune diseases, underlining the versatile immune consequences of these variants. Based on confirmed associations it is highly plausible that the SNPs affecting viral entry and innate immunity might confer altered susceptibility to SARS-CoV-2 infection and its complex clinical consequences. Anticipating several COVID-19 genomic susceptibility loci based on the ongoing genome wide association studies, our review also proposes that a well-established polygenic risk score would be able to clinically leverage the acquired knowledge.


Subject(s)
COVID-19/genetics , COVID-19/immunology , Germ Cells/immunology , SARS-CoV-2/physiology , COVID-19/virology , Genetic Predisposition to Disease , Humans , Immunity, Innate , Multifactorial Inheritance , Virus Internalization
7.
J Exp Med ; 218(5)2021 05 03.
Article in English | MEDLINE | ID: covidwho-1114805

ABSTRACT

The neutralizing antibody response to SARS-CoV-2 is dominated by antibodies deriving from germlines IGHV3-53/IGHV3-66, which are also associated with self-reacting antibodies. Could vaccines avoid the expansion of this immunodominant response, decrease the risk of autoimmunity, and still protect against emerging SARS-CoV-2 variants?


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19/immunology , Germ Cells/immunology , Host-Pathogen Interactions/immunology , SARS-CoV-2/immunology , Antigens, Viral/immunology , COVID-19/genetics , COVID-19/virology , Host-Pathogen Interactions/genetics , Humans
8.
J Clin Oncol ; 38(23): 2698, 2020 08 10.
Article in English | MEDLINE | ID: covidwho-874119
9.
Reprod Biomed Online ; 41(6): 991-997, 2020 Dec.
Article in English | MEDLINE | ID: covidwho-759281

ABSTRACT

Reopening fertility care services across the world in the midst of a pandemic brings with it numerous concerns that need immediate addressing, such as the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the male and female reproductive cells and the plausible risk of cross-contamination and transmission. Due to the novelty of the disease the literature contains few reports confirming an association of SARS-CoV-2 with reproductive tissues, gametes and embryos. Cryobanking, an essential service in fertility preservation, carries the risk of cross-contamination through cryogenic medium and thus calls for risk-mitigation strategies. This review aims to address the available literature on the presence of SARS-CoV-2 on tissues, gametes and embryos, with special reference to the possible sources of cross-contamination through liquid nitrogen. Strategies for risk mitigation have been extrapolated from reports dealing with other viruses to the current global crisis, for safety in fertility treatment services in general, and specifically for oncofertility.


Subject(s)
COVID-19/epidemiology , Cryopreservation , Equipment Contamination/prevention & control , Fertility Preservation , Germ Cells , Pandemics , Cryopreservation/standards , Female , Fertility Preservation/methods , Fertility Preservation/standards , Humans , Infection Control/methods , Infection Control/organization & administration , Infection Control/standards , Male , SARS-CoV-2/physiology
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