Risk Factors of Severe COVID-19: A Review of Host, Viral and Environmental Factors

Viruses, Journal Year: 2023, Volume and Issue: 15(1), P. 175 - 175

Published: Jan. 7, 2023

The clinical course and outcome of COVID-19 are highly variable, ranging from asymptomatic infections to severe disease death. Understanding the risk factors is relevant both in setting at epidemiological level. Here, we provide an overview host, viral environmental that have been shown or (in some cases) hypothesized be associated with outcomes. considered detail include age frailty, genetic polymorphisms, biological sex (and pregnancy), co- superinfections, non-communicable comorbidities, immunological history, microbiota, lifestyle patient; variation infecting dose; socioeconomic factors; air pollution. For each category, compile (sometimes conflicting) evidence for association factor outcomes (including strength effect) outline possible action mechanisms. We also discuss complex interactions between various factors.

Language: Английский

---

The spike gene is a major determinant for the SARS-CoV-2 Omicron-BA.1 phenotype

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Oct. 7, 2022

Abstract Variant of concern (VOC) Omicron-BA.1 has achieved global predominance in early 2022. Therefore, surveillance and comprehensive characterization advanced primary cell culture systems animal models are urgently needed. Here, we characterize recombinant spike gene mutants comparison with VOC Delta well-differentiated human nasal bronchial epithelial cells vitro, followed by vivo fitness hamsters, ferrets hACE2-expressing mice, immunized hACE2-mice. We demonstrate a spike-mediated enhancement replication cultures, but limited cultures. In shows dominance over Omicron-BA.1, infection is abortive. hACE2-knock-in clone also show an clone, respectively. Interestingly, naïve K18-hACE2 observe increased pathogenicity reduced pathogenicity, suggesting that the major determinant pathogenicity. Finally, less well-controlled mRNA-vaccination K18-hACE2-mice becomes more competitive compared to progenitor clones, gene-mediated immune evasion another important factor led dominance.

Language: Английский

---

COVID-19 and pregnancy: clinical outcomes; mechanisms, and vaccine efficacy

Translational research, Journal Year: 2022, Volume and Issue: 251, P. 84 - 95

Published: Aug. 12, 2022

Language: Английский

---

Oxidative stress status and vitamin D levels of asymptomatic to mild symptomatic COVID‐19 infections during the third trimester of pregnancy: A retrospective study in Metz, France

Journal of Medical Virology, Journal Year: 2022, Volume and Issue: 94(5), P. 2167 - 2173

Published: Jan. 21, 2022

It is believed that the subtle equilibrium between tolerance and immunity during unique biological state of pregnancy, which characterized by further physiological hormonal changes, rends pregnant women more vulnerable to coronavirus disease 2019 (COVID-19). In this retrospective study, confirmed COVID-19-positive (n = 15) their third trimester, comprising asymptomatic 7) mild symptomatic 8), healthy controls 20), were enrolled June 1, 2020 2021 from Hospital CHR Metz-Thionville in Metz, France. Vitamin D concentrations, C-reactive protein (CRP), oxidative stress markers including superoxide dismutase (SOD), catalase (CAT), reduced (GSH) oxidized (GSSG) glutathione levels, hydrogen peroxide (H2 O2 ), total antioxidant capacity, measured ferric reducing ability plasma (FRAP), evaluated serum patients controls. Results showed all (patients controls) study vitamin deficient (<20 ng/ml). However, COVID-19 severely (<12 ng/ml), may suggest a link deficiency symptomatology illness singleton pregnancy. No differences levels CRP majority studied (asymptomatic and/or mildly patients) versus COVID-19-negative found, suggesting absence or low magnitude with COVID-19. This also explain severe courses infection. More studies are warranted investigate role supplementation antioxidant-rich diets prevention against forms women.

Language: Английский

---

Effects of polycyclic aromatic hydrocarbons (PAHs) on pregnancy, placenta, and placental trophoblasts

Ecotoxicology and Environmental Safety, Journal Year: 2023, Volume and Issue: 262, P. 115314 - 115314

Published: Aug. 2, 2023

Polycyclic aromatic hydrocarbons (PAHs) are a group of persistent organic pollutants that carcinogenic, mutagenic, endocrine-toxic, and immunotoxic. PAHs can be found in maternal fetal blood the placenta during pregnancy. They may thus affect placental development. Therefore, exposure levels toxic effects deserve further study discussion. This review aims to summarize current knowledge on their metabolites pregnancy birth outcomes trophoblast cells. A growing number epidemiological studies detected PAH-DNA adducts as well 16 high-priority human showed PAH is associated with adverse outcomes. Trophoblasts important cells involved development function. In vitro have shown either mixtures, benzo(a)pyrene (BaP) or BaP metabolite benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE) affected cell viability, differentiation, migration, invasion through various signaling pathways. Furthermore, similar BPDE could also observed BaP-treated mouse models were related miscarriage. Although data show outcomes, (population studies, animal studies) necessary specific different trophoblasts

Language: Английский

---

Effects of Vertical Transmission of Respiratory Viruses to the Offspring

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: March 14, 2022

Overt and subclinical maternal infections in pregnancy can have multiple significant pathological consequences for the developing fetus, leading to acute perinatal complications and/or chronic disease throughout postnatal life. In this context, current concept of as a state systemic immunosuppression seems oversimplified outdated. Undoubtedly, immune system undergoes complex changes establish maintain tolerance fetus while still protecting from pathogens. addition downregulated immunity, hormonal changes, mechanical adaptation (e.g., restricted lung expansion) make pregnant woman more susceptible respiratory pathogens, such influenza virus, syncytial virus (RSV), severe syndrome coronavirus-2 (SARS-CoV-2). Depending on infectious agent timing infection during gestation, fetal pathology range mild severe, even fatal. Influenza is associated with higher risk morbidity mortality women than general population, and, especially third trimester pregnancy, mothers are at increased hospitalization cardiopulmonary illness, their babies show prematurity, neurological congenital anomalies, admission neonatal intensive care. RSV exposure utero selective deficit, remodeling cholinergic innervation tract, abnormal airway smooth muscle contractility, which may predispose inflammation hyperreactivity, well development dysfunction childhood. Although there limited evidence supporting occurrence vertical transmission SARS-CoV-2, high prevalence prematurity among infected by SARS-CoV-2 suggests alter responses maternal-fetal interface, affecting both mother her fetus. This review aims summarizing about short- long-term intrauterine influenza, RSV, terms pediatric outcomes.

Language: Английский

---

The influence of COVID-19 infection-associated immune response on the female reproductive system

Biology of Reproduction, Journal Year: 2022, Volume and Issue: 108(2), P. 172 - 182

Published: Sept. 29, 2022

Abstract Coronavirus disease 2019 (COVID-19) is a multi-system that has led to pandemic with unprecedented ramifications. The challenged scientists for the past 2 years and brought back previously abandoned research topics. COVID-19 infection causes myriad of symptoms ranging from mild flu-like severe illness requiring hospitalization. Case reports showed multiple systemic effects infection, including acute respiratory distress syndrome, fibrosis, colitis, thyroiditis, demyelinating syndromes, mania, indicating can affect most human body systems. Unsurprisingly, major concern women all over globe whether any long-term on their menstrual cycle, fertility, or pregnancy. Published data have suggested an effect reproductive health, we hypothesize reported adverse are due robust immune reaction against associated cytokine storm. While receptor (angiotensin converting enzyme, ACE2) expressed in ovaries, uterus, vagina, placenta, it plays less important role system. Cytokines glucocorticoids act hypothalamo–pituitary gonadal axis, arachidonic acid pathways, which leads disturbances pregnancy-related events such as preterm labor miscarriages. This hypothesis further supported by apparent lack health females, when storm its dampened, no longer affected.

Language: Английский

---

A placental model of SARS-CoV-2 infection reveals ACE2-dependent susceptibility and differentiation impairment in syncytiotrophoblasts

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(8), P. 1223 - 1234

Published: July 13, 2023

Abstract SARS-CoV-2 infection causes COVID-19. Several clinical reports have linked COVID-19 during pregnancy to negative birth outcomes and placentitis. However, the pathophysiological mechanisms underpinning placentation early are not clear. Here, shed light on this, we used induced trophoblast stem cells generate an in vitro placenta model. We identified that syncytiotrophoblasts could be infected through angiotensin-converting enzyme 2 (ACE2). Using a co-culture model of vertical transmission, confirmed ability virus infect previous endometrial cell infection. further demonstrated transcriptional changes led impairment cellular processes, reduced secretion HCG hormone morphological vital for syncytiotrophoblast function. Furthermore, different antibody strategies antiviral drugs restore these impairments. In summary, established scalable tractable platform study placental types highlighted its use studying protect placenta.

Language: Английский

---

Haemorrhage of human foetal cortex associated with SARS-CoV-2 infection

Brain, Journal Year: 2023, Volume and Issue: 146(3), P. 1175 - 1185

Published: Jan. 16, 2023

Abstract Maternal viral infection and immune response are known to increase the risk of altered development foetal brain. Given ongoing global pandemic coronavirus disease 2019 (COVID-19), investigating impact SARS-CoV-2 on brain health is critical importance. Here, we report presence in first second trimester tissue association with cortical haemorrhages. spike protein was sparsely detected within progenitors neurons cortex itself, but abundant choroid plexus haemorrhagic samples. also placenta, amnion umbilical cord tissues. Cortical haemorrhages were linked a reduction blood vessel integrity an cell infiltration into Our findings indicate that may affect during early gestation highlight need for further study its subsequent neurological development.

Language: Английский

---

SARS-CoV-2 niches in human placenta revealed by spatial transcriptomics

Med, Journal Year: 2023, Volume and Issue: 4(9), P. 612 - 634.e4

Published: July 8, 2023

BackgroundFunctional placental niches are presumed to spatially separate maternal-fetal antigens and restrict the vertical transmission of pathogens. We hypothesized a high-resolution map transcription could provide direct evidence for niche microenvironments with unique functions profiles.MethodsWe utilized Visium Spatial Transcriptomics paired H&E staining generate 17,927 spatial transcriptomes. By integrating these transcriptomes 273,944 single-cell single-nuclei transcriptomes, we generated an atlas composed at least 22 subpopulations in maternal decidua, fetal chorionic villi, chorioamniotic membranes.FindingsComparisons placentae from uninfected healthy controls (n = 4) COVID-19 asymptomatic symptomatic 5) infected participants demonstrated that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection syncytiotrophoblasts occurred both presence absence clinical disease. With transcriptomics, found limit SARS-CoV-2 was 1/7,000 cells, without detectable viral transcripts were unperturbed. In contrast, high transcript levels associated significant upregulation pro-inflammatory cytokines interferon-stimulated genes, altered metallopeptidase signaling (TIMP1), coordinated shifts macrophage polarization, histiocytic intervillositis, perivillous fibrin deposition. Fetal sex differences gene expression responses limited, confirmed mapping limited decidua males.ConclusionsHigh-resolution transcriptomics resolution revealed dynamic coordinate clinically evident disease.FundingThis work supported by NIH (R01HD091731 T32-HD098069), NSF (2208903), Burroughs Welcome Fund March Dimes Preterm Birth Research Initiatives, Career Development Award American Society Gene Cell Therapy.

Language: Английский

---