Conjunctival epithelial cells resist productive SARS-CoV-2 infection DOI Creative Commons
Robert M. Jackson, Catherine F. Hatton, Jarmila Stremenova Spegarova

et al.

Stem Cell Reports, Journal Year: 2022, Volume and Issue: 17(7), P. 1699 - 1713

Published: June 23, 2022

Conjunctival epithelial cells, which express viral-entry receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine type (TMPRSS2), constitute the largest exposed epithelium of ocular surface tissue may represent a relevant route. To address this question, we generated an organotypic air-liquid-interface model conjunctival epithelium, composed basal, suprabasal, superficial fibroblasts, could be maintained successfully up to day 75 differentiation. Using single-cell RNA sequencing (RNA-seq), with complementary imaging virological assays, observed that while all cell types were permissive severe acute respiratory syndrome coronavirus (SARS-CoV-2) genome expression, productive infection did not ensue. The early innate immune response SARS-CoV-2 in cells was characterised by robust autocrine paracrine NF-κB activity, without activation antiviral interferon signalling. Collectively, these data enrich our understanding at human surface, potential implications for design preventive strategies transplantation.

Language: Английский

SARS-CoV-2 infection and persistence in the human body and brain at autopsy DOI Open Access
Sydney Stein, Sabrina Ramelli, Alison Grazioli

et al.

Nature, Journal Year: 2022, Volume and Issue: 612(7941), P. 758 - 763

Published: Dec. 14, 2022

Language: Английский

Citations

679
SARS-CoV-2 infection and persistence throughout the human body and brain DOI Creative Commons
Daniel S. Chertow, Sydney Stein, Sabrina Ramelli

et al.

Research Square (Research Square), Journal Year: 2021, Volume and Issue: unknown

Published: Dec. 20, 2021

Abstract COVID-19 is known to cause multi-organ dysfunction 1-3 in acute infection, with prolonged symptoms experienced by some patients, termed Post-Acute Sequelae of SARS-CoV-2 (PASC) 4-5 . However, the burden infection outside respiratory tract and time viral clearance not well characterized, particularly brain 3,6-14 We performed complete autopsies on 44 patients map quantify distribution, replication, cell-type specificity across human body, including brain, from through over seven months following symptom onset. show that widely distributed, even among who died asymptomatic mild COVID-19, virus replication present multiple extrapulmonary tissues early infection. Further, we detected RNA anatomic sites, regions throughout for up 230 days Despite extensive distribution observed a paucity inflammation or direct cytopathology lungs. Our data prove causes systemic can persist body months.

Language: Английский

Citations

118
Structural and non-structural proteins in SARS-CoV-2: potential aspects to COVID-19 treatment or prevention of progression of related diseases DOI Creative Commons

Sareh Kakavandi,

Iman Zare, Maryam Vaezjalali

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: May 15, 2023

Coronavirus disease 2019 (COVID-19) is caused by a new member of the Coronaviridae family known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). There are structural and non-structural proteins (NSPs) in genome this virus. S, M, H, E proteins, NSPs include accessory replicase proteins. The NSP components SARS-CoV-2 play an important role its infectivity, some them may be pathogenesis chronic diseases, including cancer, coagulation disorders, neurodegenerative cardiovascular diseases. interact with targets such angiotensin-converting enzyme (ACE2) receptor. In addition, can stimulate pathological intracellular signaling pathways triggering transcription factor hypoxia-inducible factor-1 (HIF-1), neuropilin-1 (NRP-1), CD147, Eph receptors, which roles progression diseases like Alzheimer's disease, epilepsy, multiple sclerosis, cancers glioblastoma, lung malignancies, leukemias. Several compounds polyphenols, doxazosin, baricitinib, ruxolitinib could inhibit these interactions. It has been demonstrated that spike protein stronger affinity for human ACE2 than SARS-CoV, leading current study to hypothesize newly produced variant Omicron receptor-binding domain (RBD) binds more strongly primary strain. SARS Middle East (MERS) viruses against have become resistant previous vaccines. Therefore, review recent studies performance vaccines their effects on COVID-19 related vital need deal conditions. This examines potential initiation it anticipated serve effective vaccine or treatment Video Abstract.

Language: Английский

Citations

68
Pathophysiology of infection with SARS‐CoV‐2—What is known and what remains a mystery DOI Open Access
Siddharth Sridhar, John Nicholls

Respirology, Journal Year: 2021, Volume and Issue: 26(7), P. 652 - 665

Published: May 26, 2021

Abstract Coronavirus disease 2019 (COVID‐19), caused by coronavirus severe acute respiratory syndrome 2 (SARS‐CoV‐2), has extensive disruption and mortality since its recent emergence. Concomitantly, there been a race to understand the virus pathophysiology. The clinical manifestations of COVID‐19 are manifold not restricted tract. Extrapulmonary involving gastrointestinal tract, hepatobiliary system, cardiovascular renal systems have widely reported. However, pathophysiology many these is controversial with questionable support for direct viral invasion an abundance alternative explanations such as pre‐existing medical conditions critical illness. Prior research on SARS‐Co‐V NL63 was rapidly leveraged identify angiotensin‐converting enzyme (ACE2) receptor key cell surface SARS‐CoV‐2. distribution ACE2 used starting point estimating vulnerability various tissue types SARS‐CoV‐2 infection. Sophisticated organoid animal models demonstrate infectivity extrapulmonary tissues in vitro, but relevance findings remains uncertain. Clinical autopsy studies typically small inevitably biased towards patients prolonged hospitalization. Technical issues delay between time death autopsy, use inappropriate antibodies paraffin‐embedded sections misinterpretation cellular structures particles electron micrograph images additional problems encountered extant literature. Given that likely circulate permanently human populations, no doubt further work required clarify pathobiology COVID‐19.

Language: Английский

Citations

59
Importance of Magnesium Status in COVID-19 DOI Creative Commons
Fernando Guerrero‐Romero, Oliver Micke, Luis E. Simental‐Mendía

et al.

Biology, Journal Year: 2023, Volume and Issue: 12(5), P. 735 - 735

Published: May 18, 2023

A large amount of published research points to the interesting concept (hypothesis) that magnesium (Mg) status may have relevance for outcome COVID-19 and Mg could be protective during COVID disease course. As an essential element, plays basic biochemical, cellular, physiological roles required cardiovascular, immunological, respiratory, neurological functions. Both low serum dietary been associated with severity outcomes, including mortality; both are also risk factors such as older age, obesity, type 2 diabetes, kidney disease, cardiovascular hypertension, asthma. In addition, populations high rates mortality hospitalization tend consume diets in modern processed foods, which generally Mg. this review, we review describe consider possible impact on showing (1) between 2.19 2.26 mg/dL intakes > 329 mg/day course (2) inhaled improve oxygenation hypoxic patients. spite promise, oral has thus far studied only combination other nutrients. deficiency is involved occurrence aggravation neuropsychiatric complications COVID-19, memory loss, cognition, loss taste smell, ataxia, confusion, dizziness, headache. Potential zinc and/or useful increasing drug therapy effectiveness or reducing adverse effect anti-COVID-19 drugs reviewed. Oral trials patients warranted.

Language: Английский

Citations

21
On the Critical Role of Human Feces and Public Toilets in the Transmission of COVID-19: Evidence from China DOI Open Access

Wang Qiuyun,

Lu Liu

Sustainable Cities and Society, Journal Year: 2021, Volume and Issue: 75, P. 103350 - 103350

Published: Sept. 11, 2021

Language: Английский

Citations

38
Changes in SARS-CoV-2 viral load and titers over time in SARS-CoV-2-infected human corpses DOI Creative Commons
Sayaka Nagasawa, Yuichiro Hirata, Shô Miyamoto

et al.

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(3), P. e0287068 - e0287068

Published: March 27, 2024

High viral titers of infectious severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been detected in human corpses long after death. However, little is known about the kinetics SARS-CoV-2 corpses. In this case series study, we investigated postmortem by collecting nasopharyngeal swab samples at multiple time points from six SARS-CoV-2-infected patients their RNA was quantitative reverse transcription-polymerase chain reaction collected all deceased patients. A culture showed presence virus one patient up to 12 days Notably, had a shorter symptom onset death than other patients, and autopsy pathological findings consistent with replication upper tract. Therefore, died during shedding phase, amount corpse did not decrease over date (12 death). The study indicate that persistence can vary among individuals may be associated stage disease These important results complement many previously reported on infectivity postmortem.

Language: Английский

Citations

5
Complications Post-COVID-19 and Risk Factors among Patients after Six Months of a SARS-CoV-2 Infection: A Population-Based Prospective Cohort Study DOI Creative Commons

Salvador Domènech-Montoliu,

Joan Puig‐Barberà,

María Rosario Pac-Sa

et al.

Epidemiologia, Journal Year: 2022, Volume and Issue: 3(1), P. 49 - 67

Published: Feb. 10, 2022

In October 2020, we conducted a population-based prospective cohort study to determine post-COVID-19 complications, recovery, return usual health, and associated risk factors in 536 cases of COVID-19 outbreak Borriana (Spain) by administering an epidemiological questionnaire via phone interviews. A total 484 patients participated (90.3%), age mean 37.2 ± 17.1 years, 301 females (62.2%). Mild illness was the most common manifestation. After six months, 160 (33.1%) suffered at least one complication post-COVID-19, 47 (29.4%) them sought medical assistance. The frequent persistent symptoms were hair loss, fatigue, loss smell or taste, headache. Risk with female sex (adjusted relative risk, [aRR] = 1.93 95% confidence interval [CI] 1.41–2.65), 35 years above (aRR 1.50 CI 1.14–1.99), B blood group 1.51 1.04–2.16), current smoker (RR 1.61 1.02–2.54), exposure 2.13 1.11–4.09). Male sex, younger than low exposures better recovery health. third presented compatible long-COVID-19 syndrome. conclusion, active follow-up must be implemented.

Language: Английский

Citations

22
Visualization of Early RNA Replication Kinetics of SARS-CoV-2 by Using Single Molecule RNA-FISH Combined with Immunofluorescence DOI Creative Commons
Rajiv Pathak, Carolina Eliscovich, Ignacio Mena

et al.

Viruses, Journal Year: 2024, Volume and Issue: 16(2), P. 262 - 262

Published: Feb. 7, 2024

SARS-CoV-2 infection remains a global burden. Despite intensive research, the mechanism and dynamics of early viral replication are not completely understood, such as kinetics formation genomic RNA (gRNA), sub-genomic (sgRNA), centers/organelles (ROs). We employed single-molecule RNA-fluorescence in situ hybridization (smRNA-FISH) to simultaneously detect gRNA sgRNA immunofluorescence nsp3 protein, marker for RO, carried out time-course analysis. found that single molecules visible within cytoplasm at 30 min post (p.i.). Starting from 2 h p.i., most existed clusters/speckles, some which were surrounded by sgRNA. These speckles associated with protein starting 3 indicating these precursors ROs. Furthermore, was asynchronous, cells all stages any given time point. Our probes detected variants concern, also suggested BA.1 strain exhibited slower rate than WA1 strain. results provide insights into post-entry events, will facilitate identification new therapeutic targets early-stage combat COVID-19.

Language: Английский

Citations

4
PhosBERT: A self-supervised learning model for identifying phosphorylation sites in SARS-CoV-2-infected human cells DOI
Yong Li,

Ru Gao,

Shan Liu

et al.

Methods, Journal Year: 2024, Volume and Issue: 230, P. 140 - 146

Published: Aug. 23, 2024

Language: Английский

Citations

4