SARS-CoV-2 variants’-Alpha, Delta, and Omicron D614G and P681R/H mutations impact virus entry, fusion, and infectivity

Khatri, Ritika; Siddqui, Gazala; Sadhu, Srikanth; Maithil, Vikas; Vishwakarma, Preeti; Lohiya, Bharat; Goswami, Abhishek; Ahmed, Shubbir; Awasthi, Amit; Samal, Sweety

doi:10.21203/rs.3.rs-1310197/v1

Cited by 3 publications

(3 citation statements)

References 37 publications

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“…(38). VOCs have a better ability to survive and evade host defense mechanisms than the original virus (39). The most striking difference between the Omicron variant and previous variants was that the symptoms of OD were significantly less prevalent during Omicron's prevalence.…”

Section: Target Cells Of Sars-cov-2 In the Nasal Epitheliummentioning

confidence: 95%

The immune mechanism of the nasal epithelium in COVID-19–related olfactory dysfunction

Chen

Wang

2023

Front. Immunol.

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During the first waves of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, olfactory dysfunction (OD) was reported as a frequent clinical sign. The nasal epithelium is one of the front-line protections against viral infections, and the immune responses of the nasal mucosa may be associated with OD. Two mechanisms underlying OD occurrence in COVID-19 have been proposed: the infection of sustentacular cells and the inflammatory reaction of the nasal epithelium. The former triggers OD and the latter likely prolongs OD. These two alternative mechanisms may act in parallel; the infection of sustentacular cells is more important for OD occurrence because sustentacular cells are more likely to be the entry point of SARS-CoV-2 than olfactory neurons and more susceptible to early injury. Furthermore, sustentacular cells abundantly express transmembrane protease, serine 2 (TMPRSS2) and play a major role in the olfactory epithelium. OD occurrence in COVID-19 has revealed crucial roles of sustentacular cells. This review aims to elucidate how immune responses of the nasal epithelium contribute to COVID-19–related OD. Understanding the underlying immune mechanisms of the nasal epithelium in OD may aid in the development of improved medical treatments for COVID-19–related OD.

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Section: Target Cells Of Sars-cov-2 In the Nasal Epitheliummentioning

confidence: 95%

The immune mechanism of the nasal epithelium in COVID-19–related olfactory dysfunction

Chen

Wang

2023

Front. Immunol.

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“…A recent study conducted by Khatri et al (2022) showed that the Delta synthetic mutant exhibited a considerable increase in pseudovirus entry, fusion, and infectivity [252]. A leucine-to-arginine substitution at position 452, which is present in Delta but not in the Omicron variant, is known to boost affinity for ACE2 receptors located on the surface of a variety of human cells, including lung cells [6].…”

Section: Affinity To Angiotensin-converting Enzyme 2 (Ace2) Receptorsmentioning

confidence: 99%

“…According to Khatri et al (2022), in the absence of TMPRSS2, Omicron may enter cells easily via ACE2-dependent endocytosis and is extremely prone to cathepsin L inhibitors, such as E64d [252]. Higher transmissibility is expected if the overlapping Omicron mutations maintain their known effects, especially because of mutations near the furin cleavage site [331].…”

Section: Affinity To Angiotensin-converting Enzyme 2 (Ace2) Receptorsmentioning

confidence: 99%

Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences

Hoteit

Yassine

2022

Vaccines

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a virus that belongs to the coronavirus family and is the cause of coronavirus disease 2019 (COVID-19). As of May 2022, it had caused more than 500 million infections and more than 6 million deaths worldwide. Several vaccines have been produced and tested over the last two years. The SARS-CoV-2 virus, on the other hand, has mutated over time, resulting in genetic variation in the population of circulating variants during the COVID-19 pandemic. It has also shown immune-evading characteristics, suggesting that vaccinations against these variants could be potentially ineffective. The purpose of this review article is to investigate the key variants of concern (VOCs) and mutations of the virus driving the current pandemic, as well as to explore the transmission rates of SARS-CoV-2 VOCs in relation to epidemiological factors and to compare the virus’s transmission rate to that of prior coronaviruses. We examined and provided key information on SARS-CoV-2 VOCs in this study, including their transmissibility, infectivity rate, disease severity, affinity for angiotensin-converting enzyme 2 (ACE2) receptors, viral load, reproduction number, vaccination effectiveness, and vaccine breakthrough.

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Plasma Adsorption with the MTx.100 Column in Critically Ill COVID-19 Patients: A Prospective Study and Propensity Score Analysis

Choi,

De Simone,

Webb

et al. 2024

J Intensive Care Med

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Background Early in the COVID-19 pandemic, patients with severe disease admitted to the intensive care unit (ICU) had a high incidence of mortality. We aimed to investigate whether plasma adsorption with the MTx.100 Column could improve survival. Methods We performed a prospective, single-arm, multicenter, Emergency Use Authorization (EUA) trial in patients admitted to the ICU with severe COVID-19 who were worsening despite standard therapy. The primary outcome was all-cause mortality on day 28. Outcomes were analyzed using both a pre-specified performance goal (PG), and a propensity score-matched (PSM) analysis from the highest enrolling center, in which patients treated with the standard of care (SOC) plus the MTx.100 Column (n = 70) were compared to a contemporaneous cohort treated at the same center with SOC only (n = 244). Findings Between May 21, 2020, and November 2, 2021, 107 patients with severe COVID-19 (mean age 58.1) at 7 US centers were enrolled and had at least one plasma adsorption treatment initiated. All-cause mortality on day 28 was 37.4% (40/107), an improvement over the prespecified PG (88.1%, p < 0.0001). There were no serious adverse events attributable to the MTx.100 Column or plasmapheresis. Improvements in most metabolic and inflammatory markers were also noted. The PSM analysis showed that survival odds were three times higher for MTx.100 Column-treated patients (95% CI: 1.56-5.88) than for those treated with SOC only. Interpretation The MTx.100 Column treatment in severe COVID-19 resulted in a lower mortality than SOC by both pre-specified PG and PSM analysis. Trial Registration clinicaltrials.gov (NCT04358003).

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SARS-CoV-2 variants’-Alpha, Delta, and Omicron D614G and P681R/H mutations impact virus entry, fusion, and infectivity

Cited by 3 publications

References 37 publications

The immune mechanism of the nasal epithelium in COVID-19–related olfactory dysfunction

The immune mechanism of the nasal epithelium in COVID-19–related olfactory dysfunction

Biological Properties of SARS-CoV-2 Variants: Epidemiological Impact and Clinical Consequences

Plasma Adsorption with the MTx.100 Column in Critically Ill COVID-19 Patients: A Prospective Study and Propensity Score Analysis

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