The Immunopathobiology of SARS-CoV-2 Infection

Patel, Milankumar; Shahjin, Farah; Cohen, Jacob D.; Hasan, Mahmudul; Machhi, Jatin; Chugh, Heerak; Singh, Snigdha; Das, Srijanee; Kulkarni, Tanmay; Herskovitz, Jonathan; Meigs, Douglas D.; Chandra, Ramesh; Hettie, Kenneth S.; Mosley, R. Lee; Kevadiya, Bhavesh D.; Gendelman, Howard Eliot

doi:10.1093/femsre/fuab035

Cited by 13 publications

(12 citation statements)

References 316 publications

(338 reference statements)

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“…Thus, the greatest efficacy of antiviral agents is shown when given early during the disease course. This has already been affirmed for influenza and the human immunodeficiency virus type 1 (HIV-1) infections 5,6 . Indeed, at late stages of SARS-CoV-2 disease, antiviral efficacy wanes and treatment strategy become focused only on modulating the later sequelae of infection.…”

Section: Introductionmentioning

confidence: 84%

Oral antivirals for the prevention and treatment of SARS-CoV-2 infection

Soriano¹,

de-Mendoza²,

Edagwa³

et al. 2022

AIDSRev

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Vaccines and antivirals are the classical weapons deployed to contain, prevent, and treat life-threatening viral illnesses. Specifically, for SARS-CoV-2 infection, vaccines protect against severe COVID-19 disease manifestations and complications. However, waning immunity and emergence of vaccine escape mutants remains a growing threat. This is highlighted by the current surge of the omicron COVID-19 variant. Thus, there is a race to find treatment alternatives. We contend that oral small molecule antivirals that halt SARS-CoV-2 infection are essential. Compared to currently available monoclonal antibodies and remdesivir, where parenteral administration is required, oral antivirals offer treatments in an outpatient setting with dissemination available on a larger scale. In response to this need at 2021's end, regulatory agencies provided emergency use authorization for both molnupiravir and nirmatrelvir. These medicines act on the viral polymerase and protease, respectively. Each is given for 5 days and can reduce disease progression by 30% and 89%, respectively. The advent of additional oral antivirals, the assessment of combination therapies, the formulation of extended-release medications, and their benefit for both early treatment and prophylaxis will likely transform the landscape of the COVID-19 pandemic.

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Section: Introductionmentioning

confidence: 84%

Oral antivirals for the prevention and treatment of SARS-CoV-2 infection

Soriano¹,

de-Mendoza²,

Edagwa³

et al. 2022

AIDSRev

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show abstract

“…Upon infection with SARS-CoV-2 the innate immune system recognizes both pathogen- and damage-associated molecular patterns (PAMPs and DAMPs, respectively) and responds by activating the NLRP3 (NOD-, LRR- and pyrin domain-containing protein 3) inflammasome[54, 55]. Monocytes and macrophages respond to PAMPs and DAMPs by secreting type I IFN and the pro-inflammatory cytokines IL-1, IL-2, IL-6, IL-12, and TNFα[54, 56].…”

Section: Discussionmentioning

confidence: 99%

Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVID

Williams

Martins

Hill

et al. 2022

Preprint

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Up to half of individuals who contract SARS-CoV-2 develop symptoms of long-COVID approximately three months after initial infection. These symptoms are highly variable, and the mechanisms inducing them are yet to be understood. We compared plasma cytokine levels from individuals with long-COVID to healthy individuals and found that those with long-COVID had 100% reductions in circulating levels of interferon gamma and interleukin-8 (IL-8). Additionally, we found significant reductions in levels of IL-6, IL-2, IL-17, IL-13, and IL-4 in individuals with long-COVID. We propose immune exhaustion as the driver of long-COVID, with the complete absence of interferon gamma; and IL-8 preventing the lungs and other organs from healing after acute infection, and reducing the ability to fight off subsequent infections, both contributing to the myriad of symptoms suffered by those with long-COVID.

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“…With the recent successes in multiple phases of ongoing clinical trials, breakthrough siRNA-LNP by Alnylam, and the commercial success of mRNA-LNPs with Pfizer and Moderna COVID vaccines, it seems likely that non-viral therapy will soon be included in the treatment armamentarium for various indications [ 163 ]. Table 5 highlights nucleic acid therapies for cancer that utilize non-viral vectors that are currently in clinical trials, along with their status, cancer type, and target gene.…”

Section: Understanding the Regulatory Landscape And The Translational...mentioning

confidence: 99%

Non-Viral Vectors for Delivery of Nucleic Acid Therapies for Cancer

Kanvinde

Kulkarni

Deodhar

et al. 2022

BioTech

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The research and development of non-viral gene therapy has been extensive over the past decade and has received a big push thanks to the recent successful approval of non-viral nucleic acid therapy products. Despite these developments, nucleic acid therapy applications in cancer have been limited. One of the main causes of this has been the imbalance in development of delivery vectors as compared with sophisticated nucleic acid payloads, such as siRNA, mRNA, etc. This paper reviews non-viral vectors that can be used to deliver nucleic acids for cancer treatment. It discusses various types of vectors and highlights their current applications. Additionally, it discusses a perspective on the current regulatory landscape to facilitate the commercial translation of gene therapy.

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The Immunopathobiology of SARS-CoV-2 Infection

Cited by 13 publications

References 316 publications

Oral antivirals for the prevention and treatment of SARS-CoV-2 infection

Oral antivirals for the prevention and treatment of SARS-CoV-2 infection

Plasma cytokine levels reveal deficiencies in IL-8 and gamma interferon in Long-COVID

Non-Viral Vectors for Delivery of Nucleic Acid Therapies for Cancer

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