Human Nasal Epithelial Cells Sustain Persistent SARS-CoV-2 Infection
            <i>In Vitro</i>
            , despite Eliciting a Prolonged Antiviral Response

Gamage, Akshamal M; Tan, Kai Sen; Chan, Wharton; Lew, Zhe Zhang Ryan; Liu, Jing; Tan, Chee Wah; Rajagopalan, Deepa; Lin, Quy Xiao Xuan; Tan, Le Min; Venkatesh, Prasanna Nori; Ong, Yew Kwang; Thong, Mark; Lin, Raymond Tzer Pin; Prabhakar, Shyam; Wang, De Yun; Wang, Lin‐Fa

doi:10.1128/mbio.03436-21

Cited by 16 publications

(16 citation statements)

References 54 publications

(66 reference statements)

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“…In the case of SARS-CoV-2, it has been recently shown that the virus can establish a long-term, non-productive persistent infection in different types of cells [95,96].…”

Section: Mechanisms Of Pathogenesis: Virus Persistencementioning

confidence: 99%

Long Covid: where we stand and challenges ahead

et al. 2022

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Post-acute sequelae of SARS-CoV-2 (PASC), also known as Post-Covid Syndrome, and colloquially as Long Covid, has been defined as a constellation of signs and symptoms which persist for weeks or months after the initial SARS-CoV-2 infection. PASC affects a wide range of diverse organs and systems, with manifestations involving lungs, brain, the cardiovascular system and other organs such as kidney and the neuromuscular system. The pathogenesis of PASC is complex and multifactorial. Evidence suggests that seeding and persistence of SARS-CoV-2 in different organs, reactivation, and response to unrelated viruses such as EBV, autoimmunity, and uncontrolled inflammation are major drivers of PASC. The relative importance of pathogenetic pathways may differ in different tissue and organ contexts. Evidence suggests that vaccination, in addition to protecting against disease, reduces PASC after breakthrough infection although its actual impact remains to be defined. PASC represents a formidable challenge for health care systems and dissecting pathogenetic mechanisms may pave the way to targeted preventive and therapeutic approaches.

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“…In the case of SARS-CoV-2, it has been recently shown that the virus can establish a long-term, non-productive persistent infection in different types of cells [95,96].…”

Section: Mechanisms Of Pathogenesis: Virus Persistencementioning

confidence: 99%

Long Covid: where we stand and challenges ahead

et al. 2022

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“…Nasal ciliated cells are easily infected due to their high ACE-2 receptor expression and sustain the bulk of initial virus production in vivo ( Ahn et al, 2021 ). In vitro studies have shown that nasal epithelial cells can maintain high levels of viral replication for several weeks despite activation of IFN-α–mediated genes ( Gamage et al, 2022 ), since SARS-CoV-2 can disrupt multiple intracellular antiviral immunity pathways ( Banerjee et al, 2020 ) and block the antiviral efficacy of IFN-α ( Xia et al, 2020 ). Resident T cells that quickly recognize virus-producing infected cells in the nasal cavity can play an important role in rapidly containing and eliminating SARS-CoV-2 infection ( Ishii et al, 2022 ; Zhao et al, 2016 ), especially after the emergence of Omicron variants of concern that elude the preventive efficacy of the neutralizing antibodies induced by vaccination ( Cao et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

SARS-CoV-2 breakthrough infection in vaccinees induces virus-specific nasal-resident CD8+ and CD4+ T cells of broad specificity

Lim

Tan

Bert

et al. 2022

Journal of Experimental Medicine

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Rapid recognition of SARS-CoV-2–infected cells by resident T cells in the upper airway might provide an important layer of protection against COVID-19. Whether parenteral SARS-CoV-2 vaccination or infection induces nasal-resident T cells specific for distinct SARS-CoV-2 proteins is unknown. We isolated T cells from the nasal mucosa of COVID-19 vaccinees who either experienced SARS-CoV-2 infection after vaccination (n = 34) or not (n = 16) and analyzed their phenotype, SARS-CoV-2 specificity, function, and persistence. Nasal-resident SARS-CoV-2–specific CD8+ and CD4+ T cells were detected almost exclusively in vaccinees who experienced SARS-CoV-2 breakthrough infection. Importantly, the Spike-specific T cells primed by vaccination did not suppress the induction of T cells specific for other SARS-CoV-2 proteins. The nasal-resident T cell responses persisted for ≥140 d, with minimal sign of waning. These data highlight the importance of viral nasal challenge in the formation of SARS-CoV-2–specific antiviral immunity at the site of primary infection and further define the immunological features of SARS-CoV-2 hybrid immunity.

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“…For example, studies have shown infection of SARS-CoV-2 in airway or lung organoids greatly contribute to the understanding of viral pathogenesis in the respiratory tract and identify cellular tropisms ( Gamage et al, 2020 ; Vanderheiden et al, 2020 ; Mallapaty, 2021 ; Mulay et al, 2021 ). Furthermore, single cell analyses could be carried out to identify changes in different cell types ( Gamage et al, 2022 ). This can also be extended further to organoids from other organs to recapitulate systemic or organ tropism of SARS-CoV-2 and other novel viruses ( Giobbe et al, 2021 ; Troisi et al, 2021 ).…”

Section: Recommendation Of Approach For the Identification And Elucid...mentioning

confidence: 99%

Uncovering Novel Viral Innate Immune Evasion Strategies: What Has SARS-CoV-2 Taught Us?

et al. 2022

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The ongoing SARS-CoV-2 pandemic has tested the capabilities of public health and scientific community. Since the dawn of the twenty-first century, viruses have caused several outbreaks, with coronaviruses being responsible for 2: SARS-CoV in 2007 and MERS-CoV in 2013. As the border between wildlife and the urban population continue to shrink, it is highly likely that zoonotic viruses may emerge more frequently. Furthermore, it has been shown repeatedly that these viruses are able to efficiently evade the innate immune system through various strategies. The strong and abundant antiviral innate immunity evasion strategies shown by SARS-CoV-2 has laid out shortcomings in our approach to quickly identify and modulate these mechanisms. It is thus imperative that there be a systematic framework for the study of the immune evasion strategies of these viruses, to guide development of therapeutics and curtail transmission. In this review, we first provide a brief overview of general viral evasion strategies against the innate immune system. Then, we utilize SARS-CoV-2 as a case study to highlight the methods used to identify the mechanisms of innate immune evasion, and pinpoint the shortcomings in the current paradigm with its focus on overexpression and protein-protein interactions. Finally, we provide a recommendation for future work to unravel viral innate immune evasion strategies and suitable methods to aid in the study of virus-host interactions. The insights provided from this review may then be applied to other viruses with outbreak potential to remain ahead in the arms race against viral diseases.

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Human Nasal Epithelial Cells Sustain Persistent SARS-CoV-2 Infection In Vitro , despite Eliciting a Prolonged Antiviral Response

Cited by 16 publications

References 54 publications

Long Covid: where we stand and challenges ahead

Long Covid: where we stand and challenges ahead

SARS-CoV-2 breakthrough infection in vaccinees induces virus-specific nasal-resident CD8+ and CD4+ T cells of broad specificity

Uncovering Novel Viral Innate Immune Evasion Strategies: What Has SARS-CoV-2 Taught Us?

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