Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19

Lowery, Shea A.; Sariol, Alan; Perlman, Stanley

doi:10.1016/j.chom.2021.05.004

Cited by 220 publications

(200 citation statements)

References 94 publications

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“…However, heightened viral loads were also observed in IFNAR knockout mice and STAT2 knockout hamsters, illustrating the fact that type I IFNs can have beneficial and deleterious effects most likely depending on the stage of SARS-CoV-2 infection [ 24 , 27 ]. SARS-CoV-2 expresses a broad array of type I IFN signaling antagonists that likely account for the low sensitivity observed in post-infection type I IFN treatments in cell culture ( S7 Fig ), and for the lack of beneficial effects observed in this study when type I IFN treatment was initiated at the onset of symptoms three days post-infection [ 4 , 28 – 31 ].…”

Section: Discussionmentioning

confidence: 99%

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

et al. 2021

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Impaired type I interferons (IFNs) production or signaling have been associated with severe COVID-19, further promoting the evaluation of recombinant type I IFNs as therapeutics against SARS-CoV-2 infection. In the Syrian hamster model, we show that intranasal administration of IFN-α starting one day pre-infection or one day post-infection limited weight loss and decreased viral lung titers. By contrast, intranasal administration of IFN-α starting at the onset of symptoms three days post-infection had no impact on the clinical course of SARS-CoV-2 infection. Our results provide evidence that early type I IFN treatment is beneficial, while late interventions are ineffective, although not associated with signs of enhanced disease.

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Section: Discussionmentioning

confidence: 99%

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

et al. 2021

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“…The current data suggest that patients with severe COVID-19 may have postponed induction or no induction of IFN-I and -III [12]. In the absence of IFN-I or IFN-III, SARS-CoV-2 may replicate with high titers, leading to an exaggerated inflammatory response [9]. Figure 1.…”

Section: Innate Immunity To Sars-cov-2mentioning

confidence: 80%

“…It is well known that COVID-19 can cause serious illness, which is characterized by significant immune dysfunction, stimulated by a vigorous but dysregulated innate immune response, along with a worse adaptive response, as shown in Figure 1 [9]. In SARS-CoV infection, the delayed response of type I interferon (IFN-I) results in the rapid replication of the virus, an abnormal increase in cytokines, and an abnormal response to chemokines, resulting in high mortality.…”

Section: Innate Immunity To Sars-cov-2mentioning

confidence: 99%

Putative Role of Vitamin D for COVID-19 Vaccination

Chiu

Zheng

et al. 2021

IJMS

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Severe acute respiratory syndrome coronavirus 2 is a new, highly pathogenic virus that has recently elicited a global pandemic called the 2019 coronavirus disease (COVID-19). COVID-19 is characterized by significant immune dysfunction, which is caused by strong but unregulated innate immunity with depressed adaptive immunity. Reduced and delayed responses to interferons (IFN-I/IFN-III) can increase the synthesis of proinflammatory cytokines and extensive immune cell infiltration into the airways, leading to pulmonary disease. The development of effective treatments for severe COVID-19 patients relies on our knowledge of the pathophysiological components of this imbalanced innate immune response. Strategies to address innate response factors will be essential. Significant efforts are currently underway to develop vaccines against SARS-CoV-2. COVID-19 vaccines, such as inactivated DNA, mRNA, and protein subunit vaccines, have already been applied in clinical use. Various vaccines display different levels of effectiveness, and it is important to continue to optimize and update their composition in order to increase their effectiveness. However, due to the continuous emergence of variant viruses, improving the immunity of the general public may also increase the effectiveness of the vaccines. Many observational studies have demonstrated that serum levels of vitamin D are inversely correlated with the incidence or severity of COVID-19. Extensive evidence has shown that vitamin D supplementation could be vital in mitigating the progression of COVID-19 to reduce its severity. Vitamin D defends against SARS-CoV-2 through a complex mechanism through interactions between the modulation of innate and adaptive immune reactions, ACE2 expression, and inhibition of the renin-angiotensin system (RAS). However, it remains unclear whether Vit-D also plays an important role in the effectiveness of different COVID-19 vaccines. Based on analysis of the molecular mechanism involved, we speculated that vit-D, via various immune signaling pathways, plays a complementary role in the development of vaccine efficacy.

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“…Indeed, an elevated interferon response was detected in the lower respiratory tracts of severely infected and deceased patients (5,18,19), with the lung suffering the most damage (20). Innate immune cell-types, such as neutrophils, macrophages and natural killer cells, which are thought not to contribute significantly to clearance, may nonetheless worsen the damage (6,21). Prolonged disease, where viral load could be detected in patients over extended durations-up to 66 days on average in some cohorts-has been reported (22)(23)(24).…”

Section: Introductionmentioning

confidence: 99%

The relative strength and timing of innate immune and CD8 T-cell responses underlie the heterogeneous outcomes of SARS-CoV-2 infection

Chatterjee

Sandhu

Dixit

2021

Preprint

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SARS-CoV-2 infection results in highly heterogeneous outcomes, from cure without symptoms to acute respiratory distress and death. While immunological correlates of disease severity have been identified, how they act together to determine the outcomes is unknown. Here, using a new mathematical model of within-host SARS-CoV-2 infection, we analyze diverse clinical datasets and predict that a subtle interplay between innate and CD8 T-cell responses underlies disease heterogeneity. Our model considers essential features of these immune arms and immunopathology from cytokines and effector cells. Model predictions provided excellent fits to patient data and, by varying the strength and timing of the immune arms, quantitatively recapitulated viral load changes in mild, moderate, and severe disease, and death. Additionally, they explained several confounding observations, including viral recrudescence after symptom loss, prolonged viral positivity before cure, and mortality despite declining viral loads. Together, a robust conceptual understanding of COVID-19 outcomes emerges, bearing implications for interventions.

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Innate immune and inflammatory responses to SARS-CoV-2: Implications for COVID-19

Cited by 220 publications

References 94 publications

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Intranasal type I interferon treatment is beneficial only when administered before clinical signs onset in the SARS-CoV-2 hamster model

Putative Role of Vitamin D for COVID-19 Vaccination

The relative strength and timing of innate immune and CD8 T-cell responses underlie the heterogeneous outcomes of SARS-CoV-2 infection

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