Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract

Flerlage, Tim; Boyd, David F.; Meliopoulos, Victoria A.; Thomas, Paul G.; Schultz‐Cherry, Stacey

doi:10.1038/s41579-021-00542-7

Cited by 272 publications

(282 citation statements)

References 246 publications

(267 reference statements)

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“…Similarly, while differences in target cells and control of viral replication are recognised between COVID-19 and influenza, shared immune responses and mechanisms are also reported (Flerlage et al, 2021). Our data builds on previous blood immune signatures (Lee et al, 2020; Mudd et al, 2020; Zhu et al, 2020) to gain cellular and proteomic insights into the more severe form of these infections.…”

Section: Discussionmentioning

confidence: 99%

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

Ahern

Ainsworth

et al. 2021

Preprint

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Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete understanding of potentially druggable immune mediators of disease. To advance this, we present a comprehensive multi-omic blood atlas in patients with varying COVID-19 severity and compare with influenza, sepsis and healthy volunteers. We identify immune signatures and correlates of host response. Hallmarks of disease severity revealed cells, their inflammatory mediators and networks as potential therapeutic targets, including progenitor cells and specific myeloid and lymphocyte subsets, features of the immune repertoire, acute phase response, metabolism and coagulation. Persisting immune activation involving AP-1/p38MAPK was a specific feature of COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive of severity and outcome. Tensor and matrix decomposition of the overall dataset revealed feature groupings linked with disease severity and specificity. Our systems-based integrative approach and blood atlas will inform future drug development, clinical trial design and personalised medicine approaches for COVID-19.

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Section: Discussionmentioning

confidence: 99%

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

Ahern

Ainsworth

et al. 2021

Preprint

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“…Here we describe the natural history of SCV-2 RNA testing among all patients who tested positive multiple times at our institution during a seven-month period, revealing complex patterns of intermittent positivity and variable decline of viral RNA detected via Ct values throughout different stages of infection. Although factors observed among prolonged positive patients were similar to those described in patients with severe COVID disease, 47% of prolonged positive patients were not ill enough to require hospitalization, underscoring that a large subset of healthier patients may experience prolonged RNA positivity (1,12). Intriguingly, 11 patients without prolonged positivity demonstrated greater amounts of RNA detected at their terminal versus initial SCV-2 positive test, suggesting variable shedding even early in their infection (2).…”

Section: Discussionmentioning

confidence: 64%

Longitudinal SARS-CoV-2 testing is punctuated by intermittent positivity and variable rates of cycle-threshold decline

Hawken

Sellers

Smedberg

et al. 2021

Preprint

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The COVID-19 pandemic is complicated by cases of vaccine-breakthrough, re-infection, and widespread transmission of variants of concern (VOC). Consequently, the need to interpret longitudinal positive SARS-CoV-2 (SCV-2) tests is crucial in guiding clinical decisions regarding infection control precautions and treatment. Although quantitative tests are not routinely used diagnostically, standard diagnostic RT-PCR tests yield Ct values that are inversely correlated with RNA quantity. In this study, we performed a retrospective review of 72,217 SCV-2 PCR positive tests and identified 264 patients with longitudinal positivity prior to vaccination and VOC circulation. Patients with longitudinal positivity fell into two categories: short-term (207, 78%) or prolonged (57, 22%) positivity, defined as <= 28 (range 1-28, median 16) days and >28 (range 29- 152, median 41) days, respectively. In general, Ct values declined over time in both groups; however, 11 short-term positive patients had greater amounts of RNA detected at their terminal test compared to the first positive, and 5 patients had RNA detected at Ct < 35 at least 40 days after initial infection. Oscillating positive and negative results occurred in both groups, although oscillation was seen three times more frequently in prolonged-positive patients. Patients with prolonged positivity had diverse clinical characteristics but were often critically ill and were discharged to high-level care or deceased (22%). Overall, this study demonstrates that caution must be emphasized when interpreting Ct values as a proxy for infectivity, predictor of severity, or a guide for patient care decisions in the absence of additional clinical context.

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“…In a matter of months, SARS-CoV2 infection completely altered societal norms, stagnated economies, and overwhelmed healthcare infrastructures across the globe. Annual influenza epidemics cause up to 500,000 deaths globally and there exists an ever-present threat of the emergence of a pandemic influenza strain in the future [ 140 ]. Vaccination still remains the best approach to mitigate disease burden caused by respiratory viral infection.…”

Section: T Rh Cells As a Potential Target For Mucosal Vaccine Against Respiratory Viral Infectionmentioning

confidence: 99%

Co-Ordination of Mucosal B Cell and CD8 T Cell Memory by Tissue-Resident CD4 Helper T Cells

Son

Sun

2021

Cells

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Adaptive cellular immunity plays a major role in clearing microbial invasion of mucosal tissues in mammals. Following the clearance of primary pathogens, memory lymphocytes are established both systemically and locally at pathogen entry sites. Recently, resident memory CD8 T and B cells (TRM and BRM respectively), which are parked mainly in non-lymphoid mucosal tissues, were characterized and demonstrated to be essential for protection against secondary microbial invasion. Here we reviewed the current understanding of the cellular and molecular cues regulating CD8 TRM and BRM development, maintenance and function. We focused particularly on elucidating the role of a novel tissue-resident helper T (TRH) cell population in assisting TRM and BRM responses in the respiratory mucosa following viral infection. Finally, we argue that the promotion of TRH responses by future mucosal vaccines would be key to the development of successful universal influenza or coronavirus vaccines, providing long-lasting immunity against a broad spectrum of viral strains.

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Influenza virus and SARS-CoV-2: pathogenesis and host responses in the respiratory tract

Cited by 272 publications

References 246 publications

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

A blood atlas of COVID-19 defines hallmarks of disease severity and specificity

Longitudinal SARS-CoV-2 testing is punctuated by intermittent positivity and variable rates of cycle-threshold decline

Co-Ordination of Mucosal B Cell and CD8 T Cell Memory by Tissue-Resident CD4 Helper T Cells

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