Immunofibrotic drivers of impaired lung function in postacute sequelae of SARS-CoV-2 infection

Chun, Hyung J.; Coutavas, Elias; Pine, Alexander B; Lee, Alfred Ian; Yu, Vanessa L; Shallow, Marcus; Giovacchini, Coral; Mathews, Anne M.; Stephenson, B. M.; Que, Loretta G.; Lee, Patty J; Kraft, Bryan

doi:10.1172/jci.insight.148476

Cited by 51 publications

(53 citation statements)

References 29 publications

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“…Furthermore, sample sizes were rather limited, while control groups were lacking in 11 studies [ 74–84 ]. In terms of inclusion criteria, the studies were heterogeneous, as well: 14 exclusively included patients that were hospitalized during the acute infection phase [ 74 , 85–97 ], 11 included both hospitalized and non-hospitalized patients [ 75 , 76 , 79 , 80 , 82 , 83 , 98–102 ], while another study exclusively comprised non-hospitalized patients [ 103 ]. Five studies did not mention the hospitalization status [ 77 , 78 , 81 , 84 , 104 ].…”

Section: Resultsmentioning

confidence: 99%

Pathophysiology and mechanism of long COVID: a comprehensive review

et al. 2022

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Section: Resultsmentioning

confidence: 99%

Pathophysiology and mechanism of long COVID: a comprehensive review

et al. 2022

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“…Several of these genes (CAMP, LCN2) are known to have pro-inflammatory functions in myeloid cells and they have been linked to disease severity 14 and strongly associate with COVID-19 critical illness and mortality 20 . Elevated neutrophil activation (LCN2) was also observed in post-acute sequelae of SARS-CoV-2 infection 21 . In another study, elevated expression of pro-neutrophil genes, including CD24, OLFM4, LCN2, and BPI, has been associated with poor outcome in sepsis 22 .…”

Section: Discussionmentioning

confidence: 99%

Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module

Lee

Knabl²,

Wieser³

et al. 2022

Sci Rep

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Fast-spreading variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) energize the COVID-19 pandemic. While viral infections elicit a conserved immune response, it is not known whether SARS-CoV-2 variants, which display enhanced binding to the ACE2 receptor and reduced neutralizing activity by vaccine-elicited antibodies, prompt specific genomic immune responses. To test this, we generated and investigated the transcriptomes in BCs from hospitalized patients infected with either the Alpha variant (n = 36) or with the Alpha variant that had acquired the E484K escape mutation (Alpha+E484K) (n = 13). We identified a gene module preferentially activated in patients infected with the Alpha+E484K variant and in patients infected with the Beta (n = 9) and Gamma (n = 3) variants that also carry by the E484K escape mutation. The E484K signature was enriched for genes preferentially expressed in monocytes and linked to severe viral infection. However, both cohorts had undergone similar treatments and no differences in disease severity were reported suggesting that this signature reflects a variant response and does not necessarily associate with disease outcome. Additionally, longitudinal transcriptome analyses revealed a more persistent retention of immune signatures in Alpha+E484K patients throughout the entire course of COVID-19 disease and convalescence. While the OAS1 Neanderthal mutation has been linked to a milder COVID-19 pathology, we did not identify significant immune transcriptomes differences in the 25 patients homozygous for this mutation. Our study offers insights into distinct molecular immune responses elicited by SARS-CoV-2 variants carrying the E484K escape mutation throughout the COVID-19 disease.

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“…At the opposite end of the spectrum hyperinflammatory responses can lead to irreversible lung fibrosis that severely compromises respiratory effector function. Notably, although subjective symptoms such as fatigue and dyspnea do not track with the severity of inflammation, objective markers associated with persistent neutrophil activation (lipocalin-2), fibrosis signaling (matrix metalloprotease-7) and alveolar epithelial repair (hepatocyte growth factor) strongly associate with the severity of inflammation and impaired pulmonary function tests 25 . The development of persistent lung injuries may reflect the ability of SARS-CoV-2 to alter mechanisms of immune homeostasis that are key modulators of tissue inflammation.…”

Section: Series | Review Articlementioning

confidence: 99%

Pathological sequelae of long-haul COVID

2022

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an estimated 254 million cases and 5.1 million deaths have been ascribed to COVID-19 1 . As the world grapples with successive waves of infection fueled by the emergence of viral variants, in a subset of patients who recover, protracted disease symptoms, termed 'long COVID' , 'long-haul COVID' or 'post-COVID syndrome' , are being increasingly recognized. In the absence of a unifying disease definition, working constructs of long COVID have included the persistence of a constellation of symptoms for time periods varying from >4 weeks from symptom onset 2 to symptoms that last for more than 3 months after onset 3 . Proposed guidelines from the National Institute for Health and Care Excellence, Scottish Intercollegiate Guidelines Network and the Royal College of General Practitioners, all in the UK, define 'acute COVID-19' as signs and symptoms of COVID-19 for up to 4 weeks; 'ongoing symptomatic COVID-19' as signs and symptoms of COVID-19 present from 4 weeks to 12 weeks of infection; and post-COVID-19 syndrome as signs and symptoms consistent with COVID-19 that are present for more than 12 weeks after infection and not attributable to alternative diagnoses 4 . The US Centers for Disease Control and Prevention uses the term 'post-COVID conditions' as an umbrella term for the wide range of health consequences that are present ≥4 weeks after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Organ-specific sequelae. SARS-CoV-2, a novel β-coronavirus, is phylogenetically related to coronaviruses responsible for SARS and Middle East respiratory syndrome (MERS) (SARS-CoV and MERS-CoV, respectively). Notably, a subset of individuals who have had SARS or MERS are reported to demonstrate protracted neuropsychiatric symptoms 5-9 , sleep abnormalities 9 , persistent impairment of pulmonary function, including reductions in diffusion lung capacity (Dl CO ) 8,10-12 , pulmonary fibrosis 13 , myalgias 9 and functional disabilities such as reduced exercise tolerance [8][9][10][11][12] . Although aspects of long COVID are reminiscent of post-SARS and post-MERS syndromes, clinical and laboratory manifestations associated with long COVID appear to be protean, with the involvement of several organ systems.The severity of acute COVID-19 has been linked to post-COVID-19 syndrome in one large nationwide study based on healthcase databases of the US Department of Veterans Affairs 14 . In another systematic review, although COVID-19-associated symptomatology was more pronounced in individuals with severe disease, individuals with mild and moderate disease also reported a wide range of symptoms after the resolution of clinical disease 15 . Finally, in a recent study of home-isolated, young (16to 30-year-old) patients with COVID-19, nearly 60% reported persistent symptoms at 6 months, independent of the severity of the initial illness 16 . Although multiple organ systems can be involved in acute COVID-19, the most common manifestations are systemic, respiratory, gastrointestinal, cardiovascular and neurological. By c...

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Immunofibrotic drivers of impaired lung function in postacute sequelae of SARS-CoV-2 infection

Cited by 51 publications

References 29 publications

Pathophysiology and mechanism of long COVID: a comprehensive review

Pathophysiology and mechanism of long COVID: a comprehensive review

Immune transcriptome analysis of COVID-19 patients infected with SARS-CoV-2 variants carrying the E484K escape mutation identifies a distinct gene module

Pathological sequelae of long-haul COVID

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