Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection

Phetsouphanh, Chansavath; Darley, D.R.; Wilson, Daniel B.; Howe, Annett; Munier, C. Mee Ling; Patel, Sheila K.; Juno, Jennifer A; Burrell, Louise M; Kent, Stephen J.; Dore, Gregory J.; Kelleher, Anthony D.; Matthews, Gail

doi:10.1038/s41590-021-01113-x

Cited by 660 publications

(715 citation statements)

References 44 publications

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“…We observed an increase of proinflammatory cytokines in PCS (ie, IFN-α, TNF- α, G-CSF, IL17A, IL-6, IL1-β, and IL-13), which confirmed previous observations [ 20 , 21 ]. In addition, a significant decrease in IP-10 was noticed.…”

Section: Discussionsupporting

confidence: 92%

Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome

Acosta-Ampudia

Monsalve

Rojas

et al. 2022

The Journal of Infectious Diseases

113

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Background The immunopathological pathways enabling post-COVID syndrome (PCS) development are not entirely known. We underwent a longitudinal analysis of patients with COVID-19 who developed PCS aiming to evaluate the autoimmune and immunological status associated with this condition. Methods Thirty-three patients were included for longitudinal clinical and autoantibody analyses of whom 12 patients were assessed for cytokines and lymphocyte populations. Patients were followed during 7-11 months after acute COVID-19. Autoimmune profile and immunological status were evaluated mainly by enzyme-linked-immunosorbent assays and flow cytometry. Results Latent autoimmunity and overt autoimmunity persisted over time. A proinflammatory state was observed in patients with PCS characterized by upregulated IFN-α, TNF-α, G-CSF, IL-17A, IL-6, IL-1β, and IL-13, whereas IP-10 was decreased. In addition, PCS was characterized by increased levels of Th9, CD8+ effector T cells, naive B cells, and CD4+ effector memory T cells. Total levels of IgG S1-SARS-CoV-2 antibodies remained elevated over time. Discussion The clinical manifestations of PCS are associated with the persistence of a proinflammatory, and effector phenotype induced by SARS-CoV-2 infection. This long-term persistent immune activation may contribute to the development of latent and overt autoimmunity. Results suggest the need to evaluate the role of immunomodulation in the treatment of PCS.

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Section: Discussionsupporting

confidence: 92%

Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome

Acosta-Ampudia

Monsalve

Rojas

et al. 2022

The Journal of Infectious Diseases

113

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“…Patients with long-haul COVID demonstrated persistent increases in the frequency of activated CD14 + CD16 + monocytes and plasmacytoid dendritic cells, compared with control individuals 8 months after infection 66 . Furthermore, patients with long-haul COVID demonstrated persistent elevation in the levels of type I (IFNβ) and type III (IFNλ1) interferon 8 months post-infection 66 . In the study, a combination of IFNβ, pentraxin 3, IFNγ, IFNλ2/3 and IL-6 was associated with long-haul COVID, with an accuracy ranging from 78.5% to 81.6% 66 .…”

Section: Series | Review Articlementioning

confidence: 89%

“…A recent study prospectively examined a cohort of 31 individuals with long-haul COVID (based on the presence of one of three major symptoms: dyspnea, fatigue and chest pain), age and gender matched with 31 individuals who had prior COVID infection but lacked long-haul COVID symptoms. In addition, 25 individuals infected with common cold coronaviruses and unexposed healthy individuals (n = 46) served as controls 66 . Patients with long-haul COVID demonstrated persistent increases in the frequency of activated CD14 + CD16 + monocytes and plasmacytoid dendritic cells, compared with control individuals 8 months after infection 66 .…”

Section: Series | Review Articlementioning

confidence: 99%

“…In addition, 25 individuals infected with common cold coronaviruses and unexposed healthy individuals (n = 46) served as controls 66 . Patients with long-haul COVID demonstrated persistent increases in the frequency of activated CD14 + CD16 + monocytes and plasmacytoid dendritic cells, compared with control individuals 8 months after infection 66 . Furthermore, patients with long-haul COVID demonstrated persistent elevation in the levels of type I (IFNβ) and type III (IFNλ1) interferon 8 months post-infection 66 .…”

Section: Series | Review Articlementioning

confidence: 99%

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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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“…Secondly, what are the molecular, immunological, and psychological mechanisms underlying long covid? Suggested mechanisms include direct effects of the virus (including viral latency, persistent activation of the immune system,12 and neuronal apoptosis) and indirect effects related to mental health problems such as post-traumatic stress and social isolation 13. Thirdly, are the long term effects of covid-19 specific to SARS-CoV-2 infection or are they similar to post-viral syndromes seen after other viral infections?…”

mentioning

confidence: 99%

Long covid in children and adolescents

Zimmermann

Pittet

Curtis

2022

BMJ

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Symptoms involving almost every organ system have been reported SARS-CoV-2 infection. 1 -3 Estimates of the prevalence of long covid (also called post-covid-19 condition, post-acute sequelae of covid-19, or chronic covid syndrome) vary considerably, partly because of confusion around the definition. The term long covid encompasses a broad range of symptoms, including objective complications of covid-19 (pulmonary fibrosis, myocardial dysfunction), mental health conditions, and more subjective, non-specific symptoms resembling those seen in post-viral chronic fatigue syndrome (myalgic encephalomyelitis). Most studies to date have substantial limitations, including small cohorts, absence of control groups, non-standardised capture of symptoms, lack of correction for pre-existing medical conditions, participant reported infection, and variation in follow-up, as well as selection, non-response, misclassification, and recall biases. 4

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Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection

Cited by 660 publications

References 44 publications

Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome

Persistent Autoimmune Activation and Proinflammatory State in Post-Coronavirus Disease 2019 Syndrome

Pathological sequelae of long-haul COVID

Long covid in children and adolescents

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