Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia

Gregorová, Michaela; Morse, Daniel; Brignoli, Tarcisio; Steventon, Joseph; Hamilton, Fergus; Albur, Mahableshwar; Arnold, David; Thomas, Matthew C.; Halliday, Alice; Baum, Holly; Rice, Christopher M.; Avison, Matthew B.; Davidson, Andrew D.; Santopaolo, Marianna; Oliver, Elizabeth; Goenka, Anu; Finn, Adam; Wooldridge, Linda; Amulic, Borko; Boyton, Rosemary J.; Altmann, Daniel M.; Butler, David K.; McMurray, Claire; Stockton, Joanna; Nicholls, Samuel M.; Cooper, Charles; Loman, Nicholas J.; Cox, Michael J.; Rivino, Laura; Massey, Ruth C.

doi:10.7554/elife.63430

Cited by 27 publications

(21 citation statements)

References 35 publications

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“…It is possible that the underlying prolonged inflammation that we have shown in long COVIDs causes activation and differentiation of T and B cells, and when this inflammation is constant, exhaustion and dysfunction of these cells will eventuate. Bystander activation of these un-activated naїve subsets into more activated phenotypes is evident in long COVID, and is consistent with observations in some acute severe patients 60,61 . Increased myeloid activation is associated with activation of the antigen processing and presentation machinery and up regulation of co-stimulatory molecules necessary for differentiation and polarisation of T and B cells.…”

Section: Discussionsupporting

confidence: 89%

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

Phetsouphanh

Darley

Wilson

et al. 2021

Preprint

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A proportion of patients surviving acute COVID-19 infection develop post-COVID syndrome (long COVID) encompassing physical and neuropsychiatric symptoms lasting longer than 12 weeks. Here we studied a prospective cohort of individuals with long COVID (the ADAPT study) compared to age/gender matched subjects without long COVID, healthy donors and individuals infected with other non-SARS CoV2 human coronaviruses (the ADAPT-C study). We found an elevated diffuse serum inflammatory cytokine profile in symptomatic long COVID subjects that was maintained at 8 months post-infection and was not observed in asymptomatic COVID-19 survivors. This inflammatory profile consisted of 15 cytokines that positively correlated; revealing an apparent diffuse, potentially coordinated, low level up regulation of a spectrum of immune and inflammatory mediators. In addition, we found an absence of subsets of un-activated naive T and B cells in peripheral blood of long COVID subjects, that did not reconstitute over time. In contrast, individual serum cytokines from the interferon I and III classes, T cell activation markers and plasma ACE2, while elevated in the serum of people previously infected with SARS-CoV-2 were not further elevated in subjects with long COVID symptoms. This work defines immunological parameters associated with long COVID and suggests future opportunities to prevention and treatment.

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Section: Discussionsupporting

confidence: 89%

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

Phetsouphanh

Darley

Wilson

et al. 2021

Preprint

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“…Dani et al, described long COVID symptoms, such as tachycardia, palpitation, orthostatic intolerance, breathlessness, and chest pain as the consequences of autonomic nervous system instability caused by deconditioning, hypovolemia or immune- or virus-mediated autonomic nervous system destruction [ 110 ]. In a case report of a COVID-19 patient with anti-microbial resistant Pseudomonas Aeruginosa infection, it was documented that 6 weeks after clearing of the viral infection, a significant number of activated T-cells and T-cells-specific for unrelated antigens were present, suggesting "a significant amount of by stander activation" which might contribute to recurring anti-bacterial-resistant infections [ 148 ]. A study measuring 96 immune response-associated proteins showed that even 40 days post-COVID-19 viral infection high levels of biomarkers related to innate anti-inflammatory and stress response were present [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Long COVID, a comprehensive systematic scoping review

et al. 2021

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Purpose To find out what is known from literature about Long COVID until January 30, 2021. Methods We undertook a four-step search with no language restriction. A preliminary search was made to identify the keywords. A search strategy of all electronic databases resulted in 66 eligible studies. A forward and backward search of the references and citations resulted in additional 54 publications. Non-English language articles were translated using Google Translate. We conducted our scoping review based on the PRISMA-ScR Checklist. Results Of 120 papers, we found only one randomized clinical trial. Of the 67 original studies, 22 were cohort, and 28 were cross-sectional studies. Of the total 120 publications, 49.1% focused on signs and symptoms, 23.3% on management, and 10.8% on pathophysiology. Ten publications focused on imaging studies. The results are also presented extensively in a narrative synthesis in separated sections (nomenclature, diagnosis, pathophysiology, risk factors, signs/symptoms, management). Conclusions The controversies in its definition have impaired proper recognition and management. The predominant symptoms were: fatigue, breathlessness, arthralgia, sleep difficulties, and chest pain. Recent reports also point to the risk of long-term sequela with cutaneous, respiratory, cardiovascular, musculoskeletal, mental health, neurologic, and renal involvement in those who survive the acute phase of the illness. Supplementary Information The online version contains supplementary material available at 10.1007/s15010-021-01666-x.

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“…Further, many of the published studies are based on small cohorts (several hundred COVID-19 patients were analyzed) and relied on self-reported outcomes which can embody potential biases due to, for example, exaggeration of symptoms. 14 There have also been a number of less commonly reported symptoms including ocular inflammation 15 , cardiac involvement 16,17 , autonomic instability 18 , recurrent pseudomonas infections 19 , persistent mucous secretion 20 , micro-structural changes to the brain 21 and Guillain-Barre syndrome. 22 .…”

Section: Introductionmentioning

confidence: 99%

Evolving Phenotypes of non-hospitalized Patients that Indicate Long Covid

Estiri

Strasser

Brat

et al. 2021

Preprint

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Many of the symptoms characterized as the post-acute sequelae of SARS-CoV-2 infection (PASC) could have multiple causes or similarly seen in non-COVID patients. An accurate identification of phenotypes will be important to guide future research and the healthcare system to focus its efforts and resources on adequately controlled age- and gender-specific sequelae of COVID-19 infection. This retrospective electronic health records (EHR) cohort study, we applied a computational framework for knowledge discovery from clinical data, MLHO, to identify phenotypes that positively associate with a past positive PCR test for COVID-19. We evaluated the post-test phenotypes in two temporal windows at 3-6 and 6-9 months after the test and by age and gender. We utilized longitudinal diagnosis records stored in EHRs from Mass General Brigham (MGB) 57 thousand patients who tested positive or negative for COVID-19 and were not hospitalized. Statistical analyses were performed on data from March 2020 to March 2021. PCR test results and subsequent diagnosis records that were recorded for the first time two months or later after the PCR test. We identified 28 phenotypes among different age/gender cohorts or time windows that positively associated with a past SARS-CoV-2 infection. All identified phenotypes were newly recorded in patients’ medical records two months or longer after a COVID-19 PCR test in non-hospitalized patients regardless of the test result. Among these phenotypes, a new diagnosis record for anosmia and dysgeusia (OR 2.17, 95% CI [1.42 - 3.25]), alopecia (OR 3.54, 95% CI [2.92 - 4.3]), chest pain (OR 1.35, 95% CI [1.16 - 1.56]), or chronic fatigue syndrome (OR 1.81-2.28, 95% CI [1.38 - 3.68]) are the most significant indicators of a past COVID-19 infection, especially among women younger than 65. Among men, edema (OR 1.83, 95% CI [1.23 - 2.66]) and disease of nail (OR 3.54, 95% CI [1.63 - 7.29]) in patients 65 and older or proteinuria (OR 2.66, 95% CI [1.61 - 4.34]) in patients under 65 are associated with a positive COVID-19 PCR test in the past few months. Our approach avoids a flood of false positive discoveries, while offering a more probabilistic flexible criterion than the standard linear phenome-wide association study (PheWAS). These findings suggest that some of the previously identified post sequelae of COVID-19 may not be accurate and that most of the PASC are observed in patients under 65 years of age.

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Post-acute COVID-19 associated with evidence of bystander T-cell activation and a recurring antibiotic-resistant bacterial pneumonia

Cited by 27 publications

References 35 publications

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

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

Long COVID, a comprehensive systematic scoping review

Evolving Phenotypes of non-hospitalized Patients that Indicate Long Covid

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