key: cord-1053058-ecwudscm authors: Ahearn‐Ford, Sinead; Lunjani, Nonhlanhla; McSharry, Brian; MacSharry, John; Fanning, Liam; Murphy, Gerard; Everard, Cormac; Barry, Aoife; McGreal, Aimee; al Lawati, Sultan Mohamed; Lapthorne, Susan; Sherlock, Colin; McKeogh, Anna; Jackson, Arthur; Faller, Eamonn; Horgan, Mary; Sadlier, Corinna; O'Mahony, Liam title: Long‐term disruption of cytokine signalling networks is evident in patients who required hospitalization for SARS‐CoV‐2 infection date: 2021-06-07 journal: Allergy DOI: 10.1111/all.14953 sha: 92d44e53a0c29e18dde25523f81f9e7c2d5a153b doc_id: 1053058 cord_uid: ecwudscm nan To the Editor, The current pandemic caused by the SARS-CoV-2 virus has so far infected more than 130 million people worldwide, resulting in approximately 3 million deaths. While the current clinical and public health priorities are designed to limit severe acute and fatal episodes of the disease, and to quickly roll out vaccines to the general population, it has become apparent that there may also be significant detrimental long-term effects following SARS-CoV-2 infection that impact daily functioning and quality of life. 1 The mechanisms underpinning the post-acute sequelae of SARS-CoV-2 infection's long-lasting symptoms can include direct effects of the infection (eg endothelial damage, lung fibrosis) or indirect effects associated with changes in the microbiome or abnormalities in inflammatory and immune signalling pathways stimulated by the infection. 2, 3 In order to examine the potential long-term immune changes that Clinical severity ranged from mild to critical during hospitalization, and the most common symptoms at follow-up clinics were fatigue and/or dyspnoea (Table S1 ). Sera obtained prior to the pandemic from twenty-nine healthy volunteers (median age 43.2 years, 14 female) were analysed in parallel. Of the 52 analytes measured, 19 were significantly elevated in post-COVID patient sera compared to healthy controls (Table S2) . Table S2 ). While T H 1 responses are well described to be upregulated during acute infection, 6 the levels of these mediators (eg IFNγ, IP-10) decrease following elimination of the virus and are at control levels in our cohort of post-COVID patients (Table S2 ). Our data suggest that there are long-term immunological consequences following SARS-CoV-2 infection, at least in those who had acute symptoms severe enough to require hospitalization (summarized in Figure S1 ). While the relatively low number of patients included in our study at this stage does not allow us to perform subgroup analysis, it is possible that these immune me- F I G U R E 1 Proinflammatory and endothelial mediators in post-COVID patients. Proinflammatory mediators (A) and angiogenesisassociated factors (B) are elevated in sera from patients 3-9 months post-COVID hospital discharge compared to levels in sera from healthy controls. Results are illustrated on a log scale, and the mean ± standard error is indicated for each group. Depending on the data distribution, unpaired t-tests or Mann-Whitney tests were used to determine statistical significance. *p < .05; **p < .01; ***p < .001; and ****p < .0001 Results are illustrated on a log scale, and the mean ± standard error is indicated for each group. Depending on the data distribution, unpaired t-tests or Mann-Whitney tests were used to determine statistical significance. *p < .05; **p < .01; and ***p < .001 Immunology of COVID-19: mechanisms, clinical outcome, diagnostics, and perspectives-A report of the European Academy of Allergy and Clinical Immunology (EA ACI) Immune response to SARS-CoV-2 and mechanisms of immunopathological changes in COVID-19 Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases Endothelial dysfunction and immunothrombosis as key pathogenic mechanisms in COVID-19 The deregulated immune reaction and cytokines release storm (CRS) in COVID-19 disease Additional supporting information may be found online in the Supporting Information section.