Immunologic Features in Coronavirus Disease 2019: Functional Exhaustion of T Cells and Cytokine Storm

Mahmoudi, Shima; Rezaei, Mitra; Mansouri, Nahal; Marjani, Majid; Mansouri, Davood

doi:10.1007/s10875-020-00824-4

Cited by 62 publications

(59 citation statements)

References 18 publications

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“…Of note, our findings are consistent with previous studies reporting that patients with a high level of IL-6 and a poor prognosis also had decreased CD8 + T, NK and Treg cells. 53,54,57 In summary, we performed a systematic analysis of SARS-CoV-2 infection in the postmortem lung tissues from patients with fatal COVID-19, providing an atlas of lung immunopathology of the disease. We found a broad tropism of SARS-CoV-2 infection in pulmonary parenchymal and immune cells.…”

Section: Resultsmentioning

confidence: 99%

Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19

Silva

Meng

et al. 2020

Preprint

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Background Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection in patients with Coronavirus Disease 2019 (COVID-19) prominently manifests with pulmonary symptoms histologically reflected by diffuse alveolar damage (DAD), excess inflammation, pneumocyte hyperplasia and proliferation, and formation of platelet aggregates or thromboemboli. However, the mechanisms mediating these processes remain unclear. Methods We performed multicolor staining for viral proteins, and lineage cell markers to identify SARS-CoV-2 tropism and to define the lung pathobiology in postmortem tissues from five patients with fatal SARS-CoV-2 infections. Findings The lung parenchyma showed severe DAD with thromboemboli in all cases. SARS-CoV-2 infection was found in an extensive range of cells including alveolar epithelial type II/pneumocyte type II (AT2) cells (HT2-280), ciliated cells (tyr-α-tubulin), goblet cells (MUC5AC), club-like cells (MUC5B) and endothelial cells (CD31 and CD34). Greater than 90% of infiltrating immune cells were positive for viral proteins including macrophages and monocytes (CD68 and CD163), neutrophils (ELA-2), natural killer (NK) cells (CD56), B-cells (CD19 and CD20), and T-cells (CD3ε). Most but not all infected cells were positive for the viral entry receptor angiotensin-converting enzyme-2 (ACE2). The numbers of infected and ACE2-positive cells correlated with the extent of tissue damage. The infected tissues exhibited low numbers of B-cells and abundant CD3ε+ T-cells consisting of mainly T helper cells (CD4), few cytotoxic T cells (CTL, CD8), and no T regulatory cell (FOXP3). Antigen presenting molecule HLA-DR of B and T cells was abundant in all cases. Robust interleukin-6 (IL-6) expression was present in most uninfected and infected cells, with higher expression levels observed in cases with more tissue damage. Interpretation In lung tissues from severely affected COVID-19 patients, there is evidence for broad SARS-CoV-2 cell tropisms, activation of immune cells, and clearance of immunosuppressive cells, which could contribute to severe tissue damage, thromboemboli, excess inflammation and compromised adaptive immune responses.

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Section: Resultsmentioning

confidence: 99%

Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19

Silva

Meng

et al. 2020

Preprint

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“…MIS-C is mainly as a result of an antibody-mediated of immune system and cytokine storm leading to cardiac or renal failures [5, 13, 15, 28]. The increased level of enzymes in the liver, heart and kidneys might lead to the occurrence of multi-organ failure in MIS-C [7].…”

Section: Discussionmentioning

confidence: 99%

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran

et al. 2020

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During the coronavirus disease 2019 (COVID-19) pandemic, a new phenomenon manifesting as a multisystem inflammatory syndrome in children (MIS-C) which has a similar clinical presentation to Kawasaki disease, toxic shock syndrome and severe sepsis has emerged. Although the number of MIS-C reports is increasing, rare reports in Asia is still available. To our knowledge, this study is the largest series of published MIS-C cases in Iran. We performed a retrospective study of all patients with case definition for MIS-C admitted to the three paediatric hospitals in Iran. All of these hospitals are located within the most active COVID-19 pandemic areas (Tehran, Qom and Mazandaran) in Iran. Demographic characteristics, clinical data, laboratory findings, imaging and echocardiographic findings, treatment and outcomes were collected. Between 7 March and 23 June 2020, 45 children were included in the study. The median age of children was 7 years (range between 10 months and 17 years). Common presenting symptoms include fever (91%), abdominal pain (58%), nausea/vomiting (51%), mucocutaneous rash (53%), conjunctivitis (51%) and hands and feet oedema (40%) with median duration of symptoms prior to presentation of 5 (interquartile range (IQR) 3, 7) days. Fifty-three percent of children showed lymphopaenia. Overall, the majority of cases at admission had markedly elevated inflammatory markers erythrocyte sedimentation rate (ESR) (95.5%) and C-reactive protein (CRP) (97%). Ferritin was abnormal in 11 out of 14 tested patients (73%), and it was highly elevated (>500 ng/ml) in 47% of cases. Median fibrinogen level was 210 (IQR 165, 291) mg/dl, D-dimer was 3909 (IQR 848, 4528) ng/ml and troponin was 0.6 (IQR 0.1, 26) ng/ml, respectively. Twenty out of 31 patients (64.5%) had hypoalbuminaemia. In addition, hyponatraemia was found in 64% of cases. Twenty-five patients (56%) presented with cardiac involvement and acute renal failure was observed in 13 cases (29%). Pleural, ascitic, ileitis and pericardial effusions were found in 18%, 11%, 4% and 2% of cases, respectively. In conclusion, this is a first large case series of hospitalised children who met criteria for MIS-C in Iran. There was a wide spectrum of presenting signs and symptoms; evidence of inflammation with abnormal values of CRP, ESR, D-dimer, ferritin and albumin; and multi-organ involvement.

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“…The significant point in this regard is the severity of the underlying cardiac condition that results in worsening of the child’s conditions and holds back the effect of drugs. Moreover, immune dysregulation during the severe phase of COVID-19 following inflammatory cascade and cytokine production may result in increased risk of vascular hyperpermeability and multi-organ failure [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

COVID-19 and congenital heart disease: a case series of nine children

et al. 2021

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Immunologic Features in Coronavirus Disease 2019: Functional Exhaustion of T Cells and Cytokine Storm

Cited by 62 publications

References 18 publications

Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19

Broad SARS-CoV-2 cell tropism and immunopathology in lung tissues from fatal COVID-19

Multisystem inflammatory syndrome associated with SARS-CoV-2 infection in 45 children: a first report from Iran

COVID-19 and congenital heart disease: a case series of nine children

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