Post-mortem Histopathologic Findings of Vital Organs in Critically Ill Patients with COVID-19

Zerehpoosh, Farahnaz Bidari; Sabeti, Shahram; Bahrami‐Motlagh, Hooman; Mokhtari, Majid; Irvani, Seyed Sina Naghibi; Torabinavid, Parham; Tarki, Farzad Esmaeili; Amirdosara, Mahdi; Rezaei, Omidvar; Mostafazadeh, Babak; Hajiesmaeili, Mohammadreza; Rabiei, Mohammad Mahdi; Darazam, Ilad Alavi

doi:10.34172/aim.2021.23

Cited by 9 publications

(13 citation statements)

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“…Notably, a few chemokines, including MCP-1, RANTES, and IL-8, showed significantly positive correlations with HLA-DR + CD38 hi CD8 + T cells. Consistently, CD8 + T cells were identified in lung and liver tissues from COVID-19 patients by postmortem biopsy in previous studies ( 24 , 43 – 45 ). Thus, we speculated that these cells might accumulate in target organs towards chemokines and could be a potential culprit of tissue injury.…”

Section: Discussionsupporting

confidence: 86%

Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19

Wei

et al. 2021

Front. Immunol.

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BackgroundThe global outbreak of coronavirus disease 2019 (COVID-19) has turned into a worldwide public health crisis and caused more than 100,000,000 severe cases. Progressive lymphopenia, especially in T cells, was a prominent clinical feature of severe COVID-19. Activated HLA-DR+CD38+ CD8+ T cells were enriched over a prolonged period from the lymphopenia patients who died from Ebola and influenza infection and in severe patients infected with SARS-CoV-2. However, the CD38+HLA-DR+ CD8+ T population was reported to play contradictory roles in SARS-CoV-2 infection.MethodsA total of 42 COVID-19 patients, including 32 mild or moderate and 10 severe or critical cases, who received care at Beijing Ditan Hospital were recruited into this retrospective study. Blood samples were first collected within 3 days of the hospital admission and once every 3–7 days during hospitalization. The longitudinal flow cytometric data were examined during hospitalization. Moreover, we evaluated serum levels of 45 cytokines/chemokines/growth factors and 14 soluble checkpoints using Luminex multiplex assay longitudinally.ResultsWe revealed that the HLA-DR+CD38+ CD8+ T population was heterogeneous, and could be divided into two subsets with distinct characteristics: HLA-DR+CD38dim and HLA-DR+CD38hi. We observed a persistent accumulation of HLA-DR+CD38hi CD8+ T cells in severe COVID-19 patients. These HLA-DR+CD38hi CD8+ T cells were in a state of overactivation and consequent dysregulation manifested by expression of multiple inhibitory and stimulatory checkpoints, higher apoptotic sensitivity, impaired killing potential, and more exhausted transcriptional regulation compared to HLA-DR+CD38dim CD8+ T cells. Moreover, the clinical and laboratory data supported that only HLA-DR+CD38hi CD8+ T cells were associated with systemic inflammation, tissue injury, and immune disorders of severe COVID-19 patients.ConclusionsOur findings indicated that HLA-DR+CD38hi CD8+ T cells were correlated with disease severity of COVID-19 rather than HLA-DR+CD38dim population.

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Section: Discussionsupporting

confidence: 86%

Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19

Wei

et al. 2021

Front. Immunol.

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“…Cytokine production is an important element of immune response initiated in infected individuals. Upon binding to SARS-CoV-2, cells expressing ACE2, including alveolar epithelial cells, undergo pyroptosis and release damage associated molecular patterns (4) consistent with postmortem histopathological findings characterized by diffuse alveolar damage (DAD) (5)(6)(7). This damage is recognized by monocytes and macrophages which trigger proinflammatory cytokine and chemokine cascades (4).…”

Section: Cytokine Productionmentioning

confidence: 80%

“…Numerous circulating markers of endothelial injury, such as coagulation factor VIII, von-Willebrandfactor, and angiopoietin 2 are increased in patients with COVID-19 (14). Similarly, autopsies have also revealed the formation of hyaline membranes and micro-thromboses as key pathological patterns besides DAD (5,7).…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

“…Complex interactions between coagulopathy, thrombocytopathy, and endotheliopathy contribute to COVID-19-associated thrombo-inflammation (16,17). Also, diffuse infiltration of alveolar walls by CD4+ and CD8+ T lymphocytes has been identified in patient autopsies (7,18). Local inflammation aggravation involving increased pro-inflammatory cytokine and chemokine secretion into patient blood attracts immune cells, notably T lymphocytes from the blood to infected sites, generating lymphopenia in the peripheral blood (4,11,19).…”

Section: Endothelial Dysfunctionmentioning

confidence: 99%

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Tailoring glucocorticoids in patients with severe COVID-19: a narrative review

Luo¹,

Qian²,

Huang³

et al. 2021

Ann Transl Med

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To discuss the pathogenesis of severe coronavirus disease 2019 (COVID-19) infection and the pharmacological effects of glucocorticoids (GCs) toward this infection. To review randomized controlled trials (RCTs) using GCs to treat patients with severe COVID-19, and investigate whether GC timing, dosage, or duration affect clinical outcomes. Finally. to discuss the use of biological markers, respiratory parameters, and radiological evidence to select patients for improved GC therapeutic precision.Background: COVID-19 has become an unprecedented global challenge. As GCs have been used as key immunomodulators to treat inflammation-related diseases, they may play key roles in limiting disease progression by modulating immune responses, cytokine production, and endothelial function in patients with severe COVID-19, who often experience excessive cytokine production and endothelial and reninangiotensin system (RAS) dysfunction. Current clinical trials have partially proven this efficacy, but GC timing, dosage, and duration vary greatly, with no unifying consensus, thereby creating confusion.Methods: Publications through March 2021 were retrieved from the Web of Science and PubMed. Results from cited references in published articles were also included.Conclusions: GCs play key roles in treating severe COVID-19 infections. Pharmacologically, GCs could modulate immune cells, reduce cytokine and chemokine, and improve endothelial functions in patients with severe COVID-19. Benefits of GCs have been observed in multiple clinical trials, but the timing, dosage and duration vary across studies. Tapering as an option is not widely accepted. However, early initiation of treatment, a tailored dosage with appropriate tapering may be of particular importance, but evidence is inconclusive and more investigations are needed. Biological markers, respiratory parameters, and radiological evidence could also help select patients for specific tailored treatments.

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“…By studying H&E-stained lung sections from 8 autopsy cases from patients with COVID-19, Kianzad et al also found histological evidence of pulmonary thrombosis ( 32 ). Similarly, Romanova et al ( 33 ), Bryce et al ( 34 ), Bidari Zerehpoosh et al ( 35 ), Mauad et al ( 36 ), Bruce-Brand ( 37 ), Elsoukkary et al ( 38 ), and Grosse et al ( 39 ) used H&E staining to show evidence of lung thrombosis in COVID-19 autopsy samples. H&E staining and immunofluorescence were also employed by Nicolai et al ( 40 ) and Oprinca et al ( 41 ) in their demonstrations of pulmonary thrombosis in COVID-19 lungs.…”

Section: Two-dimensional Histology Of Covid-19 Lungsmentioning

confidence: 99%

Emerging and Established Histological Techniques for the Analysis of Thrombosis in COVID-19 Lungs

Spier

Evans

2021

Front. Cardiovasc. Med.

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Coronavirus disease 2019 (COVID-19) is the potentially lethal disease that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients with COVID-19 have an increased risk of thrombosis, but the role of thrombosis in the pathogenesis and progression of severe COVID-19 remains unclear. A better understanding of the contribution of thrombosis to the development and progression of COVID-19 could lead to the development of novel COVID-19 treatments. For this reason, established and emerging histological techniques have recently been used to analyze COVID-19 lungs quantitatively and visually and in two and three dimensions. The gold standard and novel state-of the-art histological techniques that have been used to assess thrombosis in COVID-19 lungs are described in this Mini Review.

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Post-mortem Histopathologic Findings of Vital Organs in Critically Ill Patients with COVID-19

Cited by 9 publications

References 0 publications

Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19

Persistent High Percentage of HLA-DR+CD38high CD8+ T Cells Associated With Immune Disorder and Disease Severity of COVID-19

Tailoring glucocorticoids in patients with severe COVID-19: a narrative review

Emerging and Established Histological Techniques for the Analysis of Thrombosis in COVID-19 Lungs

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