Cytokine Storm Syndrome in SARS-CoV-2 Infections: A Functional Role of Mast Cells

Kazemi, Hossein; Chan, Lily; Knapp, Jason; Karimi, Negar; Alizadeh, Kimia; Mehrani, Yeganeh; Bridle, Byram W.; Karimi, Khalil

doi:10.3390/cells10071761

Cited by 40 publications

(38 citation statements)

References 142 publications

(176 reference statements)

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“…Therefore, the lipid peroxidation trigger and 4-HNE mediated systemic vascular and oxidative stress could be associated with an uncontrolled (auto)immune stress response, which may lead to ARDS and MOF, as observed in our patients. The high importance of the malfunctioning immune system destroying vital organs, not only the lungs but even the brain, for severe/lethal SARC-CoV-2 infection is well known, even if the virus itself may not always be the [52][53][54], as is also the importance of uncontrolled oxidative stress [55,56]. Both of the supporting findings of our study suggest that lipid peroxidation, notably, 4-HNE, might be the link between these two vicious circles of lethal COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

Žarković

Jakovčević

Mataić

et al. 2022

Cells

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A recent comparison of clinical and inflammatory parameters, together with biomarkers of oxidative stress, in patients who died from aggressive COVID-19 and survivors suggested that the lipid peroxidation product 4-hydroxynonenal (4-HNE) might be detrimental in lethal SARS-CoV-2 infection. The current study further explores the involvement of inflammatory cells, systemic vascular stress, and 4-HNE in lethal COVID-19 using specific immunohistochemical analyses of the inflammatory cells within the vital organs obtained by autopsy of nine patients who died from aggressive SAR-CoV-2 infection. Besides 4-HNE, myeloperoxidase (MPO) and mitochondrial superoxide dismutase (SOD2) were analyzed alongside standard leukocyte biomarkers (CDs). All the immunohistochemical slides were simultaneously prepared for each analyzed biomarker. The results revealed abundant 4-HNE in the vital organs, but the primary origin of 4-HNE was sepsis-like vascular stress, not an oxidative burst of the inflammatory cells. In particular, inflammatory cells were often negative for 4-HNE, while blood vessels were always very strongly immunopositive, as was edematous tissue even in the absence of inflammatory cells. The most affected organs were the lungs with diffuse alveolar damage and the brain with edema and reactive astrocytes, whereas despite acute tubular necrosis, 4-HNE was not abundant in the kidneys, which had prominent SOD2. Although SOD2 in most cases gave strong immunohistochemical positivity similar to 4-HNE, unlike 4-HNE, it was always limited to the cells, as was MPO. Due to their differential expressions in blood vessels, inflammatory cells, and the kidneys, we think that SOD2 could, together with 4-HNE, be a potential link between a malfunctioning immune system, oxidative stress, and vascular stress in lethal COVID-19.

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Section: Discussionmentioning

confidence: 99%

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

Žarković

Jakovčević

Mataić

et al. 2022

Cells

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“…The patient exhibited respiratory distress two hours after admission, which may be attributable to the cytokine storm syndrome 14 . The cytokine storm may have also been responsible for the rapid deterioration of vital signs in the patient, which manifested as an increase in both body temperature and blood pressure, and abnormal SPO 2 15 . However, a D-Dimer test, chest radiography, or echocardiography was impossible at the time in the facility.…”

Section: Discussionmentioning

confidence: 99%

Parenteral Hydrocortisone treatment in a COVID-19 patient with Respiration Distress –a case report

Owhonda

Eze-Emiri

et al. 2022

Preprint

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A prospective case report study that showed the response of intravenously administered Hydrocortisone on a patient admitted to the Elekahia COVID-19 treatment centre, located in Port Harcourt, Rivers State, Nigeria. The patient was a 47-year-old man of Asian descent; he presented with pneumonia-like symptoms and developed severe breathlessness. Treatment started on 6th June 2020 and ended on the 16th of June 2020. There was a marked improvement in peripheral capillary oxygen saturation (SpO2) after hydrocortisone intervention; respiratory rate reduced from 40 cycles per minute to 18 cycles per minute, and the patient could complete sentences without developing breathlessness, three hours after receiving the first dose of intravenous hydrocortisone. The use of Hydrocortisone therapy could be of tremendous benefit in the treatment of COVID-19 patients, who present with severe respiratory distress. Controlled randomised clinical trials are required for the proper assessment of steroid use in COVID-19 treatment. and to assess its use as a prophylactic in the early management of severe COVID-19 cases.

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“…Evidence had shown that the responses of MCs to SARS‐CoV‐2 may promote cytokine storms. 9 Autopsy findings from the lungs of the patients that died from COVID‐19 showed an accumulation of MCs that was speculated to be the cause of pulmonary oedema, inflammation and thrombosis in the pathophysiology of COVID‐19. 32 , 33 The classic trigger for MCs activation is through the IgE‐mediated cross‐linking the IgE receptor, FcϵRI, thus resulting in the degranulation of MCs.…”

Section: Discussionmentioning

confidence: 99%

Hypersensitivity may be involved in severe COVID‐19

Tan

Zheng

Sun

et al. 2021

Clin Experimental Allergy

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Background Deaths attributed to Coronavirus Disease 2019 (COVID‐19) are mainly due to severe hypoxemic respiratory failure. Although the inflammatory storm has been considered the main pathogenesis of severe COVID‐19, hypersensitivity may be another important mechanism involved in severe cases, which have a perfect response to corticosteroids (CS). Method We detected the serum level of anti‐SARS‐CoV‐2–spike S1 protein‐specific IgE (SP‐IgE) and anti‐SARS‐CoV‐2 nucleocapsid protein‐specific IgE (NP‐IgE) in COVID‐19. Correlation of levels of specific IgE and clinical severity were analysed. Pulmonary function test and bronchial provocation test were conducted in early convalescence of COVID‐19. We also obtained histological samples via endoscopy to detect the evidence of mast cell activation. Result The levels of serum SP‐IgE and NP‐IgE were significantly higher in severe cases, and were correlated with the total lung severity scores (TLSS) and the PaO 2 /FiO 2 ratio. Nucleocapsid protein could be detected in both airway and intestinal tissues, which was stained positive together with activated mast cells, binded with IgE. Airway hyperresponsiveness (AHR) exists in the early convalescence of COVID‐19. After the application of CS in severe COVID‐19, SP‐IgE and NP‐IgE decreased, but maintained at a high level. Conclusion Hypersensitivity may be involved in severe COVID‐19.

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Cytokine Storm Syndrome in SARS-CoV-2 Infections: A Functional Role of Mast Cells

Cited by 40 publications

References 142 publications

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

Post-mortem Findings of Inflammatory Cells and the Association of 4-Hydroxynonenal with Systemic Vascular and Oxidative Stress in Lethal COVID-19

Parenteral Hydrocortisone treatment in a COVID-19 patient with Respiration Distress –a case report

Hypersensitivity may be involved in severe COVID‐19

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