COVID-19-associated cytokine storm
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Synonyms and keywords:
Overview
Historical Perspective
- The etiological agent is SARS-CoV-2, named for the similarity of its symptoms to those induced by the severe acute respiratory syndrome, causing coronavirus disease 2019 (COVID-19), is a virus identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China.[1][2]
- The growing number of patients however, suggest that human-to-human transmission is actively occurring.[3][4]
- The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020.
- On March 12, 2020, the World Health Organization declared the COVID-19 outbreak a pandemic.
- Cytokine storm has been the cause of death in the pandemics of many respiratory and flu viruses, especially in young adults.
Classification
There is no established system for the classification of COVID-19-associated cytokine storm.
Pathophysiology
The exact pathogenesis of [disease name] is not fully understood.
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It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
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[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
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Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
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[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
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The progression to [disease name] usually involves the [molecular pathway].
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The pathophysiology of [disease/malignancy] depends on the histological subtype.
Cytokine storms have been identified as key players in acute respiratory distress syndrome (ARDS) and multiple organ failure . (3 in ye)In SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV), cytokine storms have been associated with acute respiratory distress syndrome (ARDS). (2 in kuppali)Significant increase in pro-inflammatory cytokines (such as IL-6), reduction in CD+8 T cells, suppressed Th1 antiviral responses and increase in IL-10 (a Th2 cytokine) have been reported to be associated with severe COVID-19 infection. (kupalli) Therefore, it has been suggested that the pathogenesis of severe COVID-19 infection may be due to cytokine storm and suppressed Th1 antiviral responses. (kupalli)
Proinflammatory Cytokines and Chemokines
In SARS-CoV infection, in the early stages of the disease there is delayed release of cytokines and chemokines in respiratory epithelial cells, dendritic cells (DCs), and macrophages. However, later during the infection release of the following occurs: (28 ta 20 in ye)High levels of proinflammatory cytokines (interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF))High levels of chemokines (C-C motif chemokine ligand (CCL)-2, CCL-3, and CCL- 5)Low levels of antiviral factors interferons (IFNs)
In MERS-CoV infection there is delayed but high level of proinflammatory cytokine and chemokine release as well.(21-22 in ye) These are due to the increased neutorphils and monocytes in the lung and blood of of MERS-CoV patients which suggests their contribution to the lung effects in this infection. (24-25 ye) This has also been seen in SARS CoV infection. (27ta 34 in ye)
Antiviral Factors
The production of IFN-I or IFN-α/β is the key natural immune defense response against viral infections, and IFN-I is the key molecule that plays an antiviral role in the early stages of viral infection.35,36 Delayed release of IFNs in the early stages of SARS-CoV and MERS-CoV infection hinders the body’s antiviral response.36 Afterward, the rapidly increased cytokines and chemokines attract many inflammatory cells, such as neutrophils and monocytes, resulting in excessive infiltration of the inflammatory cells into lung tissue and thus lung injury. It appears from these studies that dysregulated and/or exaggerated cytokine nd chemokine responses by SARS-CoV-infected or MERS-CoVinfected cells could play an important role in pathogenesis of SARS or MERSThe ccumulated mononuclear macrophages receive activating signals hrough the IFN-α/β receptors on their surface and produce more onocyte chemoattractants (such as CCL2, CCL7, and CCL12), resulting in the further accumulation of mononuclear macrophages.These mononuclear macrophages produce elevated levels of proinflammatory cytokines (TNF, IL-6, IL1-β, and inducible nitric oxidesynthase), thereby increasing the severity of the diseaseIn addition, IFN-α/β or mononuclear macrophage-derivedproinflammatory cytokines induce the apoptosis of T cells, whichfurther hinders viral clearance.Another consequence of rapid viral replication and vigorous proinflammatory cytokine/chemokineresponse is the induction of apoptosis in lung epithelial and endothelial cells. IFN-αβ and IFN-γ induce inflammatory cell infiltration through mechanisms involving Fas–Fas ligand (FasL) or TRAIL–death receptor 5 (DR5) and cause the apoptosis of airwayand alveolar epithelial cells.39–41 Apoptosis of endothelial cells andepithelial cells damages the pulmonary microvascular and alveolar epithelial cell barriers and causes vascular leakage and alveolar edema, eventually leading to hypoxia in the body. Therefore,inflammatory mediators play a key role in the pathogenesis ofARDS.t is now known that several proinflammatory cytokines (IL-6, IL-8, IL-1β, granulocytemacrophage colony-stimulating factor, and reactive oxygen species) and chemokines (such as CCL2, CCL-5, IFNγ -induced protein10 (IP-10), and CCL3) all contribute to the occurrence ofARDS.44–4hese results support such points of view that, following SARS-CoV infection, high virus titers and dysregulationof cytokine/chemokine response cause an inflammatory cytokinestorm. The inflammatory cytokine storm is accompanied by immunopathological changes in the lungsHigh levels of expression of IL-1B, IFN-γ , IP-10, and monocyte hemoattractant protein 1 (MCP-1) have been detected in patientswith COVID-19.These inflammatory cytokines may activate the Thelper type 1 (Th1) cell response.47 Th1 activation is a key event in the activation of specific immunity.48 However, unlike SARS patients, patients with COVID-19 also have elevated levels of Th2 cellsecreted cytokines (such as IL-4 and IL-10), which inhibit the inflammatory response. The serum levels of IL-2R and IL-6 in patients with COVID-19 are positively correlated with the severity of the disease (i.e., critically ill patients > severely ill patients > ordinary patients).49ther studies have found that, compared with COVID-19 patients from general wards, patients in the intensive care unit (ICU) display increased serum levels of granulocyte colony-stimulating factor, IP-10, MCP-1, macrophage inflammatory protein-1A, and TNF-α. The above studies suggest that the cytokine storm is positively correlated with disease severity.47
Causes
Disease name] may be caused by [cause1], [cause2], or [cause3].
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Common causes of [disease] include [cause1], [cause2], and [cause3].
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The most common cause of [disease name] is [cause 1]. Less common causes of [disease name] include [cause 2], [cause 3], and [cause 4].
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The cause of [disease name] has not been identified. To review risk factors for the development of [disease name], click here.
Epidemiology and Demographics
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
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In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
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In [year], the incidence of [disease name] is approximately [number range] per 100,000 individuals with a case-fatality rate of [number range]%.
Patients of all age groups may develop [disease name].
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The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
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[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
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[Chronic disease name] is usually first diagnosed among [age group].
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[Acute disease name] commonly affects [age group].
There is no racial predilection to [disease name].
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[Disease name] usually affects individuals of the [race 1] race. [Race 2] individuals are less likely to develop [disease name].
[Disease name] affects men and women equally.
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[Gender 1] are more commonly affected by [disease name] than [gender 2]. The [gender 1] to [gender 2] ratio is approximately [number > 1] to 1.
The majority of [disease name] cases are reported in [geographical region].
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[Disease name] is a common/rare disease that tends to affect [patient population 1] and [patient population 2].
Risk Factors
There are no established risk factors for [disease name].
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The most potent risk factor in the development of [disease name] is [risk factor 1]. Other risk factors include [risk factor 2], [risk factor 3], and [risk factor 4].
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Common risk factors in the development of [disease name] include [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
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Common risk factors in the development of [disease name] may be occupational, environmental, genetic, and viral.
Screening
There is insufficient evidence to recommend routine screening for [disease/malignancy].
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According to the [guideline name], screening for [disease name] is not recommended.
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According to the [guideline name], screening for [disease name] by [test 1] is recommended every [duration] among patients with [condition 1], [condition 2], and [condition 3].
Natural History, Complications, and Prognosis
If left untreated, [#]% of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
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Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
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Prognosis is generally excellent/good/poor, and the 1/5/10-year mortality/survival rate of patients with [disease name] is approximately [#]%.
Diagnosis
Diagnostic Study of Choice
The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met: [criterion 1], [criterion 2], [criterion 3], and [criterion 4].
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The diagnosis of [disease name] is based on the [criteria name] criteria, which include [criterion 1], [criterion 2], and [criterion 3].
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The diagnosis of [disease name] is based on the [definition name] definition, which includes [criterion 1], [criterion 2], and [criterion 3].
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There are no established criteria for the diagnosis of [disease name].
History and Symptoms
The majority of patients with [disease name] are asymptomatic.
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The hallmark of [disease name] is [finding]. A positive history of [finding 1] and [finding 2] is suggestive of [disease name]. The most common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3]. Common symptoms of [disease] include [symptom 1], [symptom 2], and [symptom 3]. Less common symptoms of [disease name] include [symptom 1], [symptom 2], and [symptom 3].
Physical Examination
Patients with [disease name] usually appear [general appearance]. Physical examination of patients with [disease name] is usually remarkable for [finding 1], [finding 2], and [finding 3].
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Common physical examination findings of [disease name] include [finding 1], [finding 2], and [finding 3].
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The presence of [finding(s)] on physical examination is diagnostic of [disease name].
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The presence of [finding(s)] on physical examination is highly suggestive of [disease name].
Laboratory Findings
An elevated/reduced concentration of serum/blood/urinary/CSF/other [lab test] is diagnostic of [disease name].
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Laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
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[Test] is usually normal among patients with [disease name].
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Some patients with [disease name] may have elevated/reduced concentration of [test], which is usually suggestive of [progression/complication].
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There are no diagnostic laboratory findings associated with [disease name].
Electrocardiogram
There are no ECG findings associated with [disease name].
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An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
X-ray
There are no x-ray findings associated with [disease name].
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An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with [disease name].
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Echocardiography/ultrasound may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
CT scan
There are no CT scan findings associated with [disease name].
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[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
MRI
There are no MRI findings associated with [disease name].
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[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
Other Imaging Findings
There are no other imaging findings associated with [disease name].
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[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
There are no other diagnostic studies associated with [disease name].
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[Diagnostic study] may be helpful in the diagnosis of [disease name]. Findings suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
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Other diagnostic studies for [disease name] include [diagnostic study 1], which demonstrates [finding 1], [finding 2], and [finding 3], and [diagnostic study 2], which demonstrates [finding 1], [finding 2], and [finding 3].
Treatment
Medical Therapy
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
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Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
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The majority of cases of [disease name] are self-limited and require only supportive care.
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[Disease name] is a medical emergency and requires prompt treatment.
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The mainstay of treatment for [disease name] is [therapy].
OR The optimal therapy for [malignancy name] depends on the stage at diagnosis.
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[Therapy] is recommended among all patients who develop [disease name].
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Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
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Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
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Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
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Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
Surgery
Surgical intervention is not recommended for the management of [disease name].
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Surgery is not the first-line treatment option for patients with [disease name]. Surgery is usually reserved for patients with either [indication 1], [indication 2], and [indication 3]
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The mainstay of treatment for [disease name] is medical therapy. Surgery is usually reserved for patients with either [indication 1], [indication 2], and/or [indication 3].
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The feasibility of surgery depends on the stage of [malignancy] at diagnosis.
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Surgery is the mainstay of treatment for [disease or malignancy].
Primary Prevention
There are no established measures for the primary prevention of [disease name].
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There are no available vaccines against [disease name].
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Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
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[Vaccine name] vaccine is recommended for [patient population] to prevent [disease name]. Other primary prevention strategies include [strategy 1], [strategy 2], and [strategy 3].
Secondary Prevention
There are no established measures for the secondary prevention of [disease name].
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Effective measures for the secondary prevention of [disease name] include [strategy 1], [strategy 2], and [strategy 3].
References
- ↑ https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. Missing or empty
|title=(help) - ↑ Lu, Jian; Cui, Jie; Qian, Zhaohui; Wang, Yirong; Zhang, Hong; Duan, Yuange; Wu, Xinkai; Yao, Xinmin; Song, Yuhe; Li, Xiang; Wu, Changcheng; Tang, Xiaolu (2020). "On the origin and continuing evolution of SARS-CoV-2". National Science Review. doi:10.1093/nsr/nwaa036. ISSN 2095-5138.
- ↑ Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". The Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. ISSN 0140-6736.
- ↑ https://www.cdc.gov/coronavirus/2019-ncov/about/transmission.html. Missing or empty
|title=(help)