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: Shakiba Hassanzadeh, MD[2] Ramyar Ghandriz MD[3] Ifrah Fatima, M.B.B.S[4]

Synonyms and Keywords: IL-6 rise in COVID-19, severe inflammatory response in COVID-19, sars cov-2 related hyperimmune response

Overview

Cytokine storms are suspected to be the major cause of death in the previous influenza virus pandemic of 1918, H5N1 epidemic of 1991 and SARS epidemic of 2003. A cytokine storm is an immune reaction that is characterized by dysregulated and excessive release of pro-inflammatory cytokines. Cytokine storms (dysregulated and excessive release of cytokines) have been associated with ARDS in SARS coronavirus (SARS-CoV) and MERS coronavirus (MERS-CoV) infections. The characteristic of this phenomenon could be considered as an indicator of adverse clinical outcomes such as ARDS, shock, and ARF. It has been reported that in patients with COVID-19 there is increase in IL-1B, IFN-γ, IP-10, and monocyte hemoattractant protein 1 (MCP-1) and COVID-19 patients in the intensive care unit (ICU) have increased levels of granulocyte colony-stimulating factor, IP-10, MCP-1, macrophage inflammatory protein-1A, and TNF-α compared to those in general wards. However, in contrast to SARS infection, patients with COVID-19 infection have high levels of IL-4 and IL-10 (secreted by Th2 cells), which are anti-inflammatory cytokines. Potential therapies suggested for cytokine storm include: Corticosteroids, tocilizumab, etoposide and ruxolitinib.

Historical Perspective

Classification

Pathophysiology

Cytokines Involved in Cytokine Storm

Pathogenesis of Cytokine Storm

Some of The Cytokines Involved in COVID-19-Associated-Cytokine Storm
Proinflammatory Interferones
Interleukines
  • IL-1β
  • IL-6
Chemokines
Colony-stimulating

factors  

Tumor necrosis

factor  

Anti-inflammatory Interleukines

Causes

Differentiating COVID-19 cytokine storm from other Diseases

Epidemiology and Demographics

  • Estimation of an accurate number of severe acute inflammation cases is hard due to the lack of a global system to define the severity of the disease.
  • Below is a comparison of different studies on the cytokine level of IL-6 in healthy and severely infected individuals:
Plasma IL-6 concenteration reported in COVID-19
Report Total population(IL-6 level range pg/ml) Severe infection (IL-6 level range pg/ml)
Zhou et al[20] 191 (5-11) 54 (8-14)
Wu et al[21] 123 (6-9) 84 (6-11)
Mo et al[22] 155 (17-96) 85 (31-165)
  • For more information about COVID-19 epidemiology and demographics please click here.

Risk Factors

Screening

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Study of Choice

The most important cytokines that increase are :[26]

The suggested strategy is to measure the so-called cytokines.

History and Symptoms

  • COVID-19 infected individuals who go through more adverse clinical manifestations, such as ARDS and high inflammatory states, are more likely to undergo cytokine elevation.
  • For COVID-19 associated history and symptoms click here.

Physical Examination

  • For COVID-19 Physical examination click here.

Laboratory Findings

  • According to many reviews, Interleukin-6 is the best indicator of the cytokine storm.
  • IL-6 concentration has been reported by many studies and is believed to be at a maximal cut of 80 pg/ml in a severe form of the disease.
  • Patients with higher levels of IL-6 are at a greater chance of severe disease.[22]

Electrocardiogram

  • There are no ECG findings regarding COVID-19-associated Cytokine storm.

X-ray

  • COVID-19 associated cytokine storm leads to Acute respiratory distress syndrome(ARDS).
  • X-ray Findings related to COVID-19 ARDS are:
    • Ground-glass opacification and consolidation
    • Early findings on the chest radiograph include normal or diffuse alveolar opacities (consolidation), which are often bilateral and which obscure the pulmonary vascular markings.
    • Later, these opacities progress to more extensive consolidation that is diffuse, and they are often asymmetrical.
Bilateral alveolar consolidation with panlobar change, with typical radiological findings of ARDS.[27]

Echocardiography or Ultrasound

CT scan

  • COVID-19 associated cytokine storm Leads to ARDS.
  • Multifocal ground glass opacity would be found at both lungs.
Multifocal ground glass, mainly in the periphery of both lungs.[28]

MRI

Other Imaging Findings

Treatment

Medical Therapy

Surgery

Primary Prevention

  • Since there is no vaccine for COVID-19 there are plenty of primary prevention suggested from CDC such as:[42]
    • Hand washing every 10 minutes.
    • Using alcoholic hand sanitizer.
    • Self quarantine for two weeks if symptomatic.
  • To view the primary prevention measures of COVID-19, click here.

Secondary Prevention

  • WHO recommends home care for patients with suspected COVID-19 who present with mild symptoms:[43]
    • Family members of an infected patient are better to wear masks.
    • Using separate bathroom and bedroom by the infected person.
    • Using antipyretics and analgesics for fever, myalgias, and headaches
  • To view the secondary prevention measures of COVID-19, click here.

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