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 is suspected to be the major cause of death in many viral pandemics , especially in young adults:
Classification
There is no established system for the classification of COVID-19-associated cytokine storm.
Pathophysiology
Causes
Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called SARS-CoV-2 and is the cause of cytokine storm in COVID-19 infection.
Epidemiology and Demographics
The incidence/prevalence of [disease name] is approximately [number range] per 100,000 individuals worldwide.
OR
In [year], the incidence/prevalence of [disease name] was estimated to be [number range] cases per 100,000 individuals worldwide.
OR
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].
OR
The incidence of [disease name] increases with age; the median age at diagnosis is [#] years.
OR
[Disease name] commonly affects individuals younger than/older than [number of years] years of age.
OR
[Chronic disease name] is usually first diagnosed among [age group].
OR
[Acute disease name] commonly affects [age group].
There is no racial predilection to [disease name].
OR
[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.
OR
[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].
OR
[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 COVID-19-associated Cytokine storm].
Screening
There is insufficient evidence to recommend routine screening for COVID-19 related cytokine storm.
Natural History, Complications, and Prognosis
- Cytokine storm has no definition.it denotes a hyperactive immune response characterized by release of interferons, interleukins, TNF, chemokines and several other mediators. Since the SARS-Cov-1 cytokine elevation was associated with various adverse features.[5][6]
- The characteristic of this phenomena could be considered as an indicator of adverse clinical outcome such as ARDs, Shock and ARF.[7]
Diagnosis
Diagnostic Study of Choice
Most important Cytokine concentration rise is :[8]
History and Symptoms
- COVID-19 infected individual whom go through more adverse clinical manifestation, 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 done so far, Interleukin-6 is the best indicator of cytokine storm.
- Below is different studies revealing cytokine level in healthy and severe infected individuals:
| Plasma IL-6 concenteration reported in COVID-19 | ||
|---|---|---|
| Report | Total population(IL-6 level pg/ml) | Severe infection (IL-6 level pg/ml) |
| Zhou et al[9] | 191 (5-11) | 54 (8-14) |
| Wu et al[10] | 123 (6-9) | 84 (6-11) |
| Mo et al[11] | 155 (17-96) | 85 (31-165) |
Electrocardiogram
There are no ECG findings regarding to COVID-19-associated Cytokine storm.
X-ray
There are no x-ray findings regarding to COVID-19-associated Cytokine storm.
Echocardiography or Ultrasound
There are no echocardiography or ultrasound findings regarding to COVID-19-associated Cytokine storm.
CT scan
There are no CT scan findings regarding to COVID-19-associated Cytokine storm.
MRI
There are no MRI findings regarding to COVID-19-associated Cytokine storm.
Other Imaging Findings
There are no other imaging findings regarding to COVID-19-associated Cytokine storm.
Treatment
Medical Therapy
- There is no proven treatment suggested until now.
- Potential therapies for reducing inflammation are:
- Corticosteroids:[12]
- Systemic use of corticosteroid use is not recomended by WHO based on evidence from patients with MERS and ARDS.
- Tocilizumab:[13][14][15][16]
- Toclizumab is an FDA approved drug used for cytokine release syndrome after Chimeric Antigen Receptor.infusion. which cause cytokine release storm.
- It is IL-6 Receptor antibody, which is effective in similar clinical manifestations.
- In some off label studies, it is shown that tocolizumab can cause improvement in patients.
- Etoposide:[17]
- Etoposide is used for suppressing cytokine release in hemophagocytic lymphohistiocytosis
- In patients with severe disease etoposide can inhibit overwhelming inflamation.
- Ruxolitinib:[18]
- Jack1/2 inhibitor
- It is used in hemophagocytic lymphohistiocytosis
- In a prospective randomized trial it was shown to reduce levels of 7 cytokines compared to control group, which caused faster improvement in patients with sever infection.
- Corticosteroids:[12]
Surgery
Surgical intervention is not recommended for the management of COVID-19-associated cytokine storm.
Primary Prevention
There are no established measures for the primary prevention of COVID-19-associated cytokine storm.
Secondary Prevention
There are no established measures for the secondary prevention of COVID-19-associated cytokine storm.
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) - ↑ Calfee, Carolyn S; Delucchi, Kevin; Parsons, Polly E; Thompson, B Taylor; Ware, Lorraine B; Matthay, Michael A (2014). "Subphenotypes in acute respiratory distress syndrome: latent class analysis of data from two randomised controlled trials". The Lancet Respiratory Medicine. 2 (8): 611–620. doi:10.1016/S2213-2600(14)70097-9. ISSN 2213-2600.
- ↑ Famous, Katie R.; Delucchi, Kevin; Ware, Lorraine B.; Kangelaris, Kirsten N.; Liu, Kathleen D.; Thompson, B. Taylor; Calfee, Carolyn S. (2017). "Acute Respiratory Distress Syndrome Subphenotypes Respond Differently to Randomized Fluid Management Strategy". American Journal of Respiratory and Critical Care Medicine. 195 (3): 331–338. doi:10.1164/rccm.201603-0645OC. ISSN 1073-449X.
- ↑ Sinha, Pratik; Delucchi, Kevin L.; Thompson, B. Taylor; McAuley, Daniel F.; Matthay, Michael A.; Calfee, Carolyn S. (2018). "Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study". Intensive Care Medicine. 44 (11): 1859–1869. doi:10.1007/s00134-018-5378-3. ISSN 0342-4642.
- ↑ Schultz, Duane R.; Arnold, Patricia I. (1990). "Properties of four acute phase proteins: C-reactive protein, serum amyloid a protein, α1-acid glycoprotein, and fibrinogen". Seminars in Arthritis and Rheumatism. 20 (3): 129–147. doi:10.1016/0049-0172(90)90055-K. ISSN 0049-0172.
- ↑ Zhou, Fei; Yu, Ting; Du, Ronghui; Fan, Guohui; Liu, Ying; Liu, Zhibo; Xiang, Jie; Wang, Yeming; Song, Bin; Gu, Xiaoying; Guan, Lulu; Wei, Yuan; Li, Hui; Wu, Xudong; Xu, Jiuyang; Tu, Shengjin; Zhang, Yi; Chen, Hua; Cao, Bin (2020). "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study". The Lancet. 395 (10229): 1054–1062. doi:10.1016/S0140-6736(20)30566-3. ISSN 0140-6736.
- ↑ Wu, Chaomin; Chen, Xiaoyan; Cai, Yanping; Xia, Jia’an; Zhou, Xing; Xu, Sha; Huang, Hanping; Zhang, Li; Zhou, Xia; Du, Chunling; Zhang, Yuye; Song, Juan; Wang, Sijiao; Chao, Yencheng; Yang, Zeyong; Xu, Jie; Zhou, Xin; Chen, Dechang; Xiong, Weining; Xu, Lei; Zhou, Feng; Jiang, Jinjun; Bai, Chunxue; Zheng, Junhua; Song, Yuanlin (2020). "Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China". JAMA Internal Medicine. 180 (7): 934. doi:10.1001/jamainternmed.2020.0994. ISSN 2168-6106.
- ↑ Zhang, Yongxi; Wang, Fan; Cao, Qian; Zheng, Ruiying; Chen, Xiaoping; Ma, Zhiyong; Song, Shihui; Chen, Tielong; Luo, Mingqi; Liang, Ke; Gao, Shicheng; Cheng, Zhenshun; Xiong, Yong; Wang, Hongling; Zhao, Qiu; Deng, Liping; Xiao, Yu; Xing, Yuanyuan; Mo, Pingzheng (2020). "Clinical characteristics of refractory COVID-19 pneumonia in Wuhan, China". Clinical Infectious Diseases. doi:10.1093/cid/ciaa270. ISSN 1058-4838.
- ↑ 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.
- ↑ Le, Robert Q.; Li, Liang; Yuan, Weishi; Shord, Stacy S.; Nie, Lei; Habtemariam, Bahru A.; Przepiorka, Donna; Farrell, Ann T.; Pazdur, Richard (2018). "FDA Approval Summary: Tocilizumab for Treatment of Chimeric Antigen Receptor T Cell‐Induced Severe or Life‐Threatening Cytokine Release Syndrome". The Oncologist. 23 (8): 943–947. doi:10.1634/theoncologist.2018-0028. ISSN 1083-7159.
- ↑ Xu, Xiao-Jun; Tang, Yong-Min (2014). "Cytokine release syndrome in cancer immunotherapy with chimeric antigen receptor engineered T cells". Cancer Letters. 343 (2): 172–178. doi:10.1016/j.canlet.2013.10.004. ISSN 0304-3835.
- ↑ Campins L, Boixeda R, Perez-Cordon L, Aranega R, Lopera C, Force L (2020). "Early tocilizumab treatment could improve survival among COVID-19 patients". Clin Exp Rheumatol. 38 (3): 578. PMID 32456769 Check
|pmid=value (help). - ↑ Morena, Valentina; Milazzo, Laura; Oreni, Letizia; Bestetti, Giovanna; Fossali, Tommaso; Bassoli, Cinzia; Torre, Alessandro; Cossu, Maria Vittoria; Minari, Caterina; Ballone, Elisabetta; Perotti, Andrea; Mileto, Davide; Niero, Fosca; Merli, Stefania; Foschi, Antonella; Vimercati, Stefania; Rizzardini, Giuliano; Sollima, Salvatore; Bradanini, Lucia; Galimberti, Laura; Colombo, Riccardo; Micheli, Valeria; Negri, Cristina; Ridolfo, Anna Lisa; Meroni, Luca; Galli, Massimo; Antinori, Spinello; Corbellino, Mario (2020). "Off-label use of tocilizumab for the treatment of SARS-CoV-2 pneumonia in Milan, Italy". European Journal of Internal Medicine. 76: 36–42. doi:10.1016/j.ejim.2020.05.011. ISSN 0953-6205.
- ↑ La Rosée, Paul (2015). "Treatment of hemophagocytic lymphohistiocytosis in adults". Hematology. 2015 (1): 190–196. doi:10.1182/asheducation-2015.1.190. ISSN 1520-4391.
- ↑ Cao, Yang; Wei, Jia; Zou, Liang; Jiang, Tiebin; Wang, Gaoxiang; Chen, Liting; Huang, Liang; Meng, Fankai; Huang, Lifang; Wang, Na; Zhou, Xiaoxi; Luo, Hui; Mao, Zekai; Chen, Xing; Xie, Jungang; Liu, Jing; Cheng, Hui; Zhao, Jianping; Huang, Gang; Wang, Wei; Zhou, Jianfeng (2020). "Ruxolitinib in treatment of severe coronavirus disease 2019 (COVID-19): A multicenter, single-blind, randomized controlled trial". Journal of Allergy and Clinical Immunology. 146 (1): 137–146.e3. doi:10.1016/j.jaci.2020.05.019. ISSN 0091-6749.