Dr. Weeks’ Comment: Cytokine storms trigger COVID problems and inflammation drives the pathology. Anti-inflammatory diet is the smartest foundational option. “…Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals…”

Emerg Microbes Infec. 2020 Dec;9(1):1123-1130. doi: 10.1080/22221751.2020.1770129.

Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors

Abstract

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result in death. We hypothesized that cytokine storm is associated with severe outcome.

We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.

AND

Review J Med Internet Res 2020 Aug 13;22(8):e20193.  doi: 10.2196/20193.

Hazards of the Cytokine Storm and Cytokine-Targeted Therapy in Patients With COVID-19: Review

Miguel Quirch ¹, Jeannie Lee ¹, Shabnam Rehman ¹

Abstract

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has challenged medicine and health care on a global scale. Its impact and frightening mortality rate are in large part attributable to the fact that there is a lack of available treatments. (NOTE: Dr. Weeks disagrees. See Anti-inflammatory diet is the smartest foundational option.) It has been shown that in patients who are severely ill, SARS-CoV-2 can lead to an inflammatory response known as cytokine storm, which involves activation and release of inflammatory cytokines in a positive feedback loop of pathogen-triggered inflammation. Currently, cytokine storm is one of the leading causes of morbidity and mortality in SARS-CoV-2, but there is no proven treatment to combat this systemic response.

Results: A total of 38 eligible studies including 24 systematic reviews, 5 meta-analyses, 5 experimental model studies, 7 cohort studies, and 4 case reports matched the criteria.

Conclusions: The severity of the cytokine storm, measured by elevated levels of interleukin-1B, interferon-γ, interferon-inducible protein 10, and monocyte chemoattractant protein 1, was associated with COVID-19 disease severity. Many treatment options with different targets have been proposed during the early stages of the COVID-19 pandemic, ranging from targeting the virus itself to managing the systemic inflammation caused by the virus and the excessive cytokine response. Among the different agents to manage cytokine storm in patients with COVID-19, there is developing support for convalescent plasma therapy particularly for patients who are critically ill or mechanically ventilated and resistant to antivirals and supportive care. Treatment options that were proposed in the beginning phases of the pandemic were multidimensional, and further research is needed to develop a more established treatment guideline.

AND

Review Front Immunol  2020 Jun 16;11:1446. doi: 10.3389/fimmu.2020.01446. eCollection 2020.

The COVID-19 Cytokine Storm; What We Know So Far

Dina Ragab ¹, Haitham Salah Eldin ², Mohamed Taeimah ³, Rasha Khattab ⁴, Ramy Salem ¹

Abstract

COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called “cytokine storm” induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.