Capillary leak syndrome following COVID-19 vaccination: Data from the European pharmacovigilance database Eudravigilance.

Capillary leak syndrome (CLS) emerged as new adverse event after immunization (AEFI) associated to COVID-19 vaccination. CLS is a rare condition characterized by increased capillary permeability, resulting in hypoalbuminemia, hypotension, and edema mainly in the upper and lower limbs. Our pharmacovigilance study aims to evaluate the CLS onset following receipt of COVID-19 mRNA vaccines (mRNA-1273 and BNT162b2) compared to viral vector vaccines (Ad26.COV2-S and ChAdOx1-SARS-COV-2). We carried a cross-sectional study using all Individual Case Safety Reports (ICSRs) reporting a COVID-19 vaccine as suspected drug and CLS as AEFI, which were collected in the pharmacovigilance database EudraVigilance from January 1st, 2021, to January 14th, 2022. We applied the Reporting Odds Ratio (ROR) 95% CI for the disproportionality analysis. During our study period, CLS was described as AEFI in 84 out of 1,357,962 ICRs reporting a vaccine COVID-19 as suspected drug and collected in the EV database. Overall, the ICSR reported by CLS were mainly related to the viral vector COVID-19(ChAdOx1-SARS-COV-2 = 36; Ad26.COV2-S = 9). The mRNA COVID-19 vaccines were reported in 39 ICSRs (BNT162b2 =33; mRNA-1273 =6). Majority of ICSRs were reported by healthcare professionals (71.4%). Majority of the patients were adult (58.3%) and the female gender accounted in more than 65% of ICSRs referred both to classes vaccines. In particular, women were more represented in ICSRs referred to mRNA-1273 (83.3%) and to ChAdOx1-SARS-COV-2 (72.2%). The CLS outcome was more frequently favorable in mRNA ICSRs (33,3%) than the viral vector ones (13.3%). Among the ICSRs reporting CLS with unfavorable outcome, we found also 9 fatal cases (BNT162b2 = 1; ChAdOx1-SARS-COV-2 = 4; Ad26.COV2-S = 4). From disproportionality analysis emerged a lower CLS reporting probability after vaccination with mRNA vaccines compared to viral vector-based ones (ROR 0.5, 95% CI 0.3-0.7; p <0.001).Our findings, even if subject to the limitations of spontaneous reporting systems, suggest a small but statistically significant safety concern for CLS following receipt of COVID-19 viral vector vaccines, in particular with Ad26.COV2-S. Cytokine-release following T-cell activation could be involved in CLS occurrence, but a precise mechanism has been not yet identified. COVID-19 vaccines remain attentive as possible triggers of CLS.

Pathogenesis and Immune Status in COVID-19 Pneumonia-A Minireview

The novel coronavirus (SARS-CoV-2), which was isolated in January 2020, emerged as a result of natural evolution and has already infected millions of people around the world due to its extensive human-to-human transmission capacity. Highlighting the clinical manifestations, pathology and immune response against the SARS-CoV-2 infection process, this review study was con-ducted through a comprehensive bibliographic search of academic papers that are available online at the following databases Science Direct, Pub Med, ACS Publications, Nature, BioRxiv and Me-dRxiv. According to the analyzed works, people infected with SARS-CoV-2 may display fever and dry cough as the main clinical symptoms and they may also present breathing difficulty, muscle pain (myalgia), chills, lack of appetite, fatigue, sore throat, altered consciousness, diarrhea, vomit-ing, nasal discharge and syncope. When considering the immune status of patients with COVID-19, it is highlighted that hypercytokinemia contributes to the severity that can even result in death. Lymphopenia is the most frequent prognosis described in cases of COVID-19. Thus, a de-tailed understanding of the specific inflammatory pathways that result in the pathology of COVID-19 is crucial for the immediate development of clinical therapeutic approaches.Copyright © 2021 Bentham Science Publishers.

Inducible generalized activation of hSTING-N154S expression in mice leads to lethal hypercytokinemia: a model for "cytokine storm".

Excessive levels of circulating proinflammatory mediators, known as "hypercytokinemia," that are generated by overwhelming immune system activation can lead to death due to critical organ failure and thrombotic events. Hypercytokinemia has been frequently associated with a variety of infectious and autoimmune diseases, with severe acute respiratory syndrome coronavirus 2 infection currently being the commonest cause, of what has been termed the cytokine storm. Among its various functions within the host, STING (stimulator of interferon genes) is critical in the defense against certain viruses and other pathogens. STING activation, particularly within cells of the innate immune system, triggers potent type I interferon and proinflammatory cytokine production. We thus hypothesized that generalized expression of a constitutively active STING mutant in mice would lead to hypercytokinemia. To test this, a Cre-loxP-based system was used to cause the inducible expression of a constitutively active hSTING mutant (hSTING-N154S) in any tissue or cell type. Herein, we employed a tamoxifen-inducible ubiquitin C-CreERT2 transgenic to obtain generalized expression of the hSTING-N154S protein, thereby triggering the production of IFN-ß and multiple proinflammatory cytokines. This required euthanizing the mice within 3 to 4 d after tamoxifen administration. This preclinical model will allow for the rapid identification of compounds aimed at either preventing or ameliorating the lethal effects of hypercytokinemia.

Fatal Fulminant Cerebral Edema in Six Children with SARS-CoV-2 Omicron BA.2 Infection in Taiwan.

Acute fulminant cerebral edema in children following SARS-CoV-2 infection has been rarely reported. Such patients frequently demonstrate rapid progression rapid progression and are usually fatal. In this retrospective study, we describe the detailed clinical, laboratory, and neuroimaging features of six fatal cases in Taiwan. All patients had shock initially, five showed rapid progression to multi-organ failure and disseminated intravascular coagulation, and three developed acute respiratory distress syndromes. The inflammatory biomarkers in the first 3 days, including interleukin 6, ferritin, lactate dehydrogenase and D-dimer, showed significant elevation in all cases. Hyper-inflammatory response may play a role in the pathophysiology.

Interferon signaling and hypercytokinemia-related gene expression in the blood of antidepressant non-responders.

Only 50% of patients with depression respond to the first antidepressant drug administered. Thus, biomarkers for prediction of antidepressant responses are needed, as predicting which patients will not respond to antidepressants can optimize selection of alternative therapies. We aimed to identify biomarkers that could predict antidepressant responsiveness using a novel data-driven approach based on statistical pattern recognition. We retrospectively divided patients with major depressive disorder into antidepressant responder and non-responder groups. Comprehensive gene expression analysis was performed using peripheral blood without narrowing the genes. We designed a classifier according to our own discrete Bayes decision rule that can handle categorical data. Nineteen genes showed differential expression in the antidepressant non-responder group (n = 15) compared to the antidepressant responder group (n = 15). In the training sample of 30 individuals, eight candidate genes had significantly altered expression according to quantitative real-time polymerase chain reaction. The expression of these genes was examined in an independent test sample of antidepressant responders (n = 22) and non-responders (n = 12). Using the discrete Bayes classifier with the HERC5, IFI6, and IFI44 genes identified in the training set yielded 85% discrimination accuracy for antidepressant responsiveness in the 34 test samples. Pathway analysis of the RNA sequencing data for antidepressant responsiveness identified that hypercytokinemia- and interferon-related genes were increased in non-responders. Disease and biofunction analysis identified changes in genes related to inflammatory and infectious diseases, including coronavirus disease. These results strongly suggest an association between antidepressant responsiveness and inflammation, which may be useful for future treatment strategies for depression.

Mechanism and Experimental Verification of the Use of Rhodiola crenulata to Cytokine Storm Based on Network Pharmacology and Molecular Docking

Objective: To identify the potential biological mechanisms by which Rhodiola crenulata (RC) treats cytokine storm (CS) using network pharmacology, molecular docking, and experimental verification. Method(s): The ingredients and targets of RC were collected from the Organchem database. CS-related genes were collected using the GeneCards and OMIM databases. Cytoscape 3.7.2 software was used to construct the RC-CS network diagram. These data were inputted into the STRING database to construct a protein-protein interaction network. we performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes enrichment analysis using DAVID and R software. Molecular docking of the active ingredient and pathway-related targets was carried out using AutoDock Vina and PyMOL, and then a CS model was established in rats induced by lipopolysaccharide for in vivo experimental verification. Result(s): The network pharmacology results showed that kaempferol was the most important active component of RC in the treatment of CS, and IL6 and STAT3 were identified as key targets. Molecular docking results showed that RC active components kaempferol had a good binding ability to IL6/STAT3. At the same time, compared with the model group, different doses of kaempferol could down-regulate the expression of inflammatory factors (P <.05), and protect against systemic inflammatory response multiple organ damage. Conclusion(s): This study preliminarily revealed that RC can prevent and treat CS by regulating the expression of inflammatory factors, inhibiting the systemic inflammatory response induced by lipopolysaccharide, and providing a theoretical basis for the study of its pharmacodynamic material basis and mechanism of action. Copyright © The Author(s) 2022.

An autopsy case of fulminant myocarditis after severe acute respiratory syndrome coronavirus 2 vaccine inoculation.

A 61-year-old woman without significant medical history developed fever 3 days after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and went into shock the next day. She was negative for SARS-CoV-2 mRNA in real-time polymerase chain reaction (PCR). Finally, she died 10 days after vaccination. At autopsy, the heart showed moderate dilatation of both ventricles, and the myocardium showed an uneven color change and decreased elasticity. Histologically, severe myocarditis with extensive myocytolysis was observed. The myocarditis showed severe inflammatory cell infiltration with T-lymphocyte and macrophage predominance, and in addition to the inflammatory cells described above, vast nuclear dust accompanying neutrophilic infiltration was observed. In the bone marrow and lymph nodes, hemophagocytosis was observed. In postmortem examination, nucleic acids of any cardiotropic viruses including SARS-CoV-2 were not detected using multivirus real-time PCR system. We discussed the relationship between the possible immune reaction after vaccination and the myocarditis observed in this case from immunopathological viewpoints. This mRNA vaccine is the first applied nucleic acid vaccine for humans, and its mechanism of efficacy and immune acquisition remain unclear. We hope the accumulation of more detailed analyses of the similar cases to reveal the mechanism of this kind of adverse reaction.

Antiplatelet Activity of Riamilovir under Conditions of Lipopolysaccharide Intoxication.

We studied the effect of antiviral agent riamilovir on ADP-induced platelet aggregation in the absence and presence of LPS. Unlike acetylsalicylic acid (reference drug), riamilovir did not exhibit antiplatelet effect in vitro. However, it markedly suppressed platelet reactivity in LPS-treated blood samples and was 2.2-fold superior to acetylsalicylic acid in terms of IC50 value. In in vivo experiments, riamilovir under conditions of hypercytokinemia blocked platelet aggregation in rats by 64%.

Cleavage-Responsive Biofactory T Cells Suppress Infectious Diseases-Associated Hypercytokinemia.

Severe infectious diseases, such as coronavirus disease 2019 (COVID-19), can induce hypercytokinemia and multiple organ failure. In spite of the growing demand for peptide therapeutics against infectious diseases, current small molecule-based strategies still require frequent administration due to limited half-life and enzymatic digestion in blood. To overcome this challenge, a strategy to continuously express multi-level therapeutic peptide drugs on the surface of immune cells, is established. Here, chimeric T cells stably expressing therapeutic peptides are presented for treatment of severe infectious diseases. Using lentiviral system, T cells are engineered to express multi-level therapeutic peptides with matrix metallopeptidases- (MMP-) and tumor necrosis factor alpha converting enzyme- (TACE-) responsive cleavage sites on the surface. The enzymatic cleavage releases γ-carboxyglutamic acid of protein C (PC-Gla) domain and thrombin receptor agonist peptide (TRAP), which activate endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1), respectively. These chimeric T cells prevent vascular damage in tissue-engineered blood vessel and suppress hypercytokinemia and lung tissue damages in vivo, demonstrating promise for use of engineered T cells against sepsis and other infectious-related diseases.

Can smoking prevalence explain COVID-19 indicators (cases, mortality, and recovery)? A comparative study in OECD countries.

There are many risk factors associated with the spread of the COVID-19 pandemic, including low wind speed, fossil fuel energy production, air pollution, and smoking. Several studies argue that smoking is not a risk factor for COVID-19 morbidity among males or any other sub-group. The study aims to analyze the following research questions: (1) can smoking prevalence explain COVID-19 indicators (cases, mortality, and recovery)? Are these relationships monotonically increasing or decreasing? In an attempt to test the counter-intuitive possibility of a non-linear relationship, the proposed empirical model relaxes the assumption of monotonic change by applying the quadratic design and testing which one of the two competing models (quadratic or linear) better fits the data. Findings suggest more complex relationships between corona indices and prevalence of smoking than previously thought. These patterns might be explained by several conditions such as the attenuation of hypercytokinemia for mild levels of smoking prevalence compared with non-smokers, elevated social distancing of smokers in countries with lower smoking prevalence, and unidentified factors that should be examined in future research.

Blood purification in sepsis and COVID-19: what´s new in cytokine and endotoxin hemoadsorption.

Sepsis and COVID-19 are two clinical conditions that can lead to a dysregulated inflammatory state causing multiorgan dysfunction, hypercytokinemia, and a high risk of death. Specific subgroups of critically ill patients with particular characteristics could benefit from rescue treatment with hemoadsorption. There is a lack of adequately designed randomized controlled trials evaluating the potential benefits of cytokine or endotoxin hemoadsorption. Critically ill COVID-19 patients with severe acute respiratory failure poorly responsive to conventional treatment could be candidates to receive cytokine hemoadsorption in the presence of high levels of interleukin 6. This treatment can also be suitable for patients with refractory septic shock and hypercytokinemia. In the context of high endotoxin activity, hemoadsorption with polymyxin B could improve clinical parameters and the prognosis of patients with refractory septic shock. Predictive enrichment, using biomarkers or other individual features, identifies potential responders to cytokine, endotoxin, or sequential hemoadsorption. Besides, recognizing the particular subsets of patients likely to respond to one or both types of hemoadsorption will aid the design of future studies that accurately validate the effectiveness of these therapies.

Potential Immunomodulatory Properties of Biologically Active Components of Spices Against SARS-CoV-2 and Pan ß-Coronaviruses.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced COVID-19 has emerged as a defining global health crisis in current times. Data from the World Health Organization shows demographic variations in COVID-19 severity and lethality. Diet may play a significant role in providing beneficial host cell factors contributing to immunity against deadly SARS-CoV-2 pathogenesis. Spices are essential components of the diet that possess anti-inflammatory, antioxidant, and antiviral properties. Hyperinflammation, an aberrant systemic inflammation associated with pneumonia, acute respiratory failure, and multiorgan dysfunction, is a major clinical outcome in COVID-19. Knowing the beneficial properties of spices, we hypothesize that spice-derived bioactive components can modulate host immune responses to provide protective immunity in COVID-19. This study emphasizes that biologically active components of spices might alleviate the sustained pro-inflammatory condition by inhibiting the activity of tumor necrosis factor-alpha (TNF-α), interleukins (IL6, IL8), and chemokine (CCL2) known to be elevated in COVID-19. Spices may potentially prevent the tissue damage induced by oxidative stress and pro-inflammatory mediators during SARS-CoV-2 infection. The current study also highlights the effects of spices on the antioxidant pathways mediated by Nrf2 (nuclear factor erythroid 2-related factor 2) and Hmox1 (heme oxygenase 1) to restore oxidative homeostasis and protect from aberrant tissue damage. Taken together, the anti-inflammatory and antioxidant activities of bioactive components of spices may hold a promise to target the cellular pathways for developing antivirals against SARS-CoV-2 and pan ß-coronaviruses.

Determination role of some biomarkers tests for severe SARS-COV-2 infections in babylon province/IRAQ.

In a series of 30 SARS-COV-2 infected patients whom clinically proven as severe pulmonary infection form. These were found with male/female ratio of 1:1. The age range of below 50 years old account for 60% and those of above 50 years old constitute the remaining 40%. They were the residents of Merjan Teaching Hospital/ Babylon Province/Iraq, to the period of March to April 2021 and primary screen by PCR for Sars-cov-2 RNA genes, in public health central laboratory found to be positive. The over- all laboratory investigation were; D -dimer, Ferritin, LDH, acute phase reactant C, and IL6. LDH was tempted to probe the immune mediated pulmonary tissue injury (367.48 U/L.), ferritin response may indicate hemolytic and acute phase reactant expressed as hyper-inflammation (331.1 ng/L.). |The D-dimer shed a light on the fibrino-lytic responses (6049 ng/L.) post to the immune-thrombotic overreactions, where IL6 levels give a clue to the state of hyper-cytokinemia (171.92 pg/L.). The overall immune status of these patients was as; Hyper-inflammatory and immune overreaction. The inflammatory and immune herd plots were of skewed distribution types.

The role of influenza A virus-induced hypercytokinemia.

Influenza viruses are one of the leading causes of respiratory tract infections in humans and their newly emerging and re-emerging virus strains are responsible for seasonal epidemics and occasional pandemics, leading to a serious threat to global public health systems. The poor clinical outcome and pathogenesis during influenza virus infection in humans and animal models are often associated with elevated proinflammatory cytokines and chemokines production, which is also known as hypercytokinemia or "cytokine storm", that precedes acute respiratory distress syndrome (ARDS) and often leads to death. Although we still do not fully understand the complex nature of cytokine storms, the use of immunomodulatory drugs is a promising approach for treating hypercytokinemia induced by an acute viral infection, including highly pathogenic avian influenza virus infection and Coronavirus Disease 2019 (COVID-19). This review aims to discuss the immune responses and cytokine storm pathology induced by influenza virus infection and also summarize alternative experimental strategies for treating hypercytokinemia caused by influenza virus.

Cytokine Storm May Not Be the Chief Culprit for the Deterioration of COVID-19.

COVID-19 is spreading and ravaging all over the world, and the number of deaths is increasing day by day without downward trend. However, there is limited knowledge of pathogenesis on the deterioration of COVID-19 at present. In this study we aim to determine whether cytokine storm is really the chief culprit for the deterioration of COVID-19. The confirmed COVID-19 patients were divided into moderate group (n = 89), severe group (n = 37), and critical group (n = 41). Demographic data were collected and recorded on admission to ICU. Clinical data were obtained when moderate, severe, or critical COVID-19 was diagnosed, and then compared between groups. The proportion of enrolled COVID-19 patients was slightly higher among males (52.5%) than females (47.5%), with an average age of 64.87 years. The number of patients without comorbidities exceed one third (36.1%), and patients with 1, 2, 3, 4 kinds of comorbidities accounted for 23.0%, 23.0%, 13.1%, and 4.9%, respectively. IL-6, IL-10, TNF, and IFN-γ, including oxygenation index, sequential organ failure assessment score, white blood cell count, lymphocyte count, lymphocyte percentage, platelet, C-reaction protein, lactate dehydrogenase, creatine kinase isoenzyme, albumin, D-Dimer, and fibrinogen showed significant difference between groups. Some, but not all, cytokines and chemokines were involved in the deterioration of COVID-19, and thus cytokine storm maybe just the tip of the iceberg and should be used with caution to explain pathogenesis on the deterioration of COVID-19, which might be complex and related to inflammation, immunity, blood coagulation, and multiple organ functions. Future studies should focus on identification of specific signaling pathways and mechanisms after severe acute respiratory syndrome coronavirus 2 infections (IRB number: IRB-AF/SC-04/01.0).

Virus-triggered secondary hemophagocytic lymphohistiocytosis.

Primary (familial/hereditary) and secondary (non-familial/hereditary) hemophagocytic lymphohistiocytosis (HLH) are hyperinflammatory and hypercytokinemic syndromes. Secondary HLH includes infection- (eg viral/bacterial/fungal/parasitic) and non-infection- (eg collagen disease or malignancy) related diseases. Viral HLH is the major type among all age groups. Secondary viral HLH and primary HLH must be differentiated carefully because primary HLH can be associated with viral infection(s), and the outcome is dismal without a timely diagnosis and hematopoietic stem cell transplantation (HSCT). Epstein-Barr virus (EBV)-related HLH (EBV-HLH) is the most common type of viral HLH in childhood. For non-EBV-HLH, appropriate treatment of viral infection, followed by immunomodulatory agent(s) such as corticosteroids, intravenous immunoglobulin or cyclosporine A, is usually successful; however, recent SARS-CoV-2-related HLH may become life-threatening. EBV-HLH may occur heterogeneously associated with the primary infection, with chronic active EBV infection or with underlying primary HLH. Although immunomodulatory agent(s) are effective in the majority of EBV-HLH cases, management differs from that of non-EBV-HLH because severe and refractory cases may require etoposide-containing HLH-1994/2004 regimens or other experimental agents. The novel agent, emapalumab (an anti-IFN-γ monoclonal antibody) can be used to treat EBV-HLH cases to avoid the risk of secondary malignancy due to etoposide. Finally, HSCT is required for refractory EBV-HLH cases and can also be curative in some other cases.

PMX-DHP Therapy for Dyspnea and Deoxygenation in Severe COVID-19 Pneumonia: A Case Series.

Hypercytokinemia induced by coronavirus disease-19 (COVID-19) is associated with severe pulmonary involvement, which may lead to respiratory failure. These conditions play an important role in the worsening of clinical symptoms in patients with severe COVID-19. There is no established treatment for hypercytokinemia. We report on two patients whose clinical symptoms improved after direct hemoperfusion using polymyxin B-immobilized fiber column (PMX-DHP), following the administration of the anti-inflammatory agent tocilizumab. Case A was a 70-year-old man diagnosed with COVID-19 pneumonia. Despite treatment with ciclesonide and favipiravir, supplemental oxygen was administered due to the worsening of dyspnea with tachypnea. Although tocilizumab was started on day 6, the patient deteriorated into deoxygenation, presenting with the PaO2/FIO2 (P/F) ratio of 92. On days 8 and 10, the patient received PMX-DHP therapy. On day 11, his dyspnea improved. On day 13, his P/F ratio began to improve, and oxygen therapy was discontinued on day 18. The patient recovered without requiring mechanical ventilation. Case B was a 70-year-old man diagnosed with COVID-19 pneumonia and treated with favipiravir, starting on day 0. Despite starting ciclesonide inhalation and tocilizumab on day 2, his P/F ratio was 53. On day 5, he received PMX-DHP therapy. On day 6, his dyspnea improved, as did his P/F ratio, reaching 81 on day 8. Finally, his clinical symptoms resolved, and he was discharged from the intensive care unit without requiring mechanical ventilation. These cases indicate that PMX-DHP therapy might be a suitable treatment option for dyspnea and deoxygenation in COVID-19 pneumonia, especially in cases where an anti-inflammatory agent, such as tocilizumab, has failed to achieve the desired effect.

The Artificial-Liver Blood-Purification System Can Effectively Improve Hypercytokinemia for COVID-19.

Since the December 2019 outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, the infection has spread locally and globally resulting in a pandemic. As the numbers of confirmed diagnoses and deaths continue to rise, COVID-19 has become the focus of international public health. COVID-19 is highly contagious, and there is no effective treatment yet. New treatment strategies are urgently needed to improve the treatment success rate of severe and critically ill patients. Increasing evidence has shown that a cytokine storm plays an important role in the progression of COVID-19. The artificial-liver blood-purification system (ALS) is expected to improve the outcome of the cytokine storm. In the present study, the levels of cytokines were detected in 12 COVID-19 patients pre- and post-ALS with promising results. The present study shows promising evidence that ALS can block the cytokine storm, rapidly remove the inflammatory mediators, and hopefully, suppress the progression of the disease, thereby providing a new strategy for the clinical treatment of COVID-19.

Hypercytokinemia and Pathogen-Host Interaction in COVID-19.

Severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 (SARS-CoV-2) is a novel coronavirus identified as the cause of coronavirus disease-2019 (COVID-19) that began in Wuhan, China in late 2019 and spread now in 210 countries and territories around the world. Many people are asymptomatic or with mild symptoms. However, in some cases (usually the elderly and those with comorbidities) the disease may progress to pneumonia, acute respiratory distress syndrome and multi-organ dysfunction that can lead to death. Such wide interindividual differences in response to SARS-CoV-2 infection may relate to several pathogen- and host-related factors. These include the different levels of the ubiquitously present human angiotensin I converting enzyme 2 (ACE2) receptors gene expression and its variant alleles, the different binding affinities of ACE2 to the virus spike (S) protein given its L- and S-subtypes and the subsequent extent of innate immunity-related hypercytokinemia. The extensive synthesis of cytokines and chemokines in coronavirus diseases was suggested as a major factor in exacerbating lung damage and other fatal complications. The polymorphisms in genes coding for pro-inflammatory cytokines and chemokines have been associated with mediating the response and susceptibility to a wide range of infections and their severe outcomes. Understanding the nature of pathogen-host interaction in COVID-19 symptomatology together with the role of hypercytokinemia in disease severity may permit developing new avenues of approach for prevention and treatment and can delineate public health measures to control the spread of the disease.

Cytokine storm induced by SARS-CoV-2 infection: The spectrum of its neurological manifestations.

The new coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can trigger a hyperinflammatory state characterized by elevated cytokine levels known as hypercytokinemia or cytokine storm, observed most often in severe patients. Though COVID-19 is known to be a primarily respiratory disease, neurological complications affecting both the central and peripheral nervous systems have also been reported. This review discusses potential routes of SARS-CoV-2 neuroinvasion and pathogenesis, summarizes reported neurological sequelae of COVID-19, and examines how aberrant cytokine levels may precipitate these complications. Clarification of the pathogenic mechanisms of SARS-CoV-2 is needed to encourage prompt diagnosis and optimized care. In particular, identifying the presence of cytokine storm in patients with neurological COVID-19 manifestations will facilitate avenues for treatment. Future investigations into aberrant cytokine levels in COVID-19 patients with neurological symptoms as well as the efficacy of cytokine storm-targeting treatments will be critical in elucidating the pathogenic mechanisms and effective treatments of COVID-19.