Search

COVID-19 emerged in December 2019 in Wuhan, China, spread worldwide rapidly, and caused millions of deaths in a short time. Many preclinical and clinical studies were performed to discover the most efficient therapy to reduce the mortality of COVID-19 patients. Among various approaches for preventing and treating COVID-19, mesenchymal stem cell (MSC) therapy can be regarded as a novel and efficient treatment for managing COVID-19 patients. In this review, we explain the pathogenesis of COVID-19 infection in humans and discuss the role of MSCs in suppressing the inflammation and cytokine storm produced by COVID-19. Then, we reviewed the clinical trial and systematic review studies that investigated the safety and efficacy of MSC therapy in the treatment of COVID-19 infection. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 19 (COVID-19) is the disease caused by SARS-CoV-2, a highly infectious member of the coronavirus family, which emerged in December 2019 in "Wuhan, China". It induces respiratory illness ranging from mild symptoms to severe disease. It was declared a "pandemic" by the World Health Organization (WHO) in March 2020. Since then, a vast number of clinical and experimental studies have been conducted to identify effective approaches for its prevention and treatment. Main body: The pathophysiology of COVID-19 represents an unprecedented challenge; it triggers a strong immune response, which may be exacerbated by "a cytokine storm syndrome". It also induces thrombogenesis and may trigger multi-organ injury. Therefore, different drug classes have been proposed for its treatment and prevention, such as antivirals, anti-SARS-CoV-2 antibody agents (monoclonal antibodies, convalescent plasma, and immunoglobulins), anti-inflammatory drugs, immunomodulators, and anticoagulant drugs. To the best of our knowledge, this review is the first to present, discuss, and summarize the current knowledge about the different drug classes used for the treatment of COVID-19, with special emphasis on their targets, mechanisms of action, and important adverse effects and drug interactions. Additionally, we spotlight the latest "October 2023" important guidelines (NIH, IDSA, and NICE) and FDA approval or authorization regarding the use of these agents in the management of COVID-19. Conclusion: Despite the wide array of therapeutic strategies introduced for the treatment of COVID-19, one of the most prominent therapeutic challenges is SARS-CoV-2 mutations and emerging new variants and subvariants. Currently, the anti-COVID-19 drug pipeline is continuously affording novel treatments to face this growing challenge. [ABSTRACT FROM AUTHOR]

In December 2019, a new infectious complication called CoronaVirus Infectious Disease-19, briefly COVID-19, caused by SARS-COV-2, is identified in Wuhan, China. It spread all over the world and became a pandemic. In many individuals who had suffered SARS-COV-2 infection, cytokine storm starts through cytokine overproduction and leads to Acute Respiratory Syndrome (ARS), organ failure, and death. According to the obtained evidence, Vitamin D (VitD) enhances the ACE2/Ang(1–7)/MasR pathway activity, and it also reduces cytokine storms and the ARS risk. Therefore, VitD intake may be beneficial for patients with SARS-COV-2 infection exposed to cytokine storm but do not suffer hypotension. In the present review, we have explained the effects of VitD on the renin-angiotensin system (RAS) function and angiotensin-converting enzyme2 (ACE2) expression. Furthermore, we have reviewed the biochemical and immunological effects of VitD on immune function in the underlying diseases and its role in the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

The novel pathogenic virus was discovered in Wuhan, China (December 2019), and quickly spread throughout the world. Further analysis revealed that the pathogenic strain of virus was corona but it was distinct from other coronavirus strains, and thus it was renamed 2019-nCoV or SARS-CoV-2. This coronavirus shares many characteristics with other coronaviruses, including SARS-CoV and MERS-CoV. The clinical manifestations raised in the form of a cytokine storm trigger a complicated spectrum of pathophysiological changes that include cardiovascular, kidney, and liver problems. The lack of an effective treatment strategy has imposed a health and socio-economic burden. Even though the mortality rate of patients with this disease is lower, since it is judged to be the most contagious, it is considered more lethal. Globally, the researchers are continuously engaged to develop and identify possible preventive and therapeutic regimens for the management of disease. Notably, to combat SARS-CoV-2, various vaccine types have been developed and are currently being tested in clinical trials; these have also been used as a health emergency during a pandemic. Despite this, many old antiviral and other drugs (such as chloroquine/hydroxychloroquine, corticosteroids, and so on) are still used in various countries as emergency medicine. Plant-based products have been reported to be safe as alternative options for several infectious and non-infectious diseases, as many of them showed chemopreventive and chemotherapeutic effects in the case of tuberculosis, cancer, malaria, diabetes, cardiac problems, and others. Therefore, plant-derived products may play crucial roles in improving health for a variety of ailments by providing a variety of effective cures. Due to current therapeutic repurposing efforts against this newly discovered virus, we attempted to outline many plant-based compounds in this review to aid in the fight against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has had a deep impact on people worldwide since late 2019 when SARS-CoV-2 was first identified in Wuhan, China. In addition to its effect on public health, it has affected humans in various aspects of life, including social, economic, cultural, and political. It is also true that researchers have made vigorous efforts to overcome COVID-19 throughout the world, but they still have a long way to go. Accordingly, innumerable therapeutics and vaccine candidates have been studied for their efficacies and have been tried clinically in a very short span of time. For example, the versatility of extracellular vesicles, which are membrane-bound particles released from all types of cells, have recently been highlighted in terms of their effectiveness, biocompatibility, and safety in the fight against COVID-19. Thus, here, we tried to explain the use of extracellular vesicles as therapeutics and for the development of vaccines against COVID-19. Along with the mechanisms and a comprehensive background of their application in trapping the coronavirus or controlling the cytokine storm, we also discuss the obstacles to the clinical use of extracellular vesicles and how these could be resolved in the future. [ABSTRACT FROM AUTHOR]

A new coronavirus, called Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), emerged in late December 2019, Wuhan (Hubei, China). The disease, now known as COVID-19, has spread rampant and has given rise to a pandemic world that has precipitated draconian measures to limit its transmission. COVID-19 has demonstrated a wide spectrum of clinical manifestations, from asymptomatic or paucisymptomatic forms, to severe viral pneumonia with respiratory failure, multi-organ and systemic dysfunction, and high morbidity and mortality. The body's hyper inflammatory response has been associated, along with the possible direct effects of SARS-CoV-2 on organs throughout the body via ACE2. Disseminated intravascular coagulation is another common complication. The inflammatory response caused by COVID-19 in the lung due to the virus itself developing pneumonia, followed by cytokine storm and hemophagocytic syndrome causes a hyper coagulation state manifesting small and large vein and arterial thrombosis and likely DEC. Many hyper coagulation biomarkers such as D-dimer, elevated cytokines such as Il-6, and inflammation parameters such as C reactive protein support this clinical picture. Anticoagulant treatment with heparin and anti platelet should always be ordered. [ABSTRACT FROM AUTHOR]

The coronavirus disease-19 (COVID-19), at first, was reported in Wuhan, China, and then rapidly became pandemic throughout the world. Cytokine storm syndrome (CSS) in COVID-19 patients is associated with high levels of cytokines and chemokines that cause multiple organ failure, systemic inflammation, and hemodynamic instabilities. Acute respiratory distress syndrome (ARDS), a common complication of COVID-19, is a consequence of cytokine storm. In this regard, several drugs have been being investigated to suppress this inflammatory condition. Purinergic signaling receptors comprising of P1 adenosine and P2 purinoceptors play a critical role in inflammation. Therefore, activation or inhibition of some subtypes of these kinds of receptors is most likely to be beneficial to attenuate cytokine storm. This article summarizes suggested therapeutic drugs with potential anti-inflammatory effects through purinergic receptors. [ABSTRACT FROM AUTHOR]

In the Wuhan province of China, almost two years ago, in December 2019, the novel Coronavirus 2019 has caused a severe involvement of the lower respiratory tract leading to an acute life-threatening respiratory syndrome, coronavirus disease-19 (COVID-19). Subsequently, coronavirus 2 (SARS-CoV-2) rapidly spread to the entire world causing a pandemic and affected every single person on earth either directly or indirectly with destroying all facets of social life and economy. Since the announcement of COVID-19 as a global pandemic, we have witnessed tremendous scientific work on all aspects of COVID-19 across the globe, which has never been witnessed before. The most remarkable achievement would be the introduction of vaccines, which provide protection from the severe infection and is the only premise for the control of disease. However, despite the tremendous work, the number of treatments either antiviral or immunomodulatory for infected patients are considerably limited, yet disease is causing substantial morbidity and mortality. COVID-19 follows heterogenous disease course among infected individuals, and dysregulated immune system is primarily responsible for the worse outcomes. Immune deficiency, being on corticosteroids for inflammatory diseases, delayed interferon response and advanced age adversely influence prognosis with impairing viral clearance. On the other hand, exuberant immune response with features of cytokine storm is the leading cause of death, which can be alleviated by use of either general immunosuppression with corticosteroids or selective neutralization of potent pro-inflammatory cytokines such as interleukin (IL)-1 and IL-6. Herein, we summarized the potential effective immunomodulatory treatments emphasizing in which patient population it is the most suitable, which dose should be administered, and which is the most appropriate timepoint to administer the drug during the course of the disease. [ABSTRACT FROM AUTHOR]

Coronavirus disease in 2019 (COVID-19) is a pandemic declared by the World Health Organization after its appearance in the Chinese city of Wuhan in late 2019. It has infected more than 30 million people worldwide and led to the death of nearly one million of them. Orexin-A (OXA), a neuropeptide produced by the lateral hypothalamic area and several peripheral tissues, regulates appetite, reproduction, and other physiological functions. There are many symptoms associated with infection with the coronavirus, such as a cytokine storm, narcolepsy, impaired senses of smell and taste, and loss of appetite, usually are associated with high or low levels of OXA in the infected people. Moreover, some chronic diseases such as cancer, diabetes, and obesity, generally referred to as risk factors for the disease, increase the severity of infection or even lead to death and they are associated with either an increase or a decrease in OXA levels. Moreover, some factors, such as a high testosterone level, facilitate the entry of a virus into the cells, which OXA controls. In this review, we described for the first time the potential impact of high or low levels of OXA on the severity of the symptoms of COVID- 19 or the death due to this disease. [ABSTRACT FROM AUTHOR]

El inicio del nuevo coronavirus humano del síndrome respiratorio agudo grave (SARS-CoV-2) en Wuhan, China, ha desencadenado un brote respiratorio mundial (COVID-19). El síndrome de insuficiencia respiratoria agua, el fallo multiorgánico y los eventos trombóticos están entre las causas que llevan a la muerte en pacientes críticamente enfermos con COVID-19. Las citocinas inflamatorias elevadas sugieren que una «tormenta de citocinas», también conocida como síndrome de liberación de citocinas, puede desempeñar un papel principal en la patología de la COVID-19. Adicionalmente al tratamiento antiviral y la terapia de apoyo respiratorio en pacientes críticamente enfermos, están en investigación medicamentos únicos para esta condición. En esta revisión sintetizamos la evidencia más actual de opciones terapéuticas, incluyendo anticuerpos anticitocinas como una estrategia intermedia para la terapia de SARS-CoV-2. The novel SARS-CoV-2 human coronavirus in Wuhan, China, has triggered a worldwide respiratory disease outbreak (COVID-19). Acute respiratory distress syndrome, multiorgan dysfunction and thrombotic events are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a "cytokine storm", also known as cytokine release syndrome, may play a major role in the pathology of COVID-19. In addition to anti-viral therapy and supportive treatment in critically ill patients, unique medications for this condition are also under investigation. Here we reviewed therapeutic options, including the antibody therapy that might be an immediate strategy for SARS-CoV-2 therapy. [ABSTRACT FROM AUTHOR]

COVID-19, first reported in Wuhan, China in December 2019 quickly spread worldwide leading to serious health, social and economic consequences. A crucial role in the pathogenesis of severe disease has been attributed to the inflammatory status, that in more severe cases may evolve in an overproduction of pro-inflammatory cytokines ("cytokine storm)" and fatal outcome. Non-communicable diseases, nutritional disorders and advanced age, conditions associated with a low-grade systemic inflammation and immune function alterations, have been identified as major risks for severe COVID-19. General recommendations for fighting COVID-19 highlighted the paramount importance of adopting a healthy plant-based dietary pattern and healthy lifestyle. The Mediterranean dietary pattern is considered as one of the healthiest dietary patterns, and its benefits are supported by a large body of evidence. Furthermore, it is considered as a sustainable lifestyle model. The aim of this research was to update the multiple benefits of the Mediterranean dietary pattern on physical and mental health, focusing on the effects that it may have in combating COVID-19. The potential effects and mechanisms of action of the main bioactive components of Mediterranean diet were also analyzed. Considering its effects in modulating inflammation and oxidative stress and supporting the immune system, the Mediterranean dietary pattern may be considered the most promising dietary approach to combat COVID-19. [ABSTRACT FROM AUTHOR]

The nCOVID-19 pandemic initiated its course of contagion from the city of Wuhan and now it has spread all over the globe. SARS-CoV-2 is the causative virus and the infection as well as its symptoms are distributed across the multi-organ perimeters. Interactions between the host and virus governs the induction of 'cytokine storm' resulting various immunopathological consequences leading to death. Till now it has caused tens of millions of casualties and yet no credible cure has emerged to vision. This article presents a comprehensive overview on the two most promising remedial approaches that are being attempted for the management, treatment, and plausible cure of nCOVID-19. In this context, chemotherapeutic approach primarily aims to interrupt the interactions between the host and the virus causing inhibition of its entry into the host cell and/or its proliferation and suppressing the inflammatory milieu in the infected patients. On the other side, immunotherapeutic approaches aim to modulate the host immunity by fine tuning the inflammatory signaling cascades to achieve phylaxis from the virus and restoring immune-homeostasis. Considering most of the path-breaking findings, combinatorial therapy involving of chemotherapeutics as well as vaccine could usher to be a hope for all of us to eradicate the crisis [ABSTRACT FROM AUTHOR]

Millions of people across the globe have been affected by coronavirus disease 2019 (COVID-19), which began in Wuhan, China, and is caused by SARS-CoV-2. COVID-19 has a variety of clinical characteristics and triggers immune responses required for the elimination of the viral agent. Currently, no effective treatment options are available for targeting SARS-CoV-2 infection. Repurposing of drugs such as chloroquine, thalidomide, and leflunomide alongside convalescent plasma is being employed as a therapeutic strategy. Clinical studies have shown that both asymptomatic and symptomatic patients can have an extremely active immune response that is largely attributable to immune system modulations. This includes cytokine storm syndrome (CSS), which affects the adaptive immune system, leading to exhaustion of natural killer (NK) cells and thrombocytopenia in some cases. This review examines the interaction of SARS-CoV-2 with the host immune system and the potential for the development of appropriate immunotherapy for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

The novel coronavirus disease 2019 (COVID-19) has reached its pandemic scale within a short period of its first case reported in Wuhan, China in December 2019, leading to a great economic crisis all over the world. As of today, there is no clinically approved antiviral drug available for the treatment of COVID-19. Tocilizumab, a humanized monoclonal antibody against the interleukin-6 (IL-6) receptor, clinically approved for the treatment of rheumatoid arthritis, is one such drug used to manage the COVID-19 symptoms. The current study reviews the effectiveness of Tocilizumab as a treatment option for COVID-19. Research findings on Tocilizumab are effective in COVID-19 patients with the risk of cytokine storm and further complications. Nevertheless, this review also recommends further investigation on the effectiveness of this drug with a large group of patients for more accuracy in results with COVID 19 patients. [ABSTRACT FROM AUTHOR]

The world is fighting the onslaught of COVID 19 for the last 10 months, ever since the first case was reported in December 2019 in Wuhan, China. Now, it has spread to over 200 countries. COVID 19-associated respiratory syndrome is causing a lot of mortality and morbidity. There are reports suggesting that the complications and ARDS associated with COVID 19 is an immune response reaction. The cytokine storm associated with severe cases of COVID 19 acts as a cause of death in many sick patients. It has been shown that COVID 19 is associated with a peculiar immune profile: Decrease in CD3, CD4, CD8, natural killer cell and B-cells; Rise in interleukin (IL)-4, IL-6 and tumor necrosis factor (TNF) alpha; Decrease in IL-10; Decrease in interferon-gamma. Low-dose radiotherapy (LDRT) immunosuppressive features resulting from M2 macrophage phenotype activation, increase in IL-10, transforming growth factor beta, a decrease in IL-6, TNF alpha and an increase in CD3, CD4, and CD8 T cell counts may negate the harmful effects of cytokine release syndrome. Literature review shows that radiation was previously used to treat viral pneumonia with a good success rate. This practice was discontinued in view of the availability of effective antibiotics and antivirals. As there are no scientifically proven treatment for severe COVID 19-associated respiratory distress today, it is prudent that we understand the benefits of LDRT at this critical juncture and take rational decisions to treat the same. This article provides an radioimmunological rationale for the treatment of immune crisis mediated complications in severe cases of COVID 19. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a zoonotic virus which was first discovered in Wuhan, the People's Republic of China in December 2019 and has led to one of the greatest pandemics of world history in a short period of time 1. SARS-CoV-2 is a rapidly spreading infectious disease with a high mortality rate. The disease has a moderate and severe course in approximately 20% of the patients and mortality reaches up to 62% among these patients 2. The majority of the patients develop SARS-CoV-2-induced pneumonia and manifestations of pneumonia rapidly progress to respiratory failure. In severe Covid pneumonia, it has been demonstrated that increased plasma concentrations of cytokines including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-12 are involved in immune response and in cytokine storm caused by the increase in these cytokines lead to mortality1, 3. Tocilizumab (TCZ) is a promising agent that is used for the treatment of cytokine storm. TCZ is an IgG1 class recombinant humanized monoclonal antibody against IL-6 receptor 3. It has then been used for the treatment of rheumatic diseases. Due to its mechanism of action, TCZ treatment comes to the forefront particularly in cases of severe COVID-19-induced cytokine pneumonia presenting with cytokine storm 3. However, potential IgE-mediated immunological reactions against this drug, especially anaphylaxis, may deprive these patients of an important treatment option for the treatment of COVID-19-induced cytokine storm. Although TCZ-induced anaphylaxis has been reported as case reports of indicated rheumatic diseases, TCZ-induced anaphylaxis has not yet been reported in patients using TCZ for SARS-CoV-2-induced cytokine storms 4. In this case series, we aimed to represent cases of anaphylaxis which developed in two different patients using TCZ for SARS-CoV-2-induced cytokine storm. [ABSTRACT FROM AUTHOR]

Cytokine storm syndrome (CSS) is a critical clinical condition induced by a cascade of cytokine activation, characterized by overwhelming systemic inflammation, hyperferritinaemia, haemodynamic instability and multiple organ failure (MOF). At the end of 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in Wuhan, China, and rapidly developed into a global pandemic. More and more evidence shows that there is a dramatic increase of inflammatory cytokines in patients with COVID‐19, suggesting the existence of cytokine storm in some critical illness patients. Here, we summarize the pathogenesis, clinical manifestation of CSS, and highlight the current understanding about the recognition and potential therapeutic options of CSS in COVID‐19. [ABSTRACT FROM AUTHOR]

The coronavirus disease 2019 (COVID-19) has caused a global pandemic, resulting in considerable morbidity and mortality. Tocilizumab, an inhibitor of IL-6, has been widely repurposed as a treatment of severely ill patients without robust evidence supporting its use. In this study, we aimed to systematically describe the effectiveness of treatment and prevention of the cytokine storms in COVID-19 patients with tocilizumab. In this multicentered retrospective and observational cohort study, 65 patients with COVID-19 receiving tocilizumab and 130 not receiving tocilizumab were propensity score matched at a ratio of 2:1 based on age, sex, and comorbidities from January 20, 2020 to March 18, 2020 in Wuhan, China. After adjusting for confounding, the detected risk for in-hospital death was lower in the tocilizumab group versus nontocilizumab group (hazard ratio = 0.47; 95% confidence interval = 0.25-0.90; p = 0.023). Moreover, use of tocilizumab was associated with a lower risk of acute respiratory distress syndrome (odds ratio = 0.23; 95% confidence interval = 0.11-0.45; p < 0.0001). Furthermore, patients had heightened inflammation and more dysregulated immune cells before treatment, which might aggravate disease progression. After tocilizumab administration, abnormally elevated IL-6, C-reactive protein, fibrinogen, and activated partial thromboplastin time decreased. Tocilizumab may be of value in prolonging survival in patients with severe COVID-19, which provided a novel strategy for COVID-19-induced cytokine release syndrome. Our findings could inform bedside decisions until data from randomized, controlled clinical trials become available. [ABSTRACT FROM AUTHOR]

Purpose: In December 2019 there was the first report about a new viral infection in Wuhan, China. The new virus was taxonomically designed as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 (COVID-19). SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor for cell invasion, which is expressed in different tissues including lungs, small intestine, testicles, kidneys, brain, and the eye. The purpose of this article is to review the available information on the relationship of COVID-19 with the eye, as well as evaluating the possible usefulness of ocular diagnostic tests to help in the diagnosis and/or monitoring of patients with this disease. Methods: We performed a retrospective review of relevant articles from November 2019 to April 2020. Results: Ocular infection by SARS-CoV-2 is still controversial; nevertheless, the possibility of being a viral reservoir has been suggested, increasing the likelihood of infection. Some reports demonstrated the presence of SARS-CoV-2 in tears, and previously published data suggest a pathological increase of cytokine concentrations in COVID-19 patients; the cytokine release syndrome or cytokine storm contributes to lung and central nervous system damage. The usefulness of tears for the measurement of inflammatory cytokines in various diseases is well known, in particular IL-6, which has been correlated to the severity of COVID-19. Conclusion: Considering that the IL-6 signaling cascade may be activated in patients with COVID-19, makes it an excellent target for diagnostic and/or monitoring purposes. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus that emerged from Wuhan, China in late 2019 causing coronavirus disease-19 (COVID-19). SARSCoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain. Other presumptive receptors for SARS-CoV-2 attachment include CD147, neuropilin-1 (NRP1), and Myeloid C-lectin like receptor (CLR), each of which might play a role in the systemic viral spread. The pathology of SARS-CoV-2 infection ranges from asymptomatic to severe acute respiratory distress syndrome, often displaying a cytokine storm syndrome, which can be life-threatening. Despite progress made, the detailed mechanisms underlying SARS-CoV-2 interaction with the host immune system remain unclear and are an area of very active research. The process's key players include viral non-structural proteins and open reading frame products, which have been implicated in immune antagonism. The dysregulation of the innate immune system results in reduced adaptive immune responses characterized by rapidly diminishing antibody titers. Several treatment options for COVID-19 are emerging, with immunotherapies, peptide therapies, and nucleic acid vaccines showing promise. This review discusses the advances in the immunopathology of SARS-CoV-2, vaccines and therapies under investigation to counter the effects of this virus, as well as viral variants. [ABSTRACT FROM AUTHOR]

The novel severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2) which has resulted in the COVID-19 pandemic, infection by which is commonly characterized by a sore throat, fever and cough, was first reported in Wuhan, China on 31st December 2019. This novel disease is mild in certain individuals, usually younger healthy individuals, whereas the elder and those with underlying health conditions develop severe symptoms and may die as a result of the disease or associated complications. Along with pneumonia, hypercytokinemia, also termed a cytokine storm, is one of the most common pathologies observed in patients with COVID-19. As patients react to the infection with the virus differently; in certain individuals, a cytokine storm may result in death. At present, there is no cure or widely available vaccine for the novel coronavirus. However, it has been hypothesized that mesenchymal stem cells may assist in the treatment/management of the cytokine storm due to their immunomodulating properties. [ABSTRACT FROM AUTHOR]

The outbreak of a new, potentially fatal virus, SARS‐COV‐2, which started in December 2019 in Wuhan, China, and since developed into a pandemic has stimulated research for an effective treatment and vaccine. For this research to be successful, it is necessary to understand the pathology of the virus. So far, we know that this virus can harm different organs of the body. Although the exact mechanisms are still unknown, this phenomenon may result from the body's secretion of prostaglandin E2 (PGE2), which is involved in several inflammation and immunity pathways. Noticeably, the expression of this molecule can lead to a cytokine storm causing a variety of side effects. In this paper, we discuss those side effects in SARS‐COV‐2 infection separately to determine whether PGE2 is, indeed, an important causative factor. Lastly, we propose a mechanism by which PGE2 production increases in response to COVID‐19 disease and suggest the possible direct relation between PGE2 levels and the severity of this disease. Also see the video abstract here: https://youtu.be/SnPFAcjxxKw. [ABSTRACT FROM AUTHOR]

COVID-19 is an infectious disease caused by the coronavirus SARS-CoV-2, which was first reported in Wuhan, China, in December 2019 and has caused a global pandemic. Acute respiratory distress syndrome (ARDS) is a common feature of severe forms of COVID-19 and can lead to respiratory failure, especially in older individuals. The increasing recognition of the neurotropic potential of SARS-CoV-2 has sparked interest in the role of the nervous system in respiratory failure in people with COVID-19. However, the neuroimmune interactions in the lung in the context of ARDS are poorly understood. In this Perspectives article, we propose the concept of the neuroimmune unit as a critical determinant of lung function in the context of COVID-19, inflammatory conditions and ageing, focusing particularly on the involvement of the vagus nerve. We discuss approaches such as neurostimulation and pharmacological neuromodulation to reduce tissue inflammation with the aim of preventing respiratory failure. [ABSTRACT FROM AUTHOR]

COVID‐19 is a global pandemic that emerged from Wuhan, China. Besides pneumonia and acute respiratory distress syndrome, the disease leads to multisystem involvement in the form of myocarditis, arrhythmias, cardiac arrest, gastrointestinal symptoms, hypoxemic brain injury, acute liver, and renal function impairment. There are also reports of cutaneous lesions in form of urticarial and maculopapular rashes, chilblain like fingers and toes (covid feet), livedoid vasculopathy, and chicken‐pox like or varicelliform vesicles. Clinically, many of these skin lesions are likely secondary to occlusion of small to medium blood vessels due to microthrombi formation or due to viral laden antigen‐antibody immune complexes; and same explanation may hold true for possible hypoxemic injury simultaneously occurring in other vital organs like lungs, heart, brain, and kidneys. The histopathology, immunoflorescence and RT‐PCR analysis of skin biopsies can provide useful insights for ascertaining the pathogenesis of this complex viral syndrome. Apparently, it is interplay of disarmed cellular immunity and over‐activated humoral immunity that culminates in end‐organ changes. The morbidity and mortality can be significantly reduced by upgrading the cellular immunity and downgrading the humoral response; along with prevention of hypoxemic and reperfusion injuries by using antivirals, immunomodulators, antioxidants, anti‐platelets, and anticoagulants in judicious and phased manner. [ABSTRACT FROM AUTHOR]

In December 2019, a cluster of pneumonia caused by a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, Hubei province, China. Cytokine storm is an uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines and chemokines that occurs at phase 3 of viral infection. Such emergence led to the development of many clinical trials to discover efficient drugs and therapeutic protocols to fight with this single-stranded RNA virus. Corticosteroids suppress inflammation of the lungs during the cytokine storm, weaken immune responses, and inhibit the elimination of pathogen. For this reason, in COVID-19 corticosteroid therapy, systemic inhibition of inflammation is observed with a wide range of side effects. The present review discusses the effectiveness of the corticosteroid application in COVID-19 infection and the related side effects of these agents. In summary, a number of corticosteroids, including and especially methylprednisolone and dexamethasone, have demonstrated remarkable efficacy, particularly for COVID-19 patients who underwent mechanical ventilation. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome (SARS) is an infectious disease developed in Wuhan, China, at first. It involves the respiratory system and other organs like kidney, gastrointestinal tract and nervous system as well. The recent reports indicated that renal disorder is prevalent in coronavirus patients. The aim of this study was to provide a review of nephropathy caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and its mechanisms. The Web of Science, Scopus, and PubMed databases were systematically searched. Articles reporting nephropathy, coronavirus disease (COVID-19), coronavirus and the renal injury were included for assessment. Study designs, contrast agents, case reports and results were assessed. Of the assessed studies, suggested mechanisms include sepsis which caused cytokine storm syndrome or perhaps direct cellular injury due to the virus. In patients who were studied, albuminuria, proteinuria, and hematuria as well as an elevation in blood urea nitrogen and serum creatinine were observed. Additionally CT scan of the kidneys showed a decrease in tissue density suggestive of inflammation and interstitial edema. On the other hand, dialysis patients are a high-risk group than the general population. The current treatment for COVID-19 in acute kidney injury includes supportive management or kidney replacement therapy. All patients need to be quarantined. An N95 fit-tested mask and protective clothing and proper equipment are necessary. Some drugs can be effective to inhibit the outcome of this infection such as lopinavir/ritonavir, remdesvir, Chloroquine phosphate, convalescent plasma, tocilizumab, ACEi/ARBs (angiotensin-converting enzyme inhibitor/angiotensin receptor blockers), and hrsACE2 (human recombinant soluble angiotensin-converting-enzyme 2). [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) caused by "Severe Acute Respiratory Syndrome Coronavirus-2" (SARS-CoV-2) infection emerged in Wuhan, a city of China, and spread to the entire planet in early 2020. The virus enters the respiratory tract cells and other tissues via ACE2 receptors. Approximately 20% of infected subjects develop severe or critical disease. A cytokine storm leads to over inflammation and thrombotic events. The most common clinical presentation in COVID-19 is pneumonia, typically characterized by bilateral, peripheral, and patchy infiltrations in the lungs. However multi-systemic involvement including peripheral thromboembolic skin lesions, central nervous, gastrointestinal, circulatory, and urinary systems are reported. The disease has a higher mortality compared to other viral agents causing pneumonia and unfortunately, no approved specific therapy, nor vaccine has yet been discovered. Several clinical trials are ongoing with hydroxychloroquine, remdesivir, favipiravir, and low molecular weight heparins. This comprehensive review aimed to summarize coagulation abnormalities reported in COVID-19, discuss the thrombosis, and inflammation-driven background of the disease, emphasize the impact of thrombotic and inflammatory processes on the progression and prognosis of COVID-19, and to provide evidence-based therapeutic guidance, especially from antithrombotic and antiinflammatory perspectives. [ABSTRACT FROM AUTHOR]

The novel coronavirus is not only causing respiratory problems, but it may also damage the heart, kidneys, liver, and other organs; in Wuhan, 14 to 30% of COVID-19 patients have lost their kidney function and now require either dialysis or kidney transplants. The novel coronavirus gains entry into humans by targeting the ACE2 receptor that found on lung cells, which destroy human lungs through cytokine storms, and this leads to hyperinflammation, forcing the immune cells to destroy healthy cells. This is why some COVID-19 patients need intensive care. The inflammatory chemicals released during COVID-19 infection cause the liver to produce proteins that defend the body from infections. However, these proteins can cause blood clotting, which can clog blood vessels in the heart and other organs; as a result, the organs are deprived of oxygen and nutrients which could ultimately lead to multiorgan failure and consequent progression to acute lung injury, acute respiratory distress syndrome, and often death. However, there are novel protein modification tools called the QTY code, which are similar in their structure to antibodies, which could provide a solution to excess cytokines. These synthetic proteins can be injected into the body to bind the excess cytokines created by the cytokine storm; this will eventually remove the excessive cytokines and inhibit the severe symptoms caused by the COVID-19 infection. In this review, we will focus on cytokine storm in COVID-19 patients, their impact on the body organs, and the potential treatment by QTY code-designed detergent-free chemokine receptors. [ABSTRACT FROM AUTHOR]

Purpose: Novel Coronavirus disease 2019 (COVID-19), is an acute respiratory distress syndrome (ARDS), which is emerged in Wuhan, and recently become worldwide pandemic. Strangely, ample evidences have been shown that the severity of COVID-19 infections varies widely from children (asymptomatic), adults (mild infection), as well as elderly adults (deadly critical). It has proven that COVID-19 infection in some elderly critical adults leads to a cytokine storm, which is characterized by severe systemic elevation of several pro-inflammatory cytokines. Then, a cytokine storm can induce edematous, ARDS, pneumonia, as well as multiple organ failure in aged patients. It is far from clear till now why cytokine storm induces in only COVID-19 elderly patients, and not in young patients. However, it seems that aging is associated with mild elevated levels of local and systemic pro-inflammatory cytokines, which is characterized by "inflamm-aging". It is highly likely that "inflamm-aging" is correlated to increased risk of a cytokine storm in some critical elderly patients with COVID-19 infection. Methods: A systematic search in the literature was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, as well as Google Scholar pre-print database using all available MeSH terms for COVID-19, Coronavirus, SARS-CoV-2, senescent cell, cytokine storm, inflame-aging, ACE2 receptor, autophagy, and Vitamin D. Electronic database searches combined and duplicates were removed. Results: The aim of the present review was to summarize experimental data and clinical observations that linked the pathophysiology mechanisms of "inflamm-aging", mild-grade inflammation, and cytokine storm in some elderly adults with severe COVID-19 infection. [ABSTRACT FROM AUTHOR]

• Epidemiology of COVID-19 and life cycle of SARS-CoV-2 in human cells was explored. • SARS-CoV-2-induced cell-mediated immunity plays a critical role in COVID-19. • SARS-CoV-2 infection induces immune cell-mediated cytokine storms that promote pulmonary fibro-inflammation and organ failure. • This study highlights the immunotherapeutic effects of IL-15 on innate immunity to promote the clearance of SARS-CoV-2 viral loads. Coronavirus disease 2019 (COVID-19) is a pulmonary inflammatory disease induced by a newly recognized coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 infection was detected for the first time in the city of Wuhan in China and spread all over the world at the beginning of 2020. Several millions of people have been infected with SARS-CoV-2, and almost 382,867 human deaths worldwide have been reported so far. Notably, there has been no specific, clinically approved vaccine or anti-viral treatment strategy for COVID-19. Herein, we review COVID-19, the viral replication, and its effect on promoting pulmonary fibro-inflammation via immune cell-mediated cytokine storms in humans. Several clinical trials are currently ongoing for anti-viral drugs, vaccines, and neutralizing antibodies against COVID-19. Viral clearance is the result of effective innate and adaptive immune responses. The pivotal role of interleukin (IL)-15 in viral clearance involves maintaining the balance of induced inflammatory cytokines and the homeostatic responses of natural killer and CD8+ T cells. This review presents supporting evidence of the impact of IL-15 immunotherapy on COVID-19. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a novel coronavirus that was initially described in Wuhan China in December 2019. In the USA (US), the person to be diagnosed with the novel Coronavirus infection (COVID) was on 19 January 2020. On 18 March 2020, a 31-year-old morbidly obese African American woman presented with severe dyspnea with associated hypoxemia, fever and bilateral interstitial pulmonary ground glass infiltrates consistent with viral pneumonitis. Nasopharyngeal PCR testing was positive for SARS-CoV-2. Despite initiation of hydroxychloroquine and azithromycin along with supplemental oxygen therapy, rapid disease progression consistent with cytokine release syndrome ensued, leading to initiation of mechanical ventilatory support. Anti-Interleukin (IL)-6 receptor monoclonal antibody (tocilizumab) was administered. Acute respiratory distress syndrome (ARDS) leads to refractory hypoxemia and demise. Severe morbid obesity as well as race may be unidentified risk factors for the development of severe Illness in patients with COVID-19. [ABSTRACT FROM AUTHOR]

• A high proportion of COVID-19 patients were co-infected with influenza in Tongji Hospital (Wuhan). • Critically ill COVID-19 patients with influenza were more prone to cardiac injury than those without influenza. • Co-infection with the influenza virus may induce an earlier and more frequently occurring cytokine storm in critically ill COVID-19 patients. • Do not ignore detection of the influenza virus in patients with COVID-19. To delineate the clinical characteristics of critically ill COVID-19 patients co-infected with influenza. This study included adult patients with laboratory-confirmed COVID-19 form Tongji Hospital (Wuhan, China), with or without influenza, and compared their clinical characteristics. Among 93 patients, 44 died and 49 were discharged. Forty-four (47.3%) were infected with influenza virus A and two (2.2%) with influenza virus B. Twenty-two (50.0%) of the non-survivors and 24 (49.0%) of the survivors were infected with the influenza virus. Critically ill COVID-19 patients with influenza were more prone to cardiac injury than those without influenza. For the laboratory indicators at admission the following were higher in non-survivors with influenza than in those without influenza: white blood cell counts, neutrophil counts, levels of tumor necrosis factor-α, D-dimer value, and proportion of elevated creatinine. The results showed that a high proportion of COVID-19 patients were co-infected with influenza in Tongji Hospital, with no significant difference in the proportion of co-infection between survivors and non-survivors. The critically ill COVID-19 patients with influenza exhibited more severe inflammation and organ injury, indicating that co-infection with the influenza virus may induce an earlier and more frequently occurring cytokine storm. [ABSTRACT FROM AUTHOR]

During the end of 2019 a group of patients with pneumonia were described in Wuhan city of china with progression to ARDS with variable outcome. Mortality rate was higher in the oldest and in those with comorbid conditions. Kidney transplant recipients as a group of immunocompromised hosts are believed to be a high risk group in case of infection by SARS-CoV-19 virus with unfavorable outcome. On the other hand, cytokine storm with its severe inflammatory response as a major risk factor of mortality may be prevented by ongoing immunosuppressive therapy. Our knowledge about the pathophysiology and treatment options of COVID-19 in kidney transplant recipients are growing on daily bases and at the time being is derived mainly from the few published case reports, reviews and some society guidelines in the published literature. [ABSTRACT FROM AUTHOR]

Novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in Wuhan, China. Since then, COVID-19 has become a pandemic affecting more than 4.1 million people worldwide. Patients with COVID-19 have a wide spectrum of manifestations, one being cytokine release syndrome (CRS) and its fatal correlate, secondary hemophagocytic lymphohistiocytosis (sHLH). Anti-cytokine therapy such as tocilizumab, an IL-6 receptor antagonist, is a potential treatment for COVID-19; however, data regarding the efficacy of this anti-IL-6 therapy are currently lacking. We report two cases of patients who received a diagnosis of COVID-19 complicated by CRS and were treated with tocilizumab. Both patients progressed to sHLH despite treatment with tocilizumab, and one developed viral myocarditis, challenging the safety and clinical usefulness of tocilizumab in the treatment of COVID-19-induced CRS. These cases highlight the need for clinical trials to determine optimal patient selection and timing for the use of tocilizumab during this disease process. [ABSTRACT FROM AUTHOR]

Since December 2019, a novel coronavirus pneumonia (COVID-19) has broken out in Wuhan, China and spread rapidly. Recent studies have found that ⁓ 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. IL-6 is one of the key cytokines involved in infection-induced cytokine storm. Tocilizumab, which is the IL-6 receptor antagonist, has been approved by the US FDA for the treatment of cytokine release syndrome (CRS), is expected to treat cytokine storm caused by COVID-19 and is now in clinical trials. In this paper, we will elaborate the role of cytokine storm in COVID-19, the mechanism of tocilizumab on cytokine storm and the key points of pharmaceutical care based on the actual clinical application for COVID-19 in our hospital, the latest research reports, clinical trial progress of tocilizumab, drug instruction from the US FDA, and "Diagnosis and Treatment Plan of Novel Coronavirus Pneumonia (seventh trial edition)" in China, so as to provide reference for the treatment of COVID-19. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a global pandemic with 12% mortality rate. This pandemic has shattered health care sector of many developed countries across the globe. According to World Health Organization (WHO) India and Pakistan will be badly hit by the pandemic till end of June 2020. Both countries are densely populated and the fragile health sector of these countries is incapable to facilitate of large number of critically ill patients. Data analysis from different studies revealed that Cytokine Storming (CS) is main cause of COVID-19 related respiratory, renal, cardiac and neural complications in critically ill patients. Objectives: The aim of this review is to highlight the significance of CS in management of COVID-19 infection. Methods: Literature from previous studies was collected to suggest the possible diagnostic testing as well as strategies to manage these patients. Mesh terms such as Corona, COVID-19, Cytokine storming, Wuhan, Pandemic were applied on PUBMED as well as google to search for the latest published articles. Reports and newpapers were also considered as this is an ongoing pandemic and there is scarcity of knowledge and information in this regard. Results: IL6 and TNFα blockers are helpful in regulating the uncontrolled immune response due to CS. Levels of different substances like ferritin, Cytokine Reactive Proteins and D-dimer can be helpful in early detection of these complications. Conclusions: The early detection of CS can be used for selection of appropriate treatment, reduction in burden on Intensive Care Units (ICU) and ultimately saving many lives. [ABSTRACT FROM AUTHOR]

Rapidly spreading outbreak of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is causing serious health concerns worldwide. It started as an epidemic in Wuhan, Hubei province, central China, and has now become a pandemic, spreading over most of the continents of the planet. The major clinical symptoms of the infection are dry cough, fever, pneumonia, respiratory failure, hypoxia, and in certain cases, even death. Alveolar damage and respiratory system failure are observed in severe cases. Initial mild infection leads to activation of the immune system in the lungs and accumulation of various inflammatory cells and molecules. At a later phase during the infection, a "cytokine storm" causes an Acute Respiratory Distress Syndrome (ARDS), leading to an increase in the production of pro-inflammatory cytokines, migration of a large number of immune cells to the site of infection, and ultimately pulmonary damage. The rapid and uncontrolled outbreak requires putative therapeutic drugs for treatment of patients suffering from COVID-19. Amongst the currently used antiviral drugs, such as hydroxychloroquine, lopinavir, remdesivir etc. we would like to present an update on another effective drug, pentoxifylline. Pentoxifylline has anti-inflammatory, immunomodulatory, anti-viral, and bronchodilatory properties. Pentoxifylline is known to reduce cytokine production, immune cell migration, and suppress certain signal transduction pathways (e.g. NF-ĸβ and STAT3). Thus, it minimizes inflammatory damage in the lung tissues. [ABSTRACT FROM AUTHOR]

Rapidly spreading outbreak of the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is causing serious health concerns worldwide. It started as an epidemic in Wuhan, Hubei province, central China, and has now become a pandemic, spreading over most of the continents of the planet. The major clinical symptoms of the infection are dry cough, fever, pneumonia, respiratory failure, hypoxia, and in certain cases, even death. Alveolar damage and respiratory system failure are observed in severe cases. Initial mild infection leads to activation of the immune system in the lungs and accumulation of various inflammatory cells and molecules. At a later phase during the infection, a “cytokine storm” causes an Acute Respiratory Distress Syndrome (ARDS), leading to an increase in the production of pro-inflammatory cytokines, migration of a large number of immune cells to the site of infection, and ultimately pulmonary damage. The rapid and uncontrolled outbreak requires putative therapeutic drugs for treatment of patients suffering from COVID-19. Amongst the currently used antiviral drugs, such as hydroxychloroquine, lopinavir, remdesivir etc. we would like to present an update on another effective drug, pentoxifylline. Pentoxifylline has anti-inflammatory, immunomodulatory, anti-viral, and bronchodilatory properties. Pentoxifylline is known to reduce cytokine production, immune cell migration, and suppress certain signal transduction pathways (e.g. NF-κβ and STAT3). Thus, it minimizes inflammatory damage in the lung tissues. [ABSTRACT FROM AUTHOR]

On March 11th, 2020 the World Health Organization declared COVID-19 a global pandemic. The infection, transmitted by 2019 novel coronavirus (2019-nCov), was first discovered in December 2019, in Wuhan, Hubei Province, and then rapidly spread worldwide. Italy was early and severely involved, with a critical spread of the infection and a very high number of victims. Person-to-person spread mainly occurs via respiratory droplets and contact. The median incubation period is 5 days. The spectrum of respiratory symptoms may range from mild to severe, strictly depending on the age of the patient and the underlying comorbidities. In children COVID-19 related disease is less frequent and less aggressive. In Italy 1% of positive cases are under 18 years of age, and no deaths have been recorded before 29 years of age. For patients affected by rheumatic disease, despite the concerns related to the imbalance of their immune response and the effect of immunosuppressive treatments, there are still few data to understand the real consequences of this infection. Major scientific societies have issued recommendations to help rheumatologists in caring their patients. Interestingly, some of the drugs mostly used by rheumatologists appear to be promising in critical COVID-19 infected patients, where the hyperinflammation and cytokine storm seem to drive to the multiorgan failure. Pediatric rheumatologists are expected to play a supporting role in this new front of COVID-19 pandemic, both as general pediatricians treating infected children, and as rheumatologists taking care of their rheumatic patients, as well as offering their experience in the possible alternative use of immunomodulatory drugs. [ABSTRACT FROM AUTHOR]

In December 2019, a novel coronavirus (SARS-CoV-2) was identified as the cause of clustered pneumonia cases in Wuhan, a city in the Hubei Province of China. The virus rapidly spread to the rest of the world after a huge epidemic in China and WHO has declared a pandemic on March 11, 2020. SARS-CoV-2 is transmitted via respiratory droplets and fomites during close unprotected contact. The airborne spread has not been established as a major route of transmission. The mean incubation period of the illness is 5 days and it mainly presents with fever and respiratory symptoms. Myalgia, loss of taste and smell, diarrhea and dermatological findings are also common during the course of the disease. Laboratory findings are nonspecific. Significant elevations in inflammation markers can be observed in some patients due to cytokine storm. Typical CT findings are bilateral ground glass opacities and consolidation with peripheral and lower lobes distribution. COVID-19 causes mild symptoms in most cases, however it may progress to severe pneumonia leading to ARDS and death, especially in those with advanced age and comorbid diseases. There is no specific effective antiviral treatment for COVID-19. A number of in vitro effective agents have been identified. These agents such as chloroquine phosphate/hydroxychloroquine, favipiravir, remdesivir, lopinavir/ritonavir are widely used in the treatment of the disease. Convalescent plasma therapy and the cytokine inhibitory agents such as tocilizumab, used to treat disease-induced cytokine storm, are particularly preferred in the treatment severe cases. [ABSTRACT FROM AUTHOR]

A novel coronavirus (SARS-CoV-2, formerly known as nCoV-2019) that causes an acute respiratory disease has emerged in Wuhan, China and spread globally in early 2020. On January the 30th, the World Health Organization (WHO) declared spread of this virus as an epidemic and a public health emergency. With its highly contagious characteristic and long incubation time, confinement of SARS-CoV-2 requires drastic lock-down measures to be taken and therefore early diagnosis is crucial. We analysed transcriptome of SARS-CoV-2 infected human lung epithelial cells, compared it with mock-infected cells, used network-based reporter metabolite approach and integrated the transcriptome data with protein-protein interaction network to elucidate the early cellular response. Significantly affected metabolites have the potential to be used in diagnostics while pathways of protein clusters have the potential to be used as targets for supportive or novel therapeutic approaches. Our results are in accordance with the literature on response of IL6 family of cytokines and their importance, in addition, we find that matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) with keratan sulfate synthesis pathway may play a key role in the infection. We hypothesize that MMP9 inhibitors have potential to prevent "cytokine storm" in severely affected patients. [ABSTRACT FROM AUTHOR]

[Display omitted] • SARS-CoV-2 mediated cytokine storm is associated with the mortality and morbidity of COVID-19 patients. The key cytokines implicated in the onset of disease severity include TNF-α, IFN-γ, IL-6, IL-1β, GM-CSF, and G-CSF. • This review emphasizes the role of GM-CSF and G-CSF in COVID-19. • Emerging therapeutic interventions involve antibodies against TNF-α and IFN-γ, blocking IL-1 production, anti-IL-6 receptor antagonists, JAK-STAT inhibitors, and employment of mesenchymal stem cells and therapeutic plasma exchange. COVID-19 has claimed millions of lives during the last 3 years since initial cases were reported in Wuhan, China, in 2019. Patients with COVID-19 suffer from severe pneumonia, high fever, acute respiratory distress syndrome (ARDS), and multiple-organ dysfunction, which may also result in fatality in extreme cases. Cytokine storm (CS) is hyperactivation of the immune system, wherein the dysregulated production of proinflammatory cytokines could result in excessive immune cell infiltrations in the pulmonary tissues, resulting in tissue damage. The immune cell infiltration could also occur in other tissues and organs and result in multiple organs' dysfunction. The key cytokines implicated in the onset of disease severity include TNF-α, IFN-γ, IL-6, IL-1β, GM-CSF, and G-CSF. Controlling the CS is critical in treating COVID-19 disease. Therefore, different strategies are employed to mitigate the effects of CS. These include using monoclonal antibodies directed against soluble cytokines or the cytokine receptors, combination therapies, mesenchymal stem cell therapy, therapeutic plasma exchange, and some non-conventional treatment methods to improve patient immunity. The current review describes the role/s of critical cytokines in COVID-19-mediated CS and the respective treatment modalities. [ABSTRACT FROM AUTHOR]

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was identified in Wuhan, China, in December 2019. The disease has since spread worldwide, and on March 2020 the World Health Organization (WHO) declared it as pandemic, causing a public health crisis. Symptoms of COVID-19 are variable, ranging from mild symptoms like fever, cough, and fatigue to severe illness. Elderly patients and those with comorbidities like cardiovascular disease, diabetes, chronic respiratory disease, or cancer are more likely to develop severe forms of the disease. Asymptomatic infections have been well documented. Accumulating evidence suggests that the severity of COVID-19 is due to high levels of circulating inflammatory mediators including cytokines and chemokines leading to cytokine storm syndrome (CSS). Patients are admitted in ICU with severe respiratory failure, but can also develop acute renal failure and multi organ failure. Advances in science and technology have permitted the development of more sophisticated therapies such as extracorporeal organ support (ECOS) therapies that includes renal replacement therapies (RRTs), venoarterial (VA) or veno-venous (VV) extracorporeal membrane Oxygenation (ECMO), extracorporeal CO2 removal (ECCO2R), liver support systems, hemoperfusion, and various blood purification devices, for the treatment of ARDS and septic shock. [ABSTRACT FROM AUTHOR]

• Acute respiratory distress syndrome, sepsis and thromboinflammation may complicate COVID-19-associated critical illness. • The efficacy of extracorporeal blood purification therapies in COVID-19 remains questionable. • Concerns exist regarding the safety and immunosuppressive effects of therapeutic plasma exchange. • Plasma exchange pilot studies showed promise in the treatment of complex life-threatening COVID-19. COVID-19 (coronavirus disease 2019), caused by the novel coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), emerged in Wuhan, China, and has spread worldwide, resulting in over 73 million cases and more than 1 600 000 deaths as of December 2020. Although the disease is asymptomatic in most cases, some patients develop life-threatening disease characterised by acute respiratory distress syndrome, sepsis, multisystem organ failure (MSOF), extrapulmonary manifestations, thromboembolic disease and associated cytokine release syndrome. The rationale for applying therapeutic plasma exchange (TPE) early in the course of fulminant COVID-19 is the suppression of thromboinflammation and amelioration of microangiopathy, thus preventing the ensuing MSOF. In the course of complicated critical illness due to COVID-19, immune dysregulation may be as important as viral replication itself. Moreover, the natural course of SARS-CoV-2 infection remains obscure, as re-infections and/or recurrently positive real-time PCR results have been reported. Although concerns still exist regarding its potential immunosuppressive effects and safety, TPE shows promise in the management of life-threatening COVID-19 as documented by various pilot studies, which remain to be confirmed by future randomised controlled trials. However, current data suggest that TPE could be an adjunctive rescue therapy in complex COVID-19 critical illness. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak in Wuhan, China has dispersed rapidly worldwide. Although most patients present with mild fever, cough with varying pulmonary shadows, a significant portion still develops severe respiratory dysfunction. And these severe cases are often associated with manifestations outside the respiratory tract. Currently, it is not difficult to find inflammatory cytokines upregulated in the blood of infected patients. However, some complications in addition to respiratory system with the coronavirus disease 2019 (COVID-19) are impossible to explain or cannot be attributed to virus itself. Thus excessive cytokines and their potentially fatal adverse effects are probably the answer to the multiple organ dysfunctions and growing mortality. This review provides a comprehensive overview of the mechanisms underlying cytokine storm, summarizes its pathophysiology and improves understanding of cytokine storm associated with coronavirus infections by comparing SARS-CoV-2 with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). • In December 2019, a novel coronavirus of SARS-CoV-2hit Wuhan, Hubei, China, and then spread globally. • SARS-CoV-2 generally causes a mild lower respiratory infection in humans, however, in some severe cases, multiple organ dysfunction occurs. • Overproduction of cytokines, termed cytokine storm, may involve in disease progression and even be responsible for deaths. • Application of immune-modulators might become a complement to support treatment and flip on the light switch for severe patients. [ABSTRACT FROM AUTHOR]

In December 2019, the latest member of the coronavirus family, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in Wuhan, China, leading to the outbreak of an unusual viral pneumonia known as coronavirus disease 2019 (COVID-19). COVID-19 was then declared as a pandemic in March 2020 by the World Health Organization (WHO). The initial mortality rate of COVID-19 declared by WHO was 2%; however, this rate has increased to 3.4% as of 3 March 2020. People of all ages can be infected with SARS-CoV-2, but those aged 60 or above and those with underlying medical conditions are more prone to develop severe symptoms that may lead to death. Patients with severe infection usually experience a hyper pro-inflammatory immune reaction (i.e., cytokine storm) causing acute respiratory distress syndrome (ARDS), which has been shown to be the leading cause of death in COVID-19 patients. However, the factors associated with COVID-19 susceptibility, resistance and severity remain poorly understood. In this review, we thoroughly explore the correlation between various host, viral and environmental markers, and SARS-CoV-2 in terms of susceptibility and severity. [ABSTRACT FROM AUTHOR]

Background: Since December 2019, when a cluster of pneumonia cases due to SARS-CoV-2 initially emerged in Wuhan city and then rapidly spread throughout the world, the necessity for data concerning the clinical and para-clinical features of Iranian patients with COVID-19 was highlighted. Therefore, we aimed to compare the clinical, para-clinical and laboratory evidences of deceased patients with survival group.Methods: We extracted data regarding 233 patients with laboratory-confirmed COVID-19 from Buali Hospital in Iran; clinical/para-clinical and inflammatory indexes data were collected and analyzed. The data of laboratory examinations and chest CT findings were compared between deceased and survived patients.Results: The mean age of the patients was 49.8 years and 64% of our patients were male. The acute respiratory distress syndrome occurred in 64 patients, 52 who were admitted to the ICU, which all of them underwent invasive mechanical ventilation, and 28 who died. Lymphopenia (79%), neutrophilia (79%), and thrombocytopenia (21%) were the most frequently observed laboratory findings of the deceased group on admission. Most patients (68%) had a high systematic immune-inflammation (SII) index of > 500 and increased C-reactive protein level (88%). Levels of inflammatory indexes such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and SII were documented to be significantly elevated in the deceased group when compared with the patients who survived (P < 0.0001, P < 0.001, P < 0.0001, respectively). The most commonly presented symptoms were fever (70%) and cough (63%) on admission. Headache was uncommon (11%). Ground-glass opacity with consolidation (mixed) was the most common radiologic finding on chest CT (51%). No radiographic or CT abnormality was found in 15 of 204 patients (7%).Conclusion: Small fraction of patients with COVID-19 may present without fever and abnormal radiologic findings. Elevated NLR, PLR and SII can be considered as prognostic and risk stratifying factor of severe form of disease. [ABSTRACT FROM AUTHOR]

Background: In December 2019, the novel coronavirus disease 2019 (COVID-19) emerged in Wuhan, Hubei Province, China. It rapidly spread and many cases were identified in multiple countries, posing a global health problem. Here, we report the first patient cured of COVID-19 infection in Changsha, China, and the symptoms, diagnosis, treatment, and management of this patient are all described in this report.Case Presentation: A 57-year-old woman developed cough and fever after returning to Changsha from Wuhan on January 9, 2020. She tested positive for COVID-19 infection, a diagnosis which was supported by chest CT. The patient was treated with lopinavir and ritonavir tablets and interferon alfa-2b injection. A low dose of glucocorticoids was used for a short period to control bilateral lung immune response, and this patient avoided being crushed by cytokine storms that might have occurred. The clinical condition of this patient improved, and a COVID-19 assay conducted on January 25, 2020 generated negative results. This patient recovered and was discharged on January 30, 2020.Conclusions: Currently, there are numerous reports on COVID-19 infections focusing on the disease's epidemiological and clinical characteristics. This case describes the symptoms, diagnosis, treatment, and management of a patient cured of COVID-19 infection, which may serve as reference for future cases, while further studies are needed. [ABSTRACT FROM AUTHOR]

• COVID-19 is associated with cytokine storm, and eventually related to septic shock and ARDS. • Steroids are discouraged for use in viral lung infections, including COVID-19, with exceptions. • Corticosteroids are indicated for adults with refractory septic shock and moderate and severe ARDS. • Steroids are indicated for management of asthma and chronic obstructive pulmonary disease exacerbation. • Steroids reduced mortality in COVID-19 patients in need of supportive oxygenotherapy or invasive mechanical ventilation. In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed. In this short communication, we will evaluate the use of corticosteroids as an adjunctive pharmacological therapy in the management of COVID-19 and describe its pros and cons in light of the latest available evidence. [ABSTRACT FROM AUTHOR]

• Chloroquine (CQ) has diverse modes of action against viral infections. • CQ may interfere with SARS-CoV-2 attachment to the host ACE2 receptor. • CQ may hamper the STING pathway to attenuate the pro-inflammatory response. • Hydroxychloroquine (HCQ) might be a logical approach in the treatment of SARS-CoV-2 infection. • Large clinical trials are needed before clinical recommendations of HCQ against COVID-19. Chloroquine (CQ) and its analogue hydroxychloroquine (HCQ) have long been used worldwide as frontline drugs for the treatment and prophylaxis of human malaria. Since the first reported cases in Wuhan, China, in late December 2019, humans have been under threat from coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 (previously known as 2019-nCoV), subsequently declared a pandemic. While the world is searching for expedited approval for a vaccine, which may be only preventative and not a cure, physicians and country leaders are considering several concerted clinical trials suggesting that the age-old antimalarial drugs CQ/HCQ could be a potent therapeutic against COVID-19. Based on accumulating scientific reports, here we highlight the possible modes of action of CQ/HCQ that could justify its use against viral infections. Considering the global health crisis of the COVID-19 pandemic, the option of repurposing old drugs, e.g. CQ/HCQ, particularly HCQ, for the treatment of SARS-CoV-2 infection could be a good choice. CQ/HCQ has diverse modes of action, including alteration of the acidic environment inside lysosomes and late endosomes, preventing endocytosis, exosome release and phagolysosomal fusion, and inhibition of the host cytokine storm. One or more diverse mechanisms might work against viral infections and reduce mortality. As there is no cure for COVID-19, clinical testing of HCQ is urgently required to determine its potency against SARS-CoV-2, as this is the currently available treatment option. There remains a need to find other innovative drug candidates as possible candidates to enter clinical evaluation and testing. [ABSTRACT FROM AUTHOR]