COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking

Magro, Giuseppe

doi:10.1016/j.virusres.2020.198070

Cited by 120 publications

(125 citation statements)

References 133 publications

(215 reference statements)

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“…As mentioned above, excessive IL-6 levels are highly correlated with the lethal complications of COVID-19 patients [16,64,65]. Notably, a previous report showed that inhibition of the NF-κB pathway in animals infected with SARS-CoV decreases mortality and IL-6 levels [66].…”

Section: Possible Therapeutics For Covid-19mentioning

confidence: 90%

How COVID-19 induces cytokine storm with high mortality

et al. 2020

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The newly emerging coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, but has rapidly spread all over the world. Some COVID-19 patients encounter a severe symptom of acute respiratory distress syndrome (ARDS) with high mortality. This high severity is dependent on a cytokine storm, most likely induced by the interleukin-6 (IL-6) amplifier, which is hyper-activation machinery that regulates the nuclear factor kappa B (NF-κB) pathway and stimulated by the simultaneous activation of IL-6-signal transducer and activator of transcription 3 (STAT3) and NF-κB signaling in non-immune cells including alveolar epithelial cells and endothelial cells. We hypothesize that IL-6-STAT3 signaling is a promising therapeutic target for the cytokine storm in COVID-19, because IL-6 is a major STAT3 stimulator, particularly during inflammation. We herein review the pathogenic mechanism and potential therapeutic targets of ARDS in COVID-19 patients.

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Section: Possible Therapeutics For Covid-19mentioning

confidence: 90%

How COVID-19 induces cytokine storm with high mortality

et al. 2020

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“…Recent findings are optimistic, but data validation by robust scientific evidence has been hampered by the small sample size in most case reports and studies on the use of mAbs blocking other immune mediators, such as IL-1b, GM-CSF, and complement protein C5 (238,(248)(249)(250). However, seeking to verify the effectiveness of using mAbs blocking inflammatory mediators, dozens of clinical trials are currently underway.…”

Section: Antibody-based Therapymentioning

confidence: 99%

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

et al. 2020

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Coronavirus Disease 2019 (COVID-19) has been classified as a global threat, affecting millions of people and killing thousands. It is caused by the SARS-CoV-2 virus, which emerged at the end of 2019 in Wuhan, China, quickly spreading worldwide. COVID-19 is a disease with symptoms that range from fever and breathing difficulty to acute respiratory distress and death, critically affecting older patients and people with previous comorbidities. SARS-CoV-2 uses the angiotensin-converting enzyme 2 (ACE2) receptor and mainly spreads through the respiratory tract, which it then uses to reach several organs. The immune system of infected patients has been demonstrated to suffer important alterations, such as lymphopenia, exhausted lymphocytes, excessive amounts of inflammatory monocytes and macrophages, especially in the lungs, and cytokine storms, which may contribute to its severity and difficulty of establishing an effective treatment. Even though no specific treatment is currently available, several studies have been investigating potential therapeutic strategies, including the use of previously approved drugs and immunotherapy. In this context, this review addresses the interaction between SARS-CoV-2 and the patient's host immune system during infection, in addition to discussing the main immunopathological mechanisms involved in the development of the disease and potential new therapeutic approaches.

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“…The complex inflammatory and coagulation impact of COVID-19 must be understood in detail in order to mount precise treatment and patient stratification. 99 Complete biomarkers profiling using comprehensive molecular tools could be important to predict patients who are most likely to recover or progress to withstand cytokine storms. However, there is opportunity for global cooperation to advance scientific understanding of drug discovery and vaccine development.…”

Section: Resultsmentioning

confidence: 99%

Knowing When and How to Fight: COVID-19 Between Viral Clearance and Immune Tolerance

Utomo¹

2020

J. Biomed. Transl. Res.

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COVID-19 is a complex disease involving immunological, vascular, and metabolic pathology caused by and consequences of beta-coronavirus SARS-CoV-2 infection. One may use Sun Tzu analogy of war to fight COVID-19 and to survive infection. When enemy has not reached the shore, gathering much intelligence is key to know how the enemy moves and who would be the most vulnerable targets of enemy attacks. Physical distancing, massive nucleic acid testing, and identification of comorbidity may prepare for the incoming enemies. Physical distancing has helped to limit transmission of the virus that mainly due to close contacts with droplets coughed off infected individuals. Moreover, aerosolized virus particles may also contribute to spreading. Nucleic acid testing using real time PCR platform has been a diagnostic gold standard to identify infected individuals during early stage of infection. On the other hand, serological test to capture antibody against SARS-CoV-2 may be useful for immunosurveillance. Discovery of human ACE2 (angiotensin converting enzyme) protein as an obligate partner of SARS-CoV-2 viral entry has provided insights to mechanisms of serious post-infection ramifications to individuals having comorbidities such as hypertension, diabetes or heart conditions. When the enemy reaches ashore, thorough profiling of biomarkers involved in inflammation and coagulation (IL-6, lymphopenia, ground glass opacity, d-dimers, thrombocytopenia) may help predict disease progression and guide treatment strategy. While estimated 80% of infected individuals may recover on their own, the remaining 20% may require hospitalization and serious therapeutic intervention. Several clinical trials are underway such as repurposing existing drugs and evaluating efficacy of convalescence plasma therapy. Finally, vaccine development using genetic engineering may also help control the global spread if it is proven effective.

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COVID-19: Review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking

Cited by 120 publications

References 133 publications

How COVID-19 induces cytokine storm with high mortality

How COVID-19 induces cytokine storm with high mortality

A 21st Century Evil: Immunopathology and New Therapies of COVID-19

Knowing When and How to Fight: COVID-19 Between Viral Clearance and Immune Tolerance

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