Macrophage Activation and Cytokine Release Syndrome in COVID-19: Current Updates and Analysis of Repurposed and Investigational Anti-Cytokine Drugs

Iqubal, Ashif; Hoda, F.I.A.C. Rana S.; Najmi, Abul Kalam; Haque, Syed Ehtaishamul

doi:10.1055/a-1291-7692

Cited by 9 publications

(5 citation statements)

References 53 publications

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“…In this NO/ozone chemiluminescence technique, nitrate and nitrite were reconverted to NO, and the NO level was measured in a gaseous form. Since endothelial dysfunction is evident in COVID-19 ( Green, 2020 ), increased NO levels can be attributed to macrophage activation and the inflammatory processes observed in COVID-19 disease ( Merad and Martin, 2020 ; Iqubal et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Effects of antiviral drug therapy on dynamic thiol/disulphide homeostasis and nitric oxide levels in COVID-19 patients

Mete

Koçak

Saracaloglu

et al. 2021

European Journal of Pharmacology

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The novel coronavirus disease 2019 (COVID-19) has led to a serious global pandemic. Although an oxidative stress imbalance occurs in COVID-19 patients, the contributions of thiol/disulphide homeostasis and nitric oxide (NO) generation to the pathogenesis of COVID-19 have been poorly identified. Therefore, the aim of this study was to evaluate the effects of antiviral drug therapy on the serum dynamics of thiol/disulphide homeostasis and NO levels in COVID-19 patients. A total of 50 adult patients with COVID-19 and 43 sex-matched healthy control subjects were enrolled in this prospective study. Venous blood samples were collected immediately on admission to the hospital within 24 h after the diagnosis (pre-treatment) and at the 15th day of drug therapy (post-treatment). Serum native thiol and total thiol levels were measured, and the amounts of dynamic disulphide bonds and related ratios were calculated. The average pre-treatment total and native thiol levels were significantly lower than the post-treatment values (P < 0.001 for all). We observed no significant changes in disulphide levels or disulphide/total thiol, disulphide/native thiol, or native thiol/total thiol ratios between pre- and post-treatments. There was also a significant increase in serum NO levels in the pre-treatment values when compared to control (P < 0.001) and post-treatment measurements (P < 0.01). Our results strongly suggest that thiol/disulphide homeostasis and nitrosative stress can contribute to the pathogenesis of COVID-19. This study was the first to show that antiviral drug therapy can prevent the depletion in serum thiol levels and decrease serum NO levels in COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Effects of antiviral drug therapy on dynamic thiol/disulphide homeostasis and nitric oxide levels in COVID-19 patients

Mete

Koçak

Saracaloglu

et al. 2021

European Journal of Pharmacology

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“…Further detail is beyond the scope of this manuscript; however, extensive reviews have been readily available since the onset of the pandemic. ( McGonagle et al, 2020 ; Merad and Martin, 2020 ; Iqubal et al, 2021 ; Marik et al, 2021 ; McGonagle et al, 2021 ; Retamozo et al, 2021 ). In a healthy immune system, Natural Killer (NK) T lymphocytes and Cytotoxic CD8 lymphocytes provide a natural balance in our innate immune system.…”

Section: Discussionmentioning

confidence: 99%

Impact of fluvoxamine on outpatient treatment of COVID-19 in Honduras in a prospective observational real-world study

et al. 2022

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Background: The COVID-19 pandemic has impacted millions of lives globally. While COVID-19 did not discriminate against developed or developing nations, it has been a significant challenge for third world countries like Honduras to have widespread availability of advanced therapies. The concept of early treatment was almost unheard of when early outpatient treatments utilizing repurposed drugs in Latin American countries began showing promising results. One such drug is fluvoxamine, which has shown tremendous potential in two major studies. As a direct result, fluvoxamine was added to the standard of care in a major medical center outpatient COVID-19 clinic.Methods: This is a prospective observational study performed at the Hospital Centro Médico Sampedrano (CEMESA) in San Pedro Sula, Cortes, Honduras in the COVID-19 outpatient clinic. All patients were at least 15 years of age who had presented with mild or moderate signs and symptoms of COVID-19, and who also had a documented positive SARS-CoV-2 antigen or Reverse Transcription Polymerase Chain Reaction (RT-PCR) were included in the study. These patients then were all prescribed fluvoxamine. The cohort of patients who decided to take fluvoxamine were compared for primary endpoints of mortality and hospitalization risk to the cohort who did not take fluvoxamine. Patients were then monitored for 30 days with the first follow up at 7 days and the second follow up at 10–14 days of symptom onset. Categorical variables were compared by Pearson Chi-square test. The Relative risk was calculated using regression models. Continuous variables were compared by t-test and Wilcoxon rank-sum tests.Results: Out of total 657 COVID-19 cases, 594 patients took fluvoxamine and 63 did not take fluvoxamine. A total of five patients (0.76 percent) died, with only one death occurring in the fluvoxamine group. Patients who received fluvoxamine had a significantly lower relative risk of mortality (RR 0.06, p 0.011, 95% CI 0.007–0.516). There was a lower relative risk of hospitalization in the patients who in the fluvoxamine group. (−10 vs. 30 hospitalizations, RR 0.49, p = 0.035, 95% CI 0.26–0.95). There was 73 percent reduction in relative risk of requiring oxygen in the fluvoxamine group (RR 0.27, p < 0.001, 95% CI 0.14–0.54 Mean lymphocytes count on the first follow-up visit was significantly higher in the fluvoxamine group (1.72 vs. 1.38, Δ 0.33, p 0.007, CI 0.09–0.58).Conclusion: The results of our study suggest that fluvoxamine lowers the relative risk of death, hospitalization, and oxygen requirement in COVID 19 patients.

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“…At present, many of the existing drugs have been repurposed and tested in preclinical and clinical trials ( Table 2 ). However, with the advancement and better understanding of pathophysiology and clinical presentation among patients, it was noticed that the clinical efficacy of these drugs depends on timing of use, disease stage, and dose regimen ( Iqubal et al., 2021a ). Antiviral drugs are important when used during the early stage, as they inhibit viral entry and replication ( Şimşek Yavuz and Ünal, 2020 ).…”

Section: Susceptibility Of Coronavirus Disease 2019 To Clinically Used Drugsmentioning

confidence: 99%

Molecular Evolution of Severe Acute Respiratory Syndrome Coronavirus 2: Hazardous and More Hazardous Strains Behind the Coronavirus Disease 2019 Pandemic and Their Targeting by Drugs and Vaccines

Tuli

Sak²,

Aggarwal

et al. 2021

Front. Cell. Infect. Microbiol.

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Within almost the last 2 years, the world has been shaken by the coronavirus disease 2019 (COVID-19) pandemic, which has affected the lives of all people. With nearly 4.92 million deaths by October 19, 2021, and serious health damages in millions of people, COVID-19 has been the most serious global challenge after the Second World War. Besides lost lives and long-term health problems, devastating impact on economics, education, and culture will probably leave a lasting impression on the future. Therefore, the actual extent of losses will become obvious only after years. Moreover, despite the availability of different vaccines and vaccination programs, it is still impossible to forecast what the next steps of the virus are or how near we are to the end of the pandemic. In this article, the route of molecular evolution of the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is thoroughly compiled, highlighting the changes that the virus has undergone during the last 2 years and discussing the approaches that the medical community has undertaken in the fight against virus-induced damages.

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Macrophage Activation and Cytokine Release Syndrome in COVID-19: Current Updates and Analysis of Repurposed and Investigational Anti-Cytokine Drugs

Cited by 9 publications

References 53 publications

Effects of antiviral drug therapy on dynamic thiol/disulphide homeostasis and nitric oxide levels in COVID-19 patients

Effects of antiviral drug therapy on dynamic thiol/disulphide homeostasis and nitric oxide levels in COVID-19 patients

Impact of fluvoxamine on outpatient treatment of COVID-19 in Honduras in a prospective observational real-world study

Molecular Evolution of Severe Acute Respiratory Syndrome Coronavirus 2: Hazardous and More Hazardous Strains Behind the Coronavirus Disease 2019 Pandemic and Their Targeting by Drugs and Vaccines

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