Search

Figure (S5): The diagram of the Mechanism of COVID-19 Infection and the role of Imatinib &Indinavir. [Display omitted] • The SARS-CoV-2 infection caused tissue damage. • Widely dispersed, uncontrolled immune dysregulation, often known as the "cytokine storm. • Anti-TNF therapy may be an option for COVID-19 patients. • COVID-19 patients had higher NF-κB plasma concentrations. A worldwide coronavirus pandemic has affected many healthcare systems in 2019 (COVID-19). Following viral activation, cytokines and chemokines are released, causing inflammation and tissue death, particularly in the lungs, resulting in severe COVID-19 symptoms such as pneumonia and ARDS. COVID-19 induces the release of several chemokines and cytokines in different organs, such as the cardiovascular system and lungs. COVID-19 and its more severe effects, such as an elevated risk of death, are more common in patients with metabolic syndrome and the elderly. Cytokine storm and COVID-19 severity may be mitigated by immunomodulation targeting NF-κB activation in conjunction with TNF- α -inhibition. In severe cases of COVID-19, inhibiting the NF-κB/TNF- α, the pathway may be employed as a therapeutic option. The study will elaborate on the Egyptian pattern for COVID-19 patients in the first part of our study. An Egyptian patient with COVID-19 inflammatory profiling will be discussed in the second part of this article using approved marine drugs selected to inhabit the significant inflammatory signals. A biomarker profiling study is currently being performed on Egyptian patients with SARS‐COV‐2. According to the severity of the infection, participants were divided into four groups. The First Group was non-infected with SARS-CoV-2 (Control, n = 16), the Second Group was non-intensive care patients (non-ICU, n = 16), the Third Group was intensive care patients (ICU, n = 16), and the Fourth Group was ICU with endotracheal intubation (ICU + EI, n = 16). To investigate COVID-19 inflammatory biomarkers for Egyptian patients, several inflammatory, oxidative, antioxidant, and anti-inflammatory biomarkers were measured. The following are examples of blood tests: CRP, Ferritin, D-dimer, TNF-α, IL-8, IL-6., IL-Ib, CD8, NF-κB, MDA, and total antioxidants. The results of the current study revealed many logical findings, such as the elevation of CRP, Ferritin, D-dimer, TNF- α, CD8, IL-6, IL-, NF-κB, and MDA. Where a significant increase showed in ICU group results (23.05 ± 0.30, 2.35 ± 0.86, 433.4 ± 159.3, 26.67 ± 3.51, 7.52 ± 1.48, 7.49 ± 1.04, 5.76 ± 1.31, 7.41 ± 0.73) respectively, and also ICU group results (54.75 ± 3.44, 0.65 ± 0.13, 460.2 ± 121.42, 27.43 ± 2.52, 8.63 ± 2.68, 10.65 ± 2.75, 5.93 ± 1.4, 10.64 ± 0.86) respectively, as well as ICU + EI group results (117.63 ± 11.89, 1.22 ± 0.65, 918.8 ± 159.27, 26.68 ± 2.00, 6.68 ± 1.08, 11.68 ± 6.16, 6.23 ± 0.07, 22.41 ± 1.39),respectively.The elevation in laboratory biomarkers of cytokines storm in three infected groups with remarkable increases in the ICU + EI group was due to the elevation of oxidative stress and inflammatory storm molecules, which lead to highly inflammatory responses, specifically in severe patients of COVID-19. Another approach to be used in the current study is investigating new computational drug compounds for SARS‐COV‐2 protective agents from the marine environment. The results revealed that (Imatinib and Indinavir) had the highest affinity toward Inflammatory molecules and COVID-19 proteins (PDB ID: −7CZ4 and 7KJR), which may be used in the future as possible COVID-19 drug candidates. The investigated inflammatory biomarkers in Egyptian COVID-19 patients showed a strong correlation between IL6, TNF-α, NF-κB, CRB, DHL, and ferritin as COVID-19 biomarkers and determined the severity of the infection. Also, the oxidative /antioxidant showed good biomarkers for infection recovery and progression of the patients. [ABSTRACT FROM AUTHOR]

• The serum level of MCP-1 was high in COVID-19 patients. • AG genotype of the rs1024611 was associated with COVID-19 hospitalization. • The serum levels of MCP-1 could be dependent on COVID-19 and polymorphism. As a result of SARS-CoV-2 infection, the host's immune system is disrupted, and chemokines and cytokines are intensified to eliminate the virus, resulting in cytokine storm syndrome and acute respiratory distress syndrome (ARDS). Patients with COVID-19 have been observed to have elevated levels of MCP-1, a chemokine associated with the severity of the disease. In some diseases, polymorphisms in the regulatory region of the MCP-1 gene correspond to serum levels and disease severity. An attempt was made in this study to assess the relationship between MCP-1 G-2518A and serum MCP-1 levels in Iranian COVID-19 patients and the severity of the disease. In this study, patients were randomly sampled from outpatients on the first day of diagnosis and from inpatients on the first day of their hospitalization. Patients were classified into the outpatient (without symptoms or with mild symptoms) and inpatient (with moderate, severe, and critical symptoms) groups. The serum level of MCP-1 was measured by ELISA and the frequency of MCP-1 G-2518A gene polymorphism genotypes in COVID-19 patients was checked by the RFLP-PCR method. Participants with COVID-19 infection had a higher rate of underlying diseases, such as diabetes, high blood pressure, kidney disease, and cardiovascular disease than the control group (P-value < 0.001). Also, the frequency of these factors in inpatients was significantly higher compared to outpatients (P-value < 0.001). Additionally, the level of MCP-1 in serum was significantly different with an average of 11.90 in comparison to 2.98 in the control group (P-value, 0.05), which is attributed to elevated serum levels among patients in hospitals with an average of 11.72 in comparison to 2.98 in the control group. Compared with outpatients, inpatients had a higher frequency of the G allele of the MCP-1-2518 polymorphism (P-value < 0.05), while a notable difference was observed in the serum level of MCP-1 in COVID-19 patients with the MCP-1-2518 AA genotype in the whole group in comparison to the control group (P-value: 0.024). Totally, the results showed that a high frequency of the G allele is related to hospitalization and poor outcome in COVID-19 cases. [ABSTRACT FROM AUTHOR]

• The lovastatin administration was decreased inflammatory markers in COVID-19 patients. • The reduction of IL-6 and IL-8 was dose-dependent manner. • The decrease in CRP levels was not dose-dependent. • The receiving of lovastatin in COVID-19 cases was associated with reducing the time of hospitalization. • The COVID-19 cases receiving lovastatin were decreased mortality rate than the control group. The mounting evidence regarding the pathogenesis of COVID-19 indicated that the cytokine storm has an axial role in the severity of this disease, which may lead to thrombotic complications, acute respiratory distress syndrome (ARDS), and myocardial damage, among other consequences. It has recently been demonstrated that statins are known to have anti-viral, anti-inflammatory, anti-thrombotic, and immunomodulatory features; however, their advantage has not been evaluated in COVID-19. This study aimed to investigate the protective effects of lovastatin in intensive care unit (ICU) patients with COVID-19. The case-control study consists of 284 ICU patients, which classified into three groups as follows: 1) the patients who no received lovastatin as a control (92 patients), 2) patients received 20 mg per day lovastatin (99 patients), and 3) patients received 40 mg per day lovastatin (93 patients). Each group's demographic and clinical parameters, along with CRP, interleukin (IL)-6, IL-8 levels, and mortality rate, were studied in three-time points. The results showed that there was no statistically significant difference between our study groups in terms of age and sex. (P > 0.05). Besides, in patients, receiving lovastatin the CRP, IL-6, IL-8 levels were significantly decreased from T1 to T3 than to the control group. Our results also showed that the use of lovastatin in COVID-19 patients significantly reduced the length of hospitalization in the ICU compared with the control group. In addition, our results showed that the mortality rate in patients receiving lovastatin was lower when compared to the control group; however, this difference was not statistically significant. Since the cytokine storm is a significant factor in the pathology of SARS-CoV-2, our findings highlighted the potential use of lovastatin to mitigate the inflammatory response induced by SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

• The emerging COVID-19 disease outbreak continues to spread worldwide. • A randomized trial with or without O3-autohemotherapy (O3-AHT) was performed. • No differences in mortality, length of hospital stays, mechanical ventilation, admission to ICU were observed. • A score to assess clinical improvement show a significant improvement in the O3-AHT arm. • O3-AHT, as adjuvant therapy, may provide useful support in mild to moderate SARS-CoV-2 pneumonia. Following positive experience on the use of blood ozonation in SARS-CoV-2, the CORMOR randomized trial was designed to evaluate the adjuvant role of oxygen/ozone therapy in mild to moderate SARS-CoV-2 pneumonia. The trial (ClinicalTrial.gov NCT04388514) was conducted in four different Italian centers (April-October 2020). Patients were treated according to best available standard of care (SoC) therapy, with or without O3-autohemotherapy (O3-AHT). A total of 92 patients were enrolled: SoC + O3-AHT (48 patients) were compared to the SoC treatment (44 patients). The two groups differed in steroids therapy administration (72.7% in SoC arm vs. 50.0% in O3-AHT arm; p = 0.044). Steroid therapy was routinely started when it was subsequently deemed as effective for the treatment of COVID-19 disease. No significant differences in mortality rates, length of hospital stay, mechanical ventilation requirement and ICU admission were observed. Clinical improvement in patients with pneumonia was assessed according to a specifically designed score (decrease in SIMEU class, improvement in radiology imaging, improvement in PaO2/FiO2, reduction in LDH and requirement of oxygen therapy ≤ 5 days). Score assessment was performed on day-3 (T3) and day-7 (TEnd) of O3-AHT treatment. A significant increase in the score was reported at TEnd, in the O3-AHT treatment arm (0 [0–1] in the SoC arm vs. 2 [1–3] the O3-AHT arm; p = 0.018). No adverse events related O3-AHT treatment was observed. In mild-to-moderate pneumonia due to SARS-CoV-2, adjuvant oxygen/ozone therapy did not show any effect on mortality, or mechanical intubation but show a clinical improvement a day 7 from randomization in a composite clinical endpoint. Larger Randomized prospective studies alone or in combination with steroids are needed to confirm our results. [ABSTRACT FROM AUTHOR]

• Drugs to attenuate cytokine storm in COVID-19 are unavailable. • Canagliflozin attenuated inflammatory cytokine storm in LPS-treated mice.. • Atomized administration of Canagliflozin also exhibited anti-inflammatory effects. To date, drugs to attenuate cytokine storm in severe cases of Corona Virus Disease 2019 (COVID-19) are not available. In this study, we investigated the effects of intragastric and atomized administration of canagliflozin (CAN) on cytokine storm in lung tissues of lipopolysaccharides (LPS)-induced mice. Results showed that intragastric administration of CAN significantly and widely inhibited the production of inflammatory cytokines in lung tissues of LPS-induced sepsis mice. Simultaneously, intragastric administration of CAN significantly improved inflammatory pathological changes of lung tissues. Atomized administration of CAN also exhibited similar effects in LPS-induced sepsis mice. Furthermore, CAN significantly inhibited hypoxia inducible factor 1α (HIF-1α) and phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3) protein levels in LPS-treated lung tissues. These results indicated that CAN might attenuate cytokine storm and reduce the inflammatory symptoms in critical cases in COVID-19. Its action mechanism might involve the regulation of HIF-1α and glycolysis in vivo. However, further studies about clinical application and mechanism analysis should be validated in the future. [ABSTRACT FROM AUTHOR]

• Lactoferrin (LF), a first line defense protein in mammals, attenuates insult-induced oxidative stress. • LF bridges innate and adaptive immunity. • Exogenous LF may attenuate COVID-19 induced "cytokine storm". • There is growing evidence for potential utility of LF as prophylactic and therapeutic agent. The COVID-19 pandemic is a serious global health threat caused by severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). Symptoms of COVID-19 are highly variable with common hyperactivity of immune responses known as a "cytokine storm". In fact, this massive release of inflammatory cytokines into in the pulmonary alveolar structure is a main cause of mortality during COVID-19 infection. Current management of COVID-19 is supportive and there is no common clinical protocol applied to suppress this pathological state. Lactoferrin (LF), an iron binding protein, is a first line defense protein that is present in neutrophils and excretory fluids of all mammals, and is well recognized for its role in maturation and regulation of immune system function. Also, due to its ability to sequester free iron, LF is known to protect against insult-induced oxidative stress and subsequent "cytokine storm" that results in dramatic necrosis within the affected tissue. Review of the literature strongly suggests utility of LF to silence the "cytokine storm", giving credence to both prophylactic and therapeutic approaches towards combating COVID-19 infection. [ABSTRACT FROM AUTHOR]

• Cytokine release syndrome can lead to severe deterioration in COVID-19 patients. • No treatment has yet proven completely beneficial for COVID-19 patients. • Tocilizumab was administered to 40 severely ill COVID-19 patients. • Majority of our study patients showed improvement after Tocilizumab administration. COVID-19 pandemic has become a global concern. Cytokine release syndrome (CRS) complicates acute respiratory distress syndrome (ARDS) and causes multi-organ failure which can subsequently lead to mortality in COVID-19 patients. Tocilizumab, an interleukin-6 antagonist, has shown to salvage patients with cytokine release storm. In this study, we aim to evaluate therapeutic response of Tocilizumab in COVID-19 patients. A single-arm retrospective review of 40 patients with COVID-19, admitted to The Aga Khan University Hospital Karachi, from March 2020 to May 2020 was performed. Selection of patients for use of Tocilizumab was based on severity of disease, rapid clinical deterioration, presence of CRS and absence of any absolute contraindication to Tocilizumab. Improvement after Tocilizumab was defined as improvement in oxygen requirement and inflammatory parameters. Serum levels of inflammatory cytokines like C-reactive protein, ferritin, D-dimer and lactate dehydrogenase levels were monitored before and after administering Tocilizumab. Mean age was 62.4 years and 33 (82.5%) were male. 19 (47.5%) patients were critically sick, 18 (45%) were severely sick and 3 (7.5%) were moderately sick. 29 (77.5%) patients showed significant improvement in oxygen requirement, inflammatory parameters and chest x-rays, out of which 28 patients were discharged home. The mean duration between administration of Tocilizumab and overall improvement was 4.3 ± 3.2 days. Hence, Tocilizumab can be used as a possible treatment option in patients with COVID-19 induced CRS but needs monitoring for its adverse effects. [ABSTRACT FROM AUTHOR]