Effect of Pirfenidone on Risk of Pulmonary Fibrosis in COVID-19 Patients Experiencing Cytokine Storm.

OBJECTIVES: Severe stages of COVID-19 infection have been associated with the excessive discharge of pro-inflammatory mediators such as cytokines, resulting in lung deterioration, which progresses rapidly to lung fibrosis leading to acute respiratory distress syndrome. In this investigation, the efficacy and safety of the novel antifibrotic and anti-inflammatory agent, Pirfenidone, were assessed in COVID-19 patients with pulmonary fibrosis secondary to cytokine storm. In this randomized controlled study, we assigned 100 adult COVID-19 patients cytokine storm and admitted to the intensive care isolation unit into either pirfenidone added to the standard therapy (n = 47), or the standard protocol only (n = 53). High-resolution computed tomography of the chest was performed in all patients to evaluate fibrotic lesions and their progression. The results showed that the percentage of patients who developed pulmonary fibrosis during cytokine storm onset in the pirfenidone group relative to the standard group was 29.8% and 35.8%, respectively, with no significant difference between the two groups; while there was a significant increase in the proportion of patients discharged from the isolation unit with pulmonary fibrosis without progression in fibrotic lesions in the pirfenidone group compared to the standard group (21.3% and 5.7%, respectively). Furthermore, there was a significant difference concerning liver enzyme elevation and GIT disturbance incidences in the studied groups (p = 0.006 and 0.01, respectively). Our findings show that Pirfenidone inhibits fibrosis advancement in COVID-19 patients with pulmonary fibrosis and is associated with hepatotoxicity and GI distress. It may be beneficial in patients with mild to moderate COVID-19-induced pulmonary fibrosis; however, additional research is necessary.

Evidence for the Efficacy of a High Dose of Vitamin D on the Hyperinflammation State in Moderate-to-Severe COVID-19 Patients: A Randomized Clinical Trial.

Background and Objectives: Vitamin D supplementation plays a key effect in lowering cytokine storms among COVID-19 patients by influencing the activity of the renin-angiotensin system and the production of the angiotensin-2 converting enzyme. The study was conducted to explore the effect of high-dose intramuscular vitamin D in hospitalized adults infected with moderate-to-severe SARS-CoV-2 in comparison with the standard of care in the COVID-19 protocol. Materials and Methods: Two groups of patients were compared in this prospective randomized controlled trial as the vitamin D was administered orally to group 1 (alfacalcidol 1 mcg/day) and intramuscularly to group 2 (cholecalciferol 200,000 IU). One hundred and sixteen participants were recruited in total, with fifty-eight patients in each group. Following the Egyptian Ministry of Health's policy for COVID-19 management, all patients received the same treatment for a minimum of five days. Results: A significant difference was recorded in the length of hospital stay (8.6 versus 6.8 days), need for high oxygen or non-invasive mechanical ventilator (67% versus 33%), need for a mechanical ventilator (25% versus 75%), clinical improvement (45% versus 55%), the occurrence of sepsis (35% versus 65%), and in the monitored laboratory parameters in favor of high-dose vitamin D. Moreover, clinical improvement was significantly associated with the need for low/high oxygen, an invasive/non-invasive mechanical ventilator (MV/NIMV), and diabetes, while mortality was associated with the need for MV, ICU admission, atrial fibrillation, chronic obstructive pulmonary disease, asthma, and the occurrence of secondary infection. Conclusions: Our study showed that high-dose vitamin D was considered a promising treatment in the suppression of cytokine storms among COVID-19 patients and was associated with better clinical improvement and fewer adverse outcomes compared to low-dose vitamin D.

The Impact of Sociodemographic, Nutritional, and Health Factors on the Incidence and Complications of COVID-19 in Egypt: A Cross-Sectional Study.

This study was intended to explore sociodemographic, nutritional, and health-related factors on the incidence of COVID-19 infection within the Egyptian population by assessing the frequency and determinants of post-COVID-19 symptoms and complications. A cross-sectional study using a structured survey on 15,166 participants was adopted. The results revealed common symptoms including fever (79.1%), cough (74.5%), anosmia& ageusia (68.4%), and dyspnea (66.9%). The patients were nonsmokers (83.9%), while 9.7% were mild smokers. The percentage of infected patients with comorbidities versus those without comorbidities were 29%, 71%, respectively. The highest incidence of infection was in those patients with hypertension (14.8%) and diabetes (10.9%), especially females with age >50 years and obesity (BMI; 30-39.9). The highest risks were observed for anticoagulants in the age above 50 years, morbid obesity, presence of comorbidities, and being a healthcare worker. The predictors of clot risk were in the age above 50 years, non-educated, and eating meat and eggs. Nonetheless, the highest risk of using antidepressants was in patients >50 years and those who traveled abroad. These findings and similarities within the surrounding region, the Middle East, North Africa, and South Europe, indicate the possibility of sharing the same viral strain and characteristics that may predict a similar vaccine efficacy and response.

Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients.

BACKGROUND: The effectiveness of the best combination between different antiviral and anti-inflammatory drugs stills an interest in the treatment of COVID19 infection. PATIENTS AND METHODS: A prospective randomized cohort study comprised 108 adult patients with confirmed PCR COVID 19 infection with systemic hyper inflammation state, divided into two groups according to the treatment regimen, 56 in the tocilizumab- hydroxychloroquine (TCZ-HCQ) treatment, and 52 in the tocilizumab-remdesivir (TCZ-RMV) treatment. The first group received a combination of I.V. TCZ (400-800 mg every 24 h for only two doses) and HCQ (400 mg twice in the first day then 200 mg twice for 5 days) while the second group of patients received I.V. RMV of 200 mg on day 1 followed by 100 mg once daily infused over 60 min for 5 days with the same TCZ regimen used in the first group. All clinical parameters and laboratory investigations were assessed before and after treatment. RESULTS: The CRP was significantly decreased while PaO2/FiO2 (P/F) ratio post-treatment was significantly improved in both treatment groups. TCZ-HCQ group showed a significant decrease in the ferritin, LDH, and D. Dimer levels. The median days of hospitalization with interquartile range (IQR) were 10 (6-16) and 8 (5-12) for TCZ-HCQ and TCZ-RMV groups, respectively. The numbers of mechanically ventilated patients were 25 and 43 for TCZ-HCQ and TCZ-RMV groups, respectively. Therapeutic failure was about 26.8% in the TCZ-HCQ group and 30.8% in the TCZ-RMV group but there was no significant difference between both groups. Some complications were recognized only in TCZ-RMV following treatment including secondary bacterial infections (42.3%), myocarditis (15.4%), and finally pulmonary embolism (7.7%). CONCLUSION: Efficacy of both TCZ-RMV and TCZ-HCQ combinations are observed in the treatment of severe COVID-19 patients; however the increased need for ICU or mechanical ventilation in the TCZ-RMV arm contributed to the appearance of cardiac and thrombotic events. The study was registered at the Clinical Trials registry (ClinicalTrials.gov; NCT04779047).

Efficacy of the early treatment with tocilizumab-hydroxychloroquine and tocilizumab-remdesivir in severe COVID-19 Patients

Background The effectiveness of the best combination between different antiviral and anti-inflammatory drugs stills an interest in the treatment of COVID19 infection. Patients and methods A prospective randomized cohort study comprised 108 adult patients with confirmed PCR COVID 19 infection with systemic hyper inflammation state, divided into two groups according to the treatment regimen, 56 in the tocilizumab- hydroxychloroquine (TCZ-HCQ) treatment, and 52 in the tocilizumab-remdesivir (TCZ-RMV) treatment. The first group received a combination of I.V. TCZ (400–800 mg every 24 hours for only two doses) and HCQ (400 mg twice in the first day then 200 mg twice for 5 days) while the second group of patients received I.V. RMV of 200 mg on day 1 followed by 100 mg once daily infused over 60 minutes for 5 days with the same TCZ regimen used in the first group. All clinical parameters and laboratory investigations were assessed before and after treatment. Results The CRP was significantly decreased while PaO2/FiO2 (P/F) ratio post-treatment was significantly improved in both treatment groups. TCZ-HCQ group showed a significant decrease in the ferritin, LDH, and D. Dimer levels. The median days of hospitalization with interquartile range (IQR) were 10 (6–16) and 8 (5–12) for TCZ-HCQ and TCZ-RMV groups, respectively. The numbers of mechanically ventilated patients were 25 and 43 for TCZ-HCQ and TCZ-RMV groups, respectively. Therapeutic failure was about 26.8% in the TCZ-HCQ group and 30.8% in the TCZ-RMV group but there was no significant difference between both groups. Some complications were recognized only in TCZ-RMV following treatment including secondary bacterial infections (42.3%), myocarditis (15.4%), and finally pulmonary embolism (7.7%). Conclusion Efficacy of both TCZ-RMV and TCZ-HCQ combinations are observed in the treatment of severe COVID-19 patients;however the increased need for ICU or mechanical ventilation in the TCZ-RMV arm contributed to the appearance of cardiac and thrombotic events. The study was registered at the Clinical Trials registry (ClinicalTrials.gov;NCT04779047).

Hydroxychloroquine and Azithromycin Combination in the Management of COVID-19 Infection: Safety and Effectiveness Challenges.

BACKGROUND: The treatment of COVID-19 disease remains a dilemma so far because there is no approved therapy for it. This study aimed to evaluate the use of hydroxychloroquine and azithromycin combination in treatment. OBJECTIVES: This study was carried out to determine the safety and effectiveness of hydroxychloroquine and azithromycin combination in COVID 19 patients. METHODS: This study included 90 adult COVID 19 patients. Treatment of all patients followed Egyptian Ministry of Health COVID-19 protocols, receiving a combination of hydroxychloroquine 400mg twice on day 1, then 200 mg twice daily in addition to azithromycin 500mg/day for 5 days. ECG findings, especially the QTc interval, were assessed before and after 5 days from the administration. RESULTS: All patients showed a statistically significant higher post-treatment QTc readings (433.6 ± 37.2) compared to baseline QTc (402.4 ± 31.3) at p<0.005 with a median QTc prolongation by 26 mSec and IQR (17.8-41.3), but without serious clinical complications. Only 5.6% of patients showed QTc more than 500 mSec and no torsade de points or cardiac arrest. Geriatric patients were at higher risk for QTc prolongation compared to patients aged less than 65 years but without a significant difference as regards the median max QTc difference p˂0.65. The expected therapeutic effectiveness was 82.5% for moderate patients compared to 26% for severe patients (P<0.005). CONCLUSION: In a modest safety profile, we support the evidence that HQ/AZ therapy can be used to treat Covid-19 infection with more effectiveness in moderate rather than severe cases, which might be a reflection of the time of administration in the disease course.

Therapeutic efficacy, mechanical ventilation, length of hospital stay, and mortality rate in severe COVID-19 patients treated with tocilizumab.

BACKGROUND: The treatment of severe cases of COVID-19 disease remains a dilemma so far, because there is no approved therapy for it. This study aimed to estimate the therapeutic efficacy of tocilizumab and its role in reducing the need for mechanical ventilation, length of hospital stay, mortality rate for these cases. METHOD: The study included 25 adult patients with confirmed severe COVID-19 infection. Treatment of all patients followed Egyptian Ministry of Health COVID-19 protocol in addition to tocilizumab IV (400-800 mg) as a single dose and then the dose was repeated after at least 12 hours and up to 24 hours from the previous dose. All laboratory and clinical parameters were assessed before and within 24 hours after tocilizumab administration. RESULTS: After receiving TCZ, all patients showed significantly lower median IL 6, LDH, CRP, ferritin , TLC at P < .001, and D-Dimer at P = .223 than their baseline levels. Also, the number of patients who required mechanical ventilation decreased from 11 to 8. Only five patients died after TCZ treatment. A moderate correlation was found between therapeutic failure and death outcomes and mechanical ventilation need at baseline. The median days of hospitalisation (IQR) were 10 (6-16). CONCLUSION: Tocilizumab treatment in patients with severe COVID-19 is safe and has significant therapeutic effects and a significant role in the improvement of all laboratory parameters. Also TCZ plays a significant role in the reduction of the length of stay in hospital and ICU, need for mechanical ventilation, and mortality rate.What's known IL-6 plays the main role in the acute respiratory distress syndrome (ARDS) associated with severe COVID-19 infection. Consequently, serum IL-6 can be considered as an important target in therapeutic management of severe COVID-19 patients. What's new Prospective study, carried on 25 adult patients with confirmed severe COVID-19 infection using tocilizumab, showed significant improvement in their case. Tocilizumab, as an IL-6 inhibitor, not only lowered IL-6 level put also showed a significant reduction on median LDH, CRP, ferritin , TLC at P < .001 and D-Dimer at P = .223 than their baseline levels. Improvement of all laboratory parameters using TCZ was reflected in the reduction of the length of stay in hospital and ICU, need for mechanical ventilation and mortality rate.