1.Ruxolitinib and the Mitigation of Severe COVID-19: A Systematic Review and Meta-analysis
Jorge R. QUIROS ; Jennifer ROSS-COMPTIS ; Donald Hathaway III ; Azza SARFRAZ ; Zouina SARFRAZ ; Zhanna GRIGORYAN ; Kimberly Anne ROMERO ; Abubakar GAPIZOV ; Fortunato S PRÍNCIPE-MENESES ; Manoj Reddy SOMAGUTTA ; Adrian RIVA-MOSCOSO ; Abdulhusein KAPASI
Infection and Chemotherapy 2021;53(3):436-448
Background:
The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients.
Materials and Methods:
This review was conducted using preferred reporting items for aystematic reviews and meta-analyses (PRISMA) methodology. Six reviewers analyzed 1,120 results. Seven studies were selected and validated. A quantitative meta-analysis was further performed to evaluate clinical improvement at day 28, mortality at day 28, and oxygen requirements comparing treatment and standard of care groups.
Results:
168 individuals were involved in the studies selected: 122 in cohort studies, 4 in case reports, and 41 in randomized controlled studies. The ruxolitinib group had a higher likelihood of clinical improvement by the 28th day of treatment when assessed with the standard of care (SOC) group (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 0.53 -4.16; P = 0.45; I2 = 0%). The SOC group was at a higher risk of experiencing serious adverse events (OR: 0.17; 95% CI: 0.03 - 1.13; P = 0.07). Notably the SOC group had a higher likelihood of death (OR: 0.51; 95% CI: 0.11-2.29; P = 0.07; I2= 0%).
Conclusion
Prior studies on ruxolitinib have demonstrated it is able to decrease inflammatory markers. In recent studies on COVID-19, treatment with ruxolitinib decreased the time on mechanical ventilation, hospitalization time, and the need for vasopressor support. Additionally, ruxolitinib showed decreased mortality and demonstrated improvement in lung congestion as evidenced by computerized tomography imaging. These findings warrant further clinical investigation into Ruxolitinib as a potential treatment approach for severe COVID-19.
2.Ruxolitinib and the Mitigation of Severe COVID-19: A Systematic Review and Meta-analysis
Jorge R. QUIROS ; Jennifer ROSS-COMPTIS ; Donald Hathaway III ; Azza SARFRAZ ; Zouina SARFRAZ ; Zhanna GRIGORYAN ; Kimberly Anne ROMERO ; Abubakar GAPIZOV ; Fortunato S PRÍNCIPE-MENESES ; Manoj Reddy SOMAGUTTA ; Adrian RIVA-MOSCOSO ; Abdulhusein KAPASI
Infection and Chemotherapy 2021;53(3):436-448
Background:
The cause of end-organ damage and acute respiratory distress syndrome (ARDS) in coronavirus disease 2019 (COVID-19) patients is postulated to be connected to the uncontrolled increase of pro-inflammatory cytokines. The upregulation of many cytokines is dependent on signaling through the Janus kinase 1 (JAK-1) and JAK-2 pathways. Ruxolitinib, a JAK-1 and JAK-2 inhibitor, is documented to have potent anti-inflammatory activity by targeting several cytokines and growth factors with proposed efficacy in the cytokine storm observed in severe COVID-19 patients; therefore, this study examines the efficacy and tolerability of ruxolitinib for adult COVID-19 patients.
Materials and Methods:
This review was conducted using preferred reporting items for aystematic reviews and meta-analyses (PRISMA) methodology. Six reviewers analyzed 1,120 results. Seven studies were selected and validated. A quantitative meta-analysis was further performed to evaluate clinical improvement at day 28, mortality at day 28, and oxygen requirements comparing treatment and standard of care groups.
Results:
168 individuals were involved in the studies selected: 122 in cohort studies, 4 in case reports, and 41 in randomized controlled studies. The ruxolitinib group had a higher likelihood of clinical improvement by the 28th day of treatment when assessed with the standard of care (SOC) group (odds ratio [OR]: 1.48; 95% confidence interval [CI]: 0.53 -4.16; P = 0.45; I2 = 0%). The SOC group was at a higher risk of experiencing serious adverse events (OR: 0.17; 95% CI: 0.03 - 1.13; P = 0.07). Notably the SOC group had a higher likelihood of death (OR: 0.51; 95% CI: 0.11-2.29; P = 0.07; I2= 0%).
Conclusion
Prior studies on ruxolitinib have demonstrated it is able to decrease inflammatory markers. In recent studies on COVID-19, treatment with ruxolitinib decreased the time on mechanical ventilation, hospitalization time, and the need for vasopressor support. Additionally, ruxolitinib showed decreased mortality and demonstrated improvement in lung congestion as evidenced by computerized tomography imaging. These findings warrant further clinical investigation into Ruxolitinib as a potential treatment approach for severe COVID-19.
3.Omega 3 Fatty Acids and COVID-19:A Comprehensive Review
Donald HATHAWAY III ; Krunal PANDAV ; Madhusudan PATEL ; Adrian RIVA-MOSCOSO ; Bishnu Mohan SINGH ; Aayushi PATEL ; Zar CHI MIN ; Sarabjot SINGH-MAKKAR ; Muhammad KHAWAR SANA ; Rafael SANCHEZ-DOPAZO ; Rockeven DESIR ; Michael Maher MOURAD FAHEM ; Susan MANELLA ; Ivan RODRIGUEZ ; Alina ALVAREZ ; Rafael ABREU
Infection and Chemotherapy 2020;52(4):478-495
The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to “cytokine storm”. This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.
4.Effects of Interferon Beta in COVID-19 adult patients: Systematic Review
Juan Pablo SOSA ; Maria Mercedes Ferreira CACERES ; Jennifer Ross COMPTIS ; Jorge QUIROS ; Fortunato S PRÍNCIPE-MENESES ; Adrian RIVA-MOSCOSO ; Marie-Pierre BELIZAIRE ; Freda Q. MALANYAON ; Kuchalambal AGADI ; Syeda Sheharbano JAFFERY ; Juhi SAHAJWANI ; Asma ARSHIA ; Andrelle SENATUS ; Graciela VERDECIA ; Lordstrong AKANO ; Aminah Abdul RAZZACK ; Sanna SALAM ; Vinay Kumar GADAMIDI ; Sheeba MARIAN
Infection and Chemotherapy 2021;53(2):247-260
Background:
The high rate of transmission and infection of coronavirus disease 2019 (COVID-19) is a public health emergency of major epidemiological concern. No definitive treatments have been established, and vaccinations have only recently begun. We aim to review the efficacy and safety of Interferon Beta (IFN-β) in patients who have a confirmed COVID-19 diagnosis.
Materials and Methods:
A search from PubMed, Science Direct, Cochrane, and Clinicaltrials.gov databases were conducted from December 2019 to December 2020 to review the efficacy and safety of IFN-β in adult patients with COVID-19 confirmed. We included randomized controlled trials, case reports, and experimental studies. Correspondences, letters, editorials, reviews, commentaries, case control, cross-sectional, and cohort studies that did not include any new clinical data were excluded.
Results:
Of the 66 searched studies, 8 were included in our review. These studies demonstrated that although IFN-β did not reduce the time to clinical response, there was an increase in discharge rate at day 14 and a decrease in mortality at day 28. The time to negative reverse transcription polymerase chain reaction (RT-PCR) was shown to be significantly shortened in patients receiving IFN-β, along with a lower nasopharyngeal viral load.Further, patients receiving IFN-β had a less significant rise in IL-6. IFN-β was shown to decrease intensive care unit (ICU) admission rate, the requirement of invasive ventilation in severe cases, and improve the survival rate compared to control groups. There were no severe adverse events reported.Our review found that patients who received early treatment with IFN-β experienced significantly reduced length of hospitalization, mortality, ICU admission, and mechanical ventilation. A greater chance of clinical improvement and improved imaging studies was noted in patients who received IFN-β. There were no reported deaths associated with the addition of IFN-β. Further randomized trials involving more significant sample sizes are needed to better understand the effect of IFN-β on survival in COVID-19.
Conclusion
This review identified encouraging data and outcomes of incorporating IFN-βto treat COVID-19 patients. IFN-β has been shown to decrease hospital stay's overall length and decrease the severity of respiratory symptoms when added to the standard of care. Also, in some studies, it has been demonstrated to reduce the length of ICU stay, enhance survival rate, and decrease the need for invasive mechanical ventilation. There were minor side effects reported (neuropsychiatric symptoms and hypersensitivity reaction). However, randomized clinical trials with a large sample size are needed to assess IFN-β's benefit precisely.
5.Omega 3 Fatty Acids and COVID-19:A Comprehensive Review
Donald HATHAWAY III ; Krunal PANDAV ; Madhusudan PATEL ; Adrian RIVA-MOSCOSO ; Bishnu Mohan SINGH ; Aayushi PATEL ; Zar CHI MIN ; Sarabjot SINGH-MAKKAR ; Muhammad KHAWAR SANA ; Rafael SANCHEZ-DOPAZO ; Rockeven DESIR ; Michael Maher MOURAD FAHEM ; Susan MANELLA ; Ivan RODRIGUEZ ; Alina ALVAREZ ; Rafael ABREU
Infection and Chemotherapy 2020;52(4):478-495
The rapid international spread of severe acute respiratory syndrome coronavirus 2 responsible for coronavirus disease 2019 (COVID-19) has posed a global health emergency in 2020. It has affected over 52 million people and led to over 1.29 million deaths worldwide, as of November 13th, 2020. Patients diagnosed with COVID-19 present with symptoms ranging from none to severe and include fever, shortness of breath, dry cough, anosmia, and gastrointestinal abnormalities. Severe complications are largely due to overdrive of the host immune system leading to “cytokine storm”. This results in disseminated intravascular coagulation, acute respiratory distress syndrome, multiple organ dysfunction syndrome, and death. Due to its highly infectious nature and concerning mortality rate, every effort has been focused on prevention and creating new medications or repurposing old treatment options to ameliorate the suffering of COVID-19 patients including the immune dysregulation. Omega-3 fatty acids are known to be incorporated throughout the body into the bi-phospholipid layer of the cell membrane leading to the production of less pro-inflammatory mediators compared to other fatty acids that are more prevalent in the Western diet. In this article, the benefits of omega-3 fatty acids, especially eicosapentaenoic acid and docosahexaenoic acid, including their anti-inflammatory, immunomodulating, and possible antiviral effects have been discussed.
6.Effects of Interferon Beta in COVID-19 adult patients: Systematic Review
Juan Pablo SOSA ; Maria Mercedes Ferreira CACERES ; Jennifer Ross COMPTIS ; Jorge QUIROS ; Fortunato S PRÍNCIPE-MENESES ; Adrian RIVA-MOSCOSO ; Marie-Pierre BELIZAIRE ; Freda Q. MALANYAON ; Kuchalambal AGADI ; Syeda Sheharbano JAFFERY ; Juhi SAHAJWANI ; Asma ARSHIA ; Andrelle SENATUS ; Graciela VERDECIA ; Lordstrong AKANO ; Aminah Abdul RAZZACK ; Sanna SALAM ; Vinay Kumar GADAMIDI ; Sheeba MARIAN
Infection and Chemotherapy 2021;53(2):247-260
Background:
The high rate of transmission and infection of coronavirus disease 2019 (COVID-19) is a public health emergency of major epidemiological concern. No definitive treatments have been established, and vaccinations have only recently begun. We aim to review the efficacy and safety of Interferon Beta (IFN-β) in patients who have a confirmed COVID-19 diagnosis.
Materials and Methods:
A search from PubMed, Science Direct, Cochrane, and Clinicaltrials.gov databases were conducted from December 2019 to December 2020 to review the efficacy and safety of IFN-β in adult patients with COVID-19 confirmed. We included randomized controlled trials, case reports, and experimental studies. Correspondences, letters, editorials, reviews, commentaries, case control, cross-sectional, and cohort studies that did not include any new clinical data were excluded.
Results:
Of the 66 searched studies, 8 were included in our review. These studies demonstrated that although IFN-β did not reduce the time to clinical response, there was an increase in discharge rate at day 14 and a decrease in mortality at day 28. The time to negative reverse transcription polymerase chain reaction (RT-PCR) was shown to be significantly shortened in patients receiving IFN-β, along with a lower nasopharyngeal viral load.Further, patients receiving IFN-β had a less significant rise in IL-6. IFN-β was shown to decrease intensive care unit (ICU) admission rate, the requirement of invasive ventilation in severe cases, and improve the survival rate compared to control groups. There were no severe adverse events reported.Our review found that patients who received early treatment with IFN-β experienced significantly reduced length of hospitalization, mortality, ICU admission, and mechanical ventilation. A greater chance of clinical improvement and improved imaging studies was noted in patients who received IFN-β. There were no reported deaths associated with the addition of IFN-β. Further randomized trials involving more significant sample sizes are needed to better understand the effect of IFN-β on survival in COVID-19.
Conclusion
This review identified encouraging data and outcomes of incorporating IFN-βto treat COVID-19 patients. IFN-β has been shown to decrease hospital stay's overall length and decrease the severity of respiratory symptoms when added to the standard of care. Also, in some studies, it has been demonstrated to reduce the length of ICU stay, enhance survival rate, and decrease the need for invasive mechanical ventilation. There were minor side effects reported (neuropsychiatric symptoms and hypersensitivity reaction). However, randomized clinical trials with a large sample size are needed to assess IFN-β's benefit precisely.