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Objective: To determine the role of Methylprednisolone in managing COVID-19 patients. Study Design: Cross-sectional study. Place and Duration of Study: Pakistan Emirates Military Hospital (PEMH), Rawalpindi Pakistan, from Jan to Feb 2021. Methodology: This study was carried out at the Department of Medicine. Medical records of all moderate, severe and critical COVID-19 patients admitted and receiving Methylprednisolone were reviewed. Methylprednisolone was used in all patients at doses 0.-2 mg per kg. Results: A total of 200 cases were included. The most common presenting symptoms were cough (77.5%), fever (67.5%) and shortness of breath (63.5%). Most patients (85%) presented within the first week of their illness. One or more comorbidities were present in 75% of patients. Most common being hypertension in 70(35%) and diabetes mellitus in 63(31.5%). Complications seen in the study were Cytokine release storm 92(46%) and acute respiratory distress syndrome 44(22%). The median time for initiation of corticosteroid therapy was 4 hours (range 1-96 hours). Overall survival (OS) in the study was 83.5%. OS for patients with moderate, severe and critical diseases was 97.8%, 86.2% and 62%, respectively (p<0.001). Conclusion: Corticosteroids are useful in COVID-19-admitted patients and provide excellent survival outcomes. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of chloroquine and hydroxychloroquine on cytokine release syndrome (CRS) in adult patients with coronavirus disease 2019 (COVID-19) having mild to moderate symptoms. Methods: This blinded, placebo-controlled, randomized study was conducted in the Department of Medicine, Pak Emirates Military Hospital Rawalpindi, from June 1-15, 2020. A total of 150 hospitalized patients were enrolled after diagnoses with COVID-19 through reverse transcription polymerase chain reaction (RT-PCR). They were divided into three groups: hydroxychloroquine plus general care (HGC, n=50), chloroquine plus general care (CGC, n=50); and only general care (OGC, n=50). The HGC group received treatment with hydroxychloroquine 400 mg every 12 hours for day one and 200 mg for the next 4 days. The CGC group received treatment with chloroquine 250 mg every 12 hours for 7 days. The OGC group was kept as a control with only general care. After 12 days, the patients were screened for development of CRS through detection of interleukin 6 (IL-6) in serum samples by using Roche cobas e4ll electrochemiluminescence immunoassay analyzer. Results: The mean duration from onset of symptoms to randomization was 7.65 days (SD = 3.287 days; range, 2-15 days). The mean age of patients was 37.57 (range 19-63) years. Results showed that out of a total 150 patients, only 10 patients (6%, mean=1.93; CI=1.89-1.97, P=0.651) developed CRS in all study groups. Four patients (8%) developed CRS in the HGC group, 2 patients (4%) in the CGC group, and 4 patients (8%) in the OGC group. There was no significant difference in the mean level of CRS among study groups. Conclusion: Administration of hydroxychloroquine and chloroquine has no effect in reducing the development of CRS in patients with COVID-19 having mild to moderate symptoms. [ABSTRACT FROM AUTHOR]

Background: Cytokine release syndrome (CRS) plays a pivotal role in the pathophysiology and progression of Coronavirus disease-2019 (COVID-19). Therapeutic plasma exchange (TPE) by removing the pathogenic cytokines is hypothesized to dampen CRS. Objective: To evaluate the outcomes of the patients with COVID-19 having CRS being treated with TPE compared to controls on the standard of care. Methodology: Retrospective propensity score-matched analysis in a single centre from 1st April to 31st July 2020. We retrospectively analyzed data of 280 hospitalized patients developing CRS initially. PSM was used to minimize bias from non-randomized treatment assignment. Using PSM 1:1, 90 patients were selected and assigned to 2 equal groups. Forced matching was done for disease severity, routine standard care and advanced supportive care. Many other Co-variates were matched. Primary outcome was 28 days overall survival. Secondary outcomes were duration of hospitalization, CRS resolution time and timing of viral clearance on Polymerase chain reaction testing. Results: After PS-matching, the selected cohort had a median age of 60 years (range 32–73 in TPE, 37–75 in controls), p = 0.325 and all were males. Median symptoms duration was 7 days (range 3–22 days' TPE and 3–20 days controls), p = 0.266. Disease severity in both groups was 6 (6.6%) moderate, 40 (44.4%) severe and 44 (49%) critical. Overall, 28-day survival was significantly superior in the TPE group (91.1%), 95% CI 78.33–97.76; as compared to PS-matched controls (61.5%), 95% CI 51.29–78.76 (log rank 0.002), p<0.001. Median duration of hospitalization was significantly reduced in the TPE treated group (10 days vs 15 days) (p< 0.01). CRS resolution time was also significantly reduced in the TPE group (6 days vs. 12 days) (p< 0.001). In 71 patients who underwent TPE, the mortality was 0 (n = 43) if TPE was done within the first 12 days of illness while it was 17.9% (deaths 5, n = 28 who received it after 12th day (p = 0.0045). Conclusion: An earlier use of TPE was associated with improved overall survival, early CRS resolution and time to discharge compared to SOC for COVID-19 triggered CRS in this selected cohort of PS-matched male patients from one major hospital in Pakistan. [ABSTRACT FROM AUTHOR]

The infection caused by Severe Acute Respiratory Syndrome-Corona Virus 2 (SARS-CoV-2) has rapidly emerged as a serious pandemic, causing substantial morbidity and sometimes mortality with a significant healthcare burden. Unfortunately, Pakistan is among top twenty countries of the world affected by COVID-19. The clinical spectrum in COVID-19 is diverse, ranging from mild disease having flu-like symptoms to potentially fatal ARDS, cytokine storm, multiple organ failure and death. Common risk factors associated with severe outcome in COVID-19 infection include male gender, older age and presence of comorbidities such as hypertension, diabetes and cardiovascular disease. Here we reviewed the available literature and report that the underlying mechanisms that account for a broad range of symptoms during respiratory viral infections, that have been well studied in the case of influenza viruses, adenoviruses, SARS-CoV and MERS-CoV, suggest that host genetic and epigenetic factors may also play a significant role in determining susceptibility and clinical outcome in COVID-19 infection. In this review we discuss the potential roles of host genetic factors including cellular receptors for COVID-19, HLA and inflammatory cytokine genes. Based on the SARS-CoV-2 genome and protein-protein interactions map between host and viral proteins we also describe the potential roles of several viral proteins in epigenetic modulation of host inflammatory innate immune response by targeting different cellular pathways particularly NF-κB activation, which may lead to the inflammatory cytokine storm and a severe COVID-19 disease. Investigations of these genetic and epigenetic mechanisms during COVID-19, especially in local settings, will be helpful in management of patients with higher risks and in the development of novel antiviral therapeutics. [ABSTRACT FROM AUTHOR]

Background: COVID-19 is a global pandemic with 12% mortality rate. This pandemic has shattered health care sector of many developed countries across the globe. According to World Health Organization (WHO) India and Pakistan will be badly hit by the pandemic till end of June 2020. Both countries are densely populated and the fragile health sector of these countries is incapable to facilitate of large number of critically ill patients. Data analysis from different studies revealed that Cytokine Storming (CS) is main cause of COVID-19 related respiratory, renal, cardiac and neural complications in critically ill patients. Objectives: The aim of this review is to highlight the significance of CS in management of COVID-19 infection. Methods: Literature from previous studies was collected to suggest the possible diagnostic testing as well as strategies to manage these patients. Mesh terms such as Corona, COVID-19, Cytokine storming, Wuhan, Pandemic were applied on PUBMED as well as google to search for the latest published articles. Reports and newpapers were also considered as this is an ongoing pandemic and there is scarcity of knowledge and information in this regard. Results: IL6 and TNFα blockers are helpful in regulating the uncontrolled immune response due to CS. Levels of different substances like ferritin, Cytokine Reactive Proteins and D-dimer can be helpful in early detection of these complications. Conclusions: The early detection of CS can be used for selection of appropriate treatment, reduction in burden on Intensive Care Units (ICU) and ultimately saving many lives. [ABSTRACT FROM AUTHOR]

Objective: To determine the role of Methylprednisolone in managing COVID-19 patients. Study Design: Cross-sectional study. Place and Duration of Study: Pakistan Emirates Military Hospital (PEMH), Rawalpindi Pakistan, from Jan to Feb 2021. Methodology: This study was carried out at the Department of Medicine. Medical records of all moderate, severe and critical COVID-19 patients admitted and receiving Methylprednisolone were reviewed. Methylprednisolone was used in all patients at doses 0.-2 mg per kg. Results: A total of 200 cases were included. The most common presenting symptoms were cough (77.5%), fever (67.5%) and shortness of breath (63.5%). Most patients (85%) presented within the first week of their illness. One or more comorbidities were present in 75% of patients. Most common being hypertension in 70(35%) and diabetes mellitus in 63(31.5%). Complications seen in the study were Cytokine release storm 92(46%) and acute respiratory distress syndrome 44(22%). The median time for initiation of corticosteroid therapy was 4 hours (range 1-96 hours). Overall survival (OS) in the study was 83.5%. OS for patients with moderate, severe and critical diseases was 97.8%, 86.2% and 62%, respectively (p<0.001). Conclusion: Corticosteroids are useful in COVID-19-admitted patients and provide excellent survival outcomes. [ABSTRACT FROM AUTHOR]