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.

Background: Coronavirus disease 2019 (COVID-19) is a novel infectious disease of multi-system involvement with significant pulmonary manifestations. So far, many prognostic models have been introduced to guide treatment and resource management. However, data on the impact of measurable respiratory parameters associated with the disease are scarce. Objective: To demonstrate the role of Comorbidity-Age-Lymphocyte count-Lactate dehydrogenase (CALL) score and to introduce Respiratory Assessment Scoring (RAS) model in predicting disease progression and mortality in COVID-19. Methodology: Data of 252 confirmed COVID-19 patients were collected at Pak Emirates Military Hospital (PEMH) from 10th April 2020 to 31st August 2020. The CALL score and proposed factors of RAS model, namely respiratory rate, oxygen saturation at rest, alveolar arterial gradient and minimal exercise desaturation test, were calculated on the day of admission. Progression of disease was defined and correlated with measured variables. Univariate and multivariate Cox regression analysis for each variable, its hazard ratio (HR) and 95% confidence interval (CI) were calculated, and a nomogram was made using the high-risk respiratory parameters to establish the RAS model. Results: Progression of disease and death was observed in 124 (49.2%) and 49 (19.4%) patients, respectively. Presence of more than 50% of chest infiltrates was significantly associated with worsening disease and death (p-value <0.001). Death was observed in 100% of patients who had critical disease category on presentation. Regression analysis showed that the presence of comorbidity (n: 180), in contrast to other variables of CALL score, was not a good prognosticator of disease severity (p-value: 0.565). Nonetheless, the CALL model itself was validated to be a reliable prognostic indicator of disease progression and mortality. Some 10 feet oxygen desaturation test (HR: 0.99, 95%CI: 0.95-1.04, p-value: 0.706) was not a powerful predictor of the progression of disease. However, respiratory rate of more than 30 breaths/minute (b/m) (HR: 3.03, 95%CI: 1.77-5.19), resting oxygen saturation of less than 90% (HR: 2.41, 95%CI: 1.15-5.06), and an elevated alveolar-arterial oxygen gradient (HR: 2.14, 95%CI: 1.04-4.39) were considered statistically significant highrisk predictors of disease progression and death, in the formed RAS model. The model resulted in 85% (95%CI: 80%-89%) of area under the receiver operating characteristic curve (AUROC), with substantial positive (76%, 95%CI: 68%-83%) and negative predictive values (80%, 95%CI: 73%-87%) for a cutoff value of seven. Patients with higher CALL and RAS scores also resulted in higher mortality. Conclusion: CALL and RAS scores were strongly associated with progression and mortality in patients with COVID-19.

Importance: Cytokine release storm (CRS) plays pivotal role in pathophysiology and progression of COVID-19. Objective: To evaluate the outcomes of COVID-19 patients having CRS treated with Therapeutic Plasma Exchange (TPE) as compared to controls not receiving TPE. Design: Retrospective propensity score (PS) matched analysis, 1st April to 30th June 2020. Setting: Tertiary care hospital, single centre based. Participants: Using PS 1:1 matching, 90 patients were assigned 2 groups (45 receiving TPE and 45 controls). Forced matching and covariate matching was done to overcome bias between two groups. Main outcomes and measures: Primary outcome was 28 days overall survival. Secondary outcomes were duration of hospitalization, CRS resolution time and timing of PCR negativity. Results: Median age was 60 years (range 32-73 in TPE, 37-75 in non-TPE group), p= 0.325. Median symptoms duration 7 days (range 3-22 days TPE and 3-20 days non-TPE), p=0.266. Disease severity in both groups was 6.6% moderate, 44.4% severe and 49% critical. Twenty-eight-day survival was significantly superior in TPE group (91.1%) as compared to controls (61.5%), HR 0.21, 95% CI for HR 0.09-0.53, log rank 0.002. Median duration of hospitalization was significantly reduced in TPE treated group as compared to non-TPE controls 10 days and 15 days respectively (p< 0.01). CRS resolution time was also significantly reduced in TPE treated group (6 days vs. 12 days) (p< 0.001). Conclusion and Relevance: Use of TPE is associated with superior overall survival, early CRS resolution and time to discharge as compared to standard therapy for COVID-19 triggered CRS.

Objective: To assess the difference in various parameters of body composition between the diabetic patients and non-diabetic controls at Pak Emirates Military Hospital Rawalpindi. Study Design: Comparative cross-sectional study. Place and Duration of Study: Medicine and Nutrition Department, Pak Emirates Military Hospital, Rawalpindi, from Jul 2018 to Mar 2019. Methodology: This study was conducted on 100 patients of non-insulin dependent diabetes mellitus under treatment in medicine department and matched controls from the community. Patients with type I diabetes or insulin dependents or having some other com or bid metabolic illness or autoimmune disease or malignancy were not included in the study. Parameters of body composition were measured by using the INBODY machine which works on the principle of electroimpedance. Results: Cases and controls were matched for age and gender. Hundred cases and hundred controls were recruited for the final analysis Mean age of the cases was 43.41 ± 2.231 years while controls were 43.46 ± 3.122 years. Mean BMI in cases was 29.32 ± 2.561while in controls was 25.62 ± 4.483. BMI, visceral fat and skeletal muscle fat were found statistically significant to be more in cases of non-insulin dependent diabetes mellitus as compared to the controls. Conclusion: This case control study revealed that diabetes significantly affects the body composition of the patients. It also affects other parameters like skeletal muscle mass and visceral fat. Routine screening of body composition should be made part of the diabetic clinics to pick these changes early and intervene accordingly.