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.

BackgroundHydroxychloroquine (HCQ) has been considered for the treatment of coronavirus disease 2019 , but data on its efficacy are conflicting. We analyzed the efficacy of HCQ along with standard of care (SOC) treatment, compared with SOC alone, in reducing disease progression in mild COVID-19. MethodsA single-center open-label randomized controlled trial was conducted from April 10 to May 31, 2020 at Pak Emirates Military Hospital, Rawalpindi. Five hundred patients of both genders between the ages of 18 and 80 years with mild COVID-19 were enrolled in the study. A total of 349 patients were assigned to the intervention group (standard dose of HCQ plus SOC) and 151 patients were assigned to SOC only. The primary outcome was progression of disease while secondary outcome was polymerase chain reaction (PCR) negativity on days 7 and 14. The results were analyzed on Statistical Package for Social Sciences (SPSS; IBM Corp., Armonk, NY) version 23. A p-value <0.05 was considered significant. ResultsThe median age of the intervention group was 34 ± 11.778 years and control group was 34 ± 9.813 years. Disease progressed in 16 patients, 11 (3.15%) of which were in the intervention group and 5 (3.3%) in the control group (p-value = 0.940). PCR negative cases in intervention and control groups on day 7 were 182 (52.1%) and 54 (35.8%), respectively (p-value = 0.001); and on day 14 were 244 (69.9%) and 110 (72.9%), respectively (p-value = 0.508). Consecutive PCR negativity on days 7 and 14 was observed in 240 (68.8%) patients in the intervention group compared to 106 (70.2%) in the control group (p-value = 0.321). ConclusionThe addition of HCQ to SOC in hospitalized mild COVID-19 patients neither stops disease progression nor helps in early and sustained viral clearance.

Objective: To analyze the efficacy of Hydroxychloroquine (HCQ) plus standard of care (SOC) compared with SOC alone in reducing disease progression in Mild COVID-19 Design: A single centre, open label randomized controlled trial Place and Duration: Pulmonology department, Pak emirates Military Hospital (PEMH) from 10 April 2020 to 31 May 2020. Methodology: Five hundred patients of both genders having age between 18-50 years who were PCR positive and had Mild COVID-19 were selected. Patients assigned to standard dose of HCQ (400mg 12 hourly day 1 then 200mg 12 hrly for next 4 days) plus SOC were 349 while 151 patients received SOC comprising of Vit C, Vit D, and Zinc only (control group). Primary outcome was progression of disease while secondary outcome was PCR negativity on day 7 and 14. The results were analyzed on SPSS version 23. P value <0.05 was considered significant. Results: Median age of intervention group (34 + 11.778 years) and control group (34 + 9.813 years). Disease progressed in 16 patients, 11 (3.15%) were in intervention group as compared to 5 (3.35%) in control group, (p value = 0.865). PCR negativity in intervention and control groups were (day 7, 182 (52.1%) vs. 54 (35.7%) (p value = 0.001), (day 14, 244 (69.9%) vs. 110 (72.8%) (p value = 0.508). Consecutive PCR negativity at day 7 and 14 was observed in 240 (68.8%) in intervention group compared to 108 (71.5%) in control group. (p value = 0.231). Conclusion: Addition of HCQ to standard of care treatment in Mild COVID-19 neither prevents disease progression nor is it significantly associated with successive PCR negativity on day 7 and 14.

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.