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.

<b><i>Background and Purpose:</i></b> Coronavirus disease 2019 (CO­VID-19) has an increased propensity for systemic hypercoagulability and thromboembolism. An association with cerebrovascular diseases, especially cerebral venous thrombosis (CVT), has been reported among these patients. The objective of the present study was to identify risk factors for CVT as well as its presentation and outcome in COVID-19 patients. <b><i>Methods:</i></b> This is a multicenter and multinational observational study. Ten centers in 4 countries (Pakistan, Egypt, Singapore, and the United Arab Emirates) participated in this study. The study included patients (aged &#x3e;18 years) with symptomatic CVT and recent COVID-19 infection. <b><i>Results:</i></b> Twenty patients (70% men) were included. Their mean age was 42.4 years, with a male-to-female ratio of 2.3:1. Headache (85%) and seizures (65%) were the common presenting symptoms, with a mean admission Glasgow Coma Scale (GCS) score of 13. CVT was the presenting feature in 13 cases (65%), while 7 patients (35%) developed CVT while being treated for COVID-19 infection. Respiratory symptoms were absent in 45% of the patients. The most common imaging finding was infarction (65%), followed by hemorrhage (20%). The superior sagittal sinus (65%) was the most common site of thrombosis. Acute inflammatory markers were raised, including elevated serum D-dimer (87.5%), erythrocyte sedimentation rate (69%), and C-reactive protein (47%) levels. Homocysteine was elevated in half of the tested cases. The mortality rate was 20% (4 patients). A good functional outcome was seen in the surviving patients, with a mean modified Rankin Scale score at discharge of 1.3. Nine patients (45%) had a modified Rankin Scale score of 0–1 at discharge. <b><i>Conclusion:</i></b> COVID-19-related CVT is more common among males at older ages when compared to previously reported non-COVID-19-related CVT cases. CVT should be suspected in COVID-19 patients presenting with headache or seizures. Mortality is high, but functional neurological outcome is good among survivors.

Objective: An association between cerebral venous sinus thrombosis (CVST) and high altitude has been previously proposed, but limited published data exist to support this association. We investigated 28 cases of CVST occurring at high altitude and sought to describe patient demographics, altitude and acclimatization, hematological laboratory findings, neuroimaging, treatment, and prognosis in these cases. Methods: Twenty-eight cases of symptomatic CVST occurring at high altitude were identified between the months of August 2017 and December 2018, in collaboration with Military Hospital, Rawalpindi and Combined Military Hospital, Skardu (Pakistan). Follow-up visits were performed at 1 and 6 months. Results: Twenty-seven (96%) of the patients were males, and the mean age was 33 years. In total, 32.1% were smokers. The mean NIHSS score on presentation was 5.5. 85.7% of the cases occurred at altitude higher than 8,000 feet. On average 107.8 days were spent at a high altitude prior to CVST. Totally, 71.4% had acclimatized for >2 weeks. The mean hemoglobin (Hb) value was 16.7 g/dL and 50% had d-dimer levels higher than 1,000 ng/mL. On MRI, 25% showed signs of hemorrhage and 14.3% showed infarcts. Treatments provided include low-molecular-weight heparin and Rivaroxaban and were associated with good outcomes. Conclusion: CVST is not uncommon at high altitude (>8,000 feet). It is predominantly a male disease. Most patients have high Hb and high D-dimer levels. The overall outcome was good.

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.

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.