COVID-19 VACCINE BREAKTHROUGH INFECTIONS AMONG HEALTH CARE WORKERS AND SUPPORT STAFF OF MILITARY INSTITUTES IN PAKISTAN - AN UPDATE

Objective: To measure incidence, disease severity and outcome of COVID-19 Vaccine Breakthrough Infections among Health Care Workers (HCWs) and Support Staff completely vaccinated with Sinopharm Vaccine. Study Design: Prospective cohort study. Place and Duration of Study: All Military Health facilities of Pakistan reporting COVID-19 cases post vaccination, from Jul to Sep 2021. Methodology: Established Surveillance Mechanism for getting post vaccination COVID-19 cases from various health care settings of Pakistan Army enabled the collection of data on prescribed data forms. Among HCWs and support staff vaccinated with both doses or single dose regimen of COVID-19 vaccine;those who developed COVID-19 infection ≥14 days post 2nd dose were included in the study. Total 327 participants from 1st Jul till 30th September 2021 fulfilled the criteria and data pertaining to them was further analyzed. Results: Mean age of the participants was 32.38 ± 9.18 years. Males were 73.4% and 26.6% were females. Median duration from 2nd dose to development of vaccine breakthrough infection was 133 days (Inter Quartile Range: 55 days). Asymptomatic/mild infections were reported among 97.9% and only 1.5% had moderate disease. However, 0.6% reported severe/critical disease and required ventilator support. Most 79.2% breakthrough infections ocuured almost more than 3 months completion of vaccination and only 20.8% developed it before three months. Among all, 99.4% recovered completely while 0.4% couldn't survive the complications associated with COVID-19. There was no significant statistical association of job category with disease severity (p>0.05) Conclusion: Vaccines still remain a powerful tool in war against COVID-19. No vaccine has yet to be found 100% effective against all variants of concern (V°Cs) however less severe disease and mortality was observed after vaccination. Waning immunity after three months needs administration of booster dose of vaccine to HCWs and support staff working in a highly exposed environment of health facilities.

Mediastinal Lymphadenopathy As A Predictor Of Worse Outcome In Severe Covid-19 Cases.

BACKGROUND: This cross-sectional study is aimed at evaluating the association of mediastinal lymphadenopathy with COVID-19 prognosis in severe cases. Place and Duration of Study: Department of Medicine, Pak Emirates Military Hospital, Pakistan, from June to July 2020. METHODS: One hundred and fifty (150) laboratory-confirmed SARS CoV-2 infected, severe cases in Intensive Care Unit/ High Dependency Unit were included. These cases were divided into two categories, i.e., with and without mediastinal lymphadenopathy on High Resolution Computed Tomography chest. The two categories were compared on the basis of data obtained including age, gender, comorbid, White Blood Cell count, lymphocyte count, median days of hospitalization, need for invasive ventilation, Intensive Care Unit admission, clinical outcome and High-Resolution Computed Tomography chest findings. The data was compiled on a questionnaire and analysed on SPSS 24. RESULTS: Total 155 severe COVID-19 patients were reviewed, out of which 36 (23.2%) had mediastinal lymphadenopathy (category 1) and 119 (76.8%) had no mediastinal lymphadenopathy (category 2). Laboratory findings including median of white blood cells and lymphocyte percentage had no significant change in both categories. Intensive care unit admissions were 12 (33.3%) and 56 (47.1%) in category 1 and 2 respectively. Median days of hospitalization (8 days) and mortality rate (16%) were almost the same in both categories. CONCLUSIONS: Our study concludes that presence of mediastinal lymphadenopathy in severe COVID-19 cases is not associated with worse outcome. However, overall prevalence of mediastinal lymphadenopathy in severe cases is high (23.2%).

CLINICAL PROFILES AND OUTCOMES OF PATIENTS ADMITTED WITH MODERATE TO CRITICAL CORONAVIRUS DISEASE 2019 (COVID-19)

Objective: To evaluate various demographic, clinical, radiological and hematological manifestations of moderate to critical coronavirus disease 2019 (COVID-19) and to assess its complications and outcomes in the Pakistani population. Study Design: Retrospective observational study. Place and Duration of Study: Pak Emirates Military Hospital, Rawalpindi, from Apr to Jul 2020. Methodology: Demographic, clinical, radiological and hematological data of 600 consecutive patients were retrieved and analyzed from hospital registry. Results: Overall, 449 (74.8%) patients had at least 1 comorbidity, diabetes mellitus being commonest;228 (38%) [95% CI, 34.142%]. The most common symptoms were cough;451 (75.2%), fever;450 (75%) and shortness of breath;419 (69.8%). At presentation, 222 (37%) patients had moderate disease, 296 (49.3%) severe and 82 (12.7%) had critical disease. At admission, 277 (46.2%) patients required respiratory support and further 185 (30.8%) patients required treatment escalation later on correlated with disease severity and age (p<0.001). A total of 92 (15.3%) patients died out of which 38 (21.2%) were on noninvasive ventilation and 36 (66.6%) on invasive ventilation, (p<0.001). Overall survival (OS) was 84.7%;log rank <0.001. Mortality was highest in critical disease, 72 (31.3%) (p<0.001). A majority of patients, 440 (73.3%) developed complications, the most common being Cytokine release storm (CRS);57.5% respiratory failure;43.8% and Acute respiratory distress syndrome (ARDS);38.8%. Thrombotic events occurred in 106 (17.6%). Conclusion: Majority of patients with moderate to severe COVID-19 had comorbidities and ended up in various complications.

Clearing the Fog: Is Hydroxychloroquine Effective in Reducing Coronavirus Disease-2019 Progression? A Randomized Controlled Trial.

Background Hydroxychloroquine (HCQ) has been considered for the treatment of coronavirus disease 2019 (COVID-19), 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. Methods A 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.  Results The 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). Conclusion The addition of HCQ to SOC in hospitalized mild COVID-19 patients neither stops disease progression nor helps in early and sustained viral clearance.

Therapeutic plasma exchange for coronavirus disease-2019 triggered cytokine release syndrome; a retrospective propensity matched control study.

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.

CALL Score and RAS Score as Predictive Models for Coronavirus Disease 2019.

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 high-risk 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.

SHORT COMMUNICATION - COLLECTING and DISSEMINATING COVID-19 DATA - FROM FRUSTRATION TO FRUITION

ABSTRACT In the unprecedented COVID-19 situation, Medical Directorate needed to get near-real-time data for decision making and policy formulation. Crisis Management Cell was hence established with a vision to act as a data collection point and repository for Armed Forces COVID-19 PCR positive cases. Its foremost task was transforming a traditionally passive system for disease surveillance to a near-real-time semi-automated one. This coupled with the ensuing workload in the coming days especially during surge, constituted a formidable challenge. Through this work we want to share our hands-on experience of data collection and dissemination at Crisis Management Cell. We aim to inform our readers about the important points that need to be taken into account when establishing disease surveillance centers. As per our experience, these include an assessment of demand for near-real-time data, data handlers, data architecture, data security, data quality, data record, data velocity, data variety, data variability, data documentation, data reconciliation and reflection.