Has Convalescent Plasma Therapy Hesitancy Increased COVID-19 Mortality?

We bring to you our viewpoint and a snapshot of the journey of convalescent plasma therapy (CPT) in the management of ongoing coronavirus disease 2019 (COVID-19) pandemic. We also discuss how best to use the updated data on this important treatment option and maximize benefit for our patients, thereby saving lives, especially in resource constraint settings.

Biomarkers in COVID-19: Association with disease severity and outcomes

Background: In coronavirus disease 2019 (COVID-19) the need for intervention increases with disease severity and a risk prediction model that incorporates biomarkers would be beneficial for identifying patients for treatment escalation. Aim(s): To investigate biomarkers changes associated with disease severity and outcomes (mortality, thrombosis). Method(s): COVID-19 patients were sampled between April 15 and May 31 2020. Disease severity was assessed by World Health Organization (WHO) ordinal scale. 132 systemic biomarkers were investigated by routine and multiplex assays and statistical analysis performed to characterise the biomarker profile of COVID-19 patients associated with disease severity, duration, survival and thrombosis. Result(s): The study enrolled 150 COVID-19 positive adults and 16 healthy volunteers. The average age was 64 years, 59% were male, 85% had co-morbidities, 33% had a thrombotic event, and 13% died. A cross comparative analysis of biomarkers identified 13 biomarkers common to severity, mortality and thrombosis with significant correlation;including endothelial dysfunction (VWF, tPA, TFPI), hypercatabolism (low albumin, Hb, FXIII) and inflammatory response (IL-8, Osteopontin). Similarly, 14 biomarkers associated with severity and mortality included pro-inflammatory cytokines and their receptors (sTNFRII, STNFRI, sIL2a, IL6, MIP1a), neutrophils (elevated WBC, Neutrophils, TIMP1) and tissue remodelling (SCGF, EG3A). Nine biomarkers common across severity and thrombosis were angiogenesis (VEGF, LYVE1, Follistatin), acute phase response (SAP, AGP) and clot formation (Fibrinogen and PAPs). Conclusion(s): The biomarker profile associated with poorer outcomes indicates an inflammatory response, endothelial cell disruption, hypercoagulability and hypercatabolism. This study has identified several biomarkers that may be useful indicators of disease severity and progression. Further work is needed to determine how these may be used to direct clinical management. (Figure Presented).

Impact of early fluid administration on inpatient mortality and acute kidney injury in patients with COVID-19 disease

BACKGROUND AND AIMS: Initial WHO guidance advised cautious fluid administration for patients with COVID-19 due to concern about the development of acute respiratory distress syndrome (ARDS). However, as the pandemic unfolded it became apparent that patients who were admitted to hospital had high rates of AKI and this initiated a change in local clinical guidelines during early April 2020. We aimed to ascertain the impact of judicious intravenous fluid use on mortality, length of hospitalisation and AKI. METHOD: An observational cohort study of 158 adults admitted with confirmed SARS-Cov-2 between 18th March and 9th May 2020 was conducted in a teaching hospital and designated centre for infectious diseases, London, UK. Key clinical and demographic data collected included clinical severity markers on admission, biochemical and haematological parameters as well as radiological findings. Primary outcomes were inpatient mortality, mortality at 6-weeks post discharge, length of hospitalisation and intensive care (ICU) admission. We also measured requirement for kidney replacement therapy (KRT) and AKI recovery rate at discharge. Using tests of difference, we compared key outcomes between patients treated with varying fluid regimens and then identified risk factors for AKI and mortality using multivariate logistic regression with results expressed as odds ratios (OR) with corresponding 95% confidence interval (CI). RESULTS: The median age was 74.4 (IQR 59.90 - 84.35) years, 66% were male, 53% white with hypertension and diabetes being the commonest co-morbidities. The median duration of illness prior to admission was 7 days (IQR 2 - 10) with respiratory symptoms and fever most prevalent. The people who presented with AKI on admission were more likely to receive fluids (34% vs 15%, p=0.02). 118 patients (75%) received fluids within 24-hours of admission with no difference in volume administered after local guidance change (p=0.78). Comparing patients receiving fluids with those who did not, we observed no difference in mortality (p=0.97), duration of hospital stays (p=0.26) or requirement for ICU admission (p=0.70). 18% died as an inpatient, and 52 patients were either admitted with or developed AKI. Of these 52 patients, 43 received fluids and 9 did not with no difference in KRT requirement (p=0.34), mortality (p=0.50) or AKI recovery (p=0.63). Peak AKI stage was greater among participants who received fluids though stage of AKI at presentation was also greater (p=0.04). Mortality rate in patients with an AKI is higher compared to overall inpatient mortality (31% vs 18%). Of the 36 patients with AKI (Figure Presnted) who were discharged home, 25 patients (69.4%) had renal recovery by the time of discharge. Increasing age and clinical severity on admission were associated with higher mortality (see Figure 1). Older age was associated with 34 - 53 times higher risk of death compared with those aged ≥ 65 years (age 76 - 85 years: OR 34.26, 95% CI: 3.94 - 297.48, p=0.001;age > 85 years: OR 53.07, 95% CI: 5.23 - 539.03, p=0.001). Patients with NEWS2 >4 on admission has 5-fold increased risk of death than those with a score ≥4 (OR 5.26, 95% CI: 1.32 - 20.92). Black ethnicity was associated with a 16-fold increased risk of developing AKI (OR 15.86, 95% CI: 1.67 - 150.99). CONCLUSION: To our knowledge, this is the first study to examine the impact of fluid management on inpatient mortality as well as on renal-associated outcomes of COVID-19 admission. Fluid administration regimen did not have an impact on mortality, length of hospitalisation or ICU admission, nor did it affect renal outcomes. Given the high rates of AKI and KRT in COVID-19 disease, early fluid administration is likely to be an important cornerstone of future management. Further adequately powered prospective studies are required to identify whether early fluid administration can reduce renal injury.

Ward vs. emergency department discharge in patients with COVID-19: Does it make a difference to symptom burden and radiological severity at follow up?

Background During the COVID-19 pandemic patients were often discharged following assessment within the Emergency Department (ED). However, to our knowledge no data exists on whether these patients are likely to have a better trajectory of recovery. We investigated the symptom burden and radiological severity at follow-up for patients discharged directly from ED compared to those admitted. Methods Patients diagnosed with COVID-19 between 05.03.20 and 05.05.20 discharged from ED or the ward had telephone assessments 8-10 weeks post-discharge. Demographics, co-morbidities, symptom burden (quantified using a numerical rating scale) and psychological health data were collected. Patients were offered a follow-up chest radiograph (CXR) if abnormal on discharge. Results During this period we contacted 188 ED and 471 ward discharges, median (IQR) follow up 77.5 days (65-87) and 64 days (55-82) respectively. The baseline demographic data is shown in table 1. Ward patients were significantly older (62.5 vs. 53.8 years, p<0.001), more likely to be hypertensive (49% vs. 27%, p<0.001), diabetic (31% vs. 16%, p=0.004), frailer (median clinical frailty score 2(2-5) vs. 2(2-3), p<0.001) and have a higher NEWS2 score (5 (2-7) vs. 2 (1-4), p<0.001). There were no significant differences in other characteristics including ethnicity, heart disease and smoking. 115 (61%) ED and 340 (72%) ward patients completed follow-up calls. There were no significant differences in symptom burden (breathlessness, cough, fatigue, sleep quality) and psychological burden (assessed by screening questionnaires). No significant difference was noted in the proportion able to return to work (ED vs. ward: 70% vs. 59%, p=0.111). Finally, 5% of ED patients had an unchanged/worsening CXR compared to 9% discharged from the ward (p=0.42). Conclusion Our data confirms that patients admitted to hospital are likely to be more unwell, older, more frail and have hypertension and diabetes. Despite this, there were no significant differences in symptoms or radiological severity at follow up, suggesting that hospitalised patients do not appear to have worse physical or psychological sequelae compared to those discharged directly from ED. We should develop strategies to identify the patients who are more likely to suffer from longterm sequelae post COVID-19, to appropriately establish a targeted follow-up service.