Blood group A Secretors are associated with a higher risk of COVID-19 cardiovascular disease complications

The SARS-CoV-2 virus causes COVID-19, an infection capable of causing severe disease and death but which may also be asymptomatic or oligosymptomatic in many individuals. While several risk factors, including age, have been described, the mechanisms of this variation are poorly understood. Several studies have described associations between blood group and COVID-19 severity, while others do not. Expression of ABO glycans on secreted proteins and non-erythroid cells is controlled by a fucosyltransferase (FUT2). Inactivating mutations result in a non-secretor phenotype which is known to protect against some viral infections. We investigated whether ABO or secretor status was associated with COVID-19 severity. Data combined from healthcare records and laboratory tests (n=275) of SARS-CoV-2 PCR positive patients hospitalised with COVID-19, confirmed higher than expected numbers of blood group A individuals compared to O (RR=1.24, CI 95% [1.05,1.47], P=0.0111). There was also a significant association between group A and COVID-19-related cardiovascular complications (RR=2.56, CI 95% [1.43,4.55], P=0.0011) which is independent of gender. Molecular analysis of phenotype revealed that group A patients who are non-secretors are significantly less likely to be hospitalised than secretors. In a larger cohort of 1000 convalescent plasma donors, among whom the majority displayed COVID-19 symptoms and only a small minority required hospitalisation, group A non-secretors were slightly over-represented. Our findings indicate that group A non-secretors are not resistant to infection by SARS-CoV-2, but they are likely to experience a less severe form of its associated disease. Key PointsO_LIBlood group type A is associated with an increased risk of cardiovascular complications in COVID-19 patients. C_LIO_LIFUT2 "non-secretor" status reduces the risk of severe COVID-19 outcomes in patients with blood group A. C_LI

Patient outcomes after hospitalisation with COVID-19 and implications for follow-up; results from a prospective UK cohort.

BackgroundCOVID-19 causes a wide spectrum of disease. The incidence and severity of sequelae after the acute infection is uncertain. Data measuring the longer-term impact of COVID-19 on symptoms, radiology and pulmonary function are urgently needed to plan follow-up services. MethodsConsecutive patients hospitalised with COVID-19 were prospectively recruited to this observational study with outcomes recorded at 28-days. All were invited to a systematic follow up at 8-12 weeks, including chest radiograph, spirometry, exercise test, bloods, and health-related quality of life (HRQoL) questionnaires. FindingsBetween 30th March and 3rd June 2020, 163 patients with COVID-19 were recruited. Median hospital length of stay was 5 days (IQR 2-8) and 19 patients died. At 8-12 weeks post admission, 134 patients were available for follow up and 110 attended. Most (74%) had persistent symptoms (notably breathlessness and excessive fatigue) with reduced HRQoL. Only patients who required oxygen therapy in hospital had abnormal radiology, clinical examination or spirometry at follow up. Thirteen (12%) patients had an abnormal chest X-ray with improvement in all but 2 from admission. Eleven (10%) had restrictive spirometry. Blood test abnormalities had returned to baseline in the majority (104/110). InterpretationPatients with COVID-19 remain highly symptomatic at 8-12 weeks, however, clinical abnormalities requiring action are infrequent, especially in those without a supplementary oxygen requirement during their acute illness. This has significant implications for physicians assessing patients with persistent symptoms, suggesting that a more holistic approach focussing on rehabilitation and general wellbeing is paramount. FundingSouthmead Hospital Charity

Kinetics and performance of the Abbott Architect SARS-CoV-2 IgG antibody assay

ObjectivesTo assess the performance (sensitivity and specificity) of the Abbott Architect SARS-CoV-2 IgG antibody assay across three clinical settings. MethodsAntibody testing was performed on three clinical cohorts of COVID-19 disease: hospitalised patients with PCR confirmation, hospitalized patients with a clinical diagnosis but negative PCR, and symptomatic healthcare workers (HCWs). Pre-pandemic respiratory infection sera were tested as negative controls. The sensitivity of the assay was calculated at different time points (<5 days, 5-9 days, 10-14 days, 15-19 days, >20 days, >42 days), and compared between cohorts. ResultsPerformance of the Abbot Architect SARS-CoV-2 assay varied significantly between cohorts. For PCR confirmed hospitalised patients (n = 114), early sensitivity was low: <5 days: 44.4% (95%CI: 18.9%-73.3%), 5-9 days: 32.6% (95%CI, 20.5%-47.5%), 10-14 days: 65.2% (95% CI 44.9%-81.2%), 15-20 days: 66.7% (95% CI: 39.1%-86.2%) but by day 20, sensitivity was 100% (95%CI, 86.2-100%). In contrast, 17 out of 114 symptomatic healthcare workers tested at >20 days had negative results, generating a sensitivity of 85.1% (95%CI, 77.4% - 90.5%). All pre-pandemic sera were negative, a specificity of 100%. Seroconversion rates were similar for PCR positive and PCR negative hospitalised cases. ConclusionsThe sensitivity of the Abbot Architect SARS-CoV-2 IgG assay increases over time, with sensitivity not peaking until 20 days post symptoms. Performance varied markedly by setting, with sensitivity significantly worse in symptomatic healthcare workers than in the hospitalised cohort. Clinicians, policymakers, and patients should be aware of the reduced sensitivity in this setting.

Blood parameters measured on admission as predictors of outcome for COVID-19; a prospective UK cohort study

IntroductionCOVID-19 has an unpredictable clinical course so prognostic biomarkers would be invaluable when triaging patients on admission to hospital. Many biomarkers have been suggested using large observational datasets but sample timing is crucial to ensure prognostic relevance. The DISCOVER study prospectively recruited patients with COVID-19 admitted to a UK hospital and analysed a panel of putative prognostic biomarkers on the admission blood sample to identify markers of poor outcome. MethodsConsecutive patients admitted to hospital with proven or clinicoradiological suspected COVID-19 were recruited. Admission bloods were extracted from the clinical laboratory. A panel of biomarkers (IL-6, suPAR, KL-6, Troponin, Ferritin, LDH, BNP, Procalcitonin) were performed in addition to routinely performed markers (CRP, neutrophils, lymphocytes, neutrophil:lymphocyte ratio). Age, NEWS score and CURB-65 were included as comparators. All biomarkers were tested in logistic regression against a composite outcome of non-invasive ventilation, intensive care admission, or death, with Area Under the Curve (AUC) figures calculated. Results155 patients had 28-day outcomes at the time of analysis. CRP (AUC 0.51, CI:0.40-0.62), lymphocyte count (AUC 0.62, CI:0.51-0.72), and other routine markers did not predict the primary outcome. IL-6 (AUC: 0.78,0.65-0.89) and suPAR (AUC 0.77, CI: 0.66-0.85) showed some promise, but simple clinical features alone such as NEWS score (AUC: 0.74, 0.64-0.83) or age (AUC: 0.70, 0.61-0.78) performed nearly as well. DiscussionAdmission blood biomarkers have only moderate predictive value for predicting COVID-19 outcomes, while simple clinical features such as age and NEWS score outperform many biomarkers. IL-6 and suPAR had the best performance, and further studies should validate these biomarkers in a prospective fashion.

Hydroxychloroquine serum concentrations in non-critical care patients infected with SARS CoV 2

Hydroxychloroquine(HCQ) has been widely used to treat SARS-CoV-2 infection however HCQ pharmacokinetics in this condition have not been studied in non-critical care patient groups. Here we report the serum concentrations of HCQ in a small cohort of patients treated with HCQ as part of the RECOVERY trial.