Myocardial injury as a predictor of mortality and adverse outcomes in COVID-19

Background: The American College of Cardiology suggested physicians should only measure troponin and brain natriuretic peptide (BNP) if myocardial infarction or heart failure were suspected in people with COVID-19. We aimed to evaluate the use of biomarkers on admission to hospital and the impact on mortality and morbidity. Methods: Consecutive patients presenting with COVID-19(reverse transcription PCR positive) between Feb27-May20 2020 were included in this retrospective, observational, single-center study. Clinical information was collected on admission and during hospitalization by physicians and later analysed by specialist cardiology registrars. 1675 patients were PCR +ve with 1036 having a high sensitivity troponin T(hsTropT) on admission. 371(35.8%) patients were hs TropT negative(<15ng/L) and 664(64.1%) had evidence of myocardial injury on admission(hsTropT ≥15ng/L). Subsequently demographic details were compared, as well as primary outcomes of death, ICU admission and COVID severity. Secondary outcomes were ARDS, myocardial infarction (MI);comparison with other biomarkers: NT-proBNP, d-dimer, CRP,LDH and ferritin. Results: Demographic data revealed no significant increase in proportions of Black, Asian or ethnic minorities in the myocardial injury group, however, patients were older(74.9±13.5 v 54.7±13.7yrs;p <0.001) and had significantly more co-morbidities such as diabetes(37 v 13%), hypertension(34 v 29%), ischemic heart disease(16 v 2%), other cardiac conditions(59 v 5%), malignancy(11 v 1%), COPD(9 v 4%), CKD stage ≤3 (40 v 3%) (p <0.01). Mortality was significantly higher in the myocardial injury group, 302(45.5%) v 29(7.8%) p <0.001, as were secondary outcomes of critical COVID (47 v 19%;p<0.001), ARDS (20 v 4%;p<0.001), Type 1 MI (1.6 v 0.01%;p<0.01) and Type 2 MI (44 v 26%;p<0.001). Interestingly, ICU admission (19 v 23%;p=0.09), pulmonary embolism (11 v 6%;p=0.22), stroke (1.1 v 0.5%;p=0.05) did not reach significance. Analysis of bio-markers on admission (Fig 1.) demonstrated hs Trop T (AUC 0.75 CI 0.69-0.81) and NT-pro BNP (AUC 0.75 CI 0.69-0.81) had more sensitvity 83%;85% and specificty 52%;58%, respectively at predicting death than d-dimer, CRP, LDH and ferritin. Conclusion: Early detection of elevated hsTropT and NT-proBNP predicts mortality and morbidity in patient with COVID-19. Routine measurement of cardiac biomarkers should be considered in patients with COVID-19 at the time of hospital admission in order to optimise risk stratification and guide monitoring. (Figure Presented).

Characterization of SARS-CoV-2-specific responses in people living with HIV

Background: There is an urgent need to understand the nature of immune responses mounted against SARS-CoV-2, in order to better inform riskmitigation and vaccine strategies for people living with HIV (PLWH). Although not all PLWH are considered immunosuppressed, residual cellular immunodeficiency could influence COVID-19 disease severity and the evolution and durability of protective immunity. Information on the breadth, magnitude and longevity of SARS-CoV-2 specific responses in PLWH recovering from COVID-19 disease is currently lacking. In this study, we performed an integrated cross-sectional analysis of different branches of adaptive immunity to SARS-CoV-2 in PLWH and HIV negative donors in the convalescent phase of predominately mild COVID-19 disease. Methods: A total of n=47 HIV positive, controlled on ART, and n=35 HIV negative subjects were recruited at a median of 158 and 146 days post symptom onset respectively. SARS-CoV-2 antibodies against Spike (S1) and Nucleoprotein (N) were measured in serum by a Semiquantitative ELISA. A serum neutralisation assay with pseudotyped SARS-CoV-2 was performed to calculate the 50% inhibitory serum dilution (ID50). SARS-CoV-2 specific memory T cell responses were determined by IFN-γ ELISpot and intracellular cytokine production assays using peptide pools against SARS-CoV-2 structural and accessory proteins (Spike, Membrane, Nucleocapsid, Envelope, and ORF3a,6,7,8). Results: The majority of PLWH had detectable SARS-CoV-2 S-and N-specific antibodies with neutralizing activity at levels comparable to HIV negative subjects (p= 0.5753). Although, the overall magnitude of SARS-CoV-2 specific T cell responses measured by ELISpot was not significantly different between the groups (p=0.4642), this correlated with the size of the naïve CD4 T cell pool (r=0.5518, p=0.0143) and the CD4:CD8 ratio in PLWH (r= 0.3820, p=0.037). In both groups, SARS-CoV-2 specific CD4 T cells were more abundant compared to CD8 T cells (HIV-p= 0.002, HIV+ p=0.0019). Both humoral and cellular responses were detected between 5-7 months post infection, providing evidence of medium-term durability of responses irrespective of HIV serostatus. Conclusion: The majority of PLWH mount a functional adaptive immune response to SARS-CoV-2. Incomplete immune reconstitution on ART and persistent alterations in the T cell compartment could, however, impact the development of protective immunity to SARS-CoV-2. These findings have implications for the risk stratification and management of PLWH.