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American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927874


RATIONALE: Some biomarkers of host response to viral infection are associated with COVID-19 outcomes, but these biomarkers do not directly measure viral burden. The association between plasma viral antigen levels and clinical outcomes has not been previously studied. Our aim was to investigate the relationship between plasma SARS-CoV-2 viral antigen concentration and proximal clinical deterioration in hospitalized patients. METHODS: SARS-CoV-2 nucleocapsid antigen concentrations were measured using a validated microbead immunoassay (Quanterix, NIH/NIAID laboratory) in plasma collected at enrollment from 256 subjects in a prospective observational cohort of hospitalized patients with COVID-19 from 3 hospitals, admitted between March 2020 and August 2021. Relationships between viral antigen concentration and clinical status at 1 week as measured by the World Health Organization (WHO) ordinal scale as well as ICU admission were assessed. Models were adjusted for age and sex, baseline comorbidities including immunosuppression, endogenous neutralizing antibodies, baseline COVID-19 severity, smoking status, remdesivir therapy, steroid therapy, and vaccine status. Missing covariate data were imputed using multiple imputation by chained equations. RESULTS: The median viral antigen concentration for the 35 subjects who deteriorated by 1 week was 4507 (IQR 1225-9665) pg/mL compared to 494 (IQR 18-3882) pg/mL in the 212 subjects who did not (p = 0.0004 Figure a). Using ordinal regression, each doubling in viral antigen concentration was significantly associated with a worse WHO ordinal scale at 1 week (unadjusted OR 1.07, 95% CI 1.02-1.13;adjusted OR 1.10, 95% CI 1.02-1.18). Among 168 patients not in the ICU at baseline, the median viral antigen concentration for the 40 patients who progressed to the ICU was 4697 (IQR 482- 10410) pg/mL vs. 459 (IQR 15-3062) pg/mL in the 128 patients who did not progress to require ICU care (p = 0.0001 Figure b). Using logistic regression, each doubling in viral antigen concentration was significantly associated with ICU admission (unadjusted OR 1.18, 95% CI 1.06-1.32, adjusted OR 1.40, 95% CI 1.11-1.76). CONCLUSIONS: Higher plasma viral antigen concentration at hospital admission is independently associated with a significantly worse clinical status at 1 week and a higher odds of ICU admission among hospitalized patients with COVID-19. This novel finding indicates that plasma viral antigen concentration may identify hospitalized COVID-19 patients at highest risk of short-term clinical deterioration in both clinical practice and research. Results of plasma antigen tests are available within 2-3 hours and could be integrated for identifying hospitalized COVID-19 patients who might benefit from early intervention.

American Journal of Respiratory and Critical Care Medicine ; 205(1), 2022.
Article in English | EMBASE | ID: covidwho-1927743


Rationale: The ROSE trial was a multicenter unblinded randomized clinical trial comparing early neuromuscular blockade (NMB) to usual care in patients with moderate to severe ARDS (NEJM 2019). This trial (n=1006) was stopped early for futility yet a subgroup analysis found that among Hispanic/Latino participants the NMB intervention group had a significantly lower mortality (32%) compared to those in the control group (53.7% p=0.02 for interaction). To evaluate potential contributors to these differences we compared baseline clinical and biological characteristics among Hispanic/Latino participants in the intervention vs control group. Methods: We compared demographics primary ARDS risk factor illness severity ventilatory parameters comorbidities and plasma biomarkers at baseline between the NMB intervention and control group for all 118 Hispanic/Latino patients recruited to the ROSE trial (11.6% of the trial population). We used multiple logistic regression to examine whether the mortality difference by treatment group would persist after controlling for the factors that differed significantly between groups. Results: At baseline Hispanic/Latino participants randomized to the control group had greater disease severity scores (APACHE III SOFA;p<0.05 for both) and a higher prevalence of shock (p=0.01) compared to those randomized to the intervention. There were no significant differences between groups in causes of lung injury or baseline ventilatory parameters. In an unadjusted logistic regression model the NMB intervention was significantly associated with mortality (OR 0.42;95%CI 0.20-0.89 p=0.02). The NMB intervention was no longer significantly associated with mortality when adjusting for severity of by illness by either SOFA score (OR 0.53;95%CI 0.24-1.20 p=0.13), APACHE III (OR 0.51, 95%CI 0.20- 1.30 p=0.16) or shock as defined by the need for vasopressors (OR 0.48, 95%CI 0.22-1.03, p=0.06). Hispanic/Latino participants in the control group had significantly higher interleukin-8 (p=0.02) and lower bicarbonate (p=0.045) than those in the intervention group. Conclusion: Together these clinical and biomarker data support the conclusion that the lower mortality associated with NMB in the Hispanic/Latino subgroup may have been partially due to baseline imbalances in systemic severity of illness. This finding underscores the need to cautiously interpret apparent treatment benefits within small subgroups. The COVID-19 pandemic has highlighted ethnic and racial disparities in ARDS. Future trials will benefit from increased representation of populations that are disproportionately affected to minimize the impact of spurious findings related to small sample sizes while creating more statistical power to prospectively address disparities.