Early Rise In Crp Is Associated With Progression To Respiratory Failure And Intubation In Covid-19 Patients

During the course of hospitalization, it is often unclear which COVID-19 patients will progress from non-critical to critical illness. Predicting disease trajectory is crucial for resource allocation and therapeutic intervention. In our single-center retrospective cohort analysis of the first 66 patients admitted for COVID-19 infection, we examined biomarkers of inflammation to distinguish non-critically ill inpatients who remained stable from those that had progressive respiratory failure requiring intubation and ICU transfer. Unlike the typical approach where patients are grouped into the two categories of non-critical and critical illness, COVID-19 patients in our study were classified into three cohorts by severity and stability of respiratory failure: stable non-critical illness (“mild”, 38 [58%]); non-critical illness at admission that progressed to critical illness (“progressive”, 21 [32%]); and critical illness at admission (“severe”, 7 [11%]). We found that while CRP level at admission was weakly associated with future progressive respiratory failure and appeared to have limited clinical utility. The progressive cohort showed modestly increased levels of CRP compared to the mild cohort, with significant overlap (125.0 ± 74 vs. 81.3 ± 57 mg/L, P = 0.05). Despite the limited predictive value of admission CRP levels, these measurements were indeed clinically relevant as they correlated with SOFA score (ρ = 0.41, P < 0.001) and hypoxemic respiratory failure (PaO2/FiO2, r = -0.58, P < 0.001). A closer examination of CRP trend showed that dynamic trend of CRP levels within the first 72 hours of admission rather than the static CRP level at admission showed a much stronger association with respiratory deterioration. Specifically, rise in CRP levels most clearly distinguished mild and progressive cohorts (24-48h post-admission: 170.6 ± 95 vs. 91.0 ± 67 mg/L, P = 0.03; 48-72h post-admission: 185.0 ± 92 vs. 81.6 ± 63 mg/L, P = 0.002). Trends of inflammatory biomarkers, rather than absolute value at admission, may have most value for clinical triage and targeting therapeutic immunomodulation. Further, COVID-19 patients that are aggregated as “critically ill” in cross-sectional studies could represent two distinct inflammatory biomarker profiles and clinical presentations ( i.e., progressive versus severe cohorts). Funding: This work was supported by the American Heart Association Award 2014D007100 (E.Y.K.) and NIAMS T32 AR007530-35 (A.A.M.). Conflict of Interest: The authors declare no competing interests. Ethical Approval: This investigation was approved by the Partners Healthcare Institutional Review Board (Protocol 2014D007100). Opt-out consent was designated for the study.