Host Immune-Protein Signature Combining TRAIL, IP-10 and CRP for Early and Accurate Prediction of Severe COVID-19 Outcome

Background. Accurately identifying COVID-19 patients at-risk to deteriorate remains challenging. Dysregulated immune responses impact disease progression and development of life-threatening complications. Tools integrating host immune-protein expression have proven useful in determining infection etiology and hold potential for prognosticating disease severity. Methods. Adults with COVID-19 were enrolled at medical centers in Israel, Germany, and the United States (Figure 1). Severe outcome was defined as intensive care unit admission, non-invasive or invasive ventilation, or death. Tumor necrosis factor related apoptosis inducing ligand (TRAIL), interferon gamma inducible protein-10 (IP-10) and C-reactive protein (CRP) were measured using an analyzer providing values within 15 minutes (MeMed Key®). A signature indicating the likelihood of severe outcome was derived generating a score (0-100). Description of derivation cohort RT-PCR, reverse transcription polymerase chain reaction. Results. Between March and November 2020, 518 COVID-19 patients were enrolled, of whom 394 were eligible, 29% meeting a severe outcome. Age ranged between 19-98 (median 61.5), with 59.1% male. Patients meeting severe outcomes exhibited higher levels of CRP and IP-10 and lower levels of TRAIL (Figure 2;p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The signature's area under the receiver operating characteristic curve (AUC) was 0.86 (95% confidence interval: 0.81-0.91). Performance was not confounded by age, sex, or comorbidities and was superior to IL-6 (AUC 0.77;p = 0.033) and CRP (AUC 0.78;p < 0.001). Clinical deterioration proximal to blood draw was associated with higher signature score. Scores of patients meeting a first outcome over 3 days after blood draw were significantly (p < 0.001) higher than scores of non-severe patients (Figure 3). Moreover, the signature differentiated patients who further deteriorated after meeting a severe outcome from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001;Figure 4). TRAIL, IP-10, CRP and the severity signature score are differentially expressed in severe and non-severe COVID-19 infection Dots represent patients and boxes denote median and interquartile range (IQR) The signature score of patients meeting a severe outcome on or after the day of blood draw is significantly (p < 0.001) higher than the signature score of non-severe patients. Dots represents patients and boxes denote median and IQR Kaplan-Meier survival estimates for signature score bins Conclusion. The derived signature combined with a rapid measurement platform has potential to serve as an accurate predictive tool for early detection of COVID-19 patients at risk for severe outcome, facilitating timely care escalation and de-escalation and appropriate resource allocation.

Depression in Emergency Department Healthcare Workers During the COVID-19 Outbreak in Brooklyn, NY

Study Objectives: emergency department (ED) health care workers (HCW) have experienced extensive mental health burdens in the fight against COVID-19. This study measured depressive symptoms in ED HCW in Brooklyn, New York, at the peak 2020 COVID-19 pandemic. Methods: An email-distributed survey of ED HCW at Maimonides Medical Center was conducted September 8–December 31, 2020, with reference period March-May 2020. Depressive symptoms were measured by the 10- item depressive symptom scale, Centers for Epidemiologic Studies-Depression (CES-D). CES-D items were summed, with a possible total score of 0-30. A CES-D score >10 was deemed clinically relevant. Our main predictor was HCW status, which was dichotomized as clinical (MD/DO, nurses, ED technicians) vs non-clinical. Covariates included sex, age, race, SARS-CoV-2 testing status (not tested vs +test vs -test), social support (range: 0->=4 people to talk to), number of COVID-related home problems (range: 0-9), mental health care disruption during COVID-19 (yes/no), 3-item Loneliness Brief Survey (LBF) score (range: 3-9), and survey date. General linear regression and logistic regression analysis were used to predict CES-D score (β- coefficient, p-value) and clinically relevant depressive symptoms (Odds Ratio (OR), 95% Confidence Interval (95% CI)), respectively. A p-value<0.05 was considered significant. Results: Among 222 HCW respondents, the mean age was 38.2±10.8y;and 59.4% were White, 52.5% were male, 80.1% were clinical HCW (38.5% MD/DO, 29.7% nurses, 31.8% ED technicians), and 61.6% tested for SARS-CoV-2. The mean CES-D score was 11.8±8.2. A clinically relevant depressive symptom burden was reported by 51.6% of HCW-55.4% of clinical HCW vs 36.4% of non-clinical HCW (p=0.024). There was no difference in the odds of clinically relevant depressive symptoms by type of clinical HCW (MD/DO, nurses, ED technicians) compared to non-clinical HCW;and no difference in mean CES-D score by clinical vs non-clinical HCW status. Increasing CES-D scores were also observed with increasing age (β=0.12, p=0.01), number of COVID-19-related home problems (β=0.99, p=0.035), and LBF score (β= 2.17, p<0.0001). A clinically-relevant depressive symptom burden was also observed with increasing age (OR 1.07, 95% CI 1.03-1.11), among those who reported increasing COVID-19-related home problems (OR 1.46, 95% CI 1.01-2.11), and LBF score (OR 2.08, 95% CI 1.63-2.65). Conclusions: Over half of clinical HCW experienced a clinically relevant depressive symptom burden during the peak of the COVID-19 pandemic. Age, number of COVID-19-related home problems, and loneliness were also associated with higher depressive symptom burden. To deepen our understanding of mental health outcomes, create effective interventions, and promote mental health-related policy changes, such as expanding insurance coverage for mental health care, temporal associations between mental health outcomes and associated factors must continue to be investigated.

Posttraumatic Stress in Emergency Department Health Care Workers During the COVID-19 Outbreak in Brooklyn, New York

Study Objectives: Emergency department (ED) health care workers (HCW) have experienced extensive mental health burden in the fight against COVID-19. This study measured symptoms of post-traumatic stress disorder (PTSD) in ED HCW in Brooklyn, New York, experienced during the peak of the COVID-19 pandemic. Methods: An email-distributed survey of ED HCW at Maimonides Medical Center was conducted September 8–December 31, 2020, with reference period March–May 2020. Posttraumatic stress symptoms were measured by the PTSD checklist for DSM-5 (PCL-5). A PCL-5 score >32 was deemed clinically relevant. Our main predictor was HCW status, which was dichotomized as clinical (MD/DO, nurses, ED technicians) vs non-clinical. Covariates included sex, age, race, SARS-CoV-2 testing status (not tested vs +test vs -test), social support (range: 0- >4 people to talk to), number of COVID-related home problems (range: 0-9), mental health care disruption during COVID-19 (yes/no), 3-item Loneliness Brief Survey (LBF) score (range: 3-9), and survey date. General linear regression and logistic regression analyses were used to predict PCL-5 score (β-coefficient, p-value) and clinically relevant posttraumatic stress symptoms (odds ratio (OR), 95% confidence interval (95% CI)), respectively. A p-value<0.05 was considered significant. Results: Among 247 HCW respondents, 67.1% were between 25-44 years old, 56.8% were White, 51.4% were male, 79.7% were clinical HCW (30.5% MD/DO, 22.7% nurses, 25.2% ED technicians), and 63.2% had been tested for SARS-CoV-2. The median PCL-5 score was 10. A higher mean PCL-5 score was observed for clinical vs non-clinical HCW (p<0.0001). Lower PCL-5 scores were observed for males (β=-4.31, p=0.05), while higher scores were observed in association with an increased number of COVID-19-related home problems (β=2.13, p=0.04), LBF score (β= 4.09, p<0.0001) and higher number of people to talk to (β=6.97, p=0.04). A clinically relevant PTSD symptom burden was reported by 16.6% of HCW - 18.3% of clinical HCW vs 3.6% of non-clinical HCW (p=0.0048). Higher odds of clinically relevant PTSD symptoms were observed for ED technicians compared to non-clinical HCW (OR 16.16, 95% CI 1.53-170.46). A clinically relevant PTSD symptom burden was also observed among those reporting increasing COVID-19-related home problems (OR 1.69, 95% CI 1.01-2.83) and LBF score (OR 1.83, 95% CI 1.38-2.44). Conclusions: Almost one in five clinical HCW experienced a clinically relevant PTSD symptom burden during the peak of the COVID-19 pandemic. To deepen our understanding of mental health outcomes, create effective interventions, and promote mental health-related policy changes, such as expanding insurance coverage for mental health care and developing more effective wellness programs for HCW, temporal associations between mental health outcomes and associated factors must continue to be investigated.