An immune-protein score combining TRAIL, IP-10 and CRP for predicting severe COVID-19 disease.

COVID-19 patients are oftentimes over- or under-treated due to a deficit in predictive management tools. This study reports derivation of an algorithm that integrates the host levels of TRAIL, IP-10, and CRP into a single numeric score that is an early indicator of severe outcome for COVID-19 patients and can identify patients at-risk to deteriorate. 394 COVID-19 patients were eligible; 29% meeting a severe outcome (intensive care unit admission/non-invasive or invasive ventilation/death). The score's area under the receiver operating characteristic curve (AUC) was 0.86, superior to IL-6 (AUC 0.77; p = 0.033) and CRP (AUC 0.78; p < 0.001). Likelihood of severe outcome increased significantly (p < 0.001) with higher scores. The score differentiated severe patients who further deteriorated from those who improved (p = 0.004) and projected 14-day survival probabilities (p < 0.001). The score accurately predicted COVID-19 patients at-risk for severe outcome, and therefore has potential to facilitate timely care escalation and de-escalation and appropriate resource allocation.

NETosis induction reflects COVID-19 severity and long COVID: insights from a 2-center patient cohort study in Israel.

BACKGROUND: COVID-19 severity and its late complications continue to be poorly understood. Neutrophil extracellular traps (NETs) form in acute COVID-19, likely contributing to morbidity and mortality. OBJECTIVES: This study evaluated immunothrombosis markers in a comprehensive cohort of acute and recovered COVID-19 patients, including the association of NETs with long COVID. METHODS: One-hundred-seventy-seven patients were recruited from clinical cohorts at 2 Israeli centers: acute COVID-19 (mild/moderate, severe/critical), convalescent COVID-19 (recovered and long COVID), along with 54 non-COVID controls. Plasma was examined for markers of platelet activation, coagulation, and NETs. Ex vivo NETosis induction capability was evaluated after neutrophil incubation with patient plasma. RESULTS: Soluble P-selectin, factor VIII, von Willebrand factor, and platelet factor 4 were significantly elevated in patients with COVID-19 versus controls. Myeloperoxidase (MPO)-DNA complex levels were increased only in severe COVID-19 and did not differentiate between COVID-19 severities or correlate with thrombotic markers. NETosis induction levels strongly correlated with illness severity/duration, platelet activation markers, and coagulation factors, and were significantly reduced upon dexamethasone treatment and recovery. Patients with long COVID maintained higher NETosis induction, but not NET fragments, compared to recovered convalescent patients. CONCLUSIONS: Increased NETosis induction can be detected in patients with long COVID. NETosis induction appears to be a more sensitive NET measurement than MPO-DNA levels in COVID-19, differentiating between disease severity and patients with long COVID. Ongoing NETosis induction capability in long COVID may provide insights into pathogenesis and serve as a surrogate marker for persistent pathology. This study emphasizes the need to explore neutrophil-targeted therapies in acute and chronic COVID-19.

Prevalence and Persistence of Symptoms in Adult COVID-19 Survivors 3 and 18 Months after Discharge from Hospital or Corona Hotels.

COVID-19 is characterized by persistent symptoms beyond acute illness. In this prospective cohort study of patients with COVID-19, we sought to characterize the prevalence and persistence of symptoms up to 18 months after diagnosis. We followed 166 patients and assessed their symptoms during acute illness, and at 3 and 18 months after disease onset. The mean number of symptoms per patient during acute disease was 2.3 (SD:1.2), dropping to 1.8 (SD:1.1) at 3 months after recovery and to 0.6 (SD:0.9) at 18 months after recovery. However, this decrease was not unidirectional. Between acute illness and 3 months, the frequency of symptoms decreased for cough (64.5%→24.7%), ageusia (21.7% to6%), anosmia (17.5%→5.4%), and generalized pain (10.8% to 5.4%) but increased for dyspnea (53%→57.2%) weakness (47%→54.8%), and brain fog (3%→8.4%). Between 3 and 18 months, the frequency of symptoms decreased for all symptoms but remained relatively high for dyspnea (15.8%), weakness (21.2%), and brain fog (7.3%). Symptoms may persist for at least 18 months after acute COVID-19 infection. During the medium- to long-term recovery period, the prevalence of some symptoms may decrease or remain stable, and the prevalence of others may increase before slowly decreasing thereafter. These data should be considered when planning post-acute care for these patients.