Procalcitonin Is Not a Reliable Biomarker of Bacterial Coinfection in People With Coronavirus Disease 2019 Undergoing Microbiological Investigation at the Time of Hospital Admission.

Admission procalcitonin measurements and microbiology results were available for 1040 hospitalized adults with coronavirus disease 2019 (from 48 902 included in the International Severe Acute Respiratory and Emerging Infections Consortium World Health Organization Clinical Characterisation Protocol UK study). Although procalcitonin was higher in bacterial coinfection, this was neither clinically significant (median [IQR], 0.33 [0.11-1.70] ng/mL vs 0.24 [0.10-0.90] ng/mL) nor diagnostically useful (area under the receiver operating characteristic curve, 0.56 [95% confidence interval, .51-.60]).

COVID-19 and immunothrombosis: emerging understanding and clinical management.

The COVID-19 pandemic has been the most significant health crisis in recent global history. Early studies from Wuhan highlighted COVID-19-associated coagulopathy and a significant association with mortality was soon recognised. As research continues across the world, more evidence is emerging of the cross-talk between the innate immune system, coagulation activation and inflammation. Immunothrombosis has been demonstrated to play a key role in the pathophysiology of severe COVID-19, with extracellular histones and neutrophil extracellular traps detected in the plasma and cardiopulmonary tissues of critically ill patients. Targeting the components of immunothrombosis is becoming an important factor in the treatment of patients with COVID-19 infection. Recent studies report outcomes of intermediate and therapeutic anticoagulation in hospitalised patients with varying severities of COVID-19 disease, including optimal dosing and associated bleeding risks. Immunomodulatory therapies, including corticosteroids and IL-6 receptor antagonists, have been demonstrated to significantly reduce mortality in COVID-19 patients. As the pandemic continues, more studies are required to understand the driving factors and upstream mechanisms for coagulopathy and immunothrombosis in COVID-19, and thus potentially develop more targeted therapies for SARS-CoV-2 infection, both in the acute phase and in those who develop longer-term symptom burden.

Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19.

While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.