Increased Peripheral Blood Neutrophil Activation Phenotypes and Neutrophil Extracellular Trap Formation in Critically Ill Coronavirus Disease 2019 (COVID-19) Patients: A Case Series and Review of the Literature.

BACKGROUND: Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. METHODS: Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English. RESULTS: Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1ß, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death. CONCLUSIONS: Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.

Deleterious Association of Inhalant Use on Sleep Quality during the COVID-19 Pandemic.

The COVID-19 pandemic generated large amounts of stress across the globe. While acute stress negatively impacts health, defining exact consequences and behavioral interventions can be difficult. We hypothesized that a generalized increase in stress and anxiety caused by continuation of the global pandemic would negatively impact sleep quality and that ever users of e-cigarettes and conventional tobacco would have more profound alterations over time. Participants were recruited via social media to complete an online survey in April 2020 (n = 554). Inhalant use was assessed through the UCSD Inhalant Questionnaire and sleep quality was gauged through the Pittsburgh Sleep Quality Index (PSQI). A set of participants (n = 217) retook the survey in June 2020. Inhalant users-historical or current e-cigarette vapers, conventional tobacco smokers, and dual users-had higher PSQI scores than never smoker/never vapers, demonstrating worse sleep quality in inhalant users. Non-smoking/non-vaping subjects who retook the survey in June 2020 had improvement in their PSQI scores by paired t test, indicating better sleep quality as the pandemic continued, while inhalant users of all types had persistently high PSQI scores (poor sleep quality). These data suggest that ever users of tobacco products may be susceptible to overall diminished sleep quality in the setting of stressful life circumstances. These data also suggest that pandemic-initiated lifestyle changes may have led to improvements in sleep quality. Finally, these findings raise concerns for correlations between either past or active e-cigarette use on sleep, and thus overall health.