Time-Dependent Changes in Pulmonary Turnover of Thrombocytes During Critical COVID-19.

OBJECTIVES BACKGROUND: Under normal conditions, pulmonary megakaryocytes are an important source of circulating thrombocytes, causing thrombocyte counts to be higher in arterial than venous blood. In critical COVID-19, thrombocytes may be removed from the circulation by the lungs because of immunothrombosis, possibly causing venous thrombocyte counts to be higher than arterial thrombocyte counts. In the present study, we investigated time-dependent changes in pulmonary turnover of thrombocytes during critical COVID-19 by measuring arteriovenous thrombocyte differences. We hypothesized that the early stages of the disease would be characterized by a net pulmonary removal of circulating thrombocytes because of immunothrombosis and that later stages would be characterized by a net pulmonary release of thrombocytes as normal pulmonary function is restored. DESIGN: Cohort study with repeated measurements of arterial and central venous thrombocyte counts. SETTING: ICU in a large university hospital. PATIENTS: Thirty-one patients with critical COVID-19 that were admitted to the ICU and received invasive or noninvasive mechanical ventilation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We found a significant positive association between the arteriovenous thrombocyte difference and time since symptom debut. This finding indicates a negative arteriovenous thrombocyte difference and hence pulmonary removal of thrombocytes in the early stages of the disease and a positive arteriovenous thrombocyte difference and hence pulmonary release of thrombocytes in later stages. Most individual arteriovenous thrombocyte differences were smaller than the variance coefficient of the analysis. CONCLUSIONS: The results of this study support our hypothesis that early stages of critical COVID-19 are characterized by pulmonary removal of circulating thrombocytes because of immunothrombosis and that later stages are characterized by the return of normal pulmonary release of thrombocytes. However, in most cases, the arteriovenous thrombocyte difference was too small to say anything about pulmonary thrombocyte removal and release on an individual level.

Interleukin-6 in Critical Coronavirus Disease 2019, a Driver of Lung Inflammation of Systemic Origin?

To examine whether interleukin-6 in critical coronavirus disease 2019 is higher in arterial than in central venous blood, as a sign of predominantly local pulmonal rather than systemic interleukin-6 production. DESIGN: Prospective cohort pilot study with repeated weekly measurements of interleukin-6 in arterial and central venous blood. Respiratory function, assessed with Pao2/Fio2 ratio, was measured at the time of blood sampling. SETTING: ICU at a university hospital. SUBJECTS: Nine adult patients with critical coronavirus disease 2019, actively treated and receiving mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: No difference between arterial and central venous interleukin-6 was found. There was a significant negative relationship between interleukin-6 concentration and P/F ratio in both arterial (p = 0.04) and central venous (p = 0.03) blood. CONCLUSIONS: The absence of an arteriovenous interleukin-6 difference implies that interleukin-6 in critical coronavirus disease 2019 is mainly produced outside the lungs as part of a systemic inflammatory response syndrome and act as a driver of local inflammation and damage in the lungs.