Comparison of the Levels of Neopterin, CRP, and IL-6 in Patients Infected with and without SARS-CoV-2 (preprint)

Background: Neopterin (NP) is a biomarker for activated cellular immunity and is elevated in diseases including viral and bacterial infections, autoimmune diseases, and cancer. However, the clinical assessment of neopterin has not been used for these disorders because the physiological significance of measuring NP is obscure. It would be important to compare the NP profiles with those of other inflammation markers to reveal the significance of NP measurements in pathological states.Methods: Plasma NP, CRP, and IL-6 levels were measured in 46 patients with Coronavirus Disease 2019 (COVID-19) and 13 patients with non-COVID-19 respiratory disorders. The correlations between these markers were analyzed in the COVID-19 and non-COVID-19 patients independently.Results: The NP levels were significantly higher in the COVID-19 patients than in the non-COVID-19 patients, while both CRP and IL-6 were not changed significantly. Among the COVID-19 patients, all three values increased with the severity of symptoms. NP levels were not correlated with CRP or IL-6 levels in COVID-19 patients but were correlated with IL-6 levels in non-COVID-19 patients. The CRP levels were correlated with those of IL-6 in both the COVID-19 and non-COVID-19 patients.Conclusions: The elevation of NP levels was distinct from those of CRP and IL-6 in COVID-19 patients. Our data suggest that NP is produced in different signaling pathways and/or cells than CRP and IL-6. Further study on the signaling pathway to induce NP is expected

High-flow Nasal Cannula and Prone Positioning Improve Outcomes of Patients with COVID-19: A Retrospective Study (preprint)

Background: Non-invasive or invasive mechanical ventilation (NIV or IMV) is used to treat critically ill patients with the novel coronavirus disease 2019 (COVID-19). However, the mortality rate for these remains high. High-flow nasal cannula (HFNC) is an alternative device and prone position (PP) is a therapeutic option. However, there is also no evidence to support the efficacy of these methods for patients with COVID-19. Thus, our study aimed to evaluate the efficacy of the therapeutic combination of early high-flow nasal cannula and the prone position.Methods: We conducted an observational, retrospective, single-center study. We enrolled COVID-19 patients with HFNC support admitted to our hospital between February 1, 2020 and February 28, 2021. We considered the threshold level for HFNC use as Oxygen saturation (SpO2) < 90% and respiratory rate > 20 breaths/min with a non-rebreather mask at 7 L/min or more. SpO2 as measured by pulse oximetry to the fraction of inspired oxygen (FiO2) (S/F) ratio was calculated to estimate the partial pressure of arterial oxygen to FiO2 ratio. The primary outcome was the all-cause 28-day mortality. The secondary outcome was intubation rates, time until liberation from HFNC and the length of stay in the intensive care unit (ICU) and the hospital. Continuous variables with normal distribution are shown as mean ± standard deviation, others as median and interquartile range, and categorical variables as counts and percentages.Results: A total of 451 COVID-19 patients were enrolled. Of these, 54 (12%) patients required HFNC. The median S/F ratio before HFNC initiation was 103.9, and the worst median S/F ratio with HFNC was 181. Six patients (11%) died. If we exclude patients who are not eligible for IMV due to their PS, the presence of comorbidities, or the wishes of the patient or their family, only two patients (4%) died. IMV or NIV was required in five patients (9%), of whom three patients died. The median duration of HFNC use, ICU stay, and hospitalization were seven, seven, and 23 days, respectively.Conclusion: The combination therapy of early HFNC and PP has the potential to improve the mortality rate and reduce intubation.

Myeloid cell dynamics correlate with clinical outcomes of severe coronavirus disease 2019 (preprint)

An expanded myeloid cell compartment is a hallmark of severe coronavirus disease 2019 (COVID-19); however, it remains unclear whether myeloid cells are beneficial or detrimental to the clinical outcome. Here, we tracked cellular dynamics of myeloid-derived suppressor cell (MDSC) subsets and examined whether any of them correlate with disease severity and prognosis by flow cytometric analysis of blood samples from COVID-19 patients. We observed that polymorphonuclear (PMN)-MDSCs, rather than other MDSC subsets, transiently expanded in severe cases but not in mild or moderate cases. Notably, this subset was selectively expanded in survivors of severe cases and diminished during recovery. Analysis of plasma cytokines/chemokines revealed that interleukin-8 increased prior to PMN-MDSC expansion in survivors and returned to basal levels during the recovery phase. In contrast, interleukin-6 and interferon-γ-induced protein 10 were abundantly induced in non-survivors, suggesting possible downstream targets for the immunosuppressive effects of the MDSC subset. Our data indicate that increased cellularity of PMN-MDSCs might be beneficial for the clinical outcome and could be useful as a possible predictor of prognosis in cases of severe COVID-19.