Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19?

Background: Hypovitaminosis D has been suggested to play a possible role in coronavirus disease 2019 (COVID-19) infection. Methods: The aim of this study is to analyze the relationship between vitamin D status and a biochemical panel of inflammatory markers in a cohort of patients with COVID-19. A secondary endpoint was to evaluate the correlation between 25OHD levels and the severity of the disease. Ninety-three consecutive patients with COVID-19-related pneumonia were evaluated from March to May 2020 in two hospital units in Pisa, in whom biochemical inflammatory markers, 25OHD levels, P/F ratio at nadir during hospitalization, and complete clinical data were available. Results: Sixty-five percent of patients presented hypovitaminosis D (25OHD ≤ 20 ng/ml) and showed significantly higher IL-6 [20.8 (10.9-45.6) vs. 12.9 (8.7-21.1) pg/ml, p = 0.02], CRP [10.7 (4.2-19.2) vs. 5.9 (1.6-8.1) mg/dl, p = 0.003], TNF-α [8.9 (6.0-14.8) vs. 4.4 (1.5-10.6) pg/ml, p = 0.01], D-dimer [0.53 (0.25-0.72) vs. 0.22 (0.17-0.35) mg/l, p = 0.002], and IL-10 [3.7 (1.8-6.9) vs. 2.3 (0.5-5.8) pg/ml, p = 0.03]. A significant inverse correlation was found between 25OHD and all these markers, even adjusted for age and sex. Hypovitaminosis D was prevalent in patients with severe ARDS, compared with the other groups (75% vs. 68% vs. 55%, p < 0.001), and 25OHD levels were lower in non-survivor patients. Conclusions: The relationship between 25OHD levels and inflammatory markers suggests that vitamin D status needs to be taken into account in the management of these patients. If vitamin D is a marker of poor prognosis or a possible risk factor with beneficial effects from supplementation, this still needs to be elucidated.

C-C motive chemokine ligand 2 and thromboinflammation in COVID-19-associated pneumonia: A retrospective study.

PURPOSE: A derangement of the coagulation process and thromboinflammatory events has emerged as pathologic characteristics of severe COVID-19, characterized by severe respiratory failure. CC motive chemokine ligand 2 (CCL2), a chemokine originally described as a chemotactic agent for monocytes, is involved in inflammation, coagulation activation and neoangiogenesis. We investigated the association of CCL2 levels with coagulation derangement and respiratory impairment in patients with COVID-19. METHODS: We retrospectively evaluated 281 patients admitted to two hospitals in Italy with COVID-19. Among them, CCL2 values were compared in different groups (identified according to D-dimer levels and the lowest PaO2/FiO2 recorded during hospital stay, P/Fnadir) by Jonckheere-Terpstra tests; linear regression analysis was used to analyse the relationship between CCL2 and P/Fnadir. We performed Mann-Whitney test and Kaplan-Meier curves to investigate the role of CCL2 according to different clinical outcomes (survival and endotracheal intubation [ETI]). RESULTS: CCL2 levels were progressively higher in patients with increasing D-dimer levels and with worse gas exchange impairment; there was a statistically significant linear correlation between log CCL2 and log P/Fnadir. CCL2 levels were significantly higher in patients with unfavourable clinical outcomes; Kaplan-Meier curves for the composite outcome death and/or need for ETI showed a significantly worse prognosis for patients with higher (> median) CCL2 levels. CONCLUSIONS: CCL2 correlates with both indices of activation of the coagulation cascade and respiratory impairment severity, which are likely closely related in COVID-19 pathology, thus suggesting that CCL2 could be involved in the thromboinflammatory events characterizing this disease.

Comparison of percutaneous dilatational tracheotomy versus open surgical technique in severe COVID-19: Complication rates, relative risks and benefits.

OBJECTIVE: Patients with acute respiratory failure due to COVID-19 have a high likelihood of needing prolonged intubation and may subsequently require tracheotomy. Usually, the choice of technique (percutaneous dilatational tracheotomy [PDT] versus open surgical tracheotomy [OST]) depends on the preference of surgeons and patient-related factors. In case of COVID-19, airborne spread of viral particles and limited time of apnea must be considered in the choice of the safest technique. The aim of this study is to compare the complication rates and offer an assessment of relative risks and benefits of PDT versus OST in patients with severe COVID-19. METHODS: We performed a retrospective study considering 47 consecutive patients affected by severe acute respiratory distress syndrome due to SARS-CoV-2 infection, needing invasive mechanical ventilation and subsequent tracheostomy. This study was performed at the Intensive Care Unit of our tertiary referral center. Complication rates were analyzed. RESULTS: Seventeen patients underwent PDT and 30 patients were submitted to OST. Twenty-six patients (55.3%) had post-operative complications (local infection, hemorrhage, subcutaneous emphysema) with no significant difference between PDT and OST. CONCLUSION: PDT and OST are characterized by similar postoperative complication rates in severe COVID-19 patients. These findings suggest that OST might be preferred if expert ENT surgeons are available, as PDT could result in longer apnea and exposure to generated aerosol. However, authors recommend considering either OST or PDT at the discretion of the medical staff involved, according to the personal experience of the operators performing the procedure.

The Role of Tracheotomy and Timing of Weaning and Decannulation in Patients Affected by Severe COVID-19.

OBJECTIVES: Patients with acute respiratory failure due to coronavirus disease 2019 (COVID-19) have a high likelihood of needing prolonged intubation and may subsequently require tracheotomy. Indications and timing for performing tracheotomy in patients affected by severe COVID-19 pneumonia are still elusive. The aim of this study is to analyze the role of tracheotomy in the context of this pandemic. Moreover, we report the timing of the procedure and the time needed to complete weaning and decannulation in our center. METHODS: This retrospective, observational cohort study included adults (≥18 years) with severe COVID-19 pneumonia who were admitted to the intensive care unit (ICU) of the tertiary care center of Reggio Emilia (Italy). All patients underwent orotracheal intubation with invasive mechanical ventilation, followed by percutaneous or open surgical tracheotomy. Indications, timing of the procedure, and time needed to complete weaning and decannulation were reported. RESULTS: Forty-four patients were included in the analysis. Median time from orotracheal intubation to surgery was 7 (range 2-17) days. Fifteen (34.1%) patients died during the follow-up period (median 22 days, range 8-68) after the intubation. Weaning from the ventilator was first attempted on median 25th day (range 13-43) from orotracheal intubation. A median of 35 (range 18-79) days was required to complete weaning. Median duration of ICU stay was 22 (range 10-67) days. Mean decannulation time was 36 (range 10-77) days from surgery. CONCLUSIONS: Since it is not possible to establish an optimal timing for performing tracheotomy, decision-making should be made on case-by-case basis. It should be adapted to the context of the pandemic, taking into account the availability of intensive care resources, potential risks for health care workers, and benefits for the individual patient.