Extension of Lung Damage at Chest Computed Tomography in Severely Ill COVID-19 Patients Treated with Interleukin-6 Receptor Blockers Correlates with Inflammatory Cytokines Production and Prognosis.

Elevated inflammatory markers are associated with severe coronavirus disease 2019 (COVID-19), and some patients benefit from Interleukin (IL)-6 pathway inhibitors. Different chest computed tomography (CT) scoring systems have shown a prognostic value in COVID-19, but not specifically in anti-IL-6-treated patients at high risk of respiratory failure. We aimed to explore the relationship between baseline CT findings and inflammatory conditions and to evaluate the prognostic value of chest CT scores and laboratory findings in COVID-19 patients specifically treated with anti-IL-6. Baseline CT lung involvement was assessed in 51 hospitalized COVID-19 patients naive to glucocorticoids and other immunosuppressants using four CT scoring systems. CT data were correlated with systemic inflammation and 30-day prognosis after anti-IL-6 treatment. All the considered CT scores showed a negative correlation with pulmonary function and a positive one with C-reactive protein (CRP), IL-6, IL-8, and Tumor Necrosis Factor α (TNF-α) serum levels. All the performed scores were prognostic factors, but the disease extension assessed by the six-lung-zone CT score (S24) was the only independently associated with intensive care unit (ICU) admission (p = 0.04). In conclusion, CT involvement correlates with laboratory inflammation markers and is an independent prognostic factor in COVID-19 patients representing a further tool to implement prognostic stratification in hospitalized patients.

Sudden winter iloprost withdrawal in scleroderma patients during COVID-19 pandemic.

INTRODUCTION: Intravenous iloprost is currently recommended in the treatment of Raynaud's phenomenon (RP) refractory to oral therapy and of digital ulcers (DUs) related to systemic sclerosis (SSc). In real-life practice there is a huge heterogeneity about the Iloprost regimens used. METHODS: A survey was carried out on SSc patients that interrupted Iloprost infusion to compare acral vascular symptoms just before Iloprost withdrawal and just after the missed infusion. Severity, and frequency of RP, new DUs onset or aggravation of those pre-existing were reported. Last available capillaroscopic images were also evaluated. RESULTS: The analysis includes 50 patients. After iloprost withdrawal, 11 patients reported a RP worsening because of enhanced intensity (p = 0.007). Only 8 patients of them also complained of an increased frequency (p = 0.07). None of the patients experienced digital ulcers for the first-time during quarantine. Among the 27 patients with a history of digital ulcers, 9 reported worsening and 7 recurrence of DUs. Overall, 17 patients (34.0 %) complained of a worsening of SSc vascular acral manifestations, namely RP or DUs. Reduced capillary density was associated with RP worsening, in particular, each unit increase of capillary density corresponds to an average 44 % decrease in the odds of RP worsening (OR 0.56, CI 95 % 0.36-0.97, p = 0.037). As for RP worsening, the aggravation of DU was associated with a lower capillary density. CONCLUSIONS: Low capillary density can predict a worsening of both RP and DUs in controlled quarantine conditions within a month after iloprost discontinuation in SSc patients.

Sarilumab use in severe SARS-CoV-2 pneumonia.

BACKGROUND: Interleukin-6 signal blockade showed preliminary beneficial effects in treating inflammatory response against SARS-CoV-2 leading to severe respiratory distress. Herein we describe the outcomes of off-label intravenous use of Sarilumab in severe SARS-CoV-2-related pneumonia. METHODS: 53 patients with SARS-CoV-2 severe pneumonia received intravenous Sarilumab; pulmonary function improvement or Intensive Care Unit (ICU) admission rate in medical wards, live discharge rate in ICU treated patients and safety profile were recorded. Sarilumab 400 mg was administered intravenously on day 1, with eventual additional infusion based on clinical judgement, and patients were followed for at least 14 days, unless previously discharged or dead. FINDINGS: Of the 53 SARS-CoV-2pos patients receiving Sarilumab, 39(73·6%) were treated in medical wards [66·7% with a single infusion; median PaO2/FiO2:146(IQR:120-212)] while 14(26·4%) in ICU [92·6% with a second infusion; median PaO2/FiO2: 112(IQR:100-141.5)].Within the medical wards, 7(17·9%) required ICU admission, 4 of whom were re-admitted to the ward within 5-8 days. At 19 days median follow-up, 89·7% of medical inpatients significantly improved (46·1% after 24 h, 61·5% after 3 days), 70·6% were discharged from the hospital and 85·7% no longer needed oxygen therapy. Within patients receiving Sarilumab in ICU, 64·2% were discharged from ICU to the ward and 35·8% were still alive at the last follow-up. Overall mortality rate was 5·7%. INTERPRETATION: IL-6R inhibition appears to be a potential treatment strategy for severe SARS-CoV-2 pneumonia and intravenous Sarilumab seems a promising treatment approach showing, in the short term, an important clinical outcome and good safety.

Nailfold capillaroscopy findings in patients with coronavirus disease 2019: Broadening the spectrum of COVID-19 microvascular involvement.

OBJECTIVE: Increasing evidence points to endothelial dysfunction as a key pathophysiological factor in coronavirus disease-2019 (COVID-19). No specific methods have been identified to predict, detect and quantify the microvascular alterations during COVID-19. Our aim was to assess microvasculature through nailfold videocapillaroscopy (NVC) in COVID-19 patients. METHODS: We performed NVC in patients with a confirmed diagnosis of COVID-19 pneumonia. Elementary alterations were reported for each finger according to a semi-quantitative score. Capillary density, number of enlarged and giant capillaries, number of micro-hemorrhages and micro-thrombosis (NEMO score) were registered. RESULTS: We enrolled 82 patients (mean age 58.8 ± 13.2 years, male 68.3%) of whom 28 during the hospitalization and 54 after recovery and hospital discharge. At NVC examination we found abnormalities classifiable as non-specific pattern in 53 patients (64.6%). Common abnormalities were pericapillary edema (80.5%), enlarged capillaries (61.0%), sludge flow (53.7%), meandering capillaries and reduced capillary density (50.0%). No pictures suggestive of scleroderma pattern have been observed. Acute COVID-19 patients, compared to recovered patients, showed a higher prevalence of hemosiderin deposits as a result of micro-hemorrhages (P = .027) and micro-thrombosis (P < .016), sludge flow (P = .001), and pericapillary edema (P < .001), while recovered patients showed a higher prevalence of enlarged capillaries (P < .001), loss of capillaries (P = .002), meandering capillaries (P < .001), and empty dermal papillae (P = .006). CONCLUSION: COVID-19 patients present microvascular abnormalities at NVC. Currently ill and recovered subjects are characterized by a different distribution of elementary capillaroscopic alterations, resembling acute and post-acute microvascular damage. Further studies are needed to assess the clinical relevance of NVC in COVID-19.