A retrospective study on the prevalence of anti-phospholipid antibodies, thrombotic events and cutaneous signs of vasculopathy in 173 hospitalized COVID-19 patients.

BACKGROUND: Hypercoagulability is a risk factor of thromboembolic events in COVID-19. Anti-phospholipid (aPL) antibodies have been hypothesized to be involved. Typical COVID-19 dermatological manifestations of livedo reticularis and digital ischemia may resemble cutaneous manifestations of anti-phospholipid syndrome (APS). OBJECTIVES: To investigate the association between aPL antibodies and thromboembolic events, COVID-19 severity, mortality, and cutaneous manifestations in patients with COVID-19. METHODS: aPL antibodies [anti-beta2-glycoprotein-1 (B2GP1) and anti-cardiolipin (aCL) antibodies] were titered in frozen serum samples from hospitalized COVID-19 patients and the patients' clinical records were retrospectively analyzed. RESULTS: 173 patients were enrolled. aPL antibodies were detected in 34.7% of patients, anti-B2GP1 antibodies in 30.1%, and aCL antibodies in 10.4%. Double positivity was observed in 5.2% of patients. Thromboembolic events occurred in 9.8% of patients, including 11 pulmonary embolisms, 1 case of celiac tripod thrombosis, and six arterial ischemic events affecting the cerebral, celiac, splenic, or femoral-popliteal arteries or the aorta. aPL antibodies were found in 52.9% of patients with vascular events, but thromboembolic events were not correlated to aPL antibodies (adjusted OR = 1.69, p = 0.502). Ten patients (5.8%) had cutaneous signs of vasculopathy: nine livedo reticularis and one acrocyanosis. No significant association was observed between the presence of cutaneous vasculopathy and aPL antibodies (p = 0.692). CONCLUSIONS: Anti-phospholipid antibodies cannot be considered responsible for hypercoagulability and thrombotic events in COVID-19 patients. In COVID-19 patients, livedo reticularis and acrocyanosis do not appear to be cutaneous manifestations of APS.

The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient - a case study

BackgroundImmunocompromised patients show prolonged shedding of SARS-CoV-2 in nasopharyngeal swabs. We report a case of a prolonged persistence of viable SARS-CoV-2 associated with clinical relapses of COVID-19 in a lymphoma patient. MethodsNasopharyngeal swabs and blood samples were tested for SARS-CoV-2 by Real time-PCR (RT-PCR). On five positive nasopharyngeal swabs, we performed viral culture and next generation sequencing. We analysed the patients adaptive and innate immunity to characterize T and NK cell subsets. FindingsSARS-CoV-2 RT-PCR on nasopharyngeal swabs samples remained positive with cycle threshold mean values of 22 {+/-} 1{middle dot}3 for over 8 months. All five performed viral cultures were positive and genomic analysis confirmed a persistent infection with the same strain. Viremia resulted positive in three out of four COVID-19 clinical relapses and cleared each time after remdesivir treatment. T and NK cells dynamic was different in aviremic and viremic samples and no SARS-CoV-2 specific antibodies were detected throughout the disease course. InterpretationIn our patient, SARS-CoV-2 persisted with proven infectivity for over eight months. Viremia was associated with COVID-19 relapses and remdesivir treatment was effective in viremia clearance and symptoms remission, although it was unable to clear the virus from the upper respiratory airways. During the viremic phase, we observed a low frequency of terminal effector CD8+ T lymphocytes in peripheral blood that are probably recruited in inflammatory tissue for viral eradication. In addition we found a high level of NK cells repertoire perturbation with a relevant involvement during SARS-CoV-2 viremia. FundingNone.

Tocilizumab and steroid treatment in patients with severe Covid-19 pneumonia.

IntroductionCoronavirus disease 2019 (COVID-19) can lead to respiratory failure due to severe immune response. Treatment targeting this immune response might be beneficial but there is limited evidence on its efficacy. The aim of this study was to determine if early treatment of patients with COVID-19 pneumonia with tocilizumab and/or steroids was associated with better outcome. MethodsThis observational single-center study included patients with COVID-19 pneumonia who were not intubated and received either standard of care (SOC, controls) or SOC plus early (within 3 days from hospital admission) anti-inflammatory treatment. SOC consisted of hydroxychloroquine 400mg bid plus, in those admitted before March 24th, also darunavir/ritonavir. Anti-inflammatory treatment consisted of either tocilizumab (8mg/kg intravenously or 162mg subcutaneously) or methylprednisolone 1 mg/kg for 5 days or both. Failure was defined as intubation or death, and the endpoints were failure-free survival (primary endpoint) and overall survival (secondary) at day 30. Difference between the groups was estimated as Hazard Ratio by a propensity score weighted Cox regression analysis (HROW). ResultsOverall, 196 adults were included in the analyses. They were mainly male (67.4%), with comorbidities (78.1%) and severe COVID-19 pneumonia (83.7%). Median age was 67.9 years (range, 30-100) and median PaO2/FiO2 200 mmHg (IQR 133-289). Among them, 130 received early anti-inflammatory treatment with: tocilizumab (n=29, 22.3%), methylprednisolone (n=45, 34.6%), or both (n=56, 43.1%). The adjusted failure-free survival among tocilizumab/methylprednisolone/SOC treated patients vs. SOC was 80.8% (95%CI, 72.8-86.7) vs. 64.1% (95%CI, 51.3-74.0), HROW 0.48, 95%CI, 0.23-0.99; p=0.049. The overall survival among tocilizumab/methylprednisolone/SOC patients vs. SOC was 85.9% (95%CI, 80.7-92.6) vs. 71.9% (95%CI, 46-73), HROW 0.41, 95%CI: 0.19-0.89, p=0.025. ConclusionEarly adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.