Objectives To correlate a CT-based semi-quantitative score of pulmonary involvement in COVID-19 pneumonia with clinical staging of disease and laboratory findings. We also aimed to investigate whether CT findings may be predictive of patients' outcome. Methods From March 6 to March 22, 2020, 130 symptomatic SARS-CoV-2 patients were enrolled for this single-center analysis and chest CT examinations were retrospectively evaluated. A semi-quantitative CT score was calculated based on the extent of lobar involvement (0:0%; 1, < 5%; 2:5-25%; 3:26-50%; 4:51-75%; 5, > 75%; range 0-5; global score 0-25). Data were matched with clinical stages and laboratory findings. Survival curves and univariate and multivariate analyses were performed to evaluate the role of CT score as a predictor of patients' outcome. Results Ground glass opacities were predominant in early-phase (≤ 7 days since symptoms' onset), while crazy-paving pattern, consolidation, and fibrosis characterized late-phase disease (> 7 days). CT score was significantly higher in critical and severe than in mild stage (p < 0.0001), and among late-phase than early-phase patients (p < 0.0001). CT score was significantly correlated with CRP (p < 0.0001, r = 0.6204) and D-dimer (p < 0.0001, r = 0.6625) levels. A CT score of ≥ 18 was associated with an increased mortality risk and was found to be predictive of death both in univariate (HR, 8.33; 95% CI, 3.19-21.73; p < 0.0001) and multivariate analysis (HR, 3.74; 95% CI, 1.10-12.77; p = 0.0348). Conclusions Our preliminary data suggest the potential role of CT score for predicting the outcome of SARS-CoV-2 patients. CT score is highly correlated with laboratory findings and disease severity and might be beneficial to speed-up diagnostic workflow in symptomatic cases. Key Points • CT score is positively correlated with age, inflammatory biomarkers, severity of clinical categories, and disease phases. • A CT score ≥ 18 has shown to be highly predictive of patient's mortality in short-term follow-up. • Our multivariate analysis demonstrated that CT parenchymal assessment may more accurately reflect short-term outcome, providing a direct visualization of anatomic injury compared with non-specific inflammatory biomarkers. Keywords Severe acute respiratory syndrome coronavirus 2. COVID-19. Pneumonia. Tomography, X-ray computed Marco Francone and Franco Iafrate contributed equally to this work.

BackgroundEmerging evidence argues that monocytes, circulating innate immune cells, are principal players in COVID-19 pneumonia. The study aimed to investigate the role of soluble (s)CD163 and sCD14 plasmatic levels in predicting disease severity and characterize peripheral blood monocytes and dendritic cells (DCs), in patients with COVID-19 pneumonia (COVID-19 subjects).MethodsOn admission, in COVID-19 subjects sCD163 and sCD14 plasmatic levels, and peripheral blood monocyte and DC subsets were compared to healthy donors (HDs). According to clinical outcome, COVID-19 subjects were divided into ARDS and non-ARDS groups.ResultsCompared to HDs, COVID-19 subjects showed higher sCD163 (p&lt;0.0001) and sCD14 (p&lt;0.0001) plasmatic levels. We observed higher sCD163 plasmatic levels in the ARDS group compared to the non-ARDS one (p=0.002). The cut-off for sCD163 plasmatic level greater than 2032 ng/ml was predictive of disease severity (AUC: 0.6786, p=0.0022; sensitivity 56.7% [CI: 44.1–68.4] specificity 73.8% [CI: 58.9–84.7]). Positive correlation between plasmatic levels of sCD163, LDH and IL-6 and between plasmatic levels of sCD14, D-dimer and ferritin were found. Compared to HDs, COVID-19 subjects showed lower percentages of non-classical (p=0.0012) and intermediate monocytes (p=0.0447), slanDCs (p&lt;0.0001), myeloid DCs (mDCs, p&lt;0.0001), and plasmacytoid DCs (pDCs, p=0.0014). Compared to the non-ARDS group, the ARDS group showed lower percentages of non-classical monocytes (p=0.0006), mDCs (p=0.0346), and pDCs (p=0.0492).ConclusionsThe increase in sCD163 and sCD14 plasmatic levels, observed on hospital admission in COVID-19 subjects, especially in those who developed ARDS, and the correlations of these monocyte/macrophage activation markers with typical inflammatory markers of COVID-19 pneumonia, underline their potential use to assess the risk of progression of the disease. In an early stage of the disease, the assessment of sCD163 plasmatic levels could have clinical utility in predicting the severity of COVID-19 pneumonia.

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BackgroundVaccination campaign to contrast the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has raised the issue of vaccine immunogenicity in special populations such as people with multiple sclerosis (PwMS) on highly effective disease modifying treatments (DMTs). While humoral responses to SARS-CoV-2 mRNA vaccines have been well characterized in the general population and in PwMS, very little is known about cell-mediated responses in conferring protection from SARS-CoV-2 infection and severe coronavirus disease-2019 (COVID-19).MethodsPwMS on ocrelizumab, fingolimod or natalizumab, vaccinated with two doses of mRNABNT162b2 (Comirnaty®) vaccine were enrolled. Anti-Spike (S) and anti-Nucleoprotein (N) antibody titers, IFN-gamma production upon S and N peptide libraries stimulation, peripheral blood lymphocyte absolute counts were assessed after at least 1 month and within 4 months from vaccine second dose administration. A group of age and sex matched healthy donors (HD) were included as reference group. Statistical analysis was performed using GraphPad Prism 8.2.1.ResultsThirty PwMS and 9 HDs were enrolled. All the patients were negative for anti-N antibody detection, nor reported previous symptoms of COVID-19. Peripheral blood lymphocyte counts were assessed in PwMS showing: (i) reduction of circulating B-lymphocytes in PwMS on ocrelizumab; (ii) reduction of peripheral blood B- and T-lymphocyte absolute counts in PwMS on fingolimod and (iii) normal B- and T-lymphocyte absolute counts with an increase in circulating CD16+CD56+ NK-cells in PwMS on natalizumab. Three patterns of immunological responses were identified in PwMS. In patients on ocrelizumab, anti-S antibody were lacking or reduced, while T-cell responses were normal. In patients on fingolimod both anti-S titers and T-cell mediated responses were impaired. In patients on natalizumab both anti-S titers and T-cell responses were present and comparable to those observed in HD.ConclusionsThe evaluation of T-cell responses, anti-S titers and peripheral blood lymphocyte absolute count in PwMS on DMTs can help to better characterize the immunological response after SARS-CoV-2 vaccination. The evaluation of T-cell responses in longitudinal cohorts of PwMS will help to clarify their protective role in preventing SARS-CoV-2 infection and severe COVID-19. The correlation between DMT treatment and immunological responses to SARS-CoV-2 vaccines could help to better evaluate vaccination strategies in PwMS.

A teriflunomide-treated multiple sclerosis patient with COVID-19 pneumonia was hospitalized and recovered in 15 days. The immunophenotyping analysis of peripheral blood cells was performed in two time points: the first was 1 month before (pre-infection) while the second was during COVID-19 pneumonia (infection). At the infection time point, no differences in the percentages of immune activation and immunesenescence of CD4+ and CD8+ T-cells were observed compared to the pre-infection time point. Our evaluation seems to confirm that teriflunomide controls T-cells immune activation and immunosenescence suggesting that teriflunomide should not be discontinued in MS patients with an active COVID-19 pneumonia.

Ocrelizumab is an anti-CD20 monoclonal antibody for the treatment of multiple sclerosis (MS) that is closely related to rituximab. We describe a case of hepatitis B virus (HBV) reactivation in an MS patient with resolved HBV infection receiving ocrelizumab. HBV reactivation was monitored with HBV-DNA and HBV surface antigen periodic assessment. Anti-HBV treatment with entecavir was started after HBV-DNA detection. Ocrelizumab can reactivate viral replication in patients with resolved HBV infection. HBV reactivation monitoring seems an effective and safe option for the management of these patients. More studies are needed to assess the optimal management of HBV reactivation in MS patients on ocrelizumab treatment.

The pandemic acute respiratory syndrome coronavirus 2 (SARS-CoV-2) named COVID-19 is causing a severe health emergency, and an individual’s hormonal milieu may play an important role in both susceptibility to infection and severity of clinical course. We analyzed the role of testosterone in the immune response, and we hypothesized possible mechanisms to explain the high incidence of COVID-19 infection and a worse clinical course in elderly male patients. Testosterone may impair the immune response, and this effect could explain the greater susceptibility of men to infection. Transmembrane serine protease 2 (TMPRSS2) plays a crucial role in the entry of the virus into the respiratory epithelial cells, leading to COVID-19 disease. It is crucial to emphasize that testosterone levels and chemical castration (e.g. by androgen deprivation therapy for prostate cancer) may have contrasting roles in the phases of COVID-19 infection. Whereas low testosterone levels may be protective against the initial susceptibility (due to a restoration of immunological functions and a block of TMPRSS2), low testosterone may stimulate a worse clinical course in the advanced COVID-19 infection as it could exacerbate or activate the cytokine storm. If testosterone levels play these different roles, it is necessary to carefully identify patients for any indicated testosterone manipulation.

Neurofilament light chain (NfL) is a specific biomarker of neuro-axonal damage. Matrix metalloproteinases (MMPs) are zinc-dependent enzymes involved in blood–brain barrier (BBB) integrity. We explored neuro-axonal damage, alteration of BBB integrity and SARS-CoV-2 RNA presence in COVID-19 patients with severe neurological symptoms (neuro-COVID) as well as neuro-axonal damage in COVID-19 patients without severe neurological symptoms according to disease severity and after recovery, comparing the obtained findings with healthy donors (HD). Overall, COVID-19 patients (n = 55) showed higher plasma NfL levels compared to HD (n = 31) (p < 0.0001), especially those who developed ARDS (n = 28) (p = 0.0005). After recovery, plasma NfL levels were still higher in ARDS patients compared to HD (p = 0.0037). In neuro-COVID patients (n = 12), higher CSF and plasma NfL, and CSF MMP-2 levels in ARDS than non-ARDS group were observed (p = 0.0357, p = 0.0346 and p = 0.0303, respectively). SARS-CoV-2 RNA was detected in four CSF and two plasma samples. SARS-CoV-2 RNA detection was not associated to increased CSF NfL and MMP levels. During COVID-19, ARDS could be associated to CNS damage and alteration of BBB integrity in the absence of SARS-CoV-2 RNA detection in CSF or blood. CNS damage was still detectable after discharge in blood of COVID-19 patients who developed ARDS during hospitalization.