Small fibre neuropathy frequently underlies the painful long-COVID syndrome.

ABSTRACT: Approximately 10% to 20% of individuals with previous SARS-CoV-2 infection may develop long-COVID syndrome, characterized by various physical and mental health issues, including pain. Previous studies suggested an association between small fibre neuropathy and pain in long-COVID cases. In this case-control study, our aim was to identify small fibre neuropathy in patients experiencing painful long-COVID syndrome. Clinical data, quantitative sensory testing, and skin biopsies were collected from 26 selected patients with painful long-COVID syndrome. We also examined 100 individuals with past COVID-19 infection, selecting 33 patients with painless long-COVID syndrome, characterized mainly by symptoms such as brain fog and fatigue, and 30 asymptomatic post-COVID-19 controls. Demographic and clinical variables were compared among these groups. Among the 26 patients with painful long-COVID syndrome, 12 had skin biopsy and/or quantitative sensory testing abnormalities compatible with small fibre neuropathy. Demographic and clinical data did not differ across patients with small fibre neuropathy, patients with painless long-COVID syndrome, and asymptomatic post-COVID-19 controls. This case-control study showed that approximately 50% of patients experiencing painful long-COVID syndrome had small fibre neuropathy. However, in our patient cohort, this specific post-COVID-19 complication was unrelated to demographic and COVID-19 clinical variables. Approximately half of our sample of patients with painful long-COVID symptoms met diagnostic criteria for small fibre neuropathy.

The Impact of Cytomegalovirus Infection on Natural Killer and CD8+ T Cell Phenotype in Multiple Sclerosis.

Multiple sclerosis (MS) is a debilitating neurological disease that has been classified as an immune-mediated attack on myelin, the protective sheath of nerves. Some aspects of its pathogenesis are still unclear; nevertheless, it is generally established that viral infections influence the course of the disease. Cytomegalovirus (CMV) is a major pathogen involved in alterations of the immune system, including the expansion of highly differentiated cytotoxic CD8+ T cells and the accumulation of adaptive natural killer (NK) cells expressing high levels of the NKG2C receptor. In this study, we evaluated the impact of latent CMV infection on MS patients through the characterization of peripheral NK cells, CD8+ T cells, and NKT-like cells using flow cytometry. We evaluated the associations between immune cell profiles and clinical features such as MS duration and MS progression, evaluated using the Expanded Disability Status Scale (EDSS). We showed that NK cells, CD8+ T cells, and NKT-like cells had an altered phenotype in CMV-infected MS patients and displayed high levels of the NKG2C receptor. Moreover, in MS patients, increased NKG2C expression levels were found to be associated with higher EDSS scores. Overall, these results support the hypothesis that CMV infection imprints the immune system by modifying the phenotype and receptor repertoire of NK and CD8+ T cells, suggesting a detrimental role of CMV on MS progression.

Biomarkers of Neurological Damage: From Acute Stage to Post-Acute Sequelae of COVID-19.

Background: Neurological symptoms (NS) in COVID-19 are related to both acute stage and long-COVID. We explored levels of brain injury biomarkers (NfL and GFAP) and myeloid activation marker (sCD163) and their implications on the CNS. Materials and Methods: In hospitalized COVID-19 patients plasma samples were collected at two time points: on hospital admission (baseline) and three months after hospital discharge (Tpost). Patients were stratified according to COVID-19 severity based on acute respiratory distress syndrome (ARDS) onset (severe and non-severe groups). A further stratification according to the presence of NS (with and without groups) at baseline (requiring a puncture lumbar for diagnostic purposes) and according to NS self-referred at Tpost was performed. Finally, cerebrospinal fluid (CSF) samples were collected from patients with NS present at baseline. Results: We enrolled 144 COVID-19 patients (62 female/82 male; median age [interquartile range, IQR]): 64 [55-77]) and 53 heathy donors (HD, 30 female/23 male; median age [IQR]: 64 [59-69]). At baseline, higher plasma levels of NfL, GFAP and sCD163 in COVID-19 patients compared to HD were observed (p < 0.0001, p < 0.0001 and p < 0.0001, respectively), especially in those with severe COVID-19 (p < 0.0001, p < 0.0001 and p < 0.0001, respectively). Patients with NS showed higher plasma levels of NfL, GFAP and sCD163 compared to those without (p = 0.0023, p < 0.0001 and 0.0370, respectively). At baseline, in COVID-19 patients with NS, positive correlations between CSF levels of sCD163 and CSF levels of NfL (ρ = 0.7536, p = 0.0017) and GFAP were observed (ρ = 0.7036, p = 0.0045). At Tpost, the longitudinal evaluation performed on 77 COVID-19 patients showed a significant reduction in plasma levels of NfL, GFAP and sCD163 compared to baseline (p < 0.0001, p < 0.0001 and p = 0.0413, respectively). Finally, at Tpost, in the severe group, higher plasma levels of sCD163 in patients with NS compared to those without were reported (p < 0.0001). Conclusions: High plasma levels of NfL, GFAP and sCD163 could be due to a proinflammatory systemic and brain response involving microglial activation and subsequent CNS damage. Our data highlight the association between myeloid activation and CNS perturbations.

Immunogenicity and Efficacy of Vaccination in People Living with Human Immunodeficiency Virus.

People living with HIV (PLWH) remain at high risk of mortality and morbidity from vaccine-preventable diseases, even though antiretroviral therapy (ART) has restored life expectancy and general well-being. When, which, and how many doses of vaccine should be administered over the lifetime of PLWH are questions that have become clinically relevant. Immune responses to most vaccines are known to be impaired in PLWH. Effective control of viremia with ART and restored CD4+ T-cell count are correlated with an improvement in responsiveness to routine vaccines. However, the presence of immune alterations, comorbidities and co-infections may alter it. In this article, we provide a comprehensive review of the literature on immune responses to different vaccines in the setting of HIV infection, emphasizing the potential effect of HIV-related factors and presence of comorbidities in modulating such responses. A better understanding of these issues will help guide vaccination and prevention strategies for PLWH.

Tissue Inhibitor of Matrix Metalloproteinases-1 (TIMP-1) and Pulmonary Involvement in COVID-19 Pneumonia.

Background: The aim of the study was to longitudinally evaluate the association between MMP-2, MMP-9, TIMP-1 and chest radiological findings in COVID-19 patients. Methods: COVID-19 patients were evaluated based on their hospital admission (baseline) and three months after hospital discharge (T post) and were stratified into ARDS and non-ARDS groups. As a control group, healthy donors (HD) were enrolled. Results: At the baseline, compared to HD (n = 53), COVID-19 patients (n = 129) showed higher plasma levels of MMP-9 (p < 0.0001) and TIMP-1 (p < 0.0001) and the higher plasma activity of MMP-2 (p < 0.0001) and MMP-9 (p < 0.0001). In the ARDS group, higher plasma levels of MMP-9 (p = 0.0339) and TIMP-1 (p = 0.0044) and the plasma activity of MMP-2 (p = 0.0258) and MMP-9 (p = 0.0021) compared to non-ARDS was observed. A positive correlation between the plasma levels of TIMP-1 and chest computed tomography (CT) score (ρ = 0.2302, p = 0.0160) was observed. At the T post, a reduction in plasma levels of TIMP-1 (p < 0.0001), whereas an increase in the plasma levels of MMP-9 was observed (p = 0.0088). Conclusions: The positive correlation between TIMP-1 with chest CT scores highlights its potential use as a marker of fibrotic burden. At T post, the increase in plasma levels of MMP-9 and the reduction in plasma levels of TIMP-1 suggested that inflammation and fibrosis resolution were still ongoing.

Chest CT features of COVID-19 in vaccinated versus unvaccinated patients: use of CT severity score and outcome analysis.

OBJECTIVES: To evaluate the impact of vaccination on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and moreover on coronavirus disease 2019 (COVID-19) pneumonia, by assessing the extent of lung disease using the CT severity score (CTSS). METHODS: Between September 2021 and February 2022, SARS-CoV-2 positive patients who underwent chest CT were retrospectively enrolled. Anamnestic and clinical data, including vaccination status, were obtained. All CT scans were evaluated by two readers using the CTSS, based on a 25-point scale. Univariate and multivariate logistic regression analyses were performed to evaluate the associations between CTSS and clinical or demographic variables. An outcome analysis was used to differentiate clinical outcome between vaccinated and unvaccinated patients. RESULTS: Of the 1040 patients (537 males, 503 females; median age 58 years), 678 (65.2%) were vaccinated and 362 (34.8%) unvaccinated. Vaccinated patients showed significantly lower CTSS compared to unvaccinated patients (p < 0.001), also when patients without lung involvement (CTSS = 0) were excluded (p < 0.001). Older age, male gender and lower number of doses administered were associated with higher CTSS, however, in the multivariate analysis, vaccination status resulted to be the variable with the strongest association with CTSS. Clinical outcomes were significantly worse in unvaccinated patients, including higher number of ICU admissions and higher mortality rates. CONCLUSIONS: Lung involvement during COVID-19 was significantly less severe in vaccinated patients compared with unvaccinated patients, who also showed worse clinical outcomes. Vaccination status was the strongest variable associated to the severity of COVID-related, more than age, gender, and number of doses administered.

Synergistic Effect between SARS-CoV-2 Wave and COVID-19 Vaccination on the Occurrence of Mild Symptoms in Healthcare Workers.

BACKGROUND: Since the beginning of the pandemic, five variants of epidemiological interest have been identified, each of them with its pattern of symptomology and disease severity. The aim of this study is to analyze the role of vaccination status in modulating the pattern of symptomatology associated with COVID-19 infection during four waves. METHODS: Data from the surveillance activity of healthcare workers were used to carry out descriptive analysis, association analyses and multivariable analysis. A synergism analysis between vaccination status and symptomatology during the waves was performed. RESULTS: Females were found at a higher risk of developing symptoms. Four SARS-CoV-2 waves were identified. Pharyngitis and rhinitis were more frequent during the fourth wave and among vaccinated subjects while cough, fever, flu syndrome, headache, anosmia, ageusia, arthralgia/arthritis and myalgia were more frequent during the first three waves and among unvaccinated subjects. A correlation was found between vaccination and the different waves in terms of developing pharyngitis and rhinitis. CONCLUSION: Vaccination status and viruses' mutations had a synergic effect in the mitigation of the symptomatology caused by SARS-CoV-2 in healthcare workers.

Blood Biomarkers from the Emergency Department Disclose Severe Omicron COVID-19-Associated Outcomes.

BACKGROUND: Since its outbreak, Coronavirus disease 2019 (COVID-19), a life-threatening respiratory illness, has rapidly become a public health emergency with a devastating social impact. Lately, the Omicron strain is considered the main variant of concern. Routine blood biomarkers are, indeed, essential for stratifying patients at risk of severe outcomes, and a huge amount of data is available in the literature, mainly for the previous variants. However, only a few studies are available on early routine biochemical blood biomarkers for Omicron-afflicted patients. Thus, the aim and novelty of this study were to identify routine blood biomarkers detected at the emergency room for the early prediction of severe morbidity and/or mortality. METHODS: 449 COVID-19 patients from Sapienza University Hospital of Rome were divided into four groups: (1) the emergency group (patients with mild forms who were quickly discharged); (2) the hospital ward group (patients that after the admission in the emergency department were hospitalized in a COVID-19 ward); (3) the intensive care unit (ICU) group (patients that after the admission in the emergency department required intensive assistance); (4) the deceased group (patients that after the admission in the emergency department had a fatal outcome). RESULTS: ANOVA and ROC data showed that high-sensitivity troponin-T (TnT), fibrinogen, glycemia, C-reactive protein, lactate dehydrogenase, albumin, D-dimer myoglobin, and ferritin for both men and women may predict lethal outcomes already at the level of the emergency department. CONCLUSIONS: Compared to previous Delta COVID-19 parallel emergency patterns of prediction, Omicron-induced changes in TnT may be considered other early predictors of severe outcomes.

Evaluation of BAFF, APRIL and CD40L in Ocrelizumab-Treated pwMS and Infectious Risk.

BACKGROUND: The anti-CD20 monoclonal antibody ocrelizumab has been widely employed in the treatment of people with multiple sclerosis (pwMS). However, its B-cell-depleting effect may induce a higher risk of infectious events and alterations in the secretion of B-cell-activating factors, such as BAFF, APRIL and CD40L. METHODS: The aim of this study was to investigate plasma BAFF, APRIL and CD40L levels and their relationship with infectious risk in ocrelizumab-treated pwMS at baseline (T0), at 6 months (T6) and at 12 months (T12) after starting the treatment. As a control group, healthy donors (HD) were enrolled too. RESULTS: A total of 38 pwMS and 26 HD were enrolled. At baseline, pwMS showed higher plasma BAFF (p < 0.0001), APRIL (p = 0.0223) and CD40L (p < 0.0001) levels compared to HD. Compared to T0, plasma BAFF levels were significantly increased at both T6 and T12 (p < 0.0001 and p < 0.0001, respectively). Whereas plasma APRIL and CD40L levels were decreased at T12 (p = 0.0003 and p < 0.0001, respectively). When stratifying pwMS according to the development of an infectious event during the 12-month follow-up period in two groups-with (14) and without an infectious event (24)-higher plasma BAFF levels were observed at all time-points; significantly, in the group with an infectious event compared to the group without an infectious event (T0: p < 0.0001, T6: p = 0.0056 and T12: p = 0.0400). Conclusions: BAFF may have a role as a marker of immune dysfunction and of infectious risk.

Application of machine learning approach in emergency department to support clinical decision making for SARS-CoV-2 infected patients.

To support physicians in clinical decision process on patients affected by Coronavirus Disease 2019 (COVID-19) in areas with a low vaccination rate, we devised and evaluated the performances of several machine learning (ML) classifiers fed with readily available clinical and laboratory data. Our observational retrospective study collected data from a cohort of 779 COVID-19 patients presenting to three hospitals of the Lazio-Abruzzo area (Italy). Based on a different selection of clinical and respiratory (ROX index and PaO2/FiO2 ratio) variables, we devised an AI-driven tool to predict safe discharge from ED, disease severity and mortality during hospitalization. To predict safe discharge our best classifier is an RF integrated with ROX index that reached AUC of 0.96. To predict disease severity the best classifier was an RF integrated with ROX index that reached an AUC of 0.91. For mortality prediction the best classifier was an RF integrated with ROX index, that reached an AUC of 0.91. The results obtained thanks to our algorithms are consistent with the scientific literature an accomplish significant performances to forecast safe discharge from ED and severe clinical course of COVID-19.

COVID-19 Affects Serum Brain-Derived Neurotrophic Factor and Neurofilament Light Chain in Aged Men: Implications for Morbidity and Mortality.

BACKGROUND AND METHODS: Severe COVID-19 is known to induce neurological damage (NeuroCOVID), mostly in aged individuals, by affecting brain-derived neurotrophic factor (BDNF), matrix metalloproteinases (MMP) 2 and 9 and the neurofilament light chain (NFL) pathways. Thus, the aim of this pilot study was to investigate BDNF, MMP-2, MMP-9, and NFL in the serum of aged men affected by COVID-19 at the beginning of the hospitalization period and characterized by different outcomes, i.e., attending a hospital ward or an intensive care unit (ICU) or with a fatal outcome. As a control group, we used a novelty of the study, unexposed age-matched men. We also correlated these findings with the routine blood parameters of the recruited individuals. RESULTS: We found in COVID-19 individuals with severe or lethal outcomes disrupted serum BDNF, NFL, and MMP-2 presence and gross changes in ALT, GGT, LDH, IL-6, ferritin, and CRP. We also confirmed and extended previous data, using ROC analyses, showing that the ratio MMPs (2 and 9) versus BDNF and NFL might be a useful tool to predict a fatal COVID-19 outcome. CONCLUSIONS: Serum BDNF and NFL and/or their ratios with MMP-2 and MMP-9 could represent early predictors of NeuroCOVID in aged men.

Breakthrough infections after COVID-19 vaccinations do not elicit platelet hyperactivation and are associated with high platelet-lymphocyte and low platelet-neutrophil aggregates.

Background: Severe COVID-19 is associated with an excessive immunothrombotic response and thromboinflammatory complications. Vaccinations effectively reduce the risk of severe clinical outcomes in patients with COVID-19, but their impact on platelet activation and immunothrombosis during breakthrough infections is not known. Objectives: To investigate how preemptive vaccinations modify the platelet-immune crosstalk during COVID-19 infections. Methods: Cross-sectional flow cytometry study of the phenotype and interactions of platelets circulating in vaccinated (n = 21) and unvaccinated patients with COVID-19, either admitted to the intensive care unit (ICU, n = 36) or not (non-ICU, n = 38), in comparison to matched SARS-CoV-2-negative patients (n = 48), was performed. Results: In the circulation of unvaccinated non-ICU patients with COVID-19, we detected hyperactive and hyperresponsive platelets and platelet aggregates with adaptive and innate immune cells. In unvaccinated ICU patients with COVID-19, most of whom had severe acute respiratory distress syndrome, platelets had high P-selectin and phosphatidylserine exposure but low capacity to activate integrin αIIbß3, dysfunctional mitochondria, and reduced surface glycoproteins. In addition, in the circulation of ICU patients, we detected microthrombi and platelet aggregates with innate, but not with adaptive, immune cells. In vaccinated patients with COVID-19, who had no acute respiratory distress syndrome, platelets had surface receptor levels comparable to those in controls and did not form microthrombi or platelet-granulocyte aggregates but aggregated avidly with adaptive immune cells. Conclusion: Our study provides evidence that vaccinated patients with COVID-19 are not associated with platelet hyperactivation and are characterized by platelet-leukocyte aggregates that foster immune protection but not excessive immunothrombosis. These findings advocate for the importance of vaccination in preventing severe COVID-19.

Quality of T-Cell Response to SARS-CoV-2 mRNA Vaccine in ART-Treated PLWH.

We investigated specific humoral and T-cell responses in people living with HIV (PLWH) before (T0), after two (T1) and after six months (T2) from the third dose of the BNT162b2 vaccine. Healthy donors (HD) were enrolled. The specific humoral response was present in most PLWH already after the second dose, but the third dose increased both the rate of response and its magnitude. Collectively, no significant differences were found in the percentage of responding T-cells between PLWH and HD. At T0, stratifying PLWH according to CD4 cell count, a lower percentage of responding T-cells in <200 cells/µL subgroup compared to >200 cells/µL one was observed. At T1, this parameter was comparable between the two subgroups, and the same result was found at T2. However, the pattern of co-expression of IFNγ, IL2 and TNFα in PLWH was characterized by a higher expression of TNFα, independently of CD4 cell count, indicating a persistent immunological signature despite successful ART. mRNA vaccination elicited a specific response in most PLWH, although the cellular one seems qualitatively inferior compared to HD. Therefore, an understanding of the T-cell quality dynamic is needed to determine the best vaccination strategy and, in general, the capability of immune response in ART-treated PLWH.

Multiple sclerosis-disease modifying therapies affect humoral and T-cell response to mRNA COVID-19 vaccine.

Background: The mRNA vaccines help protect from COVID-19 severity, however multiple sclerosis (MS) disease modifying therapies (DMTs) might affect the development of humoral and T-cell specific response to vaccination. Methods: The aim of the study was to evaluate humoral and specific T-cell response, as well as B-cell activation and survival factors, in people with MS (pwMS) under DMTs before (T0) and after two months (T1) from the third dose of vaccine, comparing the obtained findings to healthy donors (HD). All possible combinations of intracellular IFNγ, IL2 and TNFα T-cell production were evaluated, and T-cells were labelled "responding T-cells", those cells that produced at least one of the three cytokines of interest, and "triple positive T-cells", those cells that produced simultaneously all the three cytokines. Results: The cross-sectional evaluation showed no significant differences in anti-S antibody titers between pwMS and HD at both time-points. In pwMS, lower percentages of responding T-cells at T0 (CD4: p=0.0165; CD8: p=0.0022) and triple positive T-cells at both time-points compared to HD were observed (at T0, CD4: p=0.0007 and CD8: p=0.0703; at T1, CD4: p=0.0422 and CD8: p=0.0535). At T0, pwMS showed higher plasma levels of APRIL, BAFF and CD40L compared to HD (p<0.0001, p<0.0001 and p<0.0001, respectively) and at T1, plasma levels of BAFF were still higher in pwMS compared to HD (p=0.0022).According to DMTs, at both T0 and T1, lower anti-S antibody titers in the depleting/sequestering-out compared to the enriching-in pwMS subgroup were found (p=0.0410 and p=0.0047, respectively) as well as lower percentages of responding CD4+ T-cells (CD4: p=0.0394 and p=0.0004, respectively). Moreover, the depleting/sequestering-out subgroup showed higher percentages of IFNγ-IL2-TNFα+ T-cells at both time-points, compared to the enriching-in subgroup in which a more heterogeneous cytokine profile was observed (at T0 CD4: p=0.0187; at T0 and T1 CD8: p =0.0007 and p =0.0077, respectively). Conclusion: In pwMS, humoral and T-cell response to vaccination seems to be influenced by the different DMTs. pwMS under depleting/sequestering-out treatment can mount cellular responses even in the presence of a low positive humoral response, although the cellular response seems qualitatively inferior compared to HD. An understanding of T-cell quality dynamic is needed to determine the best vaccination strategy and in general the capability of immune response in pwMS under different DMT.

COVID-19 Severity and Androgen Receptor Polymorphism.

During the COVID-19 pandemic, the most severe form of the disease was most often seen in male patients. The aim of this study was to identify any male predispositions that could be used to predict the outcome of the disease and enable early intervention. We investigated CAG polymorphism in the androgen receptor gene and serum levels of testosterone and LH, which were considered as probably responsible for this predisposition. The study involved 142 patients who had recovered from COVID-19 at least three months previously and were classified according to their disease severity using the World Health Organization (WHO) classification. We observed a significant increase in the number of CAG repeats with increasing disease severity: the percentage of patients with more than 23 repeats increased two-fold from Grade I to Grade IV. Furthermore, testosterone levels were significantly lower in patients with severe disease. Reduced androgenic signaling could predispose men to a more severe form: low testosterone levels and a reduced androgen receptor activity (CAG > 23) expose the host to an excessive inflammatory response, leading downstream to the multi-organ damage seen in severe COVID-19.

Neuro-Axonal Damage and Alteration of Blood-Brain Barrier Integrity in COVID-19 Patients.

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.

Neurofilament assessment in patients with cervical dystonia.

We evaluated levels of serum neurofilament light chains (NfL), a known biomarker of neuroaxonal damage, in patients with cervical dystonia (CD) and healthy controls (HCs). CD patients had normal NfL levels supporting the hypothesis that CD may be considered as a functional network disorder rather than as a neurodegenerative disease.

Infectious risk in multiple sclerosis patients treated with disease-modifying therapies: A three-year observational cohort study.

BACKGROUND: The disease-modifying therapies (DMTs) largely used in multiple sclerosis (MS) may result in higher infectious risk. OBJECTIVE: We aimed to investigate the infectious risk in DMT-treated MS patients. METHODS: MS patients were evaluated for infectious risk before starting, switching or during DMT. RESULTS: In this three-year observational cohort study 174 MS patients were enrolled. Among them, 18 patients were anti-HBc + and 19 patients were QuantiFERON®-TB Gold In-Tube (QFT) + . No patients with anti-HBc + showed a detectable HBV-DNA and all started DMT. Among QTB + patients, 17 latent TB infections (LTBIs) and 2 active TB infections (TBIs) were identified. After one month of LTBI prophylaxis or TB treatment, respectively, all patients started DMTs.Overall, 149 started DMTs. During DMTs, one ocrelizumab-treated patient with anti-HBc + developed HBV reactivation and six patients (3 on natalizumab, 2 on ocrelizumab and 1 on IFN-ß) showed reactivation of HSV-1, with detectable plasma DNA. Finally, 1 cladribine-treated patient experienced VZV reactivation. All the reactivations of latent infections have been successfully treated. CONCLUSION: Screening of infectious diseases in DMT candidate MS patients helps to mitigate the infectious risk. During DMTs, a regular assessment of infectious risk allows to avoid discontinuing MS therapy and guarantees a higher degree of safety.

Early IgG / IgA response in hospitalized COVID-19 patients is associated with a less severe disease.

We determined the kinetics of anti-SARS-CoV-2 antibody response in fifteen hospitalized COVID-19 patients. Patients were divided into mild/moderate (mild, n = 1; moderate, n = 4) or severe (n = 10) and virus-specific anti-Nucleocapsid IgM, anti-Spike IgG and anti-Spike IgA were measured in serial serum samples collected 0 to 15 days after hospital admission. Surrogate neutralization assays were performed by testing inhibition of ACE-2 binding to Spike. In 3 patients (2 severe and 1 moderate case), serum antibodies and T-cell memory were monitored 6 months after baseline. Although IgM response tended to appear first, patients affected by less severe disease were more prone to an early IgG/IgA response. Neutralization of Spike binding to ACE2 correlated with anti-Spike IgG and IgA. IgG and IgA antibody response persisted at the 6 months follow-up. A recall T-cell response to the Spike antigen was observed in 2 out of 3 patients, not related to disease severity.

Chest computed tomography score, cycle threshold values and secondary infection in predicting COVID-19 mortality.

This retrospective and observational cohort study investigated chest computed tomography (CT) findings, cycle threshold (Ct) values in RT-PCR of SARS-CoV-2 and secondary infection occurrence to predict prognosis in COVID-19 patients. At hospital admission, CT findings and Ct values were collected. Microbiology tests performed after 48 hours from hospitalization were reviewed. According to in-hospital mortality, patients were grouped into non-survivors and survivors. Among 283 patients evaluated, in-hospital mortality rate was 13.8% (39/283). Secondary infection occurrence was 15.2% (43/283). Cut-off values for CT score >13.5 (AUC=0.682 p=0.0009) and for Ct <23.4 (AUC=0.749, p<0.0001) were predictive of death. Super-additive and synergic effects between high CT score plus secondary infection occurrence as well as between high CT score plus low Ct values affecting patient's outcome were observed. Chest CT score and Ct values in RT-PCR of SARS-CoV-2 could have a combination role for severity stratification of COVID-19 patients.