COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context

Background and objectives: It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population. Methods: Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ2 test, and the risk excess was quantified by risk ratios (RRs). Results: The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (p < 0.001), RR = 2.19 for ICU admission (p < 0.001), and RR = 2.43 for death (p < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, p = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, p = 0.04). Discussion: Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

RET/PTC rearragements in Hashimoto’s thyroiditis nodules.

An association between Hashimoto thyroiditis (HT) and thyroid carcinoma, particularly papillary thyroid carcinoma (PTC), has been postulated for decades, although definitive molecular links remain elusive. The majority of PTC is characterized by alterations or rearrangements along the MAPK signaling cascade. Activation of RET/PTC oncogene has been reported in both non-neoplastic and neoplastic HT thyroid follicular cells (Tallini et al., 2006), but the issue is still controversial. We have investigated cells from HT nodules for RET rearrangement, using interphase fluorescence in situ hybridization (I-FISH). Dual-color I-FISH experiments, using home-brew breakapart DNA probe, able to detect RET disruptions were performed on 207 fine needle aspiration biopsies on unselected nodules from 168 patients and 38 corresponding surgical samples. Normal tissue nuclei cutoff value (mean ±3DS) was ≥ 3%. In addition, RET/PTC was investigated by RT-PCR. Coexistent overt autoimmune thyroid disease (AITD) was assessed by serological (antithyroid autoantibodies, ATA), clinical and echographic data. RET breakage (FISH+) was observed in 13/207 (6.3%) samples. RET/PTC was confirmed by RT-PCR (RT-PCR+) in 2/12 available FISH+ nodules (16.6%). RT-PCR+ corresponded to FISH+ value ≥ 8%. No correlation between RET rearrangement and ATA (5/92 patients ATA +; 8/115 ATA-), or between AITD (6/78 AITD+; 7/129 AITD-) was observed. Nodules with RET disruption were observed along the whole cytological spectrum, with prevalence significantly higher in suspect or malignant cytology (13.6% in 66 TIR 3-5 vs 3.1% in 129 TIR 2 nodules: p=0.005 by X2test). 7 of 13 FISH+ nodules were surgically removed and available for I-FISH. RET breakage was confirmed in 3 samples, all of which were classified as classic PTC type. According to our results, RET rearrangement does not seem to correlate with the HT phenotype. The number of FISH+ nodules within the cytological classes, increases according to the risk of malignancy. Sensitivity of breakapart I-FISH strategy, able to detect gene disruption in single nuclei, could explain the difference between I-FISH and RT-PCR results. Since in our experimental condition, RET-PTC m-RNA transcript can be detected in ≥ 8% FISH+ samples , the oncogenic potential of nodules below this value remains to be clarified, and FISH+ nodules with benign cytology should be considered for a careful follow-up

RET/PTC rearrangement in Hashimoto’s thyroiditis nodules: contribution to an ongoing debate.

An association between Hashimoto thyroiditis (HT) and thyroid carcinoma, has been postulated for decades, although definitive molecular links remain elusive. Activation of RET/PTC oncogene (typical of papillary thyroid carcinoma) has been reported in both non-neoplastic and neoplastic HT thyroid follicular cells (Tallini et al., 2006), but the issue is still controversial. To contribute new insight to this issue, we have investigated RET rearrangement on 207 fine needle aspiration biopsies on unselected nodules from 168 patients and 38 corresponding surgical samples. I-FISH with a homebrew-breakpart DNA probe was used. Normal tissue nuclei cutoff value (mean ± 3DS) was 3%. In addition, RET/PTC was investigated by RT-PCR. Coexistent overt autoimmune thyroid disease (AITD) was assessed by serological (antithyroid autoantibodies, ATA), clinical and echographic data. RET breakage (FISH+) was observed in 6.3% samples. RET/PTC was confirmed by RT-PCR (RT-PCR+) in 23% FISH+ nodules. RT-PCR+ corresponded to FISH+ value ≥ 6,8%. No correlation between RET rearrangement and ATA (5/92 nodules ATA +; 8/115 ATA-), or between AITD (6/78 AITD+; 7/129 AITD-) was observed. Nodules with FISH+ were observed along the whole cytological spectrum, with prevalence significantly higher in suspect or malignant cytology (13.6% TIR 3-5 vs 3.1% TIR 2 nodules). 7/13 FISH+ nodules were surgically removed and available for I-FISH. FISH+ was confirmed in 3 samples, classified as PTC classic type. Our results suggest no association between RET rearrangement and HT. The percentage of FISH+ nodules increases according to the risk of malignancy. Difference between I-FISH and RT-PCR results was observed, presumibly due to the sensitivity of I-FISH strategy. Since we detected RET-PTC m-RNA transcript in ≥ 6,8% FISH+ samples, the oncogenic potential of nodules below this value remains to be clarified, and FISH+ nodules with benign cytology should be considered for a careful follow-up