Effect of SARS-CoV-2 mRNA vaccination in MS patients treated with disease modifying therapies.

BACKGROUND: In patients with Multiple Sclerosis (pwMS) disease-modifying therapies (DMTs) affects immune response to antigens. Therefore, post-vaccination serological assessments are needed to evaluate the effect of the vaccine on SARS-CoV-2 antibody response. METHODS: We designed a prospective multicenter cohort study enrolling pwMS who were scheduled for SARS-Cov-2 vaccination with mRNA vaccines (BNT162b2, Pfizer/BioNTech,Inc or mRNA-1273, Moderna Tx,Inc). A blood collection before the first vaccine dose and 4 weeks after the second dose was planned, with a centralized serological assessment (electrochemiluminescence immunoassay, ECLIA, Roche-Diagnostics). The log-transform of the antibody levels was analyzed by multivariable linear regression. FINDINGS: 780 pwMS (76% BNT162b2 and 24% mRNA-1273) had pre- and 4-week post-vaccination blood assessments. 87 (11·2%) were untreated, 154 (19·7%) on ocrelizumab, 25 (3·2%) on rituximab, 85 (10·9%) on fingolimod, 25 (3·2%) on cladribine and 404 (51·7%) on other DMTs. 677 patients (86·8%) had detectable post-vaccination SARS-CoV-2 antibodies. At multivariable analysis, the antibody levels of patients on ocrelizumab (201-fold decrease (95%CI=128-317), p < 0·001), fingolimod (26-fold decrease (95%CI=16-42), p < 0·001) and rituximab (20-fold decrease (95%CI=10-43), p < 0·001) were significantly reduced as compared to untreated patients. Vaccination with mRNA-1273 resulted in a systematically 3·25-fold higher antibody level (95%CI=2·46-4·27) than with the BNT162b2 vaccine (p < 0·001). The antibody levels on anti-CD20 therapies correlated to the time since last infusion, and rituximab had longer intervals (mean=386 days) than ocrelizumab patients (mean=129 days). INTERPRETATION: In pwMS, anti-CD20 treatment and fingolimod led to a reduced humoral response to mRNA-based SARS-CoV-2 vaccines. As mRNA-1273 elicits 3·25-higher antibody levels than BNT162b2, this vaccine may be preferentially considered for patients under anti-CD20 treatment or fingolimod. Combining our data with those on the cellular immune response to vaccines, and including clinical follow-up, will contribute to better define the most appropriate SARS-CoV-2 vaccine strategies in the context of DMTs and MS. FUNDING: FISM[2021/Special-Multi/001]; Italian Ministry of Health'Progetto Z844A 5 × 1000'.

Rapid diagnosis of SARS-CoV-2 pneumonia on lower respiratory tract specimens.

BACKGROUND: The ongoing SARS-CoV-2 pandemic requires the availability of accurate and rapid diagnostic tests, especially in such clinical settings as emergency and intensive care units. The objective of this study was to evaluate the diagnostic performance of the Vivalytic SARS-CoV-2 rapid PCR kit in lower respiratory tract (LRT) specimens. METHODS: Consecutive LRT specimens (bronchoalveolar lavage and bronchoaspirates) were collected from Intensive Care Units of San Martino Hospital (Genoa, Italy) between November 2020 and January 2021. All samples underwent RT-PCR testing by means of the Allplex™ SARS-CoV-2 assay (Seegene Inc., South Korea). On the basis of RT-PCR results, specimens were categorized as negative, positive with high viral load [cycle threshold (Ct) ≤ 30] and positive with low viral load (Ct of 31-35). A 1:1:1 ratio was used to achieve a sample size of 75. All specimens were subsequently tested by means of the Vivalytic SARS-CoV-2 rapid PCR assay (Bosch Healthcare Solutions GmbH, Germany). The diagnostic performance of this assay was assessed against RT-PCR through the calculation of accuracy, Cohen's κ, sensitivity, specificity and expected positive (PPV) and negative (NPV) predictive values. RESULTS: The overall diagnostic accuracy of the Vivalytic SARS-CoV-2 was 97.3% (95% CI: 90.9-99.3%), with an excellent Cohen's κ of 0.94 (95% CI: 0.72-1). Sensitivity and specificity were 96% (95% CI: 86.5-98.9%) and 100% (95% CI: 86.7-100%), respectively. In samples with high viral loads, sensitivity was 100% (Table 1). The distributions of E gene Ct values were similar (Wilcoxon's test: p = 0.070), with medians of 35 (IQR: 25-36) and 35 (IQR: 25-35) on Vivalytic and RT-PCR, respectively (Fig. 1). NPV and PPV was 92.6% and 100%, respectively. Table 1 Demographic characteristics and data sample type of the study cases (N = 75) Male, N (%) 56 (74.6%) Age (yr), Median (IQR) 65 (31-81) BAS, N (%) 43 (57.3%)  Negative 30.2%  Positive-High viral load [Ct ≤ 30] 27.9%  Positive-Low viral load [Ct 31-35] 41.9% BAL, N (%) 32 (42.7%)  Negative 37.5%  Positive-High viral load [Ct ≤ 30] 40.6%  Positive-Low viral load [Ct 31-35] 21.9% Data were expressed as proportions for categorical variables. Specimens were categorized into negative, positive with high viral load [cycle threshold (Ct) ≤ 30] and positive with low viral load (Ct of 31-35). BAS bronchoaspirates, BAL bronchoalveolar lavage, Ct cycle threshold Fig. 1 Distribution of E gene cycle threshold values of the rapid PCR and RT-PCR CONCLUSIONS: Vivalytic SARS-CoV-2 can be used effectively on LRT specimens following sample liquefaction. It is a feasible and highly accurate molecular procedure, especially in samples with high viral loads. This assay yields results in about 40 min, and may therefore accelerate clinical decision-making in urgent/emergency situations.

Comparative diagnostic performance of rapid antigen detection tests for COVID-19 in a hospital setting.

BACKGROUND: The availability of accurate and rapid diagnostic tools for COVID-19 is essential for tackling the ongoing pandemic. Our study aimed to quantify the performance of available antigen-detecting rapid diagnostic tests (Ag-RDTs) in a real-world hospital setting. METHODS: In this retrospective analysis, the diagnostic performance of 7 Ag-RDTs was compared with real-time reverse transcription quantitative polymerase chain reaction assay in terms of sensitivity, specificity and expected predictive values. RESULTS: A total of 321 matched Ag-RDTreal-time reverse transcription quantitative polymerase chain reaction samples were analyzed retrospectively. The overall sensitivity and specificity of the Ag-RDTs was 78.7% and 100%, respectively. However, a wide range of sensitivity estimates by brand (66.0%-93.8%) and cycle threshold (Ct) cut-off values (Ct <25: 96.2%; Ct 30-35: 31.1%) was observed. The optimal Ct cut-off value that maximized sensitivity was 29. CONCLUSIONS: The routine use of Ag-RDTs may be convenient in moderate-to-high intensity settings when high volumes of specimens are tested every day. However, the diagnostic performance of the commercially available tests may differ substantially.

Prevalence and prognostic value of cardiac troponin in elderly patients hospitalized for COVID-19.

BACKGROUND: Increases in cardiac troponin (cTn) in coronavirus disease 2019 (COVID-19) have been associated with worse prognosis. Nonetheless, data about the significance of cTn in elderly subjects with COVID-19 are lacking. METHODS: From a registry of consecutive patients with COVID-19 admitted to a hub hospital in Italy from 25/02/2020 to 03/07/2020, we selected those ≥ 60 year-old and with cTnI measured within three days from the molecular diagnosis of SARS-CoV-2 infection. When available, a second cTnI value within 48 h was also extracted. The relationship between increased cTnI and all-cause in-hospital mortality was evaluated by a Cox regression model and restricted cubic spline functions with three knots. RESULTS: Of 343 included patients (median age: 75.0 (68.0-83.0) years, 34.7% men), 88 (25.7%) had cTnI above the upper-reference limit (0.046 µg/L). Patients with increased cTnI had more comorbidities, greater impaired respiratory exchange and higher inflammatory markers on admission than those with normal cTnI. Furthermore, they died more (73.9%vs. 37.3%, P < 0.001) over 15 (6-25) days of hospitalization. The association of elevated cTnI with mortality was confirmed by the adjusted Cox regression model (HR = 1.61, 95%CI: 1.06-2.52, P = 0.039) and was linear until 0.3 µg/L, with a subsequent plateau. Of 191 (55.7%) patients with a second cTnI measurement, 49 (25.7%) had an increasing trend, which was not associated with mortality (univariate HR = 1.39, 95%CI: 0.87-2.22, P = 0.265). CONCLUSIONS: In elderly COVID-19 patients, an initial increase in cTn is common and predicts a higher risk of death. Serial cTn testing may not confer additional prognostic information.

Tocilizumab and steroid treatment in patients with COVID-19 pneumonia.

INTRODUCTION: Coronavirus 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. METHODS: This 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). RESULTS: Overall, 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. CONCLUSION: Early adjunctive treatment with tocilizumab, methylprednisolone or both may improve outcomes in non-intubated patients with COVID-19 pneumonia.