Longitudinal characterisation of B and T-cell immune responses after the booster dose of COVID-19 mRNA-vaccine in people with multiple sclerosis using different disease-modifying therapies.

BACKGROUND: The decline of humoral response to COVID-19 vaccine led to authorise a booster dose. Here, we characterised the kinetics of B-cell and T-cell immune responses in patients with multiple sclerosis (PwMS) after the booster dose. METHODS: We enrolled 22 PwMS and 40 healthcare workers (HCWs) after 4-6 weeks from the booster dose (T3). Thirty HCWs and 19 PwMS were also recruited 6 months (T2) after the first dose. Antibody response was measured by anti-receptor-binding domain (RBD)-IgG detection, cell-mediated response by an interferon (IFN)-γ release assay (IGRA), Th1 cytokines and T-cell memory profile by flow cytometry. RESULTS: Booster dose increased anti-RBD-IgG titers in fingolimod-treated, cladribine-treated and IFN-ß-treated patients, but not in ocrelizumab-treated patients, although antibody titres were lower than HCWs. A higher number of fingolimod-treated patients seroconverted at T3. Differently, T-cell response evaluated by IGRA remained stable in PwMS independently of therapy. Spike-specific Th1-cytokine response was mainly CD4+ T-cell-mediated, and in PwMS was significantly reduced (p<0.0001) with impaired IL-2 production compared with HCWs at T3. In PwMS, total Th1 and IFN-γ CD4+ T-cell responders to spike protein were increased from T2 to T3.Compared with HCWs, PwMS presented a higher frequency of CD4+ and CD8+ terminally differentiated effector memory cells and of CD4+ effector memory (TEM) cells, independently of the stimulus suggesting the association of this phenotype with MS status. CD4+ and CD8+ TEM cell frequency was further increased at T3 compared with T2. CONCLUSIONS: COVID-19 vaccine booster strengthens humoral and Th1-cell responses and increases TEM cells in PwMS.

Third dose of SARS-CoV2 mRNA vaccination produces robust persistent cellular and humoral immune responses in liver transplant recipients.

Weaker responses have been described after two doses of anti-SARS-CoV2 vaccination in liver transplant recipients (LTRs). At the Italian National Institute for Infectious Diseases, 122 LTRs (84% males, median age 64 years) were tested for humoral and cell-mediated immune response after a third doses of anti-SARS-CoV2 mRNA vaccines. Humoral response was measured by quantifying anti-receptor binding domain and neutralizing antibodies; cell-mediated response was measured by quantifying IFN-γ after stimulation of T cells with SARS-CoV-2-specific peptides. Humoral and cellular responses improved significantly compared to the second vaccine dose; 86.4% of previous non-responders to the first 2 vaccine doses (N = 22) became responders. Mycophenolate mofetil-containing regimens were not associated with lower response rates to a third vaccine; shorter time since transplantation (<6 years) was associated with lower humoral and cellular responses to third vaccine. Protective antibodies against Omicron variant were detected in 60% of patients 12 weeks after third vaccine dose.

Dynamic Evolution of Humoral and T-Cell Specific Immune Response to COVID-19 mRNA Vaccine in Patients with Multiple Sclerosis Followed until the Booster Dose.

This study characterizes antibody and T-cell immune responses over time until the booster dose of COronaVIrus Disease 2019 (COVID-19) vaccines in patients with multiple sclerosis (PwMS) undergoing different disease-modifying treatments (DMTs). We prospectively enrolled 134 PwMS and 99 health care workers (HCWs) having completed the two-dose schedule of a COVID-19 mRNA vaccine within the last 2-4 weeks (T0) and followed them 24 weeks after the first dose (T1) and 4-6 weeks after the booster (T2). PwMS presented a significant reduction in the seroconversion rate and anti-receptor-binding domain (RBD)-Immunoglobulin (IgG) titers from T0 to T1 (p < 0.0001) and a significant increase from T1 to T2 (p < 0.0001). The booster dose in PwMS showed a good improvement in the serologic response, even greater than HCWs, as it promoted a significant five-fold increase of anti-RBD-IgG titers compared with T0 (p < 0.0001). Similarly, the T-cell response showed a significant 1.5- and 3.8-fold increase in PwMS at T2 compared with T0 (p = 0.013) and T1 (p < 0.0001), respectively, without significant modulation in the number of responders. Regardless of the time elapsed since vaccination, most ocrelizumab- (77.3%) and fingolimod-treated patients (93.3%) showed only a T-cell-specific or humoral-specific response, respectively. The booster dose reinforces humoral- and cell-mediated-specific immune responses and highlights specific DMT-induced immune frailties, suggesting the need for specifically tailored strategies for immune-compromised patients to provide primary prophylaxis, early SARS-CoV-2 detection and the timely management of COVID-19 antiviral treatments.

Humoral and Cellular Immune Response Elicited by mRNA Vaccination Against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in People Living With Human Immunodeficiency Virus Receiving Antiretroviral Therapy Based on Current CD4 T-Lymphocyte Count.

BACKGROUND: Data on SARS-CoV-2 vaccine immunogenicity in PLWH are currently limited. Aim of the study was to investigate immunogenicity according to current CD4 T-cell count. METHODS: PLWH on ART attending a SARS-CoV-2 vaccination program, were included in a prospective immunogenicity evaluation after receiving BNT162b2 or mRNA-1273. Participants were stratified by current CD4 T-cell count (poor CD4 recovery, PCDR: <200/mm3; intermediate CD4 recovery, ICDR: 200-500/mm3; high CD4 recovery, HCDR: >500/mm3). RBD-binding IgG, SARS-CoV-2 neutralizing antibodies (nAbs) and IFN-γ release were measured. As control group, HIV-negative healthcare workers (HCWs) were used. FINDINGS: Among 166 PLWH, after 1 month from the booster dose, detectable RBD-binding IgG were elicited in 86.7% of PCDR, 100% of ICDR, 98.7% of HCDR, and a neutralizing titre ≥1:10 elicited in 70.0%, 88.2%, and 93.1%, respectively. Compared to HCDR, all immune response parameters were significantly lower in PCDR. After adjusting for confounders, current CD4 T-cell <200/mm3 significantly predicted a poor magnitude of anti-RDB, nAbs and IFN-γ response. As compared with HCWs, PCDR elicited a consistently reduced immunogenicity for all parameters, ICDR only a reduced RBD-binding antibody response, whereas HCDR elicited a comparable immune response for all parameters. CONCLUSION: Humoral and cell-mediated immune response against SARS-CoV-2 were elicited in most of PLWH, albeit significantly poorer in those with CD4 T-cell <200/mm3 versus those with >500 cell/mm3 and HIV-negative controls. A lower RBD-binding antibody response than HCWs was also observed in PLWH with CD4 T-cell 200-500/mm3, whereas immune response elicited in PLWH with a CD4 T-cell >500/mm3 was comparable to HIV-negative population.

Coordinated cellular and humoral immune responses after two-dose SARS-CoV2 mRNA vaccination in liver transplant recipients.

Limited data are available on risks and benefits of anti-SARS-CoV2 vaccination in solid organ transplant recipients, and weaker responses have been described. At the Italian National Institute for Infectious Diseases, 61 liver transplant recipients underwent testing to describe the dynamics of humoral and cell-mediated immune response after two doses of anti-SARS-CoV2 mRNA vaccines and compared with 51 healthy controls. Humoral response was measured by quantifying both anti-spike and neutralizing antibodies; cell-mediated response was measured by PBMC proliferation assay with IFN-γ and IL-2 production. Liver transplant recipients showed lower response rates compared with controls in both humoral and cellular arms; shorter time since transplantation and multi-drug immunosuppressive regimen containing mycophenolate mofetil were predictive of reduced response to vaccination. Specific antibody and cytokine production, though reduced, were highly correlated in transplant recipients.

Results of an interventional HIV testing programme in the context of a mpox (formerly monkeypox) vaccination campaign in Latium Region, Italy, August to October 2022.

HIV testing was offered to 2,185 people receiving mpox (formerly monkeypox) vaccination, who reported not being HIV positive. Among them 390 were current PrEP users, and 131 had taken PrEP in the past. Of 958 individuals consenting testing, six were newly diagnosed with HIV. Two patients had symptomatic primary HIV infection. None of the six patients had ever taken PrEP. Mpox vaccination represents an important opportunity for HIV testing and counselling about risk reduction and PrEP.

Epidemiological, clinical and virological characteristics of four cases of monkeypox support transmission through sexual contact, Italy, May 2022.

Since May 2022, an outbreak of monkeypox has been ongoing in non-endemic countries. We report four cases in Italy in young adult men reporting condomless sexual intercourse. The patients are in good clinical condition with no need for specific antiviral drugs. Biological samples from seminal fluid were positive for monkeypox viral DNA. For many other viruses found in semen there is no evidence of sexual transmission. The possibility of sexual transmission of monkeypox virus needs to be investigated.

The burden of Clostridioides difficile infection in COVID-19 patients: A systematic review and meta-analysis.

OBJECTIVES: The main aim of this systematic review and meta-analysis was to assess the proportion of confirmed COVID-19 patients with Clostridioides difficile infection (CDI) and to describe risk factors and outcome of these patients. METHODS: MEDLINE and Cochrane Central Register of Controlled Trials databases were searched up to July 15, 2021. We included studies reporting data on CDI occurring in patients with a confirmed diagnosis of COVID-19. We pooled proportion of CDI patients using a random effects model (DerSimonian-Laird method) stabilising the variances using the Freeman-Tukey double arcsine transformation. RESULTS: Thirteen studies were included in the systematic review. All the studies retrospectively collected data between February 2020 and February 2021. The reported CDI incidence rates ranged from 1.4 to 4.4 CDI cases per 10,000 patient-days. Seven studies reported data on the number of COVID-19 patients who developed CDI and the total number of COVID-19 patients in the study period and were included in the meta-analysis, comprising 23,697 COVID-19 patients. The overall pooled proportion of COVID-19 patients who had CDI was 1% [95% confidence interval: 1-2]. Among studies reporting CDI occurrence in patients with and without COVID-19, the majority of them reported reduced or unchanged CDI rates compared to pre-COVID period. CONCLUSIONS: CDI is a relevant issue for COVID-19 patients. Adherence to infection prevention and control measures and to the antimicrobial stewardship principles is crucial even during the COVID-19 pandemic.

COVID-19 in people living with HIV: Clinical implications of dynamics of the immune response to SARS-CoV-2.

Little evidence on coronavirus disease 2019 (COVID-19) in people living with HIV (PLWH) is currently available. We reported clinical and viroimmunological data of all HIV-positive patients admitted to our center with COVID-19 from March 1 to May 12, 2020. Overall, five patients were included: all were virologically-suppressed on antiretroviral therapy and CD4+ count was greater than 350 cell/mm3 in all but two patients. Although all patients had evidence of pneumonia on admission, only one developed respiratory failure. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was never detected from nasopharyngeal swabs in two patients, whereas in the others, viral clearance occurred within a maximum of 43 days. Immunoglobulin G production was elicited in all patients and neutralizing antibodies in all but one patient. Specific-T-cell response developed in all patients but was stronger in those with the more severe presentations. Similarly, the highest level of proinflammatory cytokines was found in the only patient experiencing respiratory failure. Despite a mild presentation, patients with more pronounced immunosuppression showed high degrees of both cytokines production and immune activation. Our study did not find an increased risk and severity of COVID-19 in PLWH. Adaptative cellular immune response to SARS-CoV-2 appeared to correlate to disease severity. The mild clinical picture showed in advanced HIV patients, despite a significant T-cell activation and inflammatory profile, suggests a potential role of HIV-driven immunological dysregulation in avoiding immune-pathogenetic processes. However, other possible explanations, as a protective role of certain antiretroviral drugs, should be considered. Further larger studies are needed to better clarify the impact of HIV infection on COVID-19.

Predicting the protective humoral response to a SARS-CoV-2 mRNA vaccine.

OBJECTIVES: Simple and standardized methods to establish correlates to vaccine-elicited SARS-CoV-2 protection are needed. METHODS: An observational study on antibody response to a mRNA vaccine (Comirnaty) was performed on health care workers (V, n=120). Recovered COVID-19 patients (N, n=94) were used for comparison. Antibody response was evaluated by a quantitative anti-receptor binding domain IgG (anti-RBD) commercial assay and by virus microneutralization test (MNT), in order to establish a threshold of anti-RBD binding antibody units (BAU) able to predict a robust (≥1:80) MNT titer. RESULTS: Significant correlation between BAU and MNT titers was found in both V and N, being stronger in V (rs=0.91 and 0.57 respectively, p<0.001); a higher incremental trend starting from MNT titer 1:80 was observed in the V group. The 99% probability of high MNT titer (≥1:80) was reached at 1,814 and 3,564 BAU/mL, and the area under the receiver operating characteristic (ROC) curve was 0.99 (CI: 0.99-1.00) and 0.78 (CI: 0.67-0.86) in V and N, respectively. CONCLUSIONS: A threshold of 2,000 BAU/mL is highly predictive of strong MNT response in vaccinated individuals and may represent a good surrogate marker of protective response. It remains to be established whether the present results can be extended to BAU titers obtained with other assays.