Evaluation of the Factors Associated with Reinfections towards SARS-CoV-2 Using a Case Control Design.

OBJECTIVE: The risk of reinfection with SARS-CoV-2 has been rapidly increased with the circulation of concerns about variants. So, the aim of our study was to evaluate the factors that increase the risk of this reinfection in healthcare workers compared to those who have never been positive and those who have had only one positivity. METHODS: A case-control study was carried out at the Teaching Hospital Policlinico Umberto I in Rome, Sapienza University of Rome, in the period between 6 March 2020 and 3 June 2022. Cases are healthcare workers who have developed a reinfection with the SARS-CoV-2 virus, while controls were either healthcare workers who tested positive once or those who have never tested positive for SARS-CoV-2. RESULTS: 134 cases and 267 controls were recruited. Female gender is associated with a higher odds of developing reinfection (OR: 2.42; 95% CI: 1.38-4.25). Moreover, moderate or high alcohol consumption is associated with higher odds of reinfection (OR: 1.49; 95% CI: 1.19-1.87). Diabetes is also associated with higher odds of reinfection (OR: 3.45; 95% CI: 1.41-8.46). Finally, subjects with increased red blood cell counts have higher odds of reinfection (OR: 1.69; 95% CI: 1.21-2.25). CONCLUSION: From the prevention point of view, these findings indicate that particular attention should be paid to subjects with diabetes mellitus, women and alcoholic drinkers. These results could also suggest that contact tracing represents a fundamental approach model against the SARS-CoV-2 pandemic, together with the health information of participants.

Anti-N SARS-CoV-2 assays for evaluation of natural viral infection.

BACKGROUND: The 2019 coronavirus (COVID-19) epidemic, required the development of different diagnostic tests. While reverse transcriptase real-time PCR (RT-PCR) remains the first-line test of choice in acute infection diagnosis, anti-N antibodies serological assays provide a valuable tool to differentiate natural SARS-CoV-2 immunological response from that induced by vaccination, thus the goal of our study was to evaluate three serological tests agreement for these antibodies detection. METHODS: Three anti-N different tests were examined in 74 sera from patients referred or not COVID infection: immunochromatographic rapid test (Panbio™ COVID-19 IgG/IgM Rapid Test Device Abbott, Germany), ELISA kit (NovaLisa® SARS-CoV-2 IgG and IgM NovaTech Immunodiagnostic GmbH, Germany) and ECLIA immunoassay (Elecsys® Anti-SARS-CoV-2 Roche Diagnostics, Manheim, Germany). RESULTS: Qualitative comparison of the three analytical methods revealed a moderate agreement between ECLIA immunoassay and immunochromatographic rapid test (Cohen kappa coefficient κ = 0.564). Correlation analysis indicated weak positive correlation between total Ig (IgT) detected by ECLIA immunoassay and IgG by ELISA test (p < 0.0001), the analysis of ECLIA IgT and IgM ELISA detected, showed no statistical correlation. CONCLUSION: Comparison between of three analytical systems available for anti-N SARS-CoV-2 IgG and IgM antibodies showed a general agreement when compared to detect total and G class immunoglobulins, while doubtful or discordant results have been highlighted for IgT and IgM class. Anyway, all the tests examined provide reliable results to assess the serological status of SARS-CoV-2 infected patients.

Torque teno virus (TTV): A gentle spy virus of immune status, predictive marker of seroconversion to COVID-19 vaccine in kidney and lung transplant recipients.

To date, no comprehensive marker to monitor the immune status of patients is available. Given that Torque teno virus (TTV), a known human virome component, has previously been identified as a marker of immunocompetence, it was retrospectively investigated whether TTV viral load may also represent a marker of ability to develop antibody in response to COVID-19-BNT162B2 vaccine in solid organ transplant recipients (SOT). Specifically, 273 samples from 146 kidney and 26 lung transplant recipients after successive doses of vaccine were analyzed. An inverse correlation was observed within the TTV copy number and anti-Spike IgG antibody titer with a progressive decrease in viremia the further away from the transplant date. Analyzing the data obtained after the second dose, a significant difference in TTV copy number between responsive and nonresponsive patients was observed, considering a 5 log10 TTV copies/mL threshold to discriminate between the two groups. Moreover, for 86 patients followed in their response to the second and third vaccination doses a 6 log10 TTV copies/mL threshold was used to predict responsivity to the booster dose. Although further investigation is necessary, possibly extending the analysis to other patient categories, this study suggests that TTV can be used as a good marker of vaccine response in transplant patients.

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.

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.

Evaluation of Immunogenicity to Three Doses of the SARS-CoV-2 BNT162b2 mRNA Vaccine in Lung Transplant Patients.

The aim of the study was to explore the humoral and T-cell response in lung transplant (LuT) patients. Two-time points were considered, before (T0) and after (Tpost) the third dose of the BNT162b2 mRNA vaccine, comparing LuT with healthy donors (HD). LuT patients showed a lower serologic response against SARS-CoV-2 compared with HD at both time-points (p = 0.0001 and p = 0.0011, respectively). A lower percentage of IFNγ+orIL2+orTNFα+CD4+ and CD8+ T-cells LuT patients was observed in LuT patients compared with HD at T0 (CD4+: p = 0.0001; CD8+: p = 0.0005) and Tpost (CD4+: p = 0.0028; CD8+: p = 0.0114), as well as in the percentage of IFNγ+IL2+TNFα+CD4+ T-cells (T0: p = 0.0247; Tpost: p = 0.0367). Finally, at Tpost, a lower percentage of IFNγ+IL2+TNFα+ CD8+ T-cells in LuT patients compared with HD was found (p = 0.0147). LuT patients were stratified according to the lowest cut-off value for the detection of a humoral response (4.81 BAU/mL) at T0, into responder (R) and non-responder (NR) groups. In the R group, no differences in the percentage of IFNγ+or IL2+orTNFα+ and IFNγ+IL2+TNFα+CD4+ and CD8+ T-cells compared with HD at both time-points were observed. Otherwise, in the NR group, lower percentages of IFNγ+IL2+TNFα+CD4+ T-cells compared with the R group (T0: p = 0.0159; Tpost: p = 0.0159), as well as compared with the HD, at both time-points, were observed (T0: p = 0.0064; Tpost: p = 0.0064). These data seem to confirm that some LuT patients can mount cellular responses even in the absence of a positive humoral response (>33.8 BAU/mL), although this cellular response is dysfunctional and partially detrimental.

Serological Response and Relationship with Gender-Sensitive Variables among Healthcare Workers after SARS-CoV-2 Vaccination.

Vaccine-induced immunity is a key strategy in the long-term control of the COVID-19 pandemic. The aim of our study was to explore the relationship between mRNA vaccine-induced antibodies and gender-sensitive variables among healthcare workers. Two thousand-sixty-five volunteers who received the BNT162b2 vaccine were enrolled in the study and followed up. Demographic, clinical, and social variables (educational level, marital status, occupation, childcare) were evaluated through a self-administered questionnaire. Anti-Spike (S) IgG were measured at 1 month (T1) and at 5 months (T2) after the second vaccine dose. At T1, median anti-S IgG values were 693 [394->800] AU/mL (1 AU = 2.6 BAU). Values > 800 AU/mL (2080 BAU/mL) were directly associated with a previous COVID-19 (p < 0.001) infection and inversely with age (p < 0.001), smoking habit (p < 0.001), and autoimmune diseases (p < 0.001). At T2, a significant decreasing in anti-S IgG values was observed (187 [81-262] AU/mL), with a median decrease of 72 [60-82]%. On multivariate data analysis, a reduction of more than 82% was directly associated with male sex (p < 0.021), age (p < 0.001), smoking (p = 0.038), hypertension (p = 0.042), and, inversely, with previous COVID-19 infection (p < 0.001) and being "cohabiting" (p = 0.005). Our findings suggest that demographic, clinical, and social variables play a role in anti-S IgG values decreasing in long-term follow up and should be considered to find personalized vaccine schedules.

Pfizer-BioNTech COVID-19 Vaccine in Gynecologic Oncology Patients: A Prospective Cohort Study.

OBJECTIVE: To evaluate the safety and immunogenicity of the Pfizer-BioNTech COVID-19 vaccine in gynecologic oncology patients under chemotherapy. METHODS: A prospective cohort study including gynecologic oncology women who were under chemotherapy or had completed it within 6 months at the time of the study. All patients received a two-dose schedule of the Pfizer-BioNTech COVID-19 vaccine. Results were compared with a control group of healthy women vaccinated in the same period. RESULTS: Overall, 44 oncologic patients with a mean age of 61.3 ± 10.7 years were enrolled: 28 (63.6%) had ovarian cancer, 9 (20.4%) endometrial, and 7 (16%) cervical. The IgG antibody titer after 1 month from vaccination was low in 9 (20.5%) patients, moderate in 21 (47.7%), and high in 14 (31.8%). The 3-month titer was null in 2 (4.5%) patients, low in 26 (59.1%), moderate in 13 (29.5%), and high in 3 (6.8%). Patients ≥ 50 years reported lower 1-month (p = 0.018) and 3-month (p = 0.004) titers compared with <50 years. Patients with BMI < 30 kg/m2 had a higher 1-month titer compared with BMI ≥ 30 kg/m2 (p = 0.016). Compared with healthy women (n = 44), oncologic patients showed a lower 3-month titer (p < 0.001). None of the patients experienced serious adverse effects. CONCLUSIONS: The COVID-19 vaccine was safe and immunogenic in gynecologic oncology patients under chemotherapy. Serological monitoring and further vaccine shots should be considered to boost protection.