Antispike Immunoglobulin-G (IgG) Titer Response of SARS-CoV-2 mRNA-Vaccine (BNT162b2): A Monitoring Study on Healthcare Workers.

The secretion of IgG SARS-CoV-2 antispike antibodies after vaccination with BNT162b2 and the protection represent the response of the human organism to the viral vector symptomatic infections. The aim of the present investigation was to evaluate the immune reaction in health workers of the Polyclinic of Bari to identify the relationship of antispike titers with blood type, sex, age, and comorbidities. This prospective observational study (RENAISSANCE) had as its primary endpoint the assessment of serologic response to BNT162b2 at three blood titers: the first at 60 days after the second dose (3 February 2021); the second titer at 75 days after the first titer; and the third titer at 130 days after the second titer. Out of 230 enrolled staff members, all responded excellently to the mRna Pfizer (BNT162b) vaccine. Only one patient, 40 days after the second dose (3 February 2021), was positive on the swab control performed on 15 March 2021, although completely asymptomatic, and was negative on the subsequent molecular swab performed on 30 March 2021. All the patients responded to the mRNA Pfizer (BNT162b) vaccine with an antispike IgG level above 500 BAU/mL at the first antispike protein essay (60 days after the second dose on 3 April 2021); at the second titer (75 days after the first titer on 20 June 2021), 4 (1.7% of 230 enrolled) patients showed an antispike IgG level under 500 BAU/mL; at the third titer (130 days after the second titer on 30 June 2021, which means 9 months after the second dose), 37 (16.1% of 230 enrolled) patients showed an antispike IgG level under 500 BAU/mL. The data analysis demonstrated that patients belonging to blood group 0, regardless of their rhesus factor, showed the strongest level of antibodies compared to the other groups. No dependency was found between low antibodies level and sex or age. Molecular swab controls were performed every 15th of the month continuously. However, the enrolled patients' activity was at high risk because they carried out medical activities such as dental and surgical as well with droplets of water vaporized by the effect of turbines, piezosurgery. The vaccination campaign among health workers of the Policlinico of the University of Bari "Aldo Moro" led to an excellent serological response and the complete absence of COVID-19 incident cases, so the antibody response was excellent. The COVID-19 vaccine booster shot should be administered after 9 months and not without prompt antispike titer detection to assess if any sign of waning immunity is present in that specific patient.

Vaccination Offer during the Occupational Health Surveillance Program for Healthcare Workers and Suitability to Work: An Italian Retrospective Cohort Study.

The active immunization of health care workers (HCWs) is a crucial measure to avoid nosocomial infection; nevertheless, vaccine coverage (VC) among health personnel in Italy is unsatisfactory. To improve VC in the healthcare set, the Hygiene and Occupational Medicine departments of Bari Policlinico General University Hospital applied a specific program. The operative procedure demands that in the context of the occupational medical examination, all workers are evaluated for susceptibility to vaccine-preventable diseases (VDPs), with immunization prophylaxis offered to those determined to be susceptible. This study analyzed data from workers who attended the biological risk assessment protocol from December 2017 to October 2021 (n = 1477), who were evaluated for the immune status for measles, mumps, rubella, and varicella. Among the enrolled subjects, non-protective antibody titers were higher for measles and mumps (13%), followed by rubella (11%) and varicella (8%). Appropriate vaccinations were offered to all susceptible HCWs, and HCWs were re-tested one month after immunization. The seroconversion rate after the administration of one or more booster dose(s) was over 80%. Overall, 2.5% of the subjects refused the offered vaccine(s); the main determinant of immunization compliance was younger age (aOR = 0.86; 95%CI = 0.80-0.92). Especially during the COVID-19 pandemic, VPDs may still present a hazard in nosocomial environment. Our experience suggests that, despite hospital procedures and dedicated human assets, satisfactory VC cannot be reached without the provision of federal regulations. Nevertheless, public health policymakers have to improve the promotion of vaccine prophylaxis and education to reach higher VC.

Effectiveness of SARS-CoV-2 Vaccines for Short- and Long-Term Immunity: A General Overview for the Pandemic Contrast.

BACKGROUND: The recent COVID-19 pandemic produced a significant increase in cases and an emergency state was induced worldwide. The current knowledge about the COVID-19 disease concerning diagnoses, patient tracking, the treatment protocol, and vaccines provides a consistent contribution for the primary prevention of the viral infection and decreasing the severity of the SARS-CoV-2 disease. The aim of the present investigation was to produce a general overview about the current findings for the COVID-19 disease, SARS-CoV-2 interaction mechanisms with the host, therapies and vaccines' immunization findings. METHODS: A literature overview was produced in order to evaluate the state-of-art in SARS-CoV-2 diagnoses, prognoses, therapies, and prevention. RESULTS: Concerning to the interaction mechanisms with the host, the virus binds to target with its Spike proteins on its surface and uses it as an anchor. The Spike protein targets the ACE2 cell receptor and enters into the cells by using a special enzyme (TMPRSS2). Once the virion is quietly accommodated, it releases its RNA. Proteins and RNA are used in the Golgi apparatus to produce more viruses that are released. Concerning the therapies, different protocols have been developed in observance of the disease severity and comorbidity with a consistent reduction in the mortality rate. Currently, different vaccines are currently in phase IV but a remarkable difference in efficiency has been detected concerning the more recent SARS-CoV-2 variants. CONCLUSIONS: Among the many questions in this pandemic state, the one that recurs most is knowing why some people become more seriously ill than others who instead contract the infection as if it was a trivial flu. More studies are necessary to investigate the efficiency of the treatment protocols and vaccines for the more recent detected SARS-CoV-2 variant.

Long-Term Immunogenicity of Inactivated and Oral Polio Vaccines: An Italian Retrospective Cohort Study.

Oral and inactivated poliovirus (PV) vaccines have contributed toward the global eradication of wild PV2 and PV3, as well as the elimination of PV1 in most countries. While the long-term (>5−10 years) persistence of protective antibodies in ≥80% of the population vaccinated with ≥3−4 doses of oral poliovirus vaccine (OPV) has been demonstrated, the duration of immunity in people vaccinated with the inactivated poliovirus vaccine (IPV) is still unclear. This study evaluated the seroprevalence of anti-PV neutralizing antibodies and the long-term immunogenicity conferred by OPV and IPV in a sample of medical students from the University of Bari (April 2014−October 2020). The levels of neutralizing PV1, PV2, and PV3 antibodies in blood samples taken during the assessments were evaluated. Neutralizing antibodies against PV1, PV2, and PV3 were present in >90% of the study participants, with rates of >99%, >98%, and ~92−99%, respectively. IPV resulted in a higher immunological response than OPV against PV3. Protective antibodies against all three viruses persisted for at least 18 years after administration of the last vaccine dose. Until PV1 is completely eradicated, maximum vigilance from public health institutions must be maintained.

Antibody response to BNT162b2 SARS-CoV-2 mRNA vaccine is not influenced by AB0 blood group in subjects with transfusion-dependent thalassemia.

Not applicable.

Medium-to-Long-Term Immunogenicity of BNT162b2 mRNA COVID-19 Vaccine: A Retrospective Cohort Study.

To deal with the COVID-19 pandemic, a mass vaccination campaign was started in European countries on 27 December 2020. The first vaccine available to immunize healthcare workers (HCWs) was the BNT162b2 mRNA COVID-19 vaccine. While many studies have shown a high antibody response after the second vaccine dose, antibody persistence over the medium-to-long term has yet to be evaluated. The medium-to-long-term persistence of anti-SARS-CoV-2 antibodies was determined in a sample of fully vaccinated HCWs at Bari Policlinico General Hospital, Italy. This is a observational cohort study. HCWs who completed the immunization basal cycle were screened for anti-SARS-CoV-2 IgG on days 15, 30, 60, 90, and 120 after the second vaccine dose. At each time point, >99% of the screened HCWs were seroprotected. While the geometric mean titer initially declined over time, by 60 days the titer had stabilized. Older subjects seem to lose IgG faster than younger ones. The immunogenicity conferred by the vaccine provides further evidence that it is an essential weapon in efforts to bring the COVID-19 pandemic under control. Accordingly, strict measures should be implemented, ranging from the mandatory vaccination of HCWs to strong incentives aimed at achieving vaccination of the large majority of the overall population.

Reduced COVID-19 mortality linked with early antibodies against SARS-CoV-2, irrespective of age.

BACKGROUND: COVID-19 pandemic has generated a million deaths worldwide. The efficiency of the immune system can modulate individual vulnerability with variable outcomes. However, the relationships between disease severity and the titer of antibodies produced against SARS-CoV-2 in non-vaccinated, recently infected subjects need to be fully elucidated. METHODS: A total of 99 patients admitted to a COVID-unit underwent clinical assessment and measurement of serum levels of anti-spike protein (S1) IgM, and anti-nucleocapsid protein IgG. Patients were stratified according to the clinical outcome (i.e., discharged at home or in-hospital death). RESULTS: Following hospitalization, 18 died during the hospital stay. They were older, had lymphopenia, a higher co-morbidity rate, and longer hospital stay than 81 patients who were discharged after healing. Patients in this latter group had, at hospital admittance, 7.9-fold higher serum concentration of IgM, and 2.4-fold higher IgG levels. Multivariate Cox regression models indicated age and anti-nucleocapsid protein IgG concentration at admission as independently associated with the risk of in-hospital death. CONCLUSIONS: An efficient immunological response during the early phase of COVID-19 protects from mortality, irrespective of age. Advanced age is a critical risk factor for poor outcome in infected subjects. Further studies must explore potential therapeutic strategies able to restore a valid functional humoral immunity in elderly patients with poor antibody response during the early stage of COVID-19 infection.

Immunogenicity and safety of the BNT162b2 COVID-19 mRNA vaccine in PLWH: A monocentric study in Bari, Italy.

In March, people living with HIV infection (PLWH) were included in the risk category of fragile people for severe COVID-19 receiving priority access to vaccination with BNT162b2 vaccine. The aim of the study was to evaluate the immunogenicity and safety of the two doses regimen. The antibodies titer for severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) was evaluated after 21 days since the first administration (Time 1), 1 (Time 2), and 3 (Time 3) months post-vaccination. Information regarding virological and immunological conditions at baseline, previous SARS-CoV-2 state of infection, other immunodeficiencies, current antiretroviral therapy (ART), comorbidities, and severe adverse events (SAE) to vaccination was collected. Six hundred and ninety-seven patients were tested for quantitative anti-spike antibodies at Time 1, 577 patients had a second detection at Time 2, and 491 patients had the third detection. Baseline characteristics of the study population are reported in Table 1. At the time of vaccine administration, all patients were on ART (except one long-term nonprogressor); 632 (90.7%) patients had undetectable HIV-RNA; 12 (1.7%) patients were immunosuppressed due to chemotherapy or other immunosuppressive drugs; 345 (49.5%) patients had at least one COVID-19 related comorbidity and 155 (22.2%) had two or more comorbidities. No SAEs were reported. Final serological results are available for 694 patients after the first dose, 577 and 491 after the second and third ones, respectively; positive titer (values ≥ 50 AU/ml) was demonstrated in 653 (94.1%), 576 (99.8%), 484 (98.6%) patients, respectively. Only one patient was a nonresponder after completing vaccination, who was a newly diagnosed one for HIV infection. All vaccinations were well tolerated, with no SAEs. BNT162b2 mRNA vaccine was immunogenic and safe in PLWH.

Immune response to one dose of BNT162b2 mRNA Covid-19 vaccine followed by SARS-CoV-2 infection: An Italian prospective observational study.

INTRODUCTION: A mass vaccination campaign against SARS-CoV-2 was initiated in European countries on December 27, 2020. This study compared the antibody response in a sample of healthcare workers (HCWs) who, after the first dose of the BNT162b2 mRNA vaccine, were infected with SARS-CoV-2 (infection group) with the response in a control group of HCWs immunized with two doses (vaccine group). METHODS: This two-arm observational cohort study was carried out using routine health surveillance data obtained from HCWs at Bari Policlinico General Hospital (Italy). The antibody response was determined infection group and vaccine group. RESULTS: Among the 100 HCWs, 25 (25.0%) were in the infection group and 75 (75.0%) in the full-vaccine group. At the serological evaluation, all of the HCWs tested positive, with a geometric mean titer (GMT) of 7106.8 (95 %CI = 5628.5-8973.4) and a statistically significant difference (p < 0.0001) between the infection group (GMT = 2139.7; 95 %CI = 1310.4-3493.6) and the vaccine group (GMT = 10603.6; 95 %CI = 8698.0-12926.8). DISCUSSION: Our results shed light on the vaccine response of individuals in different risk categories. It also emphasizes the need for the continued use by HCWs of PPE and good practices during the window between the first and second anti-SARS-CoV-2 vaccinations.

Prospective Observational COVID-19 Screening and Monitoring of Asymptomatic Cancer Center Health-Care Workers with a Rapid Serological Test.

Health-care workers (HCW) are at high risk for SARS-CoV-2 infection and, if asymptomatic, for transmitting the virus to fragile cancer patients. We monitored all asymptomatic HCWs of a cancer institute (94% of all employees agreed to enter the study) with the rapid serological test, VivaDiagTM, identifying SARS-CoV-2 associated-IgM/IgG. The tests were performed at time 0 (n = 606) and after 14 days (n = 393). Overall, the VivaDiagTM results of nine HCWs (1.5%) were positive, with one confirmed to be SARS-CoV-2-positive after oropharyngeal swab testing by RT-PCR. At time 0, all nine cases showed IgM expression while IgG was detected in only one. After 14 days, IgM persisted in all the cases, while IgG became evident in four. A chemiluminescence immunoassay (CLIA) confirmed IgM positivity in 5/13 VivaDiagTM positive cases and IgG positivity in 4/5 VivaDiagTM positive cases. Our study suggests that the VivaDiagTM test can be of help in identifying SARS-CoV-2 infected people in cohorts of subjects with a high prevalence.

Long-term persistence of poliovirus neutralizing antibodies in the era of polio elimination: An Italian retrospective cohort study.

INTRODUCTION: The extensive use of oral and inactivated poliovirus (PV) vaccines has driven progress toward the global eradication of wild PV2 and PV3 and the elimination of PV1 in most countries, including Italy. Although the persistence of circulating neutralizing antibodies among the vaccinated is unclear, it is estimated that > 99% of the population vaccinated according to the recommended protocol should be protected for at least 18 years. METHODS: This study evaluated the seroprevalence of anti-PV neutralizing antibodies and the long-term immunogenicity of the oral poliovirus vaccine (OPV) in a sample of medical students and residents of the University of Bari who attended the Hygiene Department for a biological risk assessment between April 2014 and October 2020. RESULTS: The prevalence of protected vaccinated individuals was > 90% for PV1, PV2, and PV3. Specifically, >99% of the study group was protected against PV1, > 98% against PV2, and almost 93% against PV3. Protective antibodies against all three viruses persisted for at least up to 18 years after administration of the last OPV dose, with PV1 and PV2 antibodies detected in > 95% of the participants > 30 years after the last OPV dose. CONCLUSIONS: The childhood series of four doses of OPV guarantees a long duration of protection, despite the elimination of the virus and therefore the absence of a natural booster. However, until PV1 is completely eradicated, maximum vigilance on the part of public health institutions must be maintained.

Long -term persistence of antibodies against varicella in fully immunized healthcare workers: an Italian retrospective cohort study.

BACKGROUND: Chickenpox is a highly contagious disease caused by the varicella zoster virus (VZV), and in infants, adolescents, adults, pregnant women, and the immunocompromised it can be serious. The best way to prevent chickenpox is immunization with the varicella vaccine. Protective levels of antibodies induced by the varicella vaccine decline over time, but there is currently no formal recommendation for testing anti-varicella zoster virus (VZV) IgG levels in immunized healthcare workers (HCWs). METHODS: The aims of this study were to evaluate the seroprevalence of circulating anti-VZV IgG in a sample a sample of students and residents of the medical school of the University of Bari, the long-term immunogenicity of the varicella vaccine, and the effectiveness of a strategy consisting of a third vaccine booster dose. The study population was screened as part of a biological risk assessment conducted between April 2014 and October 2020. A strategy for the management of non-responders was also examined. RESULTS: The 182 students and residents included in the study had a documented history of immunization (two doses of varicella vaccine). The absence of anti-VZV IgG was determined in 34% (62/182; 95%CI = 27.2-41.4%), with serosusceptibility more common among males than females (p < 0.05). After a third varicella dose, seroconversion was achieved in 100% of this previously seronegative group. No serious adverse events were recorded. CONCLUSIONS: One-third of the study population immunized against VZV lacked a protective antibody titer, but a third dose of vaccine restored protection. Since it is highly unlikely that VZV will be eliminated in the immediate future, the loss of immunity in a substantial portion of the population implies a risk of varicella outbreaks in the coming years. Screening for varicella immunity in routine assessments of the biological risk of medical students and HCWs may help to prevent nosocomial VZV infections.

Large-scale IgM and IgG SARS-CoV-2 serological screening among healthcare workers with a low infection prevalence based on nasopharyngeal swab tests in an Italian university hospital: Perspectives for public health.

BACKGROUND: Healthcare workers (HCWs) are highly exposed to SARS-CoV-2 infection given their specific tasks. The IgG-IgM serological assay has demonstrated good accuracy in early detection in symptomatic patients, but its role in the diagnosis of asymptomatic patients is uncertain. The aim of our study was to assess IgM and IgG prevalence in sera in a large cohort of HCWs previously subjected to Nasopharyngeal swab test (NST) after accurate risk assessment due to positive COVID-19 patient exposure during an observation period of 90 days. METHODS: 2407 asymptomatic HCWs that had close contact with COVID-19 patients in the period between April 8th and June 7th were screened with NST based on the RT-PCR method. In parallel, they underwent large-scale chemiluminescence immunoassays involving IgM-IgG serological screening to determine actual viral spread in the same cohort. RESULTS: During the 90-day observation period, 18 workers (0.75%) resulted positive for SARS-CoV-2 infection at the NST, whereas the positivity rates for IgM and IgG were 11.51% and 2.37%, respectively (277 workers). Despite high specificity, serological tests were inadequate for detecting SARS-CoV-2 infection in patients with previous positive NST results (IgM and IgG sensitivities of 27.78% and 50.00%, respectively). CONCLUSIONS: These findings indicate a widespread low viral load of SARS-CoV-2 among hospital workers. However, serological screening showed very low sensitivity with respect to NST in identifying infected workers, and negative IgG and IgM results should not exclude the diagnosis of COVID-19. IgG-IgM chemiluminescence immunoassays could increase the diagnosis of COVID-19 only in association with NST, and this association is considered helpful for decision-making regarding returning to work.

Long time persistence of antibodies against Mumps in fully MMR immunized young adults: an Italian retrospective cohort study.

Protective levels of antibodies induced by the MMR vaccine have been shown to decline over time, but actually there is not a formal recommendation about the opportunity of testing immunized HCWs to investigate the persistence of anti-Mumps IgG. This study aims to evaluate the long-time immunogenicity of MMR vaccination in a sample of medical students and residents of the University of Bari who attended the Hygiene Department for the biological risk assessment (April 2014-June 2018). A strategy for the management of non-responder subjects has been experimented and described. Two thousand students and residents, with documented immunization status (two doses of MMR vaccine), have been tested. 120/2,000 (6%; 95%CI = 5.0-7.1%) subjects did not show anti-Mumps IgG. This percentage was similar among males and females. After a third MMR dose, we noted a seroconversion of 90% of seronegative participants. No serious adverse events were recorded. An important proportion of subjects immunized for MMR do not show an antibodies protective titer. The immunogenicity and the safety of the third dose seem confirmed by our data. Including the screening model described in the routine assessment of the biological risk of medical students and HCWs may be a winning strategy in preventing Mumps nosocomial infection.

Long-term Immunogenicity of Measles Vaccine: An Italian Retrospective Cohort Study.

BACKGROUND: Levels of antibodies induced by the measles virus-containing vaccine have been shown to decline over time, but there is no formal recommendation about testing immunized subjects (in particular, healthcare workers [HCWs]) to investigate the persistence of measles immunoglobulin G (IgG). METHODS: This study aims to evaluate the long-term immunogenicity of measles vaccine in a sample of medical students and residents of the University of Bari who attended the Hygiene Department for a biological risk assessment (April 2014-June 2018). RESULTS: Two thousand immunized (2 doses of measles-mumps-rubella [MMR] vaccine) students and residents were tested; 305 of these (15%) did not show protective anti-measles IgG. This proportion was higher among subjects who received vaccination at ≤15 months (20%) than in those who received vaccination at 16-23 months (17%) and at ≥24 months (10%) (P < .0001). After an MMR vaccine booster dose, we noted a seroconversion of 74% of seronegative HCWs. The overall seroconversion rate after a second dose (booster) was 93%. No serious adverse events were noted after the booster doses. CONCLUSIONS: An important proportion of subjects immunized for measles do not show a protective IgG titer in the 10 years after vaccination. Our management strategy seems consistent with the purpose of evidencing immunological memory.

Compliance with immunization and a biological risk assessment of health care workers as part of an occupational health surveillance program: The experience of a university hospital in southern Italy.

BACKGROUND: The active immunization of health care workers (HCWs) is a primary measure to prevent nosocomial infection; despite this, vaccine coverage among HCWs in most countries is low. To increase vaccine coverage in the health care setting, the hygiene and occupational medicine departments of Bari Policlinico General University-Hospital implemented a vaccination procedure. This operative procedure requires that during the occupational medical examination, all employees are evaluated for immunity/susceptibility to vaccine-preventable diseases, with vaccination offered to those determined to be susceptible. METHODS: The study sample comprised HCWs who attended the biological risk assessment program from December 2017 to January 2019 (n = 449). RESULTS: Susceptibility was higher for hepatitis B virus (23%), followed by rubella (11%), varicella (9%), mumps (8%), and measles (7%). The seroconversion rate after the administration of booster dose(s) was >80% for all vaccines. Overall, 15% of the HCWs refused the offered vaccine(s), and the main determinants of vaccination compliance were younger age (P < .0001) and being a physician (P < .05). DISCUSSION: Despite the several recommendations and campaigns to promote vaccinations, achieving high immunization rates among HCWs is still a challenge. CONCLUSIONS: In this scenario, public health institutions have to choose between the enforcement of the promotion or the adoption of a mandatory policy.