Correction: Guerrieri et al. Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection. Vaccines 2021, 9, 1499.

The authors wish to make the following corrections to this paper [...].

Main Predictors of COVID-19 Vaccination Uptake among Italian Healthcare Workers in Relation to Variable Degrees of Hesitancy: Result from a Cross-Sectional Online Survey.

Background: Hesitancy remains one of the major hurdles to vaccination, regardless of the fact that vaccines are indisputable preventive measures against many infectious diseases. Nevertheless, vaccine hesitancy or refusal is a growing phenomenon in the general population as well as among healthcare workers (HCWs). Many different factors can contribute to hesitancy to COVID-19 vaccination in the HCWs population, including socio-demographic characteristics (female gender, low socio-economical status, lower age), individual beliefs regarding vaccine efficacy and safety, as well as other factors (occupation, knowledge about COVID-19, etc.). Understanding the determinants of accepting or refusing the COVID-19 vaccination is crucial to plan specific interventions in order to increase the rate of vaccine coverage among health care workers. Methods: We conducted a cross-sectional online survey on HCWs in seventeen Italian regions, between 30 June and 4 July 2021, in order to collect information about potential factors related to vaccine acceptance and hesitancy. Results: We found an overall vaccine uptake rate of 96.4% in our sample. Acceptance was significantly related to job task, with physicians showing the highest rate of uptake compared to other occupations. At univariate analysis, the HCWs population's vaccine hesitancy was significantly positively associated with fear of vaccination side effects (p < 0.01), and negatively related to confidence in the safety and efficacy of the vaccine (p < 0.01). Through multivariate analysis, we found that only the fear of possible vaccination side effects (OR: 4.631, p < 0.01) and the confidence in vaccine safety and effectiveness (OR: 0.35 p < 0.05) remained significantly associated with hesitancy. Conclusion: Action to improve operator confidence in the efficacy and safety of the vaccine should improve the acceptance rate among operators.

Global Policy to Reduce the Incidence of Infection Spreading in Non-Vaccinated Healthcare Workers: A Literature Review.

Healthcare workers (HCWs) are at increased risk of SARS-CoV-2 infection because of their occupational exposure. Moreover, they can be a vehicle for the virus transmission among patients. The vaccination of healthcare personnel against COVID-19 is crucial in fighting the spread of SARS-CoV-2 infection, together with strict sanitary procedures that aim to limit the risk of contagion. Unfortunately, even if COVID-19 vaccination has been proved one of the most effective tools for protecting against COVID-19, many healthcare professionals are not yet vaccinated. The aim of the current review is to contribute to identifying an effective strategy for COVID-19 prevention especially among non-vaccinated HCWs. In this review, we collected the most recent and relevant findings from literature on the protection of unvaccinated HCWs, identifying three types of measures as principal actions to protect those operators: addressing vaccine hesitancy, improving non-pharmaceutical interventions and promoting actions at personal level (respiratory hygiene, hand hygiene and use of PPE). All these interventions are very effective in preventing contagion, if well respected and conducted; nevertheless, it is essential to promote vaccination, as it is the most effective measure.

Reduced Titers of Circulating Anti-SARS-CoV-2 Antibodies and Risk of COVID-19 Infection in Healthcare Workers during the Nine Months after Immunization with the BNT162b2 mRNA Vaccine.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has had a tremendous impact on health services; hundreds of thousands of healthcare workers (HCWs) have died from coronavirus disease 2019 (COVID-19). The introduction of the BNT162b2 mRNA vaccine in Italy provided recipients with significant protection against COVID-19 within one to two weeks after the administration of the second of the two recommended doses. While the vaccine induces a robust T cell response, the protective role of factors and pathways other than those related to memory B cell responses to specific SARS-CoV-2 antigens remains unclear. This retrospective study aimed to evaluate the determinants of serological protection in a group of vaccinated HCWs (n = 793) by evaluating circulating levels of antiviral spike receptor-binding domain (S-RBD) antibodies during the nine-month period following vaccination. We found that 99.5% of the HCWs who received the two doses of the BNT162b2 vaccine developed protective antibodies that were maintained at detectable levels for as long as 250 days after the second dose of the vaccine. Multivariate analysis was performed on anti-S-RBD titers in a subgroup of participants (n = 173) that were evaluated twice during this period. The results of this analysis reveal that the antibody titer observed at the second time point was significantly related to the magnitude of the primary response, the time that had elapsed between the first and the second evaluation, and a previous history of SARS-CoV-2 infection. Of importance is the finding that despite waning antibody titers following vaccination, none of the study participants contracted severe COVID-19 during the observational period.

Nasal and Salivary Mucosal Humoral Immune Response Elicited by mRNA BNT162b2 COVID-19 Vaccine Compared to SARS-CoV-2 Natural Infection.

SARS-CoV-2 antibody assays are crucial in managing the COVID-19 pandemic. Approved mRNA COVID-19 vaccines are well known to induce a serum antibody responses against the spike protein and its RBD. Mucosal immunity plays a major role in the fight against COVID-19 directly at the site of virus entry; however, vaccine abilities to elicit mucosal immune responses have not been reported. We detected anti-SARS-CoV-2 IgA-S1 and IgG-RBD in three study populations (healthy controls, vaccinated subjects, and subjects recovered from COVID-19 infection) on serum, saliva, and nasal secretions using two commercial immunoassays (ELISA for IgA-S1 and chemiluminescent assay for IgG-RBD). Our results show that the mRNA BNT162b2 vaccine Comirnaty (Pfizer/BioNTech, New York, NY, USA) determines the production of nasal and salivary IgA-S1 and IgG-RBD against SARS-CoV-2. This mucosal humoral immune response is stronger after the injection of the second vaccine dose compared to subjects recovered from COVID-19. Since there is a lack of validated assays on saliva and nasal secretions, this study shows that our pre-analytical and analytical procedures are consistent with the data. Our findings indicate that the mRNA COVID-19 vaccine elicits antigen-specific nasal and salivary immune responses, and that mucosal antibody assays could be used as candidates for non-invasive monitoring of vaccine-induced protection against viral infection.

Factors Associated with Pre-Vaccination SARS-CoV-2 Infection Risk among Hospital Nurses Facing COVID-19 Outbreak.

The objective of this work was to evaluate the magnitude of COVID-19 spread and the related risk factors among hospital nurses employed in a COVID hospital in Rome, before the beginning of the vaccination programmes commenced in 2021. Participants periodically underwent (every 15-30 days) nasopharyngeal swab and/or blood sample for SARS-CoV-2 IgG examination. From 1 March 2020 to 31 December 2020, we found 162 cases of COVID-19 infection (n = 143 nasopharyngeal swab and n = 19 IgG-positive) in a total of 918 hospital nurses (17.6%). Most SARS-CoV-2-infected hospital nurses were night shift workers (NSWs), smokers, with higher BMI and lower mean age than that of individuals who tested negative. After adjusting for covariates, age (OR = 0.923, 95% C.I. 0.895-0.952), night shift work (OR = 2.056, 95% C.I. 1.320-2.300), smoking status (OR = 1.603, 95% C.I. 1.080-2.378) and working in high-risk settings (OR = 1.607, 95% C.I. 1.036-2.593) were significantly associated with SARS-CoV-2 hospital infection, whereas BMI was not significantly related. In conclusion, we found a high prevalence of SARS-CoV-2 infection among hospital nurses at a Rome COVID hospital in the pre-vaccination period. Smoking, young age, night shift work and high-risk hospital settings are relevant risk factors for hospital SARS-CoV-2 infection; therefore, a close health surveillance should be necessary among hospital nurses exposed to SARS-CoV-2.

Lactoferrin as Antiviral Treatment in COVID-19 Management: Preliminary Evidence.

Lactoferrin (Lf), a multifunctional cationic glycoprotein synthesized by exocrine glands and neutrophils, possesses an in vitro antiviral activity against SARS-CoV-2. Thus, we conducted an in vivo preliminary study to investigate the antiviral effect of oral and intranasal liposomal bovine Lf (bLf) in asymptomatic and mild-to-moderate COVID-19 patients. From April 2020 to June 2020, a total of 92 mild-to-moderate (67/92) and asymptomatic (25/92) COVID-19 patients were recruited and divided into three groups. Thirty-two patients (14 hospitalized and 18 in home-based isolation) received only oral and intranasal liposomal bLf; 32 hospitalized patients were treated only with standard of care (SOC) treatment; and 28, in home-based isolation, did not take any medication. Furthermore, 32 COVID-19 negative, untreated, healthy subjects were added for ancillary analysis. Liposomal bLf-treated COVID-19 patients obtained an earlier and significant (p < 0.0001) SARS-CoV-2 RNA negative conversion compared to the SOC-treated and untreated COVID-19 patients (14.25 vs. 27.13 vs. 32.61 days, respectively). Liposomal bLf-treated COVID-19 patients showed fast clinical symptoms recovery compared to the SOC-treated COVID-19 patients. In bLf-treated patients, a significant decrease in serum ferritin, IL-6, and D-dimers levels was observed. No adverse events were reported. These observations led us to speculate a potential role of bLf in the management of mild-to-moderate and asymptomatic COVID-19 patients.

Metabolic characteristics in patients with COVID-19 and no-COVID-19 interstitial pneumonia with mild-to-moderate symptoms and similar radiological severity.

BACKGROUND AND AIMS: It is known that the highest COVID-19 mortality rates are among patients who develop severe COVID-19 pneumonia. However, despite the high sensitivity of chest CT scans for diagnosing COVID-19 in a screening population, the appearance of a chest CT is thought to have low diagnostic specificity. The aim of this retrospective case-control study is based on evaluation of clinical and radiological characteristics in patients with COVID-19 (n = 41) and no-COVID-19 interstitial pneumonia (n = 48) with mild-to-moderate symptoms. METHODS AND RESULTS: To this purpose we compared radiological, clinical, biochemical, inflammatory, and metabolic characteristics, as well as clinical outcomes, between the two groups. Notably, we found similar radiological severity of pneumonia, which we quantified using a disease score based on a high-resolution computed tomography scan (COVID-19 = 18.6 ± 14.5 vs n-COVID-19 = 23.2 ± 15.2, p = 0.289), and comparable biochemical and inflammatory characteristics. However, among patients without diabetes, we observed that COVID-19 patients had significantly higher levels of HbA1c than n-COVID-19 patients (COVID-19 = 41.5 ± 2.6 vs n-COVID-19 = 38.4 ± 5.1, p = 0.012). After adjusting for age, sex, and BMI, we found that HbA1c levels were significantly associated with the risk of COVID-19 pneumonia (odds ratio = 1.234 [95%CI = 1.051-1.449], p = 0.010). CONCLUSIONS: In this retrospective case-control study, we found similar radiological and clinical characteristics in patients with COVID-19 and n-COVID-19 pneumonia with mild-to-moderate symptoms. However, among patients without diabetes HbA1c levels were higher in COVID-19 patients than in no-COVID-19 individuals. Future studies should assess whether reducing transient hyperglycemia in individuals without overt diabetes may lower the risk of SARS-CoV-2 infection.

Persistence of Anti-S Titre among Healthcare Workers Vaccinated with BNT162b2 mRNA COVID-19.

The COVID-19 pandemic has led to health, social and economic consequences for public health systems. As a result, the development of safe and effective vaccines, in order to contain the infection quickly became a priority. The first vaccine approved by the Italian Agency for Drugs Authorization (AIFA) was the BNT162b2 mRNA vaccine, developed by BioNTech and Pfizer (Comirnaty). Comirnaty contains a molecule called messenger RNA (mRNA), which is a nucleoside-modified RNA that encodes the SARS-CoV-2 spike glycoprotein. Even if data from phase I suggest that vaccine induced antibodies can persist for up to six months following the second shot of BNT vaccine, data regarding the real duration of immunological protection are lacking. In this study, we aimed to evaluate the duration of serological protection by detecting the presence of anti-S-RBD (receptor-binding domain) antibodies for SARS-CoV-2 among a large group of healthcare workers (HCWs) three months after vaccination. 99% of HCWs had a detectable titre of anti-S SARS-CoV-2 antibodies 90 days after the second vaccine shot. Elderly operators showed significantly lower levels of protective antibodies when compared to the younger ones, thus they could become unprotected earlier than other operators.

Evaluation of Immunity for Mumps among Vaccinated Medical Students.

Healthcare workers are considered at higher risk for mumps infection than the general population. Since 2017, the national immunization plan recommended the administration of a dose of measles-mumps-rubella (MMR) vaccine to the healthcare operators who are unable to demonstrate a complete vaccination history or that are seronegative for at least one of the three agents. Regarding mumps infection, based on actual concerns regarding the loss of protection over the years after vaccination, the Advisory Committee on Immunization Practices (ACIP) recommended to administer a third dose of vaccine to operators previously vaccinated with two doses of MMR vaccine who belong to a group at increased risk of mumps infection in the event of an epidemic. This guideline, however, is not currently followed in Italy, resulting in a potential risk for vaccinated operators to become unprotected from mumps over the years. The aim of our study is to evaluate the persistence of a protective antibody level for mumps among medical students vaccinated during infancy or adolescence, at the start of their hospital internship. We retrospectively evaluated mumps-specific IgG levels in a group of medical students, in the period from 1 January to 31 December 2020. We evaluated the persistence of the detectable level of mumps-specific antibodies in relation to their vaccinal status, gender and time elapsed from vaccination. We found that 17.4% (65 subjects) of our sample were seronegative for mumps. The univariate analysis showed a significant difference in serological protection between male and female gender (77.0% vs. 86.2%; p < 0.05 with chi2 test) and between age classes (86.5% vs. 76.4%; p < 0.05 for subjects aged 18-23 years and over 23 years, respectively). Female gender was significantly related to higher serological protection even after adjusting for age classes and number of vaccine doses administered in a multivariate analysis model. Our study shows a substantial percentage of subjects lacking a protective mumps titer among medical students who were vaccinated in childhood. Given the higher risk of infection among those subjects, routine pre-employment screening should be performed among those operators regardless of their vaccination history and a third dose of MMR should be offered to unprotected students.

First Dose of the BNT162b2 mRNA COVID-19 Vaccine Reduces Symptom Duration and Viral Clearance in Healthcare Workers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than one hundred million people since the beginning of the worldwide pandemic. In this study, data from a large hospital in central Italy was used to evaluate the impact of the first dose of the BNT162b2 mRNA vaccine on SARS-CoV-2 infections in terms of the prevalence of symptomatic cases, symptom duration, and viral clearance timing. All vaccinated Healthcare Workers (HCWs) with positive RT-PCR by nasopharyngeal (NP) swabs were divided into two cohorts (positive RT-PCR within day 12 and positive RT-PCR between day 13 and day 21 after first dose administration) and compared for the presence and duration of symptoms and the timing of viral clearance. The same variables were evaluated across HCWs with positive RT-PCR within 6 days after first dose administration and non-vaccinated HCWs with positive RT-PCR between 1 October 2020 and 28 February 2021. Eighteen HCWs tested positive on RT-PCR by NP swab from day 1 to day 12 after the 1st dose administration (incidence rate 6.2 × 10-4) and 5 HCWs from day 13 to day 21 (incidence rate 2.3 × 10-4). Symptom duration and viral clearance timing are significantly shorter in the cohort of HCWs with positive RT-PCR 12 days after the first dose of the BNT162b2 mRNA vaccine. The administration of the first dose proved effective in reducing presence, symptom duration, and viral clearance even in HCWs vaccinated for less than 6 days. These results could have implications on public health and post-exposure prophylaxis.

Intention to Be Vaccinated for COVID-19 among Italian Nurses during the Pandemic.

BACKGROUND: While the COVID-19 pandemic has spread globally, health systems are overwhelmed by both direct and indirect mortality from other treatable conditions. COVID-19 vaccination was crucial to preventing and eliminating the disease, so vaccine development for COVID-19 was fast-tracked worldwide. Despite the fact that vaccination is commonly recognized as the most effective approach, according to the World Health Organization (WHO), vaccine hesitancy is a global health issue. METHODS: We conducted a cross-sectional online survey of nurses in four different regions in Italy between 20 and 28 December 2020 to obtain data on the acceptance of the upcoming COVID-19 vaccination in order to plan specific interventions to increase the rate of vaccine coverage. RESULTS: A total of 531 out of the 5000 nurses invited completed the online questionnaire. Most of the nurses enrolled in the study (73.4%) were female. Among the nurses, 91.5% intended to accept vaccination, whereas 2.3% were opposed and 6.2% were undecided. Female sex and confidence in vaccine efficacy represent the main predictors of vaccine intention among the study population using a logistic regression model, while other factors including vaccine safety concerns (side effects) were non-significant. CONCLUSIONS: Despite the availability of a safe and effective vaccine, intention to be vaccinated was suboptimal among nurses in our sample. We also found a significant number of people undecided as to whether to accept the vaccine. Contrary to expectations, concerns about the safety of the vaccine were not found to affect the acceptance rate; nurses' perception of vaccine efficacy and female sex were the main influencing factors on attitudes toward vaccination in our sample. Since the success of the COVID-19 immunization plan depends on the uptake rate, these findings are of great interest for public health policies. Interventions aimed at increasing employee awareness of vaccination efficacy should be promoted among nurses in order to increase the number of vaccinated people.

Contact Screening for Healthcare Workers Exposed to Patients with COVID-19.

In China and Italy, many cases of coronavirus disease 2019 (COVID-19) have occurred among healthcare workers (HCWs). Prompt identification, isolation and contact tracing of COVID-19 cases are key elements in controlling the COVID-19 pandemic. The aim of this study was to evaluate the rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection among HCWs exposed to patients with COVID-19 in relation to the main determinants of exposure. To assess the risk of exposure, we performed active symptom monitoring in 1006 HCWs identified as contacts of COVID19 cases. The presence of symptoms was statistically associated with a positive nasopharyngeal swab result. Only one subject was asymptomatic at the time of positive test. These data suggest that clinical history may help in the selection of subjects to be investigated by means of reverse transcriptase-polymerase chain reaction (RT-PCR) in the case of a shortage of diagnostic resources. We found that close contact (within 2 m for 15 min or more) was not statistically related to contagion. Regarding the use of personal protective equipment (PPE), only the use of facial masks was inversely related to the chance of becoming infected (p < 0.01). In conclusion, our data show that unprotected contacts between HCWs should be considered a major route of HCW contagion, suggesting that the use of facial masks should be implemented even in settings where known patients with COVID-19 are not present.