SARS-CoV-2 Breakthrough Infections According to the Immune Response Elicited after mRNA Third Dose Vaccination in COVID-19-Naïve Hospital Personnel.

BACKGROUND: Vaccine-induced SARS-CoV-2-anti-spike antibody (anti-S/RBD) titers are often used as a marker of immune protection and to anticipate the risk of breakthrough infections, although no clear cut-off is available. We describe the incidence of SARS-CoV-2 vaccine breakthrough infections in COVID-19-free personnel of our hospital, according to B- and T-cell immune response elicited one month after mRNA third dose vaccination. METHODS: The study included 487 individuals for whom data on anti-S/RBD were available. Neutralizing antibody titers (nAbsT) against the ancestral Whuan SARS-CoV-2, and the BA.1 Omicron variant, and SARS-CoV-2 T-cell specific response were measured in subsets of 197 (40.5%), 159 (32.6%), and 127 (26.1%) individuals, respectively. RESULTS: On a total of 92,063 days of observation, 204 participants (42%) had SARS-CoV-2 infection. No significant differences in the probability of SARS-CoV-2 infection for different levels of anti-S/RBD, nAbsT, Omicron nAbsT, or SARS-CoV-2 T cell specific response, and no protective thresholds for infection were found. CONCLUSIONS: Routine testing for vaccine-induced humoral immune response to SARS-CoV-2 is not recommended if measured as parameters of 'protective immunity' from SARS-CoV-2 after vaccination. Whether these findings apply to new Omicron-specific bivalent vaccines is going to be evaluated.

The Management of Workplace Violence against Healthcare Workers: A Multidisciplinary Team for Total Worker Health® Approach in a Hospital.

The risk of aggression against healthcare workers (HCWs) is a globally well-known topic. However, workplace violence (WV) is often considered as part of HCW's job, leading to a general underreporting. This cross-sectional study aims at providing a descriptive analysis of aggressive acts against HCWs registered in a 34-month period in a pediatric hospital. According to a specific protocol, each aggressive act was analyzed by a multidisciplinary team using the "Modified Overt Aggression Scale" (MOAS), the "General Health Questionnaire-12" (GHQ-12), and the "Short Form-36 Health Survey" (SF-36) to build a report addressing improvement measures. A three-domain model of WV was also developed considering: (1) assaulted HCWs, (2) attacker-related issues, and (3) environmental context. Contributing factors to overt aggression were outlined and tested using univariate analyses. Statistically significant factors were then included in a multiple linear regression model. A total of 82 aggressive acts were registered in the period. MOAS scores registered a mean value of 3.71 (SD: 4.09). Verbal abuse was the most common form of WV. HCWs professional category, minor psychiatric disorder, emotional role limitation, type of containment used, and emotion intensity were significantly associated with overt aggression (p < 0.05), as well as the attacker's role in the hospital (p < 0.05). The multiple regression analysis confirmed these findings (p < 0.001). Raising awareness on the aggression risk and contributing factors may lead to a relevant improvement of workplace environment, individual workers' health, and organizational well-being.

Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections.

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3-4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen.

Highly Specific Memory B Cells Generation after the 2nd Dose of BNT162b2 Vaccine Compensate for the Decline of Serum Antibodies and Absence of Mucosal IgA.

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA.

Recurrence, Reactivation, or Inflammatory Rebound of SARS-CoV-2 Infection With Acute Vestibular Symptoms: A Case Report and Revision of Literature.

A case of recurrent coronavirus disease 2019 (COVID-19) with neurovestibular symptoms was reported. In March 2020, a physician working in an Italian pediatric hospital had flu-like symptoms with anosmia and dysgeusia, and following a reverse transcription PCR (RT/PCR) test with a nasopharyngeal swab tested positive for SARS-CoV-2. After home quarantine, 21 days from the beginning of the symptoms, the patient tested negative in two subsequent swabs and was declared healed and readmitted to work. Serological testing showed a low level of immunoglobulin G (IgG) antibody title and absence of immunoglobulin M (IgM). However, 2 weeks later, before resuming work, the patient complained of acute vestibular syndrome, and the RT/PCR test with mucosal swab turned positive. On the basis of the literature examined and reviewed for recurrence cases and vestibular symptoms during COVID-19, to our knowledge this case is the first case of recurrence with vestibular impairment as a neurological symptom, and we defined it as probably a viral reactivation. The PCR retest positivity cannot differentiate re-infectivity, relapse, and dead-viral RNA detection. Serological antibody testing and viral genome sequencing could be always performed in recurrence cases.

Different Innate and Adaptive Immune Responses to SARS-CoV-2 Infection of Asymptomatic, Mild, and Severe Cases.

SARS-CoV-2 is a novel coronavirus, not encountered before by humans. The wide spectrum of clinical expression of SARS-CoV-2 illness suggests that individual immune responses to SARS-CoV-2 play a crucial role in determining the clinical course after first infection. Immunological studies have focused on patients with moderate to severe disease, demonstrating excessive inflammation in tissues and organ damage. In order to understand the basis of the protective immune response in COVID-19, we performed a longitudinal follow-up, flow-cytometric and serological analysis of innate and adaptive immunity in 64 adults with a spectrum of clinical presentations: 28 healthy SARS-CoV-2-negative contacts of COVID-19 cases; 20 asymptomatic SARS-CoV-2-infected cases; eight patients with Mild COVID-19 disease and eight cases of Severe COVID-19 disease. Our data show that high frequency of NK cells and early and transient increase of specific IgA, IgM and, to a lower extent, IgG are associated with asymptomatic SARS-CoV-2 infection. By contrast, monocyte expansion and high and persistent levels of IgA and IgG, produced relatively late in the course of the infection, characterize severe disease. Modest increase of monocytes and different kinetics of antibodies are detected in mild COVID-19. The importance of innate NK cells and the short-lived antibody response of asymptomatic individuals and patients with mild disease suggest that only severe COVID-19 may result in protective memory established by the adaptive immune response.