Corrigendum: Temporal trends of COVID-19 antibodies in vaccinated healthcare workers undergoing repeated serological sampling: an individual-level analysis within 13 months in the ORCHESTRA cohort.

[This corrects the article DOI: 10.3389/fimmu.2022.1079884.].

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020–2 April 2022

Background: University workers undergo intense social interactions due to frequent contact with students and colleagues and lectures in crowdy conditions. The aim of our study was to assess the incidence of COVID-19 infection and vaccine effectiveness in a cohort of workers of the University of Trieste from 1 March 2020 (start of the pandemic) through 2 April 2022. Methods: The University of Trieste implemented a number of public health policies to contain the spread of SARS-CoV-2 on the campus, including prompt contact tracing, enhanced ventilation of all premises, fomites disinfection and mandatory use of face masks indoors. In compliance with the surveillance protocol of the local public health department, university personnel were tested for SARS-CoV-2 by polymerase chain reaction (PCR) on a nasopharyngeal swab on demand, in the event of symptoms consistent with COVID-19 or for contact tracing, following close contact with a confirmed COVID-19 case. The incidence rates of SARS-CoV-2 infections were estimated as number of cases by number of person-days (p-d) at risk. Multivariable Cox proportional hazard regression model was employed to investigate the risk of primary COVID-19 infection, controlling for a number of potential confounders and expressing the risk as the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI). Results: The incidence of SARS-CoV-2 infection among university staff was lower than that of healthcare workers (HCWs) of the same area. Compared to unvaccinated colleagues (6.55 × 10,000 p-d), the raw incidence of SARS-CoV-2 infection was higher among university workers immunized with one (7.22 × 10,000 p-d) or two (7.48 × 10,000 p-d) doses of COVID-19 vaccines, decreasing in those receiving the booster (1.98 × 1000 p-d). The risk of infection increased only in postgraduate medical trainees (aHR = 2.16;95% CI: 1.04;4.48), though this was limited to the Omicron transmission period. After the implementation of the national vaccination campaign against COVID-19, workers immunized with the booster were less likely than unvaccinated workers to be infected by SARS-CoV-2 both before (aHR = 0.10;95% CI: 0.06;0.16) and after (aHR = 0.37;95% CI: 0.27;0.52) the Omicron transmission period. Vaccine effectiveness of the booster was 90% (=(1−0.10) × 100) before versus 63% (=(1−0.37) × 100) during the Omicron wave, without a significant difference between homologous (three doses of m-RNA vaccines) and heterologous immunization (first two doses of Vaxzevria followed by a third dose of m-RNA vaccine). Conclusions: The incidence of SARS-CoV-2 infection in university staff was lower than that of HCWs of ASUGI, likely because the testing-on-demand schedule inevitably missed the vast majority of asymptomatic infections. Therefore, the observed significantly protective effect of the booster dose in university personnel referred to symptomatic SARS-CoV-2 infections. The infection prevention and control policies implemented by the University of Trieste managed to equalize the biological risk between administrative and teaching staff.

Persistence of Symptoms 15 Months since COVID-19 Diagnosis: Prevalence, Risk Factors and Residual Work Ability.

Background: A proportion of patients' ailments may last after recovering from acute COVID-19, with episodic and systemic symptoms of unclear etiology potentially involving different organs. Study aim: The aim of this study was to investigate the persistence of symptoms 15 months since COVID-19 diagnosis in patients referring to the post-COVID-19 clinic in Trieste (north-eastern Italy). Methods: Two-hundred-forty-seven patients were medically examined between 8 December 2020-6 April 2021, after a median time of 49 days since first positive swab test for SARS-CoV-2. After a median time of 15 months since COVID-19 diagnosis, the same patients were contacted over the phone and investigated by standardized questionnaire collecting information on any persisting symptoms and work ability index (WAI). Four multivariable logistic regression models were fitted to investigate factors associated with persistence of any respiratory, neurological, dysautonomic, or psychiatric symptoms at first (median time 49 days since COVID-19 diagnosis) as well as second (median 15 months since COVID-19 diagnosis) follow up. A multiple linear regression was also employed to investigate factors associated with higher mean WAI, assessed only at second follow up. Additionally, factors associated with persistence of symptoms 200+ days since COVID-19 diagnosis between first and second follow-up were investigated by multivariable Generalized Estimating Equation (GEE). Results: At first follow up (median time of 49 days since COVID-19 diagnosis) symptoms more frequently reported were fatigue (80.2%), shortness of breath (69.6%), concentration deficit (44.9%), headache (44.9%), myalgia (44.1%), arthralgia (43.3%), and anosmia (42.1%). At second follow-up (median time of 15 months since COVID-19 diagnosis) 75% patients returned to their baseline status preceding COVID-19. At first follow up males were less likely to experience neurological (OR = 0.16; 95% CI: 0.08; 0.35) as well as psychiatric (OR = 0.43; 95% CI: 0.23; 0.80) symptoms as compared to females. At first follow up, the risk of neurological symptoms increased also linearly with age (OR = 1.04; 95% CI: 1.01; 1.08) and pre-existing depression was a major risk factor for persisting dysautonomic (aOR = 6.35; 95% CI: 2.01; 20.11) as well as psychiatric symptoms (omitted estimate). Consistently, at second follow up only females experience psychiatric symptoms, whereas males exhibited significantly higher mean WAI (RC = 0.50; 95% CI: 0.11; 0.88). Additionally, neurological symptoms at second follow up were more likely in patients with pre-existing comorbidities (OR = 4.31; 95% CI: 1.27; 14.7). Finally, persistence of symptoms lasting 200+ days since COVID-19 diagnosis increased linearly with age (OR = 1.03; 95% CI 1.01-1.05) and were more likely in patients affected by pre-existing depression (OR = 2.68; 95% CI 1.60; 4.49). Conclusions: Following a median time of 15 months since first positive swab test, 75% patients with symptoms returned to their baseline health status preceding COVID-19. Females had a significantly lower WAI and were more likely to experience psychiatric symptoms at second follow up (15 months since COVID-19 diagnosis). Furthermore, the risk of symptoms persisting 200+ days since COVID-19 diagnosis increased with history of depression, endorsing the hypothesis that long-COVID-19 symptoms may be at least partially explained by pre-existing psychological conditions. Patient rehabilitation and psychological support may therefore play a key role in caring patients with the so called long COVID-19 syndrome.

COVID-19 Incidence and Vaccine Effectiveness in University Staff, 1 March 2020-2 April 2022.

Background: University workers undergo intense social interactions due to frequent contact with students and colleagues and lectures in crowdy conditions. The aim of our study was to assess the incidence of COVID-19 infection and vaccine effectiveness in a cohort of workers of the University of Trieste from 1 March 2020 (start of the pandemic) through 2 April 2022. Methods: The University of Trieste implemented a number of public health policies to contain the spread of SARS-CoV-2 on the campus, including prompt contact tracing, enhanced ventilation of all premises, fomites disinfection and mandatory use of face masks indoors. In compliance with the surveillance protocol of the local public health department, university personnel were tested for SARS-CoV-2 by polymerase chain reaction (PCR) on a nasopharyngeal swab on demand, in the event of symptoms consistent with COVID-19 or for contact tracing, following close contact with a confirmed COVID-19 case. The incidence rates of SARS-CoV-2 infections were estimated as number of cases by number of person-days (p-d) at risk. Multivariable Cox proportional hazard regression model was employed to investigate the risk of primary COVID-19 infection, controlling for a number of potential confounders and expressing the risk as the adjusted hazard ratio (aHR) with a 95% confidence interval (95% CI). Results: The incidence of SARS-CoV-2 infection among university staff was lower than that of healthcare workers (HCWs) of the same area. Compared to unvaccinated colleagues (6.55 × 10,000 p-d), the raw incidence of SARS-CoV-2 infection was higher among university workers immunized with one (7.22 × 10,000 p-d) or two (7.48 × 10,000 p-d) doses of COVID-19 vaccines, decreasing in those receiving the booster (1.98 × 1000 p-d). The risk of infection increased only in postgraduate medical trainees (aHR = 2.16; 95% CI: 1.04; 4.48), though this was limited to the Omicron transmission period. After the implementation of the national vaccination campaign against COVID-19, workers immunized with the booster were less likely than unvaccinated workers to be infected by SARS-CoV-2 both before (aHR = 0.10; 95% CI: 0.06; 0.16) and after (aHR = 0.37; 95% CI: 0.27; 0.52) the Omicron transmission period. Vaccine effectiveness of the booster was 90% (=(1-0.10) × 100) before versus 63% (=(1-0.37) × 100) during the Omicron wave, without a significant difference between homologous (three doses of m-RNA vaccines) and heterologous immunization (first two doses of Vaxzevria followed by a third dose of m-RNA vaccine). Conclusions: The incidence of SARS-CoV-2 infection in university staff was lower than that of HCWs of ASUGI, likely because the testing-on-demand schedule inevitably missed the vast majority of asymptomatic infections. Therefore, the observed significantly protective effect of the booster dose in university personnel referred to symptomatic SARS-CoV-2 infections. The infection prevention and control policies implemented by the University of Trieste managed to equalize the biological risk between administrative and teaching staff.

Supporting the Aspecific Physiological Defenses of Upper Airways against Emerging SARS-CoV-2 Variants.

The rapid rollout of COVID-19 vaccines in 2021 sparked general optimism toward controlling the severe form of the disease, preventing hospitalizations and COVID-19-associated mortality, and the transmissibility of SARS-CoV-2 infection [...].

Allergic Reactions to COVID-19 Vaccination in High-Risk Allergic Patients: The Experience of Trieste University Hospital (North-Eastern Italy).

Background. Allergic patients may develop reactions following COVID-19 vaccination more frequently than non-allergic individuals. The aim of our study was to assess the risk of reactions in high-risk allergic patients vaccinated for COVID-19 at the University Health Agency Giuliano-Isontina (ASUGI) of Trieste (northeastern Italy). Methods. Patients were considered at high risk for allergic reactions in case of: prior anaphylactic reaction to any drug/vaccine; multiple drug allergy; intolerance to polyethylene glycol (PEG) or polysorbate 80 (PS80) containing drugs; and mast cell disorders. High-risk allergic patients were immunized in hospital by a dedicated allergy team supported by resuscitation staff. Patients were interviewed over the phone one month after vaccination to complete a structured questionnaire investigating signs and symptoms developed after immunization. Results. From March 2021 to February 2022, 269 patients with a history of severe allergic reactions were assessed, of whom 208 (77.3%) eventually received COVID-19 vaccination, 50 (18.6%) refused to be immunized, 10 (3.7%) were deferred for medical reasons and one was declared exempted due to testing positive for PS80. Mild reactions (urticaria, angioedema, rhinitis, erythema) to COVID-19 vaccines were reported by 30.3% of patients, 8.7% within 4 h and 21.6% > 4 h after immunization. No anaphylactic events were observed. Although they were 80 times (3.8%) more prevalent than in COVID-19 vaccinees from the general population (0.047%), vaccine allergic reactions in high-risk patients were mainly mild and late, more likely affecting women (OR = 3.05; 95% CI 1.22-7.65). Conclusions. High-risk allergic patients with urticaria and angioedema may experience mild flare-ups of mast cell activation-like symptoms following COVID-19 vaccination, supporting antihistamine premedication before vaccination and to be continued for one week afterwards.

Primary SARS-CoV-2 Infections, Re-infections and Vaccine Effectiveness during the Omicron Transmission Period in Healthcare Workers of Trieste and Gorizia (Northeast Italy), 1 December 2021-31 May 2022.

Objective: To evaluate the incidence of primary and recurrent COVID-19 infections in healthcare workers (HCWs) routinely screened for SARS-CoV-2 by nasopharyngeal swabs during the Omicron wave. Design: Dynamic Cohort study of HCWs (N = 7723) of the University Health Agency Giuliano Isontina (ASUGI), covering health services of the provinces of Trieste and Gorizia (Northeast Italy). Cox proportional hazard model was employed to estimate the risk of primary as well as recurrent SARS-CoV-2 infection from 1 December 2021 through 31 May 2022, adjusting for a number of confounding factors. Results: By 1 December 2021, 46.8% HCWs of ASUGI had received the booster, 37.2% were immunized only with two doses of COVID-19 vaccines, 6.0% only with one dose and 10.0% were unvaccinated. During 1 March 2020-31 May 2022, 3571 primary against 406 SARS-CoV-2 recurrent infections were counted among HCWs of ASUGI, 59.7% (=2130/3571) versus 95.1% (=386/406) of which occurring from 1 December 2021 through 31 May 2022, respectively. All HCWs infected by SARS-CoV-2 during 1 December 2021 through 31 May 2022 presented mild flu-like disease. Compared to staff working in administrative services, the risk of primary as well as recurrent SARS-CoV-2 infection increased in HCWs with patient-facing clinical tasks (especially nurses and other categories of HCWs) and in all clinical wards but COVID-19 units and community health services. Regardless of the number of swab tests performed during the study period, primary infections were less likely in HCWs immunized with one dose of COVID-19 vaccine. By contrast, the risk of SARS-CoV-2 re-infection was significantly lower in HCWs immunized with three doses (aHR = 0.58; 95%CI: 0.41; 0.80). During the study period, vaccine effectiveness (VE = 1-aHR) of the booster dose declined to 42% against re-infections, vanishing against primary SARS-CoV-2 infections. Conclusions: Though generally mild, SARS-CoV-2 infections and re-infections surged during the Omicron transmission period. Compared to unvaccinated colleagues, the risk of primary SARS-CoV-2 infection was significantly lower in HCWs immunized just with one dose of COVID-19 vaccines. By Italian law, HCWs immunized only with one dose were either suspended or re-assigned to job tasks not entailing patient facing contact; hence, while sharing the same biological risk of unvaccinated colleagues, they arguably had a higher level of protection against COVID-19 infection. By contrast, SARS-CoV-2 re-infections were less likely in HCWs vaccinated with three doses, suggesting that hybrid humoral immunity by vaccination combined with natural infection provided a higher level of protection than vaccination only. In this stage of the pandemic, where SARS-CoV-2 is more infectious yet much less pathogenic, health protection measures in healthcare premises at higher biological risk seem the rational approach to control the transmission of the virus.

Incidence of skin diseases in healthcare workers before and during the COVID-19 pandemic at Trieste hospitals (northeastern Italy).

BACKGROUND: Occupational skin diseases (OSDs) are common in healthcare workers (HCWs). OBJECTIVES: To investigate and compare the incidence and clinical features of OSDs among HCWs before and during the COVID-19 pandemic. MATERIALS AND METHODS: Incident cases of OSDs were investigated in the cohort of HCWs at Trieste Hospitals from 1 July 2018 (3340 workers) to 31 October 2021 (137 532 person-months). RESULTS: The monthly incidence was ranging from 0 to 11.90 cases per 10 000 person-months in pre-COVID-19 period (cumulative incidence 4.22; 95% confidence interval [CI]: 2.9-6.0) and from 0 to 13.61 cases per 10 000 person-months in COVID-19 period (cumulative incidence 5.06; 95% CI: 3.6-6.9). The incidence rate ratio (IRR) between COVID-19 and pre-COVID-19 period was 1.22 (95% CI: 0.73-1.98). The incidence of OSDs in the COVID-19 period was 6.1 (4.2-8.6) and 2.7 (95% CI: 1.1-5.6) cases × 10 000 person-months for women and men, respectively, with an IRR of 2.25 (95% CI: 0.98-5.9). Incidence in nurses in the COVID-19 period was 6.7 (95% CI: 4.2-10.2) cases × 10 000 person-months. CONCLUSIONS: Incidence of OSDs was a little bit higher during the COVID-19 pandemic compared to the previous period but fluctuation of numbers were mainly related to calendar period, with higher incidence in winter and spring. Incidence data were higher than that observed in 2004-2013 in the same cohort. Face dermatitis cases doubled after the start of COVID-19 pandemic. Overall data demonstrated a non-significant increase of OSDs in HCWs during the pandemic, probably due to the preventive strategies set up in our cohort over the years.

SARS-CoV-2 Breakthrough Infections: Incidence and Risk Factors in a Large European Multicentric Cohort of Health Workers.

BACKGROUND: The research aimed to investigate the incidence of SARS-CoV-2 breakthrough infections and their determinants in a large European cohort of more than 60,000 health workers. METHODS: A multicentric retrospective cohort study, involving 12 European centers, was carried out within the ORCHESTRA project, collecting data up to 18 November 2021 on fully vaccinated health workers. The cumulative incidence of SARS-CoV-2 breakthrough infections was investigated with its association with occupational and social-demographic characteristics (age, sex, job title, previous SARS-CoV-2 infection, antibody titer levels, and time from the vaccination course completion). RESULTS: Among 64,172 health workers from 12 European health centers, 797 breakthrough infections were observed (cumulative incidence of 1.2%). The primary analysis using individual data on 8 out of 12 centers showed that age and previous infection significantly modified breakthrough infection rates. In the meta-analysis of aggregated data from all centers, previous SARS-CoV-2 infection and the standardized antibody titer were inversely related to the risk of breakthrough infection (p = 0.008 and p = 0.007, respectively). CONCLUSION: The inverse correlation of antibody titer with the risk of breakthrough infection supports the evidence that vaccination plays a primary role in infection prevention, especially in health workers. Cellular immunity, previous clinical conditions, and vaccination timing should be further investigated.