COVID-19 and Seasonal Influenza Vaccination: Cross-Protection, Co-Administration, Combination Vaccines, and Hesitancy

SARS-CoV-2 and influenza are the main respiratory viruses for which effective vaccines are currently available. Strategies in which COVID-19 and influenza vaccines are administered simultaneously or combined into a single preparation are advantageous and may increase vaccination uptake. Here, we comprehensively review the available evidence on COVID-19/influenza vaccine coadministration and combination vaccine candidates from the standpoints of safety, immunogenicity, efficacy, policy and public acceptance. While several observational studies have shown that the trained immunity induced by influenza vaccines can protect against some COVID-19-related endpoints, it is not yet understood whether co-administration or combination vaccines can exert additive effects on relevant outcomes. In randomized controlled trials, co-administration has proved safe, with a reactogenicity profile similar to that of either vaccine administered alone. From the immunogenicity standpoint, the immune response towards four influenza strains and the SARS-CoV-2 spike protein in co-administration groups is generally non-inferior to that seen in groups receiving either vaccine alone. Several public health authorities have advocated co-administration. Different combination vaccine candidates are in (pre)-clinical development. The hesitancy towards vaccine co-administration or combination vaccines is a multifaceted phenomenon and may be higher than the acceptance of either vaccine administered separately. Public health implications are discussed

Reactivation of Herpes Simplex Virus Type 1 (HSV-1) Detected on Bronchoalveolar Lavage Fluid (BALF) Samples in Critically Ill COVID-19 Patients Undergoing Invasive Mechanical Ventilation: Preliminary Results from Two Italian Centers

Reactivation of herpes simplex virus type 1 (HSV-1) has been described in critically ill patients with coronavirus disease 2019 (COVID-19) pneumonia. In the present two-center retrospective experience, we primarily aimed to assess the cumulative risk of HSV-1 reactivation detected on bronchoalveolar fluid (BALF) samples in invasively ventilated COVID-19 patients with worsening respiratory function. The secondary objectives were the identification of predictors for HSV-1 reactivation and the assessment of its possible prognostic impact. Overall, 41 patients met the study inclusion criteria, and 12/41 patients developed HSV-1 reactivation (29%). No independent predictors of HSV-1 reactivation were identified in the present study. No association was found between HSV-1 reactivation and mortality. Eleven out of 12 patients with HSV-1 reactivation received antiviral therapy with intravenous acyclovir. In conclusion, HSV-1 reactivation is frequently detected in intubated patients with COVID-19. An antiviral treatment in COVID-19 patients with HSV-1 reactivation and worsening respiratory function might be considered

In-depth phylogenetic analysis of the hemagglutinin gene of influenza A(H3N2) viruses circulating during the 2016-2017 season revealed egg-adaptive mutations of vaccine strains

Objectives: The authors conducted an in-depth phylogenetic analysis of the hemagglutinin (HA) gene of A(H3N2) identified during the 2016\u20132017 season to compare the circulating strains with both the egg-derived and cell-derived 2016\u20132017 candidate vaccine virus (CVV). Methods: 162 HA1 sequences of H3N2 viruses identified during the 2016\u20132017 season were phylogenetically analyzed and compared with egg-/cell-derived CVV. The predicted vaccine efficacy (pVE) of egg-/cell-derived CVV against field strains was quantified by Pepitope model. Results: All H3N2 belonged to 3C.2a genetic clade, most (80.2%) to 3C.2a1 sub-clade. Several H3N2 variants circulated in the 2016\u20132017 season. HA sequences of field H3N2 strains displayed greater identity with cell-derived CVV than with egg-derived CVV. The amino acid substitutions in positions 160 and 194 identified in egg-derived CVV affected the pVE, which was lower for egg-derived CVV than for cell-derived CVV. Conclusions: The results suggested that reduced vaccine effectiveness observed in 2016\u20132017 season was probably due to changes in the HA of vaccine strains acquired upon adaptation in eggs, which are the basis of most manufacturing systems currently used globally. Egg-free vaccine manufacturing systems would be advisable to improve the effectiveness of influenza vaccines

Response to COVID-19 Vaccination in Patients with Inflammatory Bowel Disease on Biological Treatment

Background: The antibody response to coronavirus disease 2019 (COVID-19) vaccination in patients with inflammatory bowel disease (IBD) on biological drugs is still unclear. Aim: To determine the anti-SARS-CoV-2 spike 1 (anti-S1-IgG) response rate and antibody levels following a complete COVID-19 vaccination cycle in patients with IBD on biological treatment. Methods: We assessed antibody response to COVID-19 in consecutive patients with IBD on biological drugs and without prior exposure to COVID-19. Sera were prospectively collected at baseline and at 21 days (T1), 42 days (T2), and 3 months (T3) after the first vaccine dose. Results: Among the 42 patients included in the study, the overall response rate at T3 was 97.6%, with no difference across the various biological drugs. After the first dose (T1), the response rate was higher in patients receiving anti-tumour necrosis factor (TNF) compared to patients treated with other biologics (p = 0.031). Among the responders, the anti-S1 levels were not significantly different among the various biological drugs at all study timepoints. Concomitant corticosteroids and disease activity had no impact on the response rate at all study timepoints. No unexpected side events were observed. Discussion: The antibody response to vaccination against COVID-19 in patients with IBD on biological drugs is optimal, independently of their mechanism of action. Patients treated with anti-TNF seem to have an earlier response to vaccination, while concomitant low-dose corticosteroids and disease activity does not seem to impact response. This information can be used to program vaccination and inform patients

Investigating SARS-CoV-2 transmission among co-workers in a University of Northern Italy during COVID-19 pandemic: an observational study

BACKGROUND: This study aimed to investigate SARS-CoV-2 transmission among co-workers at the University of Genoa, Italy, during the second COVID-19 pandemic wave. METHODS: A cross-sectional study was carried out in October 2020 - March 2021: RT-PCR confirmed cases of COVID-19 notified to the Occupational Health Service were included in the analysis. RESULTS: Among the n = 201 notified cases, contact tracing of n = 53 individuals identified n = 346 close contacts. The household setting (IRR = 36.8; 95% CI: 4.9-276.8; p < 0.001) and sharing eating areas (IRR = 19.5; 95% CI: 2.5-153.9; p = 0.005) showed the highest Secondary Attack Rates (SARs) compared to the office setting. Fatigue (IRR= 17.1; 95% CI: 5.2-55.8; p < 0.001), gastrointestinal symptoms (IRR= 6.6; 95% CI: 2.9-15.2; p< 0.001) and cough (IRR= 8.2; 95% CI: 3.7-18.2; p= p< 0.001) were associated with transmission of infection. Polysymptomatic cases (IRR= 23.1; 95% CI: 3.1-169.2; p = 0.02) were more likely to transmit the infection. Among COVID-19 index cases aged >60 years (OR = 7.7; 95% CI: 1.9-31.9; p = 0.0046) SARs were higher than in other age groups. Wearing respiratory protections by both the case and the close contact resulted an effective measure compared with no use (IRR = 0.08; 95% CI: 0.03-0.2; p = < 0.0001). CONCLUSIONS: Accurate infection monitoring and contact tracing was useful to identify the main situations Conclusions: Accurate infection monitoring and contact tracing was useful to identify the main situations of SARS-CoV-2 transmission in the workplace, and hence for risk assessment and prevention programs

Moderate vaccine effectiveness against severe acute respiratory infection caused by a(H1N1)pdm09 influenza virus and no effectiveness against a(H3N2)) influenza virus in the 2018/2019 season in Italy

Every season, circulating influenza viruses change; therefore, vaccines must be reformulated each year. We aimed to estimate vaccine effectiveness (VE) against severe influenza infection for the 2018/19 season in Italy. We conducted a test-negative design case-control study at five Italian hospitals. We estimated influenza VE against severe acute respiratory infection (SARI) requiring hospitalisation overall, and by virus subtype, vaccine brand, and age. The 2018/19 season was characterised by A(H1N1)pmd09 and A(H3N2) influenza viruses. Vaccine coverage among <18 years recruited SARI cases was very low (3.2%). Seasonal vaccines were moderately effective against type A influenza overall (adjusted VE = 40.5%; 95% confidence interval (CI) = 18.7\u201356.4%) and subtype A(H1N1)pmd09 viruses (adjusted VE = 55%; 95% CI = 34.5\u201369.1%), but ineffective against subtype A(H3N2) viruses (adjusted VE = 2.5%; 95% CI = 1250.0\u201336.7%). Both Fluad and Fluarix Tetra vaccines were effective against type A influenza overall and subtype A(H1N1)pdm09 viruses. VE appeared to be similar across age groups (0\u201364 years, 6565 years). Seasonal influenza vaccines in the 2018/19 season were moderately effective in preventing SARI caused by A(H1N1)pdm09 influenza but ineffective against A(H3N2)

Influenza vaccination in italian healthcare workers (2018\u20132019 season): Strengths and weaknesses. results of a cohort study in two large italian hospitals

Background: Annual vaccination is the most effective way to combat influenza. As influenza viruses evolve, seasonal vaccines are updated annually. Within the European project Development of Robust and Innovative Vaccine Effectiveness (DRIVE), a cohort study involving Italian healthcare workers (HCWs) was carried out during the 2018-2019 season. Two aims were defined: to measure influenza vaccine effectiveness (IVE) against laboratory-confirmed influenza cases and to conduct an awareness-raising campaign to increase vaccination coverage. Methods: Each subject enrolled was followed up from enrollment to the end of the study. Each HCW who developed ILI was swabbed for laboratory confirmation of influenza. Influenza viruses were identified by molecular assays. A Cox regression analysis, crude and adjusted for confounding variables, was performed to estimate the IVE. Results: Among the 4483 HCWs enrolled, vaccination coverage was 32.5%, and 308 ILI cases were collected: 23.4% were positive for influenza (54.2% A(H1N1) pdm09; 45.8% A(H3N2)). No influenza B viruses were detected. No overall IVE was observed. Analyzing the subtypes of influenza A viruses, the IVE was estimated as 45% (95% CI:-59 to 81) for A(H1N1) pdm09. Conclusions: Vaccination coverage among HCWs increased. Study difficulties and the circulation of drifted variants of A(H3N2) could partly explain the observed IVE