Real-world evidence on the efficacy of bivalent booster doses of SARS-CoV-2 vaccine in respect of monovalent boosters or primary cycle of vaccination: a narrative review.

OBJECTIVES: the objective of this review is to give an overall view of the knowledge on COVID-19 bivalent vaccines and to explore the available real-world evidence on their effectiveness in the Omicron era. Currently, bivalent vaccines are generally offered to all groups eligible for their next booster, as defined by the national vaccination campaigns, with varying policies between countries.The use of bivalent vaccines is supported by immunogenity studies, but these have produced contradictory conclusions and are not generally designed to measure clinical impact. DESIGN: in order to critically evaluate the available research on real-world efficacy, a systematic literature search was performed; three different web engines were used, including early-stage search platforms: PubMed, medRxiv and the Global research on coronavirus disease (COVID-19) database. SETTING: no restrictions were imposed on language, setting or publication date. The research was last updated on 20 March 2023. MAIN OUTCOME MEASURES: the following outcomes were considered: infection, hospitalisation due to COVID-19 disease, admission to the emergency/urgency department, death. The following were considered as additional outcomes: variant-specific vaccine effectiveness; vaccine effectiveness waning over time. RESULTS: out of 876 references reviewed, 14 studies were finally included and extracted. The results of this review show modest to moderate additional protection from vaccination with bivalent BA.4-5 or BA.1 vaccines mRNA-booster against COVID-19-associated disease - Relative VE% ranging from 8 (95% CI 0-16) to 58.7 (95% 54.6-62.5)- and hospitalisation - Relative VE% ranging from 32.2 (2.5-60.1) to 80.5 (95% CI 69.5-91.5)-, when compared with a booster with a monovalent vaccine or with having completed only the primary course, during a period when BA.5 and other Omicron sublineage viruses predominated globally. CONCLUSIONS: the additional benefit of bivalent booster vaccines - compared to one or two monovalent booster vaccinations or compared to the primary course alone - in the prevention of SARS-CoV-2 Omicron infection appears to be small, especially in persons with previous Omicron infection, whereas modest to moderate protection from vaccination with bivalent BA.4-5 or BA.1 mRNA-booster vaccines as a fourth dose against COVID-19-associated illness and hospitalisation has been reported.

Tracking the progressive spread of the SARS-CoV-2 Omicron variant in Italy, December 2021 to January 2022.

BackgroundThe SARS-CoV-2 variant of concern Omicron was first detected in Italy in November 2021.AimTo comprehensively describe Omicron spread in Italy in the 2 subsequent months and its impact on the overall SARS-CoV-2 circulation at population level.MethodsWe analyse data from four genomic surveys conducted across the country between December 2021 and January 2022. Combining genomic sequencing results with epidemiological records collated by the National Integrated Surveillance System, the Omicron reproductive number and exponential growth rate are estimated, as well as SARS-CoV-2 transmissibility.ResultsOmicron became dominant in Italy less than 1 month after its first detection, representing on 3 January 76.9-80.2% of notified SARS-CoV-2 infections, with a doubling time of 2.7-3.3 days. As of 17 January 2022, Delta variant represented < 6% of cases. During the Omicron expansion in December 2021, the estimated mean net reproduction numbers respectively rose from 1.15 to a maximum of 1.83 for symptomatic cases and from 1.14 to 1.36 for hospitalised cases, while remaining relatively stable, between 0.93 and 1.21, for cases needing intensive care. Despite a reduction in relative proportion, Delta infections increased in absolute terms throughout December contributing to an increase in hospitalisations. A significant reproduction numbers' decline was found after mid-January, with average estimates dropping below 1 between 10 and 16 January 2022.ConclusionEstimates suggest a marked growth advantage of Omicron compared with Delta variant, but lower disease severity at population level possibly due to residual immunity against severe outcomes acquired from vaccination and prior infection.

Effectiveness of vaccination against SARS-CoV-2 Omicron variant infection, symptomatic disease, and hospitalization: a systematic review and meta-analysis.

BACKGROUND: This meta-analysis aims to assess the effectiveness of the current Sars-Cov2 vaccine regimens against Omicron infection. A secondary endpoint aims to investigate the waning effectiveness of primary vaccination against symptomatic infection and related hospitalization. RESEARCH DESIGN AND METHODS: The systematic review started on 1 December 2021 and was concluded on 1 March 2022. Random-effects frequentist meta-analyses and multiple meta-regressions were performed. RESULTS: In total, 15 studies are included in the quantitative synthesis. According to the meta-analysis results, the overall risk of Sars-Cov2 infection in vaccinated individuals is on average 31 · 5% lower than the infection risk in unvaccinated while vaccinated with one booster dose have a 70 · 4% risk reduction of Omicron infection compared to unvaccinated. In particular, one booster dose significantly decreases by 69% the risk of symptomatic Omicron infection with respect to unvaccinated. Six months after the primary vaccination, the average risk reduction declines to 22% against symptomatic infection and to 55% against hospitalization. CONCLUSIONS: Primary vaccination does not provide sufficient protection against symptomatic Omicron infection. Although the effectiveness of the primary vaccination against hospitalization due to Omicron remains significantly above 50% after 3 months, it dramatically fades after 6 months.

Effectiveness of Vaccination against SARS-CoV-2 Infection in the Pre-Delta Era: A Systematic Review and Meta-Analysis.

(1) Background: The objective of this study was to assess the effectiveness of SARS-CoV-2 vaccines in terms of prevention of disease and transmission in the pre-Delta era. The evaluation was narrowed to two mRNA vaccines and two modified adenovirus-vectored vaccines. (2) Methods: The overall risk of any SARS-CoV-2 infection confirmed by positive real-time Polymerase Chain Reaction (PCR) test was estimated in partially and fully vaccinated individuals. The evidence synthesis was pursued through a random-effects meta-analysis. The effect size was expressed as relative risk (RR) and RRR (RR reduction) of SARS-CoV-2 infection following vaccination. Heterogeneity was investigated through a between-study heterogeneity analysis and a subgroup meta-analysis. (3) Results: The systematic review identified 27 studies eligible for the quantitative synthesis. Partially vaccinated individuals presented a RRR = 73% (95%CI = 59-83%) for positive SARS-CoV-2 PCR (RR = 0.27) and a RRR=79% (95%CI = 30-93%) for symptomatic SARS-CoV-2 PCR (RR = 0.21). Fully vaccinated individuals showed a RRR = 94% (95%CI = 88-98%) for SARS-CoV-2 positive PCR (RR = 0.06) compared to unvaccinated individuals. The full BNT162b2 vaccination protocol achieved a RRR = 84-94% against any SARS-CoV-2-positive PCR and a RRR = 68-84% against symptomatic positive PCR. (4) Conclusions: The meta-analysis results suggest that full vaccination might block transmission. In particular, the risk of SARS-CoV-2 infection appeared higher for non-B.1.1.7 variants and individuals aged ≥69 years. Considering the high level of heterogeneity, these findings must be taken with caution. Further research on SARS-CoV-2 vaccine effectiveness against emerging SARS-CoV-2 variants is encouraged.

Co-circulation of SARS-CoV-2 Alpha and Gamma variants in Italy, February and March 2021.

BackgroundSeveral SARS-CoV-2 variants of concern (VOC) have emerged through 2020 and 2021. There is need for tools to estimate the relative transmissibility of emerging variants of SARS-CoV-2 with respect to circulating strains.AimWe aimed to assess the prevalence of co-circulating VOC in Italy and estimate their relative transmissibility.MethodsWe conducted two genomic surveillance surveys on 18 February and 18 March 2021 across the whole Italian territory covering 3,243 clinical samples and developed a mathematical model that describes the dynamics of co-circulating strains.ResultsThe Alpha variant was already dominant on 18 February in a majority of regions/autonomous provinces (national prevalence: 54%) and almost completely replaced historical lineages by 18 March (dominant across Italy, national prevalence: 86%). We found a substantial proportion of the Gamma variant on 18 February, almost exclusively in central Italy (prevalence: 19%), which remained similar on 18 March. Nationally, the mean relative transmissibility of Alpha ranged at 1.55-1.57 times the level of historical lineages (95% CrI: 1.45-1.66). The relative transmissibility of Gamma varied according to the assumed degree of cross-protection from infection with other lineages and ranged from 1.12 (95% CrI: 1.03-1.23) with complete immune evasion to 1.39 (95% CrI: 1.26-1.56) for complete cross-protection.ConclusionWe assessed the relative advantage of competing viral strains, using a mathematical model assuming different degrees of cross-protection. We found substantial co-circulation of Alpha and Gamma in Italy. Gamma was not able to outcompete Alpha, probably because of its lower transmissibility.

The 2008 Financial Crisis and Changes in Lifestyle-Related Behaviors in Italy, Greece, Spain, and Portugal: A Systematic Review.

Italy, Greece, Spain, and Portugal have all been strongly affected by the 2008 financial crisis, which has had a negative impact on health. We systematically evaluated the effects of the crisis on lifestyle and socioeconomic inequalities. We conducted a literature search using MEDLINE, Embase, the Cochrane Library, and health economics databases for studies reporting quantitative comparisons before and after (or during) the crisis on the following risk behaviors: alcohol consumption, smoking habit, healthy diet, physical activity, and psychotropic drugs and substance abuse, without setting any age restrictions. We selected 34 original articles published between 2011 and 2020. During/after the crisis, alcohol consumption and substance abuse decreased, while psychotropic drug use increased. We also observed a deterioration in healthy eating behavior, with a reduction in fruit and vegetable consumption. Smoking habit and physical activity showed a more complex, controversial trend. Socioeconomic inequalities were affected by the recession, and the negative effects on unhealthy lifestyle tended to be more pronounced among the disadvantaged. These results suggest the need to implement health policies and interventions aimed at monitoring risk behaviors, with special regard to disadvantaged people, and considering the potential additional impact of the COVID-19 pandemic.

Burden and Characteristics of the Comorbidity Tuberculosis-Diabetes in Europe: TBnet Prevalence Survey and Case-Control Study.

BACKGROUND: The growing burden of diabetes mellitus (DM) is posing a threat to global tuberculosis (TB) control. DM triples the risk of developing TB, modifies the presenting features of pulmonary TB, and worsens TB treatment outcomes. We aimed to analyze the prevalence of DM among TB patients and to describe the characteristics and clinical presentation of TB-DM patients in Europe. METHODS: We performed a cross-sectional survey on the prevalence of DM among consecutively diagnosed adult TB patients in 11 European TB referral centers located in France, Germany, Greece, Italy, Russia, Slovakia, Spain, and the United Kingdom over the period 2007-2015. We also selected DM-TB cases and TB only controls with a 1:3 ratio to perform a case-control analysis, including patients selected from the countries mentioned above plus Norway and Ukraine. RESULTS: Among 3143 TB enrolled patients, DM prevalence overall was 10.7% and ranged from 4.4% in Greece to 28.5% in the United Kingdom. Patients' median ages ranged from 36 to 49 years, and all centers had >60% males; the proportion of foreign-born patients varied widely across sites. In the case-control study, DM was independently associated with older age and, among older patients, with being foreign-born. Among patients with pulmonary involvement, cavities on chest imaging were more frequently observed among those with DM. CONCLUSIONS: Diabetes mellitus represents a challenge for TB control in Europe, especially in foreign-born and in elderly patients. Specific screening strategies should be evaluated.

The global dynamics of diabetes and tuberculosis: the impact of migration and policy implications.

The convergence between tuberculosis (TB) and diabetes mellitus (DM) will represent a major public health challenge in the near future. DM increases the risk of developing TB by two to three times and also increases the risk of TB treatment failure, relapse, and death. The global prevalence of DM is predicted to rise significantly in the next two decades, particularly in some of the low- and middle-income countries with the highest TB burden. Migration may add further complexity to the effort to control the impact on TB of the growing DM pandemic. Migration may increase the risk of DM, although the magnitude of this association varies according to country of origin and ethnic group, due to genetic factors and lifestyle differences. Migrants with TB may have an increased prevalence of DM compared to the native population, and the risk of TB among persons with DM may be higher in migrants than in autochthonous populations. Screening for DM among migrants, screening migrants with DM for active and latent TB, and improving access to DM care, could contribute to mitigate the effects of DM on TB.

Lessons learnt from TB screening in closed immigration centres in Italy.

BACKGROUND: Between June 2012 and December 2013 Médecins Sans Frontières launched a pilot project with the aim of testing a strategy for improving timely diagnosis of active pulmonary TB among migrants hosted in four centres of identification and expulsion (CIE) in Italy. METHODS: This is a descriptive study. For active TB case finding we used an active symptom screening approach among migrants at admission in four CIE's. Here we describe the feasibility and the yield of this programme. RESULTS: Overall, 3588 migrants were screened, among whom 87 (2.4%) had a positive questionnaire. Out of 30 migrants referred for further investigations, three were diagnosed as having TB, or 0.1% out of 3588 individuals that underwent screening. Twenty-five (29%, 25/87) migrants with positive questionnaires were not referred for further investigation, following the doctors' decision; however, for 32 (37%, 32/87) migrants the diagnostic work-out was not completed. In multivariate analyses, being over 35 years (OR 1.7; 95% CI 1.1-2.6) and being transgender (OR 4.9; 95% CI 2.1-11.7), was associated with a positive questionnaire. CONCLUSIONS: TB screening with symptom screening questionnaires of migrants at admission in closed centres is feasible. However, to improve the yield, follow-up of patients with symptoms or signs suggestive for TB needs to be improved.

Tuberculosis case finding based on symptom screening among immigrants, refugees and asylum seekers in Rome.

BACKGROUND: In Italy the proportion of cases of tuberculosis in persons originating from high-prevalence countries has been increasing in the last decade. We designed a study to assess adherence to and yield of a tuberculosis screening programme based on symptom screening conducted at primary care centres for regular and irregular immigrants and refugees/asylum seekers. METHODS: Presence of symptoms suggestive of active tuberculosis was investigated by verbal screening in migrants presenting for any medical condition to 3 free primary care centres in the province of Rome. Individuals reporting at least one symptom were referred to a tuberculosis clinic for diagnostic workup. RESULTS: Among 2142 migrants enrolled, 254 (11.9%) reported at least one symptom suggestive of active tuberculosis and 176 were referred to the tuberculosis clinic. Of them, 80 (45.4%) did not present for diagnostic evaluation. Tuberculosis was diagnosed in 7 individuals representing 0.33% of those screened and 7.3% of those evaluated for tuberculosis. CONCLUSION: The overall yield of this intervention was in the range reported for other tuberculosis screening programmes for migrants, although we recorded an unsatisfactory adherence to diagnostic workup. Possible advantages of this intervention include low cost and reduced burden of medical procedures for the screened population. Further evaluation of this approach appears to be warranted.

Accuracy of malaria diagnosis by microscopy, rapid diagnostic test, and PCR methods and evidence of antimalarial overprescription in non-severe febrile patients in two Tanzanian hospitals.

The study was aimed to evaluate the malaria over/underdiagnosis and over/underprescription of antimalarial drugs. Between February and March 2007 blood samples were collected from 336 non-severe febrile outpatients attended in two peripheral Tanzanian hospitals. Microscopy and a rapid diagnostic test (RDT) were done locally and the accuracy evaluated by qualitative polymerase chain reaction (PCR) for Plasmodium spp. The testing was performed at National Institute for Infectious Diseases Lazzaro Spallanzani (INMI), Rome, Italy. As a result of PCR, we identified 26 malaria cases out of 336 (7.7%) patients. Microscopy and RDT accuracies were 93.5% and 97.6%, respectively. Overprescription and underdiagnosis rates were 29.3% and 30.8%, respectively. On-field training, clinical management of febrile illness, and malaria microscopy in remote settings should be considered.