Evolution of seroprevalence to SARS-CoV-2 in blood donors in Sarajevo Canton, Federation of Bosnia and Herzegovina: Cross-sectional and longitudinal studies.

Background: Sarajevo Canton in the Federation of Bosnia and Herzegovina has recorded several waves of high SARS-CoV-2 transmission and has struggled to reach adequate vaccination coverage. We describe the evolution of infection- and vaccine-induced SARS-CoV-2 antibody response and persistence. Methods: We conducted repeated cross-sectional analyses of blood donors aged 18-65 years in Sarajevo Canton in November-December 2020 and 2021. We analyzed serum samples for anti-nucleocapsid (anti-N) and anti-spike (anti-S) antibodies. To assess immune durability, we conducted longitudinal analyses of seropositive participants at 6 and 12 months. Results: One thousand fifteen participants were included in Phase 1 (November-December 2020) and 1152 in Phase 2 (November-December 2021). Seroprevalence increased significantly from 19.2% (95% CI: 17.2%-21.4%) in Phase 1 to 91.6% (95% CI: 89.8%-93.1%) in Phase 2. Anti-S IgG titers were significantly higher among vaccinated (58.5%) than unvaccinated infected participants across vaccine products (p < 0.001), though highest among those who received an mRNA vaccine. At 6 months, 78/82 (95.1%) participants maintained anti-spike seropositivity; at 12 months, 58/58 (100.0%) participants were seropositive, and 33 (56.9%) had completed the primary vaccine series within 6 months. Among 11 unvaccinated participants who were not re-infected at 12 months, anti-S IgG declined from median 770.1 (IQR 615.0-1321.7) to 290.8 (IQR 175.7-400.3). Anti-N IgG antibodies waned earlier, from 35.4% seropositive at 6 months to 24.1% at 12 months. Conclusions: SARS-CoV-2 seroprevalence increased significantly over 12 months from end of 2020 to end of 2021. Although individuals with previous infection may have residual protection, COVID-19 vaccination is vital to strengthening population immunity.

Primary series COVID-19 vaccine effectiveness among healthcare workers in Albania, February-December 2021.

Background: Healthcare workers have experienced high rates of morbidity and mortality from coronavirus disease 2019 (COVID-19). Methods: A prospective cohort study was conducted in three Albanian hospitals between 19 February and 14 December 2021. All participants underwent polymerase chain reaction (PCR) and serological testing at enrolment, regular serology throughout, and PCR testing when symptomatic.Vaccine effectiveness (VE) against COVID-19 and against all severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections (symptomatic or asymptomatic) was estimated. VE was estimated using a Cox regression model, with vaccination status as a time-varying variable. Findings: In total, 1504 HCWs were enrolled in this study; 70% had evidence of prior SARS-CoV-2 infection. VE was 65.1% [95% confidence interval (CI) 37.7-80.5] against COVID-19, 58.2% (95% CI 15.7-79.3) among participants without prior SARS-CoV-2 infection, and 73.6% (95% CI 24.3-90.8) among participants with prior SARS-CoV-2 infection. For BNT162b2 alone, VE was 69.5% (95% CI 44.5-83.2). During the period when the Delta variant was predominant, VE was 67.1% (95% CI 38.3-82.5). VE against SARS-CoV-2 infection for the full study period was 36.9% (95% CI 15.8-52.7). Interpretation: This study found moderate primary series VE against COVID-19 among healthcare workers in Albania. These results support the continued promotion of COVID-19 vaccination in Albania, and highlight the benefits of vaccination in populations with high levels of prior infection.

Key lessons learnt from COVID-19 intra-action reviews in the Republic of Moldova, Montenegro, Kosovo and North Macedonia 2020-2021: a qualitative study.

OBJECTIVES: Our study described how the WHO intra-action review (IAR) methodology was operationalised and customised in three Western Balkan countries and territories and the Republic of Moldova and analysed the common key findings to inform analyses of the lessons learnt from the pandemic response. DESIGN: We extracted data from the respective IAR reports and performed a qualitative thematic content analysis to identify common (between countries and territories) and cross-cutting (across the response pillars) themes on best practices, challenges and priority actions. The analysis involved three stages, namely: extraction of data, initial identification of emerging themes and review and definition of the themes. SETTING: IARs were conducted in the Republic of Moldova, Montenegro, Kosovo and the Republic of North Macedonia between December 2020 and November 2021. The IARs were conducted at different time points relative to the respective pandemic trajectories (14-day incidence rate ranging from 23 to 495 per 100 000). RESULTS: Case management was reviewed in all the IARs, while the infection prevention and control, surveillance and country-level coordination pillars were reviewed in three countries. The thematic content analysis identified four common and cross-cutting best practices, seven challenges and six priority recommendations. Recommendations included investing in sustainable human resources and technical capacities developed during the pandemic, providing continuous capacity-building and training (with regular simulation exercises), updating legislation, improving communication between healthcare providers at all levels of healthcare and enhancing digitalisation of health information systems. CONCLUSIONS: The IARs provided an opportunity for continuous collective reflection and learning with multisectoral engagement. They also offered an opportunity to review public health emergency preparedness and response functions in general, thereby contributing to generic health systems strengthening and resilience beyond COVID-19. However, success in strengthening the response and preparedness requires leadership and resource allocation, prioritisation and commitment by the countries and territories themselves.

The SARS-CoV-2 Delta (B.1.617.2) variant with spike N501Y mutation in the shadow of Omicron emergence.

Circulation of the Omicron variant with the reemergence of the N501Y mutation along with many others in the spike protein has once again stirred the academic community. Interestingly, tracing the genetic diversity of SARS-CoV-2 shed light on a less frequent N501Y + Delta variant which has been in the global circulation for some time before the Omicron appearance. This paper aims to present the molecular characteristics of the SARS-CoV-2 Spike_N501Y + Delta variant detected in Bosnia and Herzegovina. The study was conducted during November and December 2021. All patients were tested using real-time RT-PCR for detection of SARS-CoV-2. A representative number of SARS-CoV-2 positive samples was pre-screened using VirSNiP SARS-CoV-2 Spike N501Y kit. The characterization of the viruses was carried out with Illumina RNA Prep with enrichment and the Respiratory Virus Oligo Panel kit. Among the analyzed sequences, we found two isolates of the Delta variant that differ from their most related clade- GK AY.4.3 in additional mutations N501Y and L54F. In this study, we described the presence of a rare form of Delta variant with Spike_N501Y mutation in the shadow of the Omicron emergence. Despite the set of mutations in the Spike protein, this form of Delta variant does not indicate the large-scale consequences for the general population. Further functional studies of this form could provide more information about its antigenicity and infectivity.

A Comprehensive Molecular and Epidemiological Characterization of Influenza Viruses Circulating 2016-2020 in North Macedonia.

Influenza viruses know no boundaries, representing an example of rapid virus evolution combined with pressure exerted by the host's immune system. Seasonal influenza causes 4-50 million symptomatic cases in the EU/EEA each year, with a global death toll reaching 650,000 deaths. That being the case, in 2014 North Macedonia introduced the sentinel surveillance in addition to the existing influenza surveillance in order to obtain more precise data on the burden of disease, circulating viruses and to implement timely preventive measures. The aims of this study were to give a comprehensive virological and epidemiological overview of four influenza seasons (2016-2020), assess the frequency and distribution of influenza circulating in North Macedonia and to carry out molecular and phylogenetic analyses of the hemagglutinin (HA) and neuraminidase (NA) genes of influenza A(H1N1)pdm09, A(H3N2) from ILI and SARI patients. Our results showed that out of 1,632 tested samples, 46.4% were influenza positive, with influenza A(H1N1)pdm09 accounting for the majority of cases (44%), followed by influenza B (32%) and A(H3N2) (17%). By comparing the sentinel surveillance system to the routine surveillance system, we showed that the newly applied system works efficiently and gives great results in the selection of cases. Statistically significant differences (p = < 0.0000001) were observed when comparing the number of reported ILI cases among patients aged 0-4, 5-14, 15-29, and 30-64 years to the reference age group. The phylogenetic analysis of the HA sequences unveiled the resemblance of mutations circulating seasonally worldwide, with a vast majority of circulating viruses belonging to subclade 6B.1A. The PROVEAN analysis showed that the D187A substitution in the receptor binding site (RBS) of the A(H1N1)pdm09 HA has a deleterious effect on the its function. The A(H3N2) viruses fell into the 3C.2a and 3C.3a throughout the analyzed seasons. Molecular characterization revealed that various substitutions in the A(H3N2) viruses gradually replaced the parental variant in subsequent seasons before becoming the dominant variant. With the introduction of sentinel surveillance, accompanied by the advances made in whole-genome sequencing and vaccine therapeutics, public health officials can now modify their approach in disease management and intervene effectively and in a timely manner to prevent major morbidity and mortality from influenza.

Building antimicrobial stewardship through massive open online courses: a pilot study in Macedonia.

BACKGROUND: The global struggle against antibiotic resistance requires antimicrobial stewardship (AMS). Massive open online courses (MOOCs) offer health professionals unprecedented access to high-quality instructional material on AMS; the question is how apprehensible it is to non-native English speakers. Furthermore, to better understand how education interventions promote change towards rational antibiotic prescribing, leading institutions call for studies integrating behavioural science. Research from lower- and middle-income countries is particularly needed. OBJECTIVES: To measure the knowledge improvement from an AMS MOOC, the influence of language, course satisfaction and subsequent effect on intention to change antibiotic prescribing behaviour. METHODS: Fifty-five physicians from Macedonia completed the MOOC. Pre- and post-course knowledge test scores were compared using a one-sample t-test. The effect of a language barrier was assessed using self-reported English level. Scores were compared with participants' intention to change behaviour in clinical practice. RESULTS: Scores significantly improved from 77.8% to 82.2%. Participants with a higher English level improved most, while the low-level group showed no significant improvement. Physicians reported a high or very high intention to change behaviour. This was independent of knowledge improvements. CONCLUSIONS: First, lower self-reported English proficiency hindered knowledge acquisition from a MOOC platform. AMS programmes should commit to bridge this barrier so as to enable a global spread of education in AMS. Second, factors underlying the physicians' intentions to engage in AMS appear to be more complex than simple knowledge improvements. This suggests that less time-consuming interventions could be as effective.