mRNA vaccine effectiveness against hospitalisation due to severe acute respiratory infection (SARI) COVID-19 during Omicron variant predominance estimated from real-world surveillance data, Slovenia, February to March 2022

For the period of predominance of SARS-CoV-2 Omicron variant in Slovenia, February to March 2022, we estimated mRNA vaccine effectiveness (VE) against severe acute respiratory infection (SARI) COVID-19 using surveillance data. In the most vulnerable age group comprising individuals aged 65 years and more, VE against SARI COVID-19 was 95% (95% CI: 95–96%) for those vaccinated with three doses, in comparison to 82% (95% CI: 79–84%) for those vaccinated with two doses. Such levels of protection were maintained for at least 6 months.

SARI was defined as any acute respiratory infection of such severity that it results in admission to hospital. SARI confirmed COVID-19 case admission was defined as a SARI case admitted to hospital with a positive SARS-CoV-2 polymerase chain reaction (PCR) or positive antigen test result at admission (2). Confirmed COVID-19 case admission for other reasons, not SARI, was defined as admission of a patient with a positive SARS-CoV-2 PCR or positive antigen test result at admission when the patient did not have symptoms and signs of SARI at admission. The discrimination between community-acquired and healthcare-associated COVID-19 cases diagnosed during hospitalisation is at the discretion of the EPISARI contact points in hospitals, who had been made aware of respective European Centre for Disease Prevention and Control (ECDC) surveillance definitions for COVID-19 (3).
The data collection procedures in hospitals are at their discretion. Hospital EPISARI contact points report weekly EPISARI data to NIJZ, by each Wednesday for the preceding week (defined from 00:00 on Monday morning to 24:00 on Sunday evening). The data include weekly numbers of: SARI cases admitted to hospital and to ICUs; SARI cases admitted to hospital and to ICUs tested for SARS-CoV-2 infection; SARI confirmed COVID-19 cases admitted to hospital and to ICUs; confirmed COVID-19 cases admitted to hospital for other reasons, not SARI; diagnoses of community-acquired COVID-19 cases and diagnoses of healthcare-associated COVID-19 cases during hospitalisation. In addition, a unique national identifier for each COVID-19 case containing information on age and sex of the patient is reported according to the Law on healthcare datasets (4).
The magnitude of severe COVID-19 morbidity is the key factor for informed and proportional public health response. Within the comprehensive Slovenian COVID-19 surveillance system, enhanced national surveillance of SARI (EPISARI) is a "surveillance tool" to above all monitoring trends in weekly absolute numbers or rates of SARI confirmed COVID-19 admissions to all Slovenian hospitals. This is essential in the context of evolving epidemic waves, changing vaccination coverage, changes in predominant SARS-CoV-2 variants circulating and threatening emergence of new SARS-CoV-2 variants of concern that might overcome previous SARS-CoV-2 infection or vaccine-induced immunity against severe COVID-19 disease.
SARI surveillance was recommended as one of the approaches within comprehensive COVID-19 surveillance by ECDC (5). Similarly, the World Health Organisation (WHO) provided guidance for adapting influenza SARI sentinel surveillance systems to complement COVID-19 surveillance (6).
The strength of EPISARI is the national coverage. Limitations of EPISARI may include variation in methods for SARI and different COVID-19 cases ascertainment between hospitals as the data collection process is at the discretion of individual hospitals, and possible validity issues of the data submitted to the NIJZ. Some SARI cases as well as some COVID-19 cases may be misclassified, especially community-acquired and healthcare-associated COVID-19 cases. Especially SARI cases and community-acquired and healthcareassociated COVID-19 cases may also be underreported from some hospitals. However, it is rather unlikely that SARI COVID-19 cases admissions to hospitals, the outcome used in the analysis for the abovementioned paper would not be ascertained correctly and reported.
To conclude, we believe that EPISARI COVID-19 admissions to hospitals data are of good enough quality and well representative of the Slovenian population old 18 years or more, although no formal validation was performed.

National Electronic registry of vaccinated individuals and adverse events following immunisation (eRCO)
In 2017, according to the Healthcare Databases Act (4), NIJZ launched the Slovenian national Electronic registry of vaccinated individuals and adverse events following immunization (AEFI) (eRCO) within eHealth (8). The objectives were to monitor the implementation of vaccination according to the Communicable Diseases Act (9) and annual national immunization programmes (10) and to monitor vaccination coverage and AEFI.
According to the Rules on certificates, records and reports on vaccination and vaccination adverse effects and errors (11), vaccination providers (public and private) are obliged to keep records of completed vaccinations and protection with specific immunoglobulins as well as AEFI and report to eRCO. The administrators of software solutions at vaccination providers adjusted their software programs so that standardised recording of vaccination and AEFI data as well as data transfer to the eRCO central database is ensured. To minimize error, education on reporting protocols is routinely performed.
eRCO database includes the following information: unique national identifier, number of health insurance, name and surname of vaccinated person, residence data, date of vaccination, vaccine used, method and location of application, date of expiration, serial number of vaccine used, dose number, and the name of the health care provider who performed the vaccination.
As part of the national vaccination campaign against COVID-19 in Slovenia, the reporting of all providers of vaccination against COVID-19 to eRCO was established under the intense supervision of the Health Inspectorate. This provided for accurate real-time monitoring of vaccination against COVID-19 coverage and regular publishing of the results through an interactive dashboard on the NIJZ website (12). It also provided for the issuance of digital COVID-19 certificates (DCC) to vaccinated persons.
Due to the enhanced scrutiny of vaccination data by all stakeholders and their linkage to digital COVID-19 certificates essential for day-to-day activities of individuals during periods of non-pharmaceutical interventions nationwide, vaccination providers identified and corrected data-entry errors swiftly. Possible limitations regarding the data quality may include some remaining data-entry errors. In addition to legal obligation to report, the good completeness of data on vaccination against COVID-19 was additionally stimulated by reimbursing only the vaccinations reported to eRCO.
To conclude, we believe that our data on vaccination against COVID-19 are of good enough quality and well representative of the Slovenian population old 18 years or more, although no formal validation was performed.

National COVID-19 database
National COVID-19 database is a subset of National database on communicable diseases (Evidenca nalezljivih bolezni) based on the Communicable Diseases Act (9) and defined by the Healthcare Databases Act (4).
in March 2020, with the epidemic of COVID-19 declared in Slovenia, mandatory reporting of every confirmed case of SARS-CoV-2 infection in accordance with the case definition (2)  In addition to legal obligation to report, the completeness of COVID-19 cases in the national COVID-19 database was stimulated by the reimbursement of testing costs only, if testing data was reported to the CPDR. Since the data about positive SARS-CoV-2 testing results entered in the CPDR were also the basis for issuing of digital COVID-19 certificates (DCC) for individuals with previous COVID-19, data entry mistakes by reporting testing providers were identified and corrected swiftly.
It is a fact that not all previous COVID-19 cases are recorded in the COVID-19 database, as not all SARS-CoV-2 infections were diagnosed. Some infected individuals were asymptomatic or had only mild symptoms and were not tested for SARS-CoV-2. In addition, all individuals with positive self-test result for SARS-CoV-2 infection may have not asked for confirmatory testing. However, we believe that a great majority of previous COVID-19 cases were diagnosed and reported to the CPDR and consequently recorded in the national COVID-19 database.
To conclude, we believe that our COVID-19 data are of good enough quality and well representative of the Slovenian population old 18 years or more, although no formal validation was performed.