Monitoring of anti-SARS-CoV-2 IgG antibody immune responses in two cohorts of Hungarian healthcare workers following infection or immunization / Az anti-SARS-CoV-2-IgG-antitest-immunválaszok monitorozása magyarországi egészségügyi dolgozók két kohorszában fertozést, illetve immunizálást követoen.

Összefoglaló. Bevezetés: A SARS-CoV-2-fertozések és az anti-SARS-CoV-2-vakcinák által kiváltott immunvédelem tartóssága, nagysága és különbségeinek háttere nem teljesen tisztázott, az oltási protokollok optimális idozítése vitatott. Célkituzés: A humorális immunválaszok nagyságát, idobeli változását, a reinfekciók gyakoriságát, demográfiai és klinikai paraméterekkel való összefüggését vizsgáltuk magyarországi egészségügyi dolgozóknál. Módszerek: Megyei egyetemi oktató kórházunkban prospektív, longitudinális vizsgálatot végeztünk egészségügyi dolgozók két csoportjában. 1. kohorsz: SARS-CoV-2-fertozésen átesett, oltatlan 42 dolgozó (no: 100%) antinukleokapszid-IgG-szintjét mértük 8 hónapon keresztül (2020. június-2021. február). Az immunválasznak a változását és az életkorral, a krónikus betegségekkel, a vércsoporttal és a tünetek súlyosságával való összefüggését vizsgáltuk. 2. kohorsz: két dózis mRNS-vakcinával (Pfizer-BioNTech) végzett immunizálást követoen, fertozésnaiv 49 dolgozó (no: 73%) anti-spike-RBD-protein-IgG-szintjét monitoroztuk 8 hónapig (2020. december-2021. augusztus). Medián analízis, lineáris regresszió, ANCOVA, Kruskal-Wallis- és Skillings-Mack-teszt-elemzéseket végeztünk. Eredmények: 1. kohorsz: az IgG-szintek átlagosan a betegség 4-es súlyossági kategóriájában voltak a legmagasabbak, a negatív tartományba csökkenés medián ideje 6 hónap volt. 2. kohorsz: a második vakcina hatására az IgG-szint a 25-szörösére nott, majd 210 nap után a csúcsszint 6%-ra csökkent. Az ellenanyagtiter negatív összefüggést mutatott az idosebb életkorral és a férfinemmel. Tünetmentes (újra)fertozodést valószínusítettünk a fertozésen átesettek 17%-ánál és az immunizált kohorsz 14%-ánál. Az érintettek magas kockázatú osztályokon dolgoztak. Következtetés: 6 hónap után mind a fertozésen átesettek, mind az immunizáltak jelentosen csökkeno IgG-védelmet mutattak. A (re)infekciók átlagosan 15%-ban, tünetmentesen zajlottak. Az eredmények megerosítik az oltás hatékonyságát a betegség megelozésében, a harmadik emlékezteto vakcina fontosságát 6 hónap után és az anti-SARS-CoV-2-IgG-monitorozás potenciális értékét. Orv Hetil. 2022; 163(12): 455-462. INTRODUCTION: The length, level and variation of immune responses to infection with SARS-CoV-2 or following anti-SARS-CoV-2 vaccination remains unclear, optimal (re)vaccination protocols remain debated. OBJECTIVE: We investigated the magnitude of humoral immune responses, their over-time changes, the frequency of (re)infections and the association with demographic and clinical parameters in Hungarian healthcare workers. METHODS: We conducted a prospective, longitudinal study in two groups of healthcare workers of a public, county-level teaching hospital. Cohort 1: The anti-nucleocapsid IgG levels of 42 workers (female: 100%) were followed up over 8 months after SARS-CoV-2 infection (June 2020-February 2021). The change in humoral immune response and its associations with age, existing chronic conditions, blood type and severity of symptoms were investigated. Cohort 2: The anti-spike-RBD protein IgG levels of 49 workers (female: 73%) with no prior COVID-19 infection were monitored over 8 months (December 2020-August 2021) following immunisation with two doses of mRNA vaccine (Pfizer-BioNTech). Analyses included median analysis, linear regression, ANCOVA, Kruskal-Wallis and Skilling-Mack tests. RESULTS: Cohort 1: IgG levels were on average the highest among those in illness severity category 4, the median time of IgG level reduction below the positive test cut-off was 6 months. Cohort 2: The IgG levels increased 25-fold between the first and second immunisations, but decreased to 6% of the peak level after 210 days. They showed an overall negative association with older age and male sex. The suspected levels of (re)infections were 17% and 14% within the infected and the immunised cohorts, respectively, all symptomless. Those affected all worked on high-risk wards. CONCLUSION: Both the infected and the immunised cohorts showed significantly declining IgG protections beyond 6 months. The average observed rate of (re)infections was 15%, all asymptomatic. Our findings are confirmative of the effectiveness of vaccination to prevent illness, the importance of booster vaccination due to declining humoral immune protection beyond 6 months, and the potential value of anti-SARS-CoV-2 IgG monitoring. Orv Hetil. 2022; 163(12): 455-462.

Nationwide effectiveness of five SARS-CoV-2 vaccines in Hungary-the HUN-VE study.

OBJECTIVES: The Hungarian vaccination campaign was conducted with five different vaccines during the third wave of the coronavirus disease 2019 (COVID-19) pandemic in 2021. This observational study (HUN-VE: Hungarian Vaccine Effectiveness) estimated vaccine effectiveness against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19-related mortality in 3.7 million vaccinated individuals. METHODS: Incidence rates of SARS-CoV-2 infection and COVID-19-related mortality were calculated using data from the National Public Health Centre surveillance database. Estimated vaccine effectiveness was calculated as 1 - incidence rate ratio ≥7 days after the second dose for each available vaccine versus an unvaccinated control group using mixed-effect negative binomial regression controlling for age, sex and calendar day. RESULTS: Between 22 January 2021 and 10 June 2021, 3 740 066 Hungarian individuals received two doses of the BNT162b2 (Pfizer-BioNTech), HB02 (Sinopharm), Gam-COVID-Vac (Sputnik-V), AZD1222 (AstraZeneca), or mRNA-1273 (Moderna) vaccines. Incidence rates of SARS-CoV-2 infection and COVID-19-related death were 1.73-9.3/100 000 person-days and 0.04-0.65/100 000 person-days in the fully vaccinated population, respectively. Estimated adjusted effectiveness varied between 68.7% (95% CI 67.2%-70.1%) and 88.7% (95% CI 86.6%-90.4%) against SARS-CoV-2 infection, and between 87.8% (95% CI 86.1%-89.4%) and 97.5% (95% CI 95.6%-98.6%) against COVID-19-related death, with 100% effectiveness in individuals aged 16-44 years for all vaccines. CONCLUSIONS: Our observational study demonstrated the high or very high effectiveness of five different vaccines in the prevention SARS-CoV-2 infection and COVID-19-related death.

The Algerian Chapter of SARS-CoV-2 Pandemic: An Evolutionary, Genetic, and Epidemiological Prospect.

To explore the SARS-CoV-2 pandemic in Algeria, a dataset comprising ninety-five genomes originating from SARS-CoV-2 sampled from Algeria and other countries worldwide, from 24 December 2019, through 4 March 2021, was thoroughly examined. While performing a multi-component analysis regarding the Algerian outbreak, the toolkit of phylogenetic, phylogeographic, haplotype, and genomic analysis were effectively implemented. We estimated the Time to the Most Recent Common Ancestor (TMRCA) in reference to the Algerian pandemic and highlighted the multiple introductions of the disease and the missing data depicted in the transmission loop. In addition, we emphasized the significant role played by local and international travels in disease dissemination. Most importantly, we unveiled mutational patterns, the effect of unique mutations on corresponding proteins, and the relatedness regarding the Algerian sequences to other sequences worldwide. Our results revealed individual amino-acid replacements such as the deleterious replacement A23T in the orf3a gene in Algeria_EPI_ISL_418241. Additionally, a connection between Algeria_EPI_ISL_420037 and sequences originating from the USA was observed through a USA characteristic amino-acid replacement T1004I in the nsp3 gene, found in the aforementioned Algerian sequence. Similarly, successful tracing could be established, such as Algeria/G37318-8849/2020|EPI_ISL_766863, which was imported from Saudi Arabia during the pilgrimage. Lastly, we assessed the Algerian mitigation measures regarding disease containment using statistical analyses.

Analysis of COVID-19-Related RT-qPCR Test Results in Hungary: Epidemiology, Diagnostics, and Clinical Outcome.

Background: Effective testing is an essential tool for controlling COVID-19. We aimed to analyse the data from first-wave PCR test results in Hungary's Southern Transdanubian region to improve testing strategies. Methods: We performed a retrospective analysis of all suspected COVID-19 cases between 17 March and 8 May 2020, collecting epidemiological, demographic, clinical and outcome data (ICU admission and mortality) with RT-qPCR test results. Descriptive and comparative statistical analyses were conducted. Results: Eighty-six infections were confirmed among 3,657 tested patients. There was no difference between the positive and negative cases in age and sex distribution; however, ICU admission (8.1 vs. 3.1%, p = 0.006) and in-hospital mortality (4.7 vs. 1.6%, p = 0.062) were more frequent among positive cases. Importantly, none of the initially asymptomatic patients (n = 20) required ICU admission, and all survived. In almost all cases, if the first test was negative, second and third tests were performed with a 48-h delay for careful monitoring of disease development. However, the positive hit rate decreased dramatically with the second and third tests compared to the first (0.3 vs. 2.1%, OR = 0.155 [0.053-0.350]). Higher E-gene copy numbers were associated with a longer period of PCR positivity. Conclusion: In our immunologically naïve suspected COVID-19 population, coronavirus infection increased the need for intensive care and mortality by 3-4 times. In the event of the exponential phase of the pandemic involving a bottleneck in testing capacity, a second or third test should be reconsidered to diagnose more coronavirus infections.

Translating Scientific Knowledge to Government Decision Makers Has Crucial Importance in the Management of the COVID-19 Pandemic.

In times of epidemics and humanitarian crises, it is essential to translate scientific findings into digestible information for government policy makers who have a short time to make critical decisions. To predict how far and fast the disease would spread across Hungary and to support the epidemiological decision-making process, a multidisciplinary research team performed a large amount of scientific data analysis and mathematical and socioeconomic modeling of the COVID-19 epidemic in Hungary, including modeling the medical resources and capacities, the regional differences, gross domestic product loss, the impact of closing and reopening elementary schools, and the optimal nationwide screening strategy for various virus-spreading scenarios and R metrics. KETLAK prepared 2 extensive reports on the problems identified and suggested solutions, and presented these directly to the National Epidemiological Policy-Making Body. The findings provided crucial data for the government to address critical measures regarding health care capacity, decide on restriction maintenance, change the actual testing strategy, and take regional economic, social, and health differences into account. Hungary managed the first part of the COVID-19 pandemic with low mortality rate. In times of epidemics, the formation of multidisciplinary research groups is essential for policy makers. The establishment, research activity, and participation in decision-making of these groups, such as KETLAK, can serve as a model for other countries, researchers, and policy makers not only in managing the challenges of COVID-19, but in future pandemics as well.

Multiple SARS-CoV-2 Introductions Shaped the Early Outbreak in Central Eastern Europe: Comparing Hungarian Data to a Worldwide Sequence Data-Matrix.

Severe Acute Respiratory Syndrome Coronavirus 2 is the third highly pathogenic human coronavirus in history. Since the emergence in Hubei province, China, during late 2019, the situation evolved to pandemic level. Following China, Europe was the second epicenter of the pandemic. To better comprehend the detailed founder mechanisms of the epidemic evolution in Central-Eastern Europe, particularly in Hungary, we determined the full-length SARS-CoV-2 genomes from 32 clinical samples collected from laboratory confirmed COVID-19 patients over the first month of disease in Hungary. We applied a haplotype network analysis on all available complete genomic sequences of SARS-CoV-2 from GISAID database as of 21 April 2020. We performed additional phylogenetic and phylogeographic analyses to achieve the recognition of multiple and parallel introductory events into our region. Here, we present a publicly available network imaging of the worldwide haplotype relations of SARS-CoV-2 sequences and conclude the founder mechanisms of the outbreak in Central-Eastern Europe.