A Perspective on Current Flavivirus Vaccine Development: A Brief Review.

The flavivirus genus contains several clinically important pathogens that account for tremendous global suffering. Primarily transmitted by mosquitos or ticks, these viruses can cause severe and potentially fatal diseases ranging from hemorrhagic fevers to encephalitis. The extensive global burden is predominantly caused by six flaviviruses: dengue, Zika, West Nile, yellow fever, Japanese encephalitis and tick-borne encephalitis. Several vaccines have been developed, and many more are currently being tested in clinical trials. However, flavivirus vaccine development is still confronted with many shortcomings and challenges. With the use of the existing literature, we have studied these hurdles as well as the signs of progress made in flavivirus vaccinology in the context of future development strategies. Moreover, all current licensed and phase-trial flavivirus vaccines have been gathered and discussed based on their vaccine type. Furthermore, potentially relevant vaccine types without any candidates in clinical testing are explored in this review as well. Over the past decades, several modern vaccine types have expanded the field of vaccinology, potentially providing alternative solutions for flavivirus vaccines. These vaccine types offer different development strategies as opposed to traditional vaccines. The included vaccine types were live-attenuated, inactivated, subunit, VLPs, viral vector-based, epitope-based, DNA and mRNA vaccines. Each vaccine type offers different advantages, some more suitable for flaviviruses than others. Additional studies are needed to overcome the barriers currently faced by flavivirus vaccine development, but many potential solutions are currently being explored.

Tick-borne encephalitis epidemiology and surveillance in Poland, and comparison with selected European countries before and during the COVID-19 pandemic, 2008 to 2020.

BackgroundTick-borne encephalitis (TBE) is the most common viral central nervous system (CNS) infection in Poland. Previous research suggests that its incidence was underestimated in the pre-pandemic period. The COVID-19 pandemic caused a considerable burden on surveillance systems, which could further impact reporting.AimWe aimed to assess the completeness of reporting of TBE in the years 2008 to 2020 and explore the potential impact of the COVID-19 pandemic on reporting to the epidemiological surveillance system, compared with hospitalisations for TBEV and other viral neuro-infections.MethodsWe compared the Polish epidemiology of TBE and other viral infections of the CNS from national surveillance reports with data on hospitalisations from 2008 to 2020 and data from selected European countries.ResultsBetween 2008 and 2020, 3,016 TBE cases were reported to surveillance compared with 3,620 hospitalisations. There was an increasing trend in hospitalisations, while surveillance data demonstrated the opposite, with the largest discrepancy observed in the first pandemic year (354 hospitalisations vs 159 cases reported to surveillance). Serological testing for TBE was used more in the known endemic region of north-eastern Poland and less in non-endemic areas. Other European countries reported higher TBE case numbers and an increase during the COVID-19 pandemic, whereas Poland observed an opposite trend.ConclusionThe sensitivity of TBE surveillance in Poland requires improvement. There are considerable regional differences. Regions that test for TBE intensively report most cases. Policymakers should be made aware of the value of quality epidemiological data for planning prophylactic measures in risk areas.

[Influence of the COVID-19 pandemic on the occurrence of neurological infectious diseases]. / Einfluss der COVID-19-Pandemie auf das Auftreten neuroinfektiologischer Erkrankungen.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic a wide range of hygiene measures were implemented to contain the spread of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Besides a mitigation of SARS-CoV­2, a decline in the number of other respiratory tract infections could be observed. Interestingly, the numbers for some infections of the central nervous system (CNS) decreased as well. OBJECTIVE: This review article shows the development of important CNS infections in Germany during the COVID-19 pandemic. MATERIAL AND METHOD: This article is based on relevant literature on the epidemiology of CNS infections during the COVID-19 pandemic up to autumn 2022. RESULTS: During the COVID-19 pandemic the frequency of bacterial meningitis caused by Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae significantly declined. The frequency of viral meningitis, particularly those caused by Enterovirus, decreased as well. In contrast, the number of patients suffering from tick-borne encephalitis significantly increased within the first year of the pandemic. DISCUSSION: During the pandemic there was a decrease in cases of bacterial and viral meningitis, most likely due to the general containment strategies and social contact restrictions. The increase of infections transmitted by ticks could be a consequence of changed leisure activities during the pandemic.

Redox Imbalance and Its Metabolic Consequences in Tick-Borne Diseases.

One of the growing global health problems are vector-borne diseases, including tick-borne diseases. The most common tick-borne diseases include Lyme disease, tick-borne encephalitis, human granulocytic anaplasmosis, and babesiosis. Taking into account the metabolic effects in the patient's body, tick-borne diseases are a significant problem from an epidemiological and clinical point of view. Inflammation and oxidative stress are key elements in the pathogenesis of infectious diseases, including tick-borne diseases. In consequence, this leads to oxidative modifications of the structure and function of phospholipids and proteins and results in qualitative and quantitative changes at the level of lipid mediators arising in both reactive oxygen species (ROS) and ROS enzyme-dependent reactions. These types of metabolic modifications affect the functioning of the cells and the host organism. Therefore, links between the severity of the disease state and redox imbalance and the level of phospholipid metabolites are being searched, hoping to find unambiguous diagnostic biomarkers. Assessment of molecular effects of oxidative stress may also enable the monitoring of the disease process and treatment efficacy.

Subsequent vaccinations in VITT patients other than SARS-CoV2 vaccination

Introduction Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare, but severe side effect after vaccination with adenovirus vector-based vaccines (ChAdOx1 nCoV-19, AstraZeneca and Ad26.COV2.S, Johnson & Johnson/ Janssen) in which platelet activating anti-platelet factor 4 (PF4) antibodies cause thrombocytopenia and thrombosis at unusual sites. Patients and treating physicians are concerned about whether other vaccinations can also trigger thrombosis in patients with a history of VITT. We showed that VITT patients can safely receive their second and third vaccination against Covid-19 with an mRNA-based vaccine. [1] However, there is limited information on whether other vaccines than against Covid-19 could booster platelet activating anti-PF4 antibodies. Uncertainty increased after a report of VITT caused by human papilloma vaccination. [2] Method In our follow-up study of patients with laboratory confirmed VITT (EUPAS45098), an anti-PF4/heparin IgG enzyme immune assay (EIA) and a PF4-dependent platelet activation assay (PIPA) were performed at regular intervals and after each vaccination reported to us. Results Seventy-one VITT patients (43 female, median age at VITT diagnosis 48, range 18-80) were followed for a median of 56 weeks (range: 13-77 weeks). During the follow-up period, eight vaccinations other than against Covid-19 were reported: Six vaccinations against influenza (three Influvac, two Vaxigrip Tetra, one Influsplit Tetra) and two consecutive vaccinations against tick-borne encephalitis (TBE) in one patient. In six patients who received vaccination against influenza, all patients showed decreasing or stable EIA optical density (OD) levels. None of them showed a reactivation of platelet-activating anti- PF4-antibodies in the PIPA. The patient who was vaccinated against TBE twice showed stable EIA OD levels and remained negative in the PIPA throughout. No new thrombosis or recurrent thrombocytopenia were observed after any vac- cination. Five out of six patients still received therapeutic anticoagulation, one patient did not receive any anticoagulative drug (Fig. 1). Conclusion Similar to observations after consecutive mRNA-vaccinations against Covid-19 in VITT patients, vaccinations against influenza and TBE very unlikely reactivate platelet-activating anti-PF4-antibodies. Further follow up of the VITT patient cohort is performed to detect any new safety signal related to recurrence of VITT. (Table Presented).

Spatiotemporal spread of tick-borne encephalitis in the EU/EEA, 2012 to 2020.

BackgroundTick-borne encephalitis (TBE) is a vaccine-preventable disease involving the central nervous system. TBE became a notifiable disease on the EU/EEA level in 2012.AimWe aimed to provide an updated epidemiological assessment of TBE in the EU/EEA, focusing on spatiotemporal changes.MethodsWe performed a descriptive analysis of case characteristics, time and location using data of human TBE cases reported by EU/EEA countries to the European Centre for Disease Prevention and Control with disease onset in 2012-2020. We analysed data at EU/EEA, national, and subnational levels and calculated notification rates using Eurostat population data. Regression models were used for temporal analysis.ResultsFrom 2012 to 2020, 19 countries reported 29,974 TBE cases, of which 24,629 (98.6%) were autochthonous. Czechia, Germany and Lithuania reported 52.9% of all cases. The highest notification rates were recorded in Lithuania, Latvia, and Estonia (16.2, 9.5 and 7.5 cases/100,000 population, respectively). Fifty regions from 10 countries, had a notification rate ≥ 5/100,000. There was an increasing trend in number of cases during the study period with an estimated 0.053 additional TBE cases every week. In 2020, 11.5% more TBE cases were reported than predicted based on data from 2016 to 2019. A geographical spread of cases was observed, particularly in regions situated north-west of known endemic regions.ConclusionA close monitoring of ongoing changes to the TBE epidemiological situation in Europe can support the timely adaption of vaccination recommendations. Further analyses to identify populations and geographical areas where vaccination programmes can be of benefit are needed.

Human Arboviral Infections in Italy: Past, Current, and Future Challenges.

Arboviruses represent a public health concern in many European countries, including Italy, mostly because they can infect humans, causing potentially severe emergent or re-emergent diseases, with epidemic outbreaks and the introduction of endemic circulation of new species previously confined to tropical and sub-tropical regions. In this review, we summarize the Italian epidemiology of arboviral infection over the past 10 years, describing both endemic and imported arboviral infections, vector distribution, and the influence of climate change on vector ecology. Strengthening surveillance systems at a national and international level is highly recommended to be prepared to face potential threats due to arbovirus diffusion.

Comparison of Extraction Methods for the Detection of Tick-Borne Encephalitis Virus RNA in Goat Raw Milk and Cream Cheese.

Infection with the tick-borne encephalitis virus (TBEV) can cause meningitis, meningoencephalitis and myelitis in humans. TBEV is an enveloped RNA virus of the family Flaviviridae, which is mostly transmitted via tick bites. However, transmission by consumption of virus-contaminated goat raw milk and goat raw milk products has also been described. Only a few methods have been reported for the detection of TBEV in food so far. Here, we compare different virus extraction methods for goat raw milk and goat raw milk cream cheese and subsequent detection of TBEV-RNA by RT-qPCR. Langat virus (LGTV), a naturally attenuated TBEV strain, was used for artificial contamination experiments. Mengovirus and the human coronavirus 229E were compared to assess their suitability to serve as internal process controls. Out of three tested extraction protocols for raw milk, sample centrifugation followed by direct RNA extraction from the aqueous interphase yielded the best results, with a recovery rate (RR) of 31.8 ± 4.9% for LGTV and a detection limit of 6.7 × 103 LGTV genome copies/ml. Out of two methods for cream cheese, treatment of the samples with TRI Reagent® and chloroform prior to RNA extraction showed the best RR of 4.7 ± 1.6% for LGTV and a detection limit of 9.4 × 104 LGTV genome copies/g. RRs of Mengovirus and LGTV were similar for both methods; therefore, Mengovirus is suggested as internal process control virus. The developed methods may be useful for screening or surveillance studies, as well as in outbreak investigations.

[130th anniversary of virology].

130 years ago, in 1892, our great compatriot Dmitry Iosifovich Ivanovsky (18641920) discovered a new type of pathogen viruses. Viruses have existed since the birth of life on Earth and for more than three billion years, as the biosphere evolved, they are included in interpopulation interactions with representatives of all kingdoms of life: archaea, bacteria, protozoa, algae, fungi, plants, invertebrates, and vertebrates, including the Homo sapiens (Hominidae, Homininae). Discovery of D.I. Ivanovsky laid the foundation for a new science virology. The rapid development of virology in the 20th century was associated with the fight against emerging and reemerging infections, epidemics (epizootics) and pandemics (panzootics) of which posed a threat to national and global biosecurity (tick-borne and other encephalitis, hemorrhagic fevers, influenza, smallpox, poliomyelitis, HIV, parenteral hepatitis, coronaviral and other infections). Fundamental research on viruses created the basis for the development of effective methods of diagnostics, vaccine prophylaxis, and antiviral drugs. Russian virologists continue to occupy leading positions in some priority areas of modern virology in vaccinology, environmental studies oz zoonotic viruses, studies of viral evolution in various ecosystems, and several other areas. A meaningful combination of theoretical approaches to studying the evolution of viruses with innovative methods for studying their molecular genetic properties and the creation of new generations of vaccines and antiviral drugs on this basis will significantly reduce the consequences of future pandemics or panzootics. The review presents the main stages in the formation and development of virology as a science in Russia with an emphasis on the most significant achievements of soviet and Russian virologists in the fight against viral infectious diseases.

VERIFICATION OF A CASE OF MIXED INFECTION WITH LYME DISEASE, TICK-BORNE ENCEPHALITIS AND COVID-19

Background. The relationship between pathogens of new diseases and tick-borne infections is an underinvestigated direction in the problem of infectious diseases. The aim. To show the features ofidentifying the markers ofBorrelia burgdorferi, tick-borne encephalitis and SARS-CoV-2 pathogens on the example of a case of a triple mixed infection (Lyme disease, tick-borne encephalitis and COVID-19) and using comprehensive studies. Methods. In 2019-2021, a comprehensive study of 7 blood samples from a patient with mixed infection was carried out. We used real-time polymerase chain reaction (PCR), enzyme immunoassay (ELISA) and determined antigen, IgM, IgG antibodies, and avidity index (AI) of IgG antibodies. Results. Ixodid tick-borne borreliosis was diagnosed in a patient 5 months after contagion. Only high-avid Lyme-IgG antibodies were detected. Low-avid Lyme-IgG antibodies appeared against the background of a reduced general condition. Atthe same time, high-avidIgG(cut-offindex (COI)- 7.8)andIgM(COI= 1.2)antibod-ies to the TBE virus were detected. In July 2020, the patient was infected with SARS-CoV-2. TBE virus which passed into the body simultaneously with Borrelia in the fall of 2019 was activated. Although the patient did not have specific symptoms of TBE, in subsequentbloodsamples (No. 4, 5, 6)we foundTBEVantigen (opticaldensity (OD) - 4.3;1.9and2.0respectively)andIgM(COI= 1.3;0,9and0respectively). These results were recognized as TBEV activation, which contributed to an increase in the avidity of IgG antibodies (AI = 65 %;100 % and 63 % respectively). IgM antibodies to SARS-CoV-2 virus were not detected, as opposed to the high levels of IgG (COI = 8.2;8.1;8.4 and 14.7 respectively). Conclusions. Therefore, using not only the common methods of diagnosing (PCR andELISA), butalso the determination ofthe antibody avidity degree, we have shown that when analyzing a case of a triple mixed infection, B. burgdorferi dominates in the human body and causes a long-term chronic course of the disease. © 2022 Acta Biomedica Scientifica. All rights reserved.

Tick-Borne Encephalitis Virus RNA Found in Frozen Goat's Milk in a Family Outbreak.

Tick-borne encephalitis (TBE) is one of the commonest arthropod-borne viral diseases in Middle-East Europe and North Asia. The main reservoir of the virus is comprised of small rodents and domestic mammals with the common tick (Ixodes) being the usual vector. The clinical spectrum of TBE ranges from mild meningitis to severe meningoencephalomyelitis. This disease can lead to severe sequelae and has a mortality up to 2% in Europe. Even though the majority of cases are transmitted through bites of infected ticks, infections through ingestion of contaminated milk and dairy products from farms in endemic areas have been reported. We report a family outbreak of a febrile disease, initially suggestive of human-to-human infection, during the early summertime in Austria. Tick-borne encephalitis was diagnosed following consumption of unpasteurised goat's milk and the virus was subsequently detected in frozen milk samples. Although this is a rare manifestation of TBE, this case series shows that TBE should be included in the differential diagnosis of an outbreak of febrile disease, and a careful clinical history with reference to unpasteurized dairy products is crucial in order to prevent further disease spread. The best preventive measure is active immunisation of people living in, or travelling to, endemic areas.

Paraneoplastic Anti-Ma2-antibody associated encephalitis: a case report

Background and aims: A 36-years-old man was admitted to the neurological department with complaints on severe drowsiness, sudden falling asleep, fatigue, unsteadiness when standing and walking, inability to speak and write intelligibly, increased body temperature and appetite. The first symptoms occurred 2 month before admission. To note, before the onset of the disease, patient felt a pain and dissension in the testes. Methods: There weren't any significant findings in neurological status, unless mild cognitive (MMSE - 20 points) and behavioral impairments. He had been administered a list of analysis: hematology (WBC 10.9 10

Vaccination against tick-borne encephalitis

During the ongoing COVID-19 epidemic, the number of reported cases of selected infectious diseases is decreasing thanks to the applied distance measures. In contrast, in 2020, the increase in tick-borne encephalitis continued for the sixth year. As found by an agency survey on a representative sample of the population, despite the high awareness in society of the existence of this disease (92%), the possibility of vaccination (81%), the vaccination rate in the Czech Republic is still only 33%. In the Czech Republic, the highest incidence of tick-borne encephalitis is reported among all countries of the European Union, yet the vaccination rate is the lowest of all endemic countries. In 2020, the number of reported cases of tick-borne encephalitis rose to a record 854 cases and the corresponding incidence of 7.98 per 100 thousand inhabitants. The most affected age group for 2020 was the 60-64 age group, but a doubling of the number of reported diseases compared to the previous year was observed even in the smallest and preschool children. For the evaluation of vaccination programmes at national levels, the analysis of vaccination coverage data is one of the main starting points. To monitor vaccination coverage in the case of vaccinations not covered by public health insurance, we use agency surveys that we have had available according to a comparable methodology for the last three years, not only in the Czech Republic, but also in neighboring countries. By introducing a reimbursed vaccination against tick-borne encephalitis from 1 January 2022 for people over 50 years of age, it will be possible to use data from the National Register of Reimbursed Health Services (NR-HZS) to monitor vaccination coverage in this group. From 1 January 2022, the obligation of health service providers to create records of vaccinations carried out in the national register, which will be administered by the State Institute for Drug Control (SÚKL) as an electronic vaccination card system, has come into force. In the future, this offers another possibility of recording vaccinations carried out and monitoring vaccination coverage for vaccinations not covered by health insurance, but recommended. Without sufficient data on vaccination coverage, it is impossible to monitor the level of immunization and susceptibility of the population to this disease. © 2022, Czech Medical Association J.E. Purkyne. All rights reserved.

Virus et Interférons : le choc des Titans

The interferon (IFN) response is a critical arm of the innate immune response and a major host defense mechanism against viral infections. Numerous genes that contribute to this antiviral state remain to be identified and characterized. Using large-scale loss-of-function strategies, we screened siRNAs or gRNAs libraries targeting hundreds of IFNstimulated genes (ISGs) in IFN-treated cells infected with human RNA viruses, including SARS-CoV-2, Zika virus or tick-borne encephalitis virus. We recovered previously unrecognized human genes able to modulate the replication of these RNA viruses in an IFN-dependent manner. For instance, we identified the chromatin remodeling protein MTA2 as a potent flavivirus-specific antiviral factor. Mechanistic studies to decipher the molecular mechanisms by which these novel antiviral genes are functioning are on-going. We are also expanding our studies to the identification and characterization of ISGs in animal species that serve as viral reservoirs, such as bats. Our work should open new perspectives to target weakness points in the life cycle of these emerging RNA viruses.

Tick-Borne Encephalitis Risk Increases with Dog Ownership, Frequent Walks, and Gardening: A Case-Control Study in Germany 2018-2020.

In Germany, tick-borne encephalitis (TBE) infections mainly occur in southern regions. Despite recent increases in incidence, TBE vaccination coverage remains low, necessitating additional preventive strategies against TBE. Our case-control study in Southern Germany from 2018 to 2020 mapped knowledge/application of tick-protective strategies and identified TBE risk factors. We calculated odds ratios (OR), with 95% confidence intervals (CI). We interviewed 581 cases and 975 matched controls. Most participants recalled lifetime tick bites, mainly while walking, gardening, or hiking. However, only 45% of cases noticed ticks during exposure time; another 12% reported unpasteurized milk intake. While tick-protection knowledge was satisfactory, application lagged behind. Risk factors included dog ownership (OR = 2.45, 95% CI: 1.85-3.24), walks ≥ 4×/week (OR = 2.11, 95% CI: 1.42-3.12), gardening ≥ 4×/week (OR = 1.83, 95% CI: 1.11-3.02), and garden proximity < 250 m of forests (OR = 2.54, 95% CI: 1.82-3.56). Applying ≥2 tick-protective strategies (OR = 0.52, 95% CI: 0.40-0.68) and keeping lawns mowed (OR = 0.63, 95% CI: 0.43-0.91) were inversely associated with TBE. In 2020 (likely pandemic-related), cases reported significantly more walks than previously, potentially explaining the record high case numbers. Our findings provide guidance on targets for TBE prevention. Persons with gardens near forests, frequent outdoor activities, or dogs could particularly benefit from targeted information, including on vaccination and preventing tick bites.

Severe tick-borne encephalitis in a patient recovered from COVID 19.

North-eastern Poland is an endemic region for tick-borne encephalitis (TBE). The COVID-19 pandemic overlapped with the activity period of ticks that are the main vectors for TBE. As we know from short observation worldwide, SARS-CoV-2 virus affects significantly the immune system and can lead to serious complications of other infections even in previously healthy patients. A 24-year-old female patient, who lived close to the forest, was admitted to the Department of Neurology at Medical University of Bialystok with fever, dizziness, and progressive left-sided hemiparesis for three days. She had no medical history of chronic disease and was not vaccinated against TBE. The patient had SARS-CoV-2 infection three weeks prior to admission to the hospital (positive IgG against SARS-CoV-2). During COVID-19 infection she had fever, myalgia, a mild dyspnoea without indications for oxygen therapy and recovered after one week. During hospitalisation in the Department of Neurology the patient presented neck stiffness, progressing tetraparesis, dysarthria and weakness of the neck muscles. The magnetic resonance of the head revealed numerous lesions, mainly in both thalamus, longitudinal lesion was found in the cervical spinal cord. The cerebrospinal fluid analysis indicated lymphocytic inflammation. A high level of TBE antibodies in both serum and CSF was found. After immunoglobulin and symptomatic treatment her condition gradually improved. The recovery after SARS-CoV-2 infection overlapping with TBE might have influenced the course of tick-borne disease in a bad manner. The correct diagnosis can be a challenge as COVID-19 can lead to further complications, also neurological. The co-incidence we observed is very rare, however during the pandemic it is pivotal to remember about possible occurrence of other infections and their atypical course.

Incidence of Tick-Borne Encephalitis during the COVID-19 Pandemic in Selected European Countries.

Ixodes ricinus ticks are one of the most important vectors and reservoirs of infectious diseases in Europe, and tick-borne encephalitis (TBE) is one of the most dangerous human diseases transmitted by these vectors. The aim of the present study was to investigate the TBE incidence in some European countries during the COVID-19 pandemic. To this end, we analyzed the data published by the European Center for Disease Prevention and Control (ECDC) and Eurostat on the number of reported TBE and COVID-19 cases in 2020 and TBE cases in 2015-2019 (reference period). Significant differences in the TBE incidence were found between the analyzed countries. The highest TBE incidence was found in Lithuania (25.45/100,000 inhabitants). A high TBE incidence was also observed in Central European countries. In 12 of the 23 analyzed countries, there was significant increase in TBE incidence during the COVID-19 pandemic during 2020 compared to 2015-2019. There was no correlation between the incidence of COVID-19 and TBE and between the availability of medical personnel and TBE incidence in the studied countries. In conclusion, Central Europe and the Baltic countries are areas with a high risk of TBE infection. Despite the COVID-19 pandemic and imposed restrictions, the incidence of TBE is increasing in more than half of the analyzed countries.

Socioeconomic analysis of infectious diseases based on different scenarios using uncertain SEIAR system dynamics with effective subsystems and ANFIS

Purpose This paper aims to analyze the socioeconomic impacts of infectious diseases based on uncertain behaviors of social and effective subsystems in the countries. The economic impacts of infectious diseases in comparison with predicted gross domestic product (GDP) in future years could be beneficial for this aim along with predicted social impacts of infectious diseases in countries. Design/methodology/approach The proposed uncertain SEIAR (susceptible, exposed, infectious, asymptomatic and removed) model evaluates the impacts of variables on different trends using scenario base analysis. This model considers different subsystems including healthcare systems, transportation, contacts and capacities of food and pharmaceutical networks for sensitivity analysis. Besides, an adaptive neuro-fuzzy inference system (ANFIS) is designed to predict the GDP of countries and determine the economic impacts of infectious diseases. These proposed models can predict the future socioeconomic trends of infectious diseases in each country based on the available information to guide the decisions of government planners and policymakers. Findings The proposed uncertain SEIAR model predicts social impacts according to uncertain parameters and different coefficients appropriate to the scenarios. It analyzes the sensitivity and the effects of various parameters. A case study is designed in this paper about COVID-19 in a country. Its results show that the effect of transportation on COVID-19 is most sensitive and the contacts have a significant effect on infection. Besides, the future annual costs of COVID-19 are evaluated in different situations. Private transportation, contact behaviors and public transportation have significant impacts on infection, especially in the determined case study, due to its circumstance. Therefore, it is necessary to consider changes in society using flexible behaviors and laws based on the latest status in facing the COVID-19 epidemic. Practical implications The proposed methods can be applied to conduct infectious diseases impacts analysis. Originality/value In this paper, a proposed uncertain SEIAR system dynamics model, related sensitivity analysis and ANFIS model are utilized to support different programs regarding policymaking and economic issues to face infectious diseases. The results could support the analysis of sensitivities, policies and economic activities.

Clinical and diagnostic manifestations of tickborne mixed infection in combination with COVID-19.

The coexistence of various pathogens inside the patient's body is one of the poorly studied and current issues. The aim of the study is to identify the relationship between the indicators of complex laboratory diagnostics and the clinical manifestations of a mixed disease during subsequent infection with the SARS-CoV-2 virus using the example of a case of chronic encephalitis-borreliosis infection. Seven blood serum samples were collected from the patient over the course of a year. For the etiological verification of the causative agents of TBE, Lyme disease and COVID-19, the methods of ELISA and PCR diagnostics were used. The patient was diagnosed with Lyme disease on the basis of the detection of IgG antibodies to Borrelia 5 months after the onset of the disease, since she denied the tick bite. In the clinical picture, there was an articular syndrome and erythema migrans. Later, IgG antibodies to the TBEV were found in the blood. Throughout the study, IgM antibodies to Borrelia were not detected. The exacerbation of Lyme disease could be judged by the clinical manifestations of this disease and by the growth of specific IgG antibodies. A feature of this case was that during an exacerbation of the Lyme disease, an infection with the SARS-CoV-2 virus occurred. Treatment (umifenovir, hydroxychloroquine, azithromycin, ceftriaxone) was prescribed, which improved the condition of the underlying disease, decreased joint pain, decreased IgG levels to borrelia. However, during this period, serological markers of TBEV appear: antigen, IgM antibodies, and the titer of IgG antibodies increases. Most likely, this was facilitated by the switching of the immune system to the SARS-CoV-2 virus, with the simultaneous suppression of borrelia with antibiotics and the appointment of hydroxychloroquine, which has an immunosuppressive effect. Despite the activation of the virus, clinical manifestations of TBE were not observed in the patient, which is most likely associated with infection with a weakly virulent TBEV strain. The further course of tick-borne infections revealed the dominant influence of B. burgdorferi in relation to TBEV. Laboratory studies have shown that suppression of the activity of the borreliosis process by etiotropic treatment subsequently led to the activation of the persistent TBEV.