Atypical Influenza A(H3N2) Activity Patterns in Germany, 2021-2023, and Characterization of Newly Emerged Virus Clades.

The first waves of the COVID-19 pandemic were accompanied by an unprecedented decrease of influenza activity which persisted throughout the 2020/21 and 2021/22 winter seasons. Here, we report on the unusual influenza circulation patterns that followed in the year 2022, which was dominated throughout by A(H3N2) influenza viruses. After a delayed spring wave in 2022, A(H3N2) influenza viruses circulated at low levels throughout the summer and rose to a prominent, prematurely-timed fall/winter wave peaking in December, with highest positivity rates observed in 10-12-years old children.

SARS-CoV-2 evolution on a dynamic immune landscape.

Since the onset of the pandemic, many SARS-CoV-2 variants have emerged, exhibiting substantial evolution in the virus' spike protein, the main target of neutralizing antibodies. A plausible hypothesis proposes that the virus evolves to evade antibody-mediated neutralization (vaccine- or infection-induced) to maximize its ability to infect an immunologically experienced population. Because viral infection induces neutralizing antibodies, viral evolution may thus navigate on a dynamic immune landscape that is shaped by local infection history.

A robust, scalable, and cost-efficient approach to whole genome sequencing of RSV directly from clinical samples.

Unlabelled: Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections causing significant morbidity and mortality among children and the elderly; two RSV vaccines and a monoclonal antibody have recently been approved. Thus, there is an increasing need for a detailed and continuous genomic surveillance of RSV circulating in resource-rich and resource-limited settings worldwide. However, robust, cost-effective methods for whole genome sequencing of RSV from clinical samples that are amenable to high-throughput are still scarce.

Preparing for the Next Influenza Season: Monitoring the Emergence and Spread of Antiviral Resistance.

Purpose: The relaxation of pandemic restrictions in 2022 has led to a reemergence of respiratory virus circulation worldwide and anticipation of substantial influenza waves for the 2022/2023 Northern Hemisphere winter. Therefore, the antiviral susceptibility profiles of human influenza viruses circulating in Germany were characterized.

Methods: Between October 2019 (week 40/2019) and March 2022 (week 12/2022), nasal swabs from untreated patients with acute respiratory symptoms were collected in the national German influenza surveillance system.

Vaccination against Borna Disease: Overview, Vaccine Virus Characterization and Investigation of Live and Inactivated Vaccines.

(1) Background: Vaccination of horses and sheep against Borna disease (BD) was common in endemic areas of Germany in the 20th century but was abandoned in the early 1990s. The recent occurrence of fatal cases of human encephalitis due to Borna disease virus 1 (BoDV-1) has rekindled the interest in vaccination. (2) Methods: The full genomes of the BD live vaccine viruses "Dessau" and "Giessen" were sequenced and analyzed for the first time.

SARS-CoV-2 Omicron variant is attenuated for replication in a polarized human lung epithelial cell model.

SARS-CoV-2 and its emerging variants of concern remain a major threat for global health. Here we introduce an infection model based upon polarized human Alveolar Epithelial Lentivirus immortalized (hAELVi) cells grown at the air-liquid interface to estimate replication and epidemic potential of respiratory viruses in the human lower respiratory tract. hAELVI cultures are highly permissive for different human coronaviruses and seasonal influenza A virus and upregulate various mediators following virus infection.

Advancing Precision Vaccinology by Molecular and Genomic Surveillance of Severe Acute Respiratory Syndrome Coronavirus 2 in Germany, 2021.

Background: Comprehensive pathogen genomic surveillance represents a powerful tool to complement and advance precision vaccinology. The emergence of the Alpha variant in December 2020 and the resulting efforts to track the spread of this and other severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern led to an expansion of genomic sequencing activities in Germany.

Methods: At Robert Koch Institute (RKI), the German National Institute of Public Health, we established the Integrated Molecular Surveillance for SARS-CoV-2 (IMS-SC2) network to perform SARS-CoV-2 genomic surveillance at the national scale, SARS-CoV-2-positive samples from laboratories distributed across Germany regularly undergo whole-genome sequencing at RKI.

An early warning system for emerging SARS-CoV-2 variants.

Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence, and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic.

A Genetic Variation of Lipopolysaccharide Binding Protein Affects the Inflammatory Response and Is Associated with Improved Outcome during Sepsis.

LPS binding protein (LBP) is an important innate sensor of microbial cell wall structures. Frequent functionally relevant mutations exist and have been linked to influence susceptibility to and course of bacterial infections. We examined functional properties of a single nucleotide polymorphism resulting in an exchange of phenylalanine to leucine at position 436 of LBP (rs2232618) and compared the frequent variant of the molecule with the rare one in ligand binding experiments.

Virological Surveillance and Molecular Characterization of Human Parainfluenzavirus Infection in Children with Acute Respiratory Illness: Germany, 2015-2019.

Human parainfluenza viruses (HPIVs) are important causes of respiratory illness, especially in young children. However, surveillance for HPIV is rarely performed continuously, and national-level epidemiologic and genetic data are scarce. Within the German sentinel system, to monitor acute respiratory infections (ARI), 4463 respiratory specimens collected from outpatients < 5 years of age between October 2015 and September 2019 were retrospectively screened for HPIV 1-4 using real-time PCR.

[SARS-CoV-2 transmission routes and implications for self- and non-self-protection].

The global spread of the coronavirus SARS-CoV‑2 has massively impacted health, economic, and social systems. Although effective vaccines are now available, it is likely that this pathogen will become endemic and stay with us for years. In order to most effectively protect others and oneself from SARS-CoV‑2 infection, an understanding of how SARS-CoV‑2 is transmitted is of utmost importance.

Trends in respiratory virus circulation following COVID-19-targeted nonpharmaceutical interventions in Germany, January - September 2020: Analysis of national surveillance data.

Background: During the initial COVID-19 response, Germany's Federal Government implemented several nonpharmaceutical interventions (NPIs) that were instrumental in suppressing early exponential spread of SARS-CoV-2. NPI effect on the transmission of other respiratory viruses has not been examined at the national level thus far.

Methods: Upper respiratory tract specimens from 3580 patients with acute respiratory infection (ARI), collected within the nationwide German ARI Sentinel, underwent RT-PCR diagnostics for multiple respiratory viruses.

COVIDStrategyCalculator: A software to assess testing and quarantine strategies for incoming travelers, contact management, and de-isolation.

While large-scale vaccination campaigns against SARS-CoV-2 are rolled out at the time of writing, non-pharmaceutical interventions (NPIs), including the isolation of infected individuals and quarantine of exposed individuals, remain central measures to contain the spread of SARS-CoV-2. Strategies that combine NPIs with innovative SARS-CoV-2 testing strategies may increase containment efficacy and help to shorten quarantine durations. We developed a user-friendly software tool that implements a recently published stochastic within-host viral dynamics model that captures temporal attributes of the viral infection, such as test sensitivity, infectiousness, and the occurrence of symptoms.

An intra-host SARS-CoV-2 dynamics model to assess testing and quarantine strategies for incoming travelers, contact management, and de-isolation.

Non-pharmaceutical interventions (NPIs) remain decisive tools to contain SARS-CoV-2. Strategies that combine NPIs with testing may improve efficacy and shorten quarantine durations. We developed a stochastic within-host model of SARS-CoV-2 that captures temporal changes in test sensitivities, incubation periods, and infectious periods.

[Recording of SARS-CoV-2 laboratory tests in Germany].

The collection of data on SARS-CoV‑2 tests is central to the assessment of the infection rate in the context of the COVID-19 pandemic. At the Robert Koch Institute (RKI), data collected from various laboratory data recording systems are consolidated. First, this article aims to exemplify significant aspects regarding test procedures.

Zoonotic infection with swine A/H1N1 influenza virus in a child, Germany, June 2020.

A zoonotic A/sw/H1N1 1C.2.2 influenza virus infection was detected in a German child that presented with influenza-like illness, including high fever.

From CD4-Based Initiation to Treating All HIV-Infected Adults Immediately: An Evidence-Based Meta-analysis.

Background: The World Health Organization (WHO) Consolidated antiretroviral therapy (ART) guidelines set the CD4 T-cell counts threshold to 500 cells/mm in 2013, and 2015 guidelines recommend treating all HIV-infected adults regardless of their CD4 T-cell counts. To inform the decision-making around ART guidelines for people living with HIV, we systematically reviewed the literature to estimate differences in clinical benefits between individuals starting treatment with baseline CD4 T-cell counts ≥500 cells/mm (early initiation) as compared to <500 cells/mm (deferred initiation).

Methods: We systematically searched the electronic databases and abstracts for randomized controlled trials (RCT) and observational studies.

Adjuvant-induced Human Monocyte Secretome Profiles Reveal Adjuvant- and Age-specific Protein Signatures.

Adjuvants boost vaccine responses, enhancing protective immunity against infections that are most common among the very young. Many adjuvants activate innate immunity, some via Toll-Like Receptors (TLRs), whose activities varies with age. Accordingly, characterization of age-specific adjuvant-induced immune responses may inform rational adjuvant design targeting vulnerable populations.

Toll-like receptor 1 variations influence susceptibility and immune response to Mycobacterium tuberculosis.

Background: Tuberculosis (TB), a disease caused by Mycobacterium tuberculosis (MTB) infection, is still a global public health problem. TB susceptibility varies greatly in infected individuals, and mycobacterial recognition by the innate immune system likely affects disease course and outcome. This research describes a single nucleotide polymorphism in the Toll-like receptor (TLR) 1 gene that functionally alters the innate immune response to MTB and is associated with TB susceptibility in India.

Cryptococcal osteomyelitis in an adolescent survivor of T-cell acute lymphoblastic leukemia.

Cryptococcosis is infrequent in children, and isolated cryptococcal osteomyelitis is rarely encountered. Here, we describe a 14-year-old patient in remission from T-cell acute lymphoblastic leukemia with osteomyelitis because of Cryptococcus neoformans var. grubii.