Mild respiratory COVID can cause multi-lineage neural cell and myelin dysregulation.

COVID survivors frequently experience lingering neurological symptoms that resemble cancer-therapy-related cognitive impairment, a syndrome for which white matter microglial reactivity and consequent neural dysregulation is central. Here, we explored the neurobiological effects of respiratory SARS-CoV-2 infection and found white-matter-selective microglial reactivity in mice and humans. Following mild respiratory COVID in mice, persistently impaired hippocampal neurogenesis, decreased oligodendrocytes, and myelin loss were evident together with elevated CSF cytokines/chemokines including CCL11. Systemic CCL11 administration specifically caused hippocampal microglial reactivity and impaired neurogenesis. Concordantly, humans with lasting cognitive symptoms post-COVID exhibit elevated CCL11 levels. Compared with SARS-CoV-2, mild respiratory influenza in mice caused similar patterns of white-matter-selective microglial reactivity, oligodendrocyte loss, impaired neurogenesis, and elevated CCL11 at early time points, but after influenza, only elevated CCL11 and hippocampal pathology persisted. These findings illustrate similar neuropathophysiology after cancer therapy and respiratory SARS-CoV-2 infection which may contribute to cognitive impairment following even mild COVID.

Passive immunotherapies for the next influenza pandemic.

Influenzavirus is among the most relevant candidates for a next pandemic. We review here the phylogeny of former influenza pandemics, and discuss candidate lineages. After briefly reviewing the other existing antiviral options, we discuss in detail the evidences supporting the efficacy of passive immunotherapies against influenzavirus, with a focus on convalescent plasma.

A Eurasian avian-like H1N1 swine influenza reassortant virus became pathogenic and highly transmissible due to mutations in its PA gene.

Previous studies have shown that the Eurasian avian-like H1N1 (EA H1N1) swine influenza viruses circulated widely in pigs around the world and formed multiple genotypes by acquiring non-hemagglutinin and neuraminidase segments derived from other swine influenza viruses. Swine influenza control is not a priority for the pig industry in many countries, and it is worrisome that some strains may become more pathogenic and/or transmissible during their circulation in nature. Our routine surveillance indicated that the EA H1N1 viruses obtained different internal genes from different swine influenza viruses and formed various new genotypes. In this study, we found that a naturally isolated swine influenza reassortant, A/swine/Liaoning/265/2017 (LN265), a representative strain of one of the predominant genotypes in recent years, is lethal in mice and transmissible in ferrets. LN265 contains the hemagglutinin, neuraminidase, and matrix of the EA H1N1 virus; the basic polymerase 2, basic polymerase 1, acidic polymerase (PA), and nucleoprotein of the 2009 H1N1 pandemic virus; and the nonstructural protein of the North American triple-reassortment H1N2 virus. By generating and testing a series of reassortants and mutants, we found that four gradually accumulated mutations in PA are responsible for the increased pathogenicity and transmissibility of LN265. We further revealed that these mutations increase the messenger RNA transcription of viral proteins by enhancing the endonuclease cleavage activity and viral RNA-binding ability of the PA protein. Our study demonstrates that EA H1N1 swine influenza virus became pathogenic and transmissible in ferrets by acquiring key mutations in PA and provides important insights for monitoring field strains with pandemic potential.

Antibody-Mediated Suppression Regulates the Humoral Immune Response to Influenza Vaccination in Humans.

BACKGROUND: Preexisting immunity, including memory B cells and preexisting antibodies, can modulate antibody responses to influenza in vivo to antigenically related antigens. We investigated whether preexisting hemagglutination inhibition (HAI) antibodies targeting the K163 epitope on the hemagglutinin (K163 antibodies) could affect antibody responses following vaccination with A/California/07/2009-like A(H1N1)pdm09 influenza viruses in humans. METHODS: Pre- and postvaccination sera collected from 300 adults (birth years, 1961-1998) in 6 seasons (2010-2016) were analyzed by HAI assays with 2 reverse genetics viruses and A(H1N1) viruses circulated from 1977 to 2018. Antibody adsorption assays were used to verify the preexisting K163 antibody-mediated suppression effect. RESULTS: Preexisting K163 antibody titers ≥80 affected HAI antibody responses following influenza vaccination containing A/California/07/2009-like antigens. At high K163 antibody concentrations (HAI antibody titers ≥160), all HAI antibody responses were suppressed. However, at moderate K163 antibody concentrations (HAI antibody titer, 80), only K163 epitope-specific antibody responses were suppressed, and novel HAI antibody responses targeting the non-K163 epitopes were induced by vaccination. Novel antibodies targeting non-K163 epitopes cross-reacted with newly emerging A(H1N1)pdm09 strains with a K163Q mutation rather than historic 1977-2007 A(H1N1) viruses. CONCLUSIONS: K163 antibody-mediated suppression shapes antibody responses to A(H1N1)pdm09 vaccination. Understanding how preexisting antibodies suppress and redirect vaccine-induced antibody responses is of great importance to improve vaccine effectiveness.

Multicountry Spread of Influenza A(H1N1)pdm09 Viruses with Reduced Oseltamivir Inhibition, May 2023-February 2024.

Since May 2023, a novel combination of neuraminidase mutations, I223V + S247N, has been detected in influenza A(H1N1)pdm09 viruses collected in countries spanning 5 continents, mostly in Europe (67/101). The viruses belong to 2 phylogenetically distinct groups and display ≈13-fold reduced inhibition by oseltamivir while retaining normal susceptibility to other antiviral drugs.

Persistence of Influenza H5N1 and H1N1 Viruses in Unpasteurized Milk on Milking Unit Surfaces.

Examining the persistence of highly pathogenic avian influenza A(H5N1) from cattle and human influenza A(H1N1)pdm09 pandemic viruses in unpasteurized milk revealed that both remain infectious on milking equipment materials for several hours. Those findings highlight the risk for H5N1 virus transmission to humans from contaminated surfaces during the milking process.

Avian Influenza A(H5N1) Neuraminidase Inhibition Antibodies in Healthy Adults after Exposure to Influenza A(H1N1)pdm09.

We detected high titers of cross-reactive neuraminidase inhibition antibodies to influenza A(H5N1) virus clade 2.3.4.4b in 96.8% (61/63) of serum samples from healthy adults in Hong Kong in 2020. In contrast, antibodies at low titers were detected in 42% (21/50) of serum samples collected in 2009. Influenza A(H1N1)pdm09 and A(H5N1) titers were correlated.

Characteristics of two zoonotic swine influenza A(H1N1) viruses isolated in Germany from diseased patients.

Interspecies transmission of influenza A viruses (IAV) from pigs to humans is a concerning event as porcine IAV represent a reservoir of potentially pandemic IAV. We conducted a comprehensive analysis of two porcine A(H1N1)v viruses isolated from human cases by evaluating their genetic, antigenic and virological characteristics. The HA genes of those human isolates belonged to clades 1C.2.1 and 1C.2.2, respectively, of the A(H1N1) Eurasian avian-like swine influenza lineage. Antigenic profiling revealed substantial cross-reactivity between the two zoonotic H1N1 viruses and human A(H1N1)pdm09 virus and some swine viruses, but did not reveal cross-reactivity to H1N2 and earlier human seasonal A(H1N1) viruses. The solid-phase direct receptor binding assay analysis of both A(H1N1)v showed a predominant binding to α2-6-sialylated glycans similar to human-adapted IAV. Investigation of the replicative potential revealed that both A(H1N1)v viruses grow in human bronchial epithelial cells to similar high titers as the human A(H1N1)pdm09 virus. Cytokine induction was studied in human alveolar epithelial cells A549 and showed that both swine viruses isolated from human cases induced higher amounts of type I and type III IFN, as well as IL6 compared to a seasonal A(H1N1) or a A(H1N1)pdm09 virus. In summary, we demonstrate a remarkable adaptation of both zoonotic viruses to propagate in human cells. Our data emphasize the needs for continuous monitoring of people and regions at increased risk of such trans-species transmissions, as well as systematic studies to quantify the frequency of these events and to identify viral molecular determinants enhancing the zoonotic potential of porcine IAV.

Different populations of A(H1N1)pdm09 viruses in a patient with hemolytic-uremic syndrome.

Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized. A patient (age group 5-15 years) displaying symptoms of hemolytic uremic syndrome died one day after hospitalization. qPCR, next generation sequencing, virus isolation, antigenic characterization, resistance analysis was performed and virus replication kinetics in well-differentiated airway cells were determined. Autopsy revealed hemorrhagic pneumonia as major pathological manifestation. Lung samples harbored a large population of A(H1N1)pdm09 viruses with the polymorphism H456H/Y in PB1 polymerase. The H456H/Y viruses replicated much faster to high viral titers than upper respiratory tract viruses in vitro. H456H/Y-infected air-liquid interface cultures of differentiated airway epithelial cells did reflect a more pronounced loss of ciliated cells. A different pattern of virus quasispecies was found in the upper airway samples where substitution S263S/F (HA1) was observed. The data support the notion that viral quasispecies had evolved locally in the lung to support high replicative fitness. This change may have initiated further pathogenic processes leading to rapid dissemination of inflammatory mediators followed by development of hemorrhagic lung lesions and fatal outcome.

Development of a virus-based affinity ultrafiltration method for screening virus-surface-protein-targeted compounds from complex matrixes: Herbal medicines as a case study.

Herbal medicines (HMs) are one of the main sources for the development of lead antiviral compounds. However, due to the complex composition of HMs, the screening of active compounds within these is inefficient and requires a significant time investment. We report a novel and efficient virus-based screening method for antiviral active compounds in HMs. This method involves the centrifugal ultrafiltration of viruses, known as the virus-based affinity ultrafiltration method (VAUM). This method is suitable to identify virus specific active compounds from complex matrices such as HMs. The effectiveness of the VAUM was evaluated using influenza A virus (IAV) H1N1. Using this method, four compounds that bind to the surface protein of H1N1 were identified from dried fruits of Terminalia chebula (TC). Through competitive inhibition assays, the influenza surface protein, neuraminidase (NA), was identified as the target protein of these four TC-derived compounds. Three compounds were identified by high performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS), and their anti-H1N1 activities were verified by examining the cytopathic effect (CPE) and by performing a virus yield reduction assay. Further mechanistic studies demonstrated that these three compounds directly bind to NA and inhibit its activity. In summary, we describe here a VAUM that we designed, one that can be used to accurately screen antiviral active compounds in HMs and also help improve the efficiency of screening antiviral drugs found in natural products.

Characterizing the antigenic evolution of pandemic influenza A (H1N1) pdm09 from 2009 to 2023.

The H1N1pdm09 virus has been a persistent threat to public health since the 2009 pandemic. Particularly, since the relaxation of COVID-19 pandemic mitigation measures, the influenza virus and SARS-CoV-2 have been concurrently prevalent worldwide. To determine the antigenic evolution pattern of H1N1pdm09 and develop preventive countermeasures, we collected influenza sequence data and immunological data to establish a new antigenic evolution analysis framework. A machine learning model (XGBoost, accuracy = 0.86, area under the receiver operating characteristic curve = 0.89) was constructed using epitopes, physicochemical properties, receptor binding sites, and glycosylation sites as features to predict the antigenic similarity relationships between influenza strains. An antigenic correlation network was constructed, and the Markov clustering algorithm was used to identify antigenic clusters. Subsequently, the antigenic evolution pattern of H1N1pdm09 was analyzed at the global and regional scales across three continents. We found that H1N1pdm09 evolved into around five antigenic clusters between 2009 and 2023 and that their antigenic evolution trajectories were characterized by cocirculation of multiple clusters, low-level persistence of former dominant clusters, and local heterogeneity of cluster circulations. Furthermore, compared with the seasonal H1N1 virus, the potential cluster-transition determining sites of H1N1pdm09 were restricted to epitopes Sa and Sb. This study demonstrated the effectiveness of machine learning methods for characterizing antigenic evolution of viruses, developed a specific model to rapidly identify H1N1pdm09 antigenic variants, and elucidated their evolutionary patterns. Our findings may provide valuable support for the implementation of effective surveillance strategies and targeted prevention efforts to mitigate the impact of H1N1pdm09.

Causal relationship between blood traits and severe influenza A(H1N1)pdm09 infection in East Asian: A Mendelian randomization study.

Although a range of blood traits have been reported to be associated with influenza A(H1N1)pdm09 (H1N1pdm09) disease severity, their underlying causal relationships and biological mechanisms have remained unclear. This study aimed to investigate the causal relationship between blood traits and H1N1pdm09 using a two-sample Mendelian randomization analysis. Based on the data from our in-house genome-wide association study (GWAS) on H1N1pdm09 disease severity (Ncase [severe] = 70, Ncontrol [mild] = 95) and GWAS summaries of 44 blood traits from Biobank Japan (N = 12 303-143 658), we identified the potential causal effect of blood traits on severe H1N1pdm09. The inverse variance weighted method analysis revealed significant causal effects of lower aspartate aminotransferase (AST, ß = -3.212, p = 0.019), low-density-lipoprotein cholesterol (LDL-C, ß = -1.372, p = 0.045), and basophil counts (Baso, ß = -1.638, p = 0.047) on severe H1N1pdm09 disease. Additionally, polygenic risk score analysis further confirmed genetic overlap between these blood traits and severe H1N1pdm09 disease. This study provided evidence linking the lower level of AST, LDL-C, and lower count of Baso with severe H1N1pdm09 disease, potentially identifying new therapeutic targets for patients with severe influenza.

Optimization of an allelic discrimination real-time RT-PCR assay for detection of H275Y oseltamivir resistance gene mutation among influenza A(H1N1)pdm09 patients from 2020 to 2022.

Influenza virus is known to cause mild to severe respiratory infections and is also prone to genetic mutations. Of all the mutations, neuraminidase (NA) gene mutations are a matter of concern, as most approved antivirals target this protein. During the 2020 influenza season, an emergence of mutation in the NA gene, affecting the binding of the World Health Organization (WHO)-recommended probes to the specific site of the NA gene, was reported by our group. As a result of this mutation, the WHO-recommended allelic discrimination real-time reverse transcriptase polymerase chain reaction (RT-PCR) assay was unable to detect wild-type (H275) or mutant oseltamivir-resistant (Y275) strains of influenza A(H1N1)pmd09 viruses. In the current study, the WHO-recommended probes were redesigned according to the mutation in the probe binding site. Fifty undetermined samples (2020-2021) from the previous study were retested with the newly designed probes and found to be positive for H275 and/or Y275. The results obtained were similar to the Sanger sequencing results from the previous study, suggesting that the redesigned probes were efficient in discriminating between wild-type and mutant-type viruses. Furthermore, 133 samples from 2022, making a total of 183 samples (2020-2022), were tested using improved allelic discrimination real-time RT-PCR, and the overall prevalence rate of oseltamivir resistance in 2020-2022 was found to be 0.54%.

Antigenic drift and immunity gap explain reduction in protective responses against influenza A(H1N1)pdm09 and A(H3N2) viruses during the COVID-19 pandemic: a cross-sectional study of human sera collected in 2019, 2021, 2022, and 2023.

BACKGROUND: Non-pharmaceutical interventions implemented during the COVID-19 pandemic resulted in a marked reduction in influenza infections globally. The absence of influenza has raised concerns of waning immunity, and potentially more severe influenza seasons after the pandemic. METHODS: To evaluate immunity towards influenza post-COVID-19 pandemic we have assessed influenza A epidemics in Norway from October 2016 to June 2023 and measured antibodies against circulating strains of influenza A(H1N1)pdm09 and A(H3N2) in different age groups by hemagglutination inhibition (HAI) assays in a total of 3364 serum samples collected in 2019, 2021, 2022 and 2023. RESULTS: Influenza epidemics in Norway from October 2016 until June 2023 were predominately influenza As, with a mixture of A(H1N1)pdm09 and A(H3N2) subtype predominance. We did not observe higher numbers of infections during the influenza epidemics following the COVID-19 pandemic than in pre-COVID-19 seasons. Frequencies of protective HAI titers against A(H1N1)pdm09 and A(H3N2) viruses were reduced in sera collected in 2021 and 2022, compared to sera collected in 2019. The reduction could, however, largely be explained by antigenic drift of new virus strains, as protective HAI titers remained stable against the same strain from one season to the next. However, we observed the development of an immunity gap in the youngest children during the pandemic which resulted in a prominent reduction in HAI titers against A(H1N1)pdm09 in 2021 and 2022. The immunity gap was partially closed in sera collected in 2023 following the A(H1N1)pdm09-dominated influenza seasons of 2022/2023. During the 2022/2023 epidemic, drift variants of A(H1N1)pdm09 belonging to the 5a.2a.1 clade emerged, and pre-season HAI titers were significantly lower against this clade compared to the ancestral 5a.2 clade. CONCLUSION: The observed reduction in protective antibodies against A(H1N1)pdm09 and A(H3N2) viruses post COVID-19 is best explained by antigenic drift of emerging viruses, and not waning of antibody responses in the general population. However, the absence of influenza during the pandemic resulted in an immunity gap in the youngest children. While this immunity gap was partially closed following the 2022/2023 influenza season, children with elevated risk of severe infection should be prioritized for vaccination.

Emergence of Eurasian Avian-Like Swine Influenza A (H1N1) virus in a child in Shandong Province, China.

BACKGROUND: Influenza A virus infections can occur in multiple species. Eurasian avian-like swine influenza A (H1N1) viruses (EAS-H1N1) are predominant in swine and occasionally infect humans. A Eurasian avian-like swine influenza A (H1N1) virus was isolated from a boy who was suffering from fever; this strain was designated A/Shandong-binzhou/01/2021 (H1N1). The aims of this study were to investigate the characteristics of this virus and to draw attention to the need for surveillance of influenza virus infection in swine and humans. METHODS: Throat-swab specimens were collected and subjected to real-time fluorescent quantitative polymerase chain reaction (RT‒PCR). Positive clinical specimens were inoculated onto Madin-Darby canine kidney (MDCK) cells to isolate the virus, which was confirmed by a haemagglutination assay. Then, whole-genome sequencing was carried out using an Illumina MiSeq platform, and phylogenetic analysis was performed with MEGA X software. RESULTS: RT‒PCR revealed that the throat-swab specimens were positive for EAS-H1N1, and the virus was subsequently successfully isolated from MDCK cells; this strain was named A/Shandong-binzhou/01/2021 (H1N1). Whole-genome sequencing and phylogenetic analysis revealed that A/Shandong-binzhou/01/2021 (H1N1) is a novel triple-reassortant EAS-H1N1 lineage that contains gene segments from EAS-H1N1 (HA and NA), triple-reassortant swine influenza H1N2 virus (NS) and A(H1N1) pdm09 viruses (PB2, PB1, PA, NP and MP). CONCLUSIONS: The isolation and analysis of the A/Shandong-binzhou/01/2021 (H1N1) virus provide further evidence that EAS-H1N1 poses a threat to human health, and greater attention should be given to the surveillance of influenza virus infections in swine and humans.

A sensitive fluorescence biosensor based on ligation-transcription and CRISPR/Cas13a-assisted cascade amplification strategies to detect the H1N1 virus.

We propose a sensitive H1N1 virus fluorescence biosensor based on ligation-transcription and CRISPR/Cas13a-assisted cascade amplification strategies. Products are generated via the hybridization of single-stranded DNA (ssDNA) probes containing T7 promoter and crRNA templates to a target RNA sequence using SplintR ligase. This generates large crRNA quantities in the presence of T7 RNA polymerase. At such crRNA quantities, ternary Cas13a, crRNA, and activator complexes are successfully constructed and activate Cas13a to enhance fluorescence signal outputs. The biosensor sensitively and specifically monitored H1N1 viral RNA levels down to 3.23 pM and showed good linearity when H1N1 RNA concentrations were 100 pM-1 µM. Biosensor specificity was also excellent. Importantly, our biosensor may be used to detect other viral RNAs by altering the sequences of the two probe junctions, with potential applications for the clinical diagnosis of viruses and other biomedical studies.

Using a targeted metabolomics approach to explore differences in ARDS associated with COVID-19 compared to ARDS caused by H1N1 influenza and bacterial pneumonia.

RATIONALE: Acute respiratory distress syndrome (ARDS) is a life-threatening critical care syndrome commonly associated with infections such as COVID-19, influenza, and bacterial pneumonia. Ongoing research aims to improve our understanding of ARDS, including its molecular mechanisms, individualized treatment options, and potential interventions to reduce inflammation and promote lung repair. OBJECTIVE: To map and compare metabolic phenotypes of different infectious causes of ARDS to better understand the metabolic pathways involved in the underlying pathogenesis. METHODS: We analyzed metabolic phenotypes of 3 ARDS cohorts caused by COVID-19, H1N1 influenza, and bacterial pneumonia compared to non-ARDS COVID-19-infected patients and ICU-ventilated controls. Targeted metabolomics was performed on plasma samples from a total of 150 patients using quantitative LC-MS/MS and DI-MS/MS analytical platforms. RESULTS: Distinct metabolic phenotypes were detected between different infectious causes of ARDS. There were metabolomics differences between ARDSs associated with COVID-19 and H1N1, which include metabolic pathways involving taurine and hypotaurine, pyruvate, TCA cycle metabolites, lysine, and glycerophospholipids. ARDSs associated with bacterial pneumonia and COVID-19 differed in the metabolism of D-glutamine and D-glutamate, arginine, proline, histidine, and pyruvate. The metabolic profile of COVID-19 ARDS (C19/A) patients admitted to the ICU differed from COVID-19 pneumonia (C19/P) patients who were not admitted to the ICU in metabolisms of phenylalanine, tryptophan, lysine, and tyrosine. Metabolomics analysis revealed significant differences between C19/A, H1N1/A, and PNA/A vs ICU-ventilated controls, reflecting potentially different disease mechanisms. CONCLUSION: Different metabolic phenotypes characterize ARDS associated with different viral and bacterial infections.

Influenza a H1N1 infection complicated with encephalopathy and acute pancreatitis: a case report.

This paper reports a case of influenza complicated with influenza associated encephalopathy complicated with acute pancreatitis. This kind of disease is relatively rare, we hope to draw people's attention to it in order to improve early detection and prognosis.

Evaluation of disease severity and prediction of severe cases in children hospitalized with influenza A (H1N1) infection during the post-COVID-19 era: a multicenter retrospective study.

BACKGROUND: The rebound of influenza A (H1N1) infection in post-COVID-19 era recently attracted enormous attention due the rapidly increased number of pediatric hospitalizations and the changed characteristics compared to classical H1N1 infection in pre-COVID-19 era. This study aimed to evaluate the clinical characteristics and severity of children hospitalized with H1N1 infection during post-COVID-19 period, and to construct a novel prediction model for severe H1N1 infection. METHODS: A total of 757 pediatric H1N1 inpatients from nine tertiary public hospitals in Yunnan and Shanghai, China, were retrospectively included, of which 431 patients diagnosed between February 2023 and July 2023 were divided into post-COVID-19 group, while the remaining 326 patients diagnosed between November 2018 and April 2019 were divided into pre-COVID-19 group. A 1:1 propensity-score matching (PSM) was adopted to balance demographic differences between pre- and post-COVID-19 groups, and then compared the severity across these two groups based on clinical and laboratory indicators. Additionally, a subgroup analysis in the original post-COVID-19 group (without PSM) was performed to investigate the independent risk factors for severe H1N1 infection in post-COIVD-19 era. Specifically, Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select candidate predictors, and logistic regression was used to further identify independent risk factors, thus establishing a prediction model. Receiver operating characteristic (ROC) curve and calibration curve were utilized to assess discriminative capability and accuracy of the model, while decision curve analysis (DCA) was used to determine the clinical usefulness of the model. RESULTS: After PSM, the post-COVID-19 group showed longer fever duration, higher fever peak, more frequent cough and seizures, as well as higher levels of C-reactive protein (CRP), interleukin 6 (IL-6), IL-10, creatine kinase-MB (CK-MB) and fibrinogen, higher mechanical ventilation rate, longer length of hospital stay (LOS), as well as higher proportion of severe H1N1 infection (all P < 0.05), compared to the pre-COVID-19 group. Moreover, age, BMI, fever duration, leucocyte count, lymphocyte proportion, proportion of CD3+ T cells, tumor necrosis factor α (TNF-α), and IL-10 were confirmed to be independently associated with severe H1N1 infection in post-COVID-19 era. A prediction model integrating these above eight variables was established, and this model had good discrimination, accuracy, and clinical practicability. CONCLUSIONS: Pediatric H1N1 infection during post-COVID-19 era showed a higher overall disease severity than the classical H1N1 infection in pre-COVID-19 period. Meanwhile, cough and seizures were more prominent in children with H1N1 infection during post-COVID-19 era. Clinicians should be aware of these changes in such patients in clinical work. Furthermore, a simple and practical prediction model was constructed and internally validated here, which showed a good performance for predicting severe H1N1 infection in post-COVID-19 era.

Origin of the H1N1 (Russian influenza) pandemic of 1977-A risk assessment using the modified Grunow-Finke tool (mGFT).

In 1977, the Soviet Union (Union of Soviet Socialist Republics [USSR]) notified the World Health Organization (WHO) about an outbreak of H1N1 influenza, which later spread to many countries. The H1N1 strain of 1977 reappeared after being absent from the world for over 20 years. This pandemic simultaneously spread to several cities in the USSR and China. Many theories have been postulated to account for the emergence of this pandemic, including natural and unnatural origins. The purpose of this study was to use the modified Grunow-Finke risk assessment tool (modified Grunow-Finke tool [mGFT]) to investigate the origin of the 1977 H1N1 pandemic. Data was collected from WHO archives and published documents. The assessment of the pandemic's origin involved the utilization of a modified version of the original Grunow-Finke risk assessment tool (GFT). Using the mGFT, the final score was 37 out of 60 points (probability: 62%), indicating a high likelihood that the Russian influenza pandemic of 1977 was of unnatural origin. Several variables supported this finding, including the sudden re-emergence of a previously extinct strain, a genetic signature of laboratory modification for vaccine development, and unusual epidemiology. Inter-rater reliability was moderate to high. By applying the mGFT to the 1977 Russian influenza pandemic, we established a high probability that this pandemic was of unnatural origin. Although this is not definitive, it is consistent with the possibility that it originated from an incompletely attenuated live influenza vaccine. The mGFT is a useful risk analysis tool to evaluate the origin of epidemics.