Niños hospitalizados con influenza en un hospital pediátrico de Argentina durante 2019-2022: ¿qué ha cambiado luego de la pandemia por COVID-19? / Children with influenza admitted at a children's hospital in Argentina in the 2019­2022 period: What has changed after the COVID-19 pandemic?

Introducción. Durante 2020 y 2021, la circulación de los virus influenza se mantuvo por debajo de lo esperado en todo el mundo. En Argentina, en el año 2022 observamos una circulación ininterrumpida de influenza todo el año. Nuestros objetivos fueron describir los patrones de circulación y las características clínicas de niños internados con influenza. Población y métodos. Estudio retrospectivo, analítico, observacional. Se incluyeron todos los niños internados en un centro pediátrico con detección del virus influenza durante los años 2019-2022. Resultados. Se internaron 138 pacientes en 4 años; en 2019 se observó una tasa del 4,5/1000 egresos hospitalarios mientras que en 2022, fue del 15,1/1000. En 2020 y 2021 no hubo casos. En el 2019 la mayoría de los casos ocurrieron en invierno, la causa de la internación fue la infección respiratoria aguda baja (IRAB) en el 79 % y se detectó influenza A en el 92 % de los casos. En el 2022, la mayoría de los casos ocurrieron en primavera, el 62 % presentó IRAB y en el 56 % se detectó influenza A. Ambos períodos tuvieron similares frecuencias de vacunación y de comorbilidades. Conclusiones. En el 2022 se registraron más internaciones por influenza, lo que podría corresponder a que se realizaron métodos diagnósticos moleculares, que son más sensibles, y se observó un cambio en la estacionalidad con más casos en primavera. En 2019 predominó influenza A en infecciones del tracto respiratorio inferior, mientras que en el 2022 influenza A y B fueron similares, y hubo más formas extrapulmonares.

Introduction. During 2020 and 2021, the circulation of influenza virus remained below expectations worldwide. In Argentina, in 2022, we observed an uninterrupted circulation of influenza all year round. Our objectives were to describe the circulation patterns and clinical characteristics of hospitalized children with influenza. Population and methods. Retrospective, analytical, observational study. All children with influenza virus admitted to a children's hospital during the 2019­2022 period were included. Results. A total of 138 patients were admitted over 4 years; in 2019, the rate of hospital discharges was 4.5/1000, compared to 15.1/1000 in 2022. No cases were recorded in 2020 and 2021. In 2019, most cases were observed in the winter; in 79%, the cause was acute lower respiratory tract infection (ALRTI); influenza A was detected in 92%. In 2022, most cases occurred in the spring; 62% developed ALRTI; and influenza A was detected in 56%. Similar rates of vaccination and comorbidities were observed in both periods. Conclusions. In 2022, more hospitalizations due to influenza were recorded, which may have correlated with the use of more sensitive molecular diagnostic testing and a change in seasonality, with more cases observed in the spring. In 2019, influenza A predominated in lower respiratory tract infections, while in 2022, cases of influenza A and B were similar, with more extra-pulmonary forms.

Comparison of CT Features of Omicron and Influenza A-H1N1-Associated Viral Pneumonia:Initial Onset and Follow-Up / 中国医学影像学杂志

Purpose To compare the CT imaging features of the novel coronavirus Omicron variant and influenza A-H1N1-associated viral pneumonia,and to investigate the factors associated with the uptake process of the two pneumonias.Materials and Methods A total of 43 patients with Omicron virus pneumonia(Omicron group)and 30 patients with influenza A(H1N1)virus pneumonia[influenza A(H1N1)group]in Civil Aviation General Hospital from December 2022 to March 2023 were retrospectively collected.The clinical data of the two groups were compared,including age,gender,symptoms(fever or not),duration of symptoms and incidence of complications.White blood cells,monocytes,lymphocytes,neutrophils,C-reactive protein,etc.]and initial and follow-up CT imaging features[lesion density,distribution,signs and qualitative CT severity score(CTSS)].Results The mean age of patients in Omicron group was higher versus that in H1N1 group[(68.61±15.94)years vs.(51.20±16.39)years,P<0.000 1],and the fever rate in Omicron group(58.1%vs.86.7%,P=0.009)and monocyte count[(0.40±0.16)vs.(0.58±0.19),P<0.000 1]were lower than those in the influenza A(H1N1)group.Chest CT showed that the lesions of patients in the Omicron group were mainly distributed under the pleura,and the lesions of patients in the influenza A(H1N1)group were mainly distributed under the pleura and along the bronchovascular bundle(χ2=8.592,P=0.035).Patients in the Omicron group were more likely to have interlobular septal thickening(χ2=11.753,P=0.001),paving pattern(χ2=16.216,P<0.000 1),air bronchogram(χ2=16.216,P<0.000 1),pleural effusion(P=0.039)and pleural thickening(χ2=4.067,P=0.044)than patients in the influenza A(H1N1)group,while patients in the influenza A(H1N1)group were more likely to have nodules than those in the omicron group(χ2=6.971,P=0.008).The CTSS scores of patients in the omicron group were higher than those in the influenza A(H1N1)group at the initial diagnosis(Z=413,P=0.009)and follow-up(Z=107,P=0.027).The correlation between the change of follow-up CTSS and the initial CTSS in the Omicron group was the strongest(r=0.689,P<0.000 1).There was the strongest correlation between the change of follow-up CTSS and the duration of symptoms in influenza A(H1N1)group(r=0.954,P<0.000 1).Conclusion Patients in the Omicron group have a higher range of initial and follow-up lesions than those in influenza A(H1N1)group,and the degree of pneumonia absorption in the omicron group may be related to the initial CTSS,whereas in the influenza A(H1N1)group it may be related to the duration of symptoms.

Etiological analysis of influenza-like cases in Taizhou City， Zhejiang Province from 2013 to 2022 / 上海预防医学

ObjectiveTo analyze the etiological results of influenza-like case surveillance in Taizhou， Zhejiang Province from 2013 to 2022， to timely understand the epidemic trend of influenza viruses and the change rule of dominant virus strains， and to provide reference for the prevention and control of influenza in this region. MethodsInfluenza virus nucleic acid was detected by real-time PCR in 24 183 influenza-like cases. ResultsThe positive rate of influenza virus in 24 183 samples was 18.43%， the highest positive type was seasonal H3 （37.34%）. There was no a significant difference in positive rate between different genders （χ2=0.148， P=0.701）. There was significant difference in the positive rate among different age groups （χ2=496.626， P<0.001）， and the highest positive rate was found in the 25‒59 age group （22.56%）. The positive rate in different years was statistically significant （χ2=1 670.922， P<0.001）. The positive rate from 2013 to 2019 showed an upward trend （χ2=30.559， P<0.001）. The lowest positive rate was in 2020 （0.04%）， and the positive rate from 2021 to 2022 showed an upward trend （χ2=304.465， P<0.001）. The dominant strains were different in different monitoring years. There was a significant difference in the positive rate of influenza in different months （χ2=1 652.455， P<0.001）， and the peak of influenza was mainly concentrated in December‒March and July‒August. ConclusionFrom 2013 to 2022， the positive rate of influenza virus in Taizhou showed a wavy dynamic change， and the dominant strains were different in different years， presenting alternate epidemic characteristics. It is necessary to strengthen the etiological surveillance of influenza virus and improve the prevention and control measures with influenza vaccine.

Host Targets Interacting with Influenza Virus NP and Mechanism of Gardenia Jasminoides Iridoid Glycoside Against Influenza Virus / 中国实验方剂学杂志

ObjectiveTo explore host factors interacting with influenza virus nucleoprotein （NP） and study their effects on influenza virus replication， as well as the mechanism of gardenia jasminoides iridoid glycoside （IGE） in inhibiting influenza virus. MethodA yeast two-hybrid system was utilized to screen host factors that interacted with influenza virus NP. Heterogeneous nuclear ribonucleoprotein D0 （HNRNPD）， glucosamine-6-phosphate deaminase 1 （GNPDA1）， poly（rC）-binding protein 1 （PCBP1）， and protein inhibitor of activated signal transducer and activator of transcription （STAT） protein 1 （PIAS1） were validated by immunoprecipitation assay. The effects of PIAS1 and HNRNPD on influenza virus replication were compared by a dual luciferase assay， and the effects of IGE on influenza virus replication were examined in the presence of transfected ribonucleoprotein （RNP） and knockdown of PIAS1. ICR mice were randomly divided into a normal group， model group， oseltamivir phosphate group， and high， medium， and low dose IGE groups， with 10 mice in each group. In addition to the normal group， each group was infected with the influenza A virus FM1 strain by nasal drip to establish a viral pneumonia model. The high， medium， and low dose IGE groups were given drugs of 50， 25， and 12.5 mg∙kg-1 by gavage， and the oseltamivir phosphate group was given the drug of 27.5 mg∙kg-1 by gavage. Equal amounts of distilled water were instilled in the normal and model groups for four consecutive days. Later， protein expression of PIAS1， NP， phosphorylated （p）-STAT3， STAT3， p-STAT1， and STAT1 were detected in the lung tissue by Western blot. ResultIn yeast two-hybrid assays， 16 potential host targets interacting with influenza virus NP were identified. Immunoprecipitation experiments revealed that HNRNPD and PIAS1 could interact with influenza virus NP. The dual luciferase reporter assays found that both PIAS1 knockdown and overexpression significantly affected IAV RNP activity （P<0.05， P<0.01）， and the effect of HNRNPD on IAV RNP was not significant. Both high and low dose IGE groups reduced influenza virus replication （P<0.05） and reversed the increase in influenza virus replication caused by the knockdown of PIAS1（P<0.05， P<0.01）. The expressions of PIAS1， NP， p-STAT3， p-STAT1， and STAT1 in the lung tissue of infected mice were reduced to different degrees in each IGE group （P<0.05， P<0.01）. ConclusionPIAS1 interacts with influenza virus NP and is able to inhibit influenza virus replication. IGE may exert antiviral effects by inhibiting the activity of IAV RNP through the PIAS1/STAT1 pathway.

Signal mining and analysis of adverse events of oseltamivir，zanamivir and baloxavir marboxil / 中国药房

OBJECTIVE To provide reference for safe drug use in clinic by mining the adverse drug events （ADE） of 3 kinds of anti-influenza A virus drugs （oseltamivir， zanamivir， baloxavir marboxil）. METHODS The ADE data of oseltamivir， zanamivir and baloxavir marboxil were collected from the FDA adverse event reporting system （FAERS） between the first quarter in 2004 and the third quarter in 2022， and mined by using reporting odds ratio （ROR） method. The designated medical events （DME） were estimated. The system organ class （SOC） in the Medical Dictionary for Regulatory Activities （MedDRA， version 25.0） was used for the classification and statistics of drug ADE terminology. RESULTS A total of 12 636， 1 749 and 1 283 ADE reports were retrieved for oseltamivir， zanamivir and baloxavir marboxil， involving 26， 16 and 17 SOCs， respectively. Oseltamivir was strongly associated with sleep terror， abnormal behavior， hallucination and delirium. Zanamivir was implicated in abnormal behavior， delirium， incoherence， and altered state of consciousness with prominent signal intensity. Baloxavir marboxil was strongly associated with ischemic colitis， hemorrhagic cystitis， erythema multiforme and melaena. Erythema multiform was detected in the DME of three drugs with strong signals. CONCLUSIONS When clinically administering the three drugs， it is crucial to pay close attention to both common adverse reactions and those ADEs that are not explicitly mentioned in the drug instructions. For oseltamivir， clinicians should exercise caution due to the potential risk of acute kidney injury and fulminant hepatitis， necessitating regular monitoring of the patient’s liver and kidney function. When prescribing zanamivir， caution should be exercised due to ADEs related to the respiratory system， including acute respiratory distress syndrome and respiratory failure， necessitating close monitoring of the patient’s respiratory status. Similarly， for baloxavir marboxil， clinicians should be vigilant for potential ADEs such as erythema multiforme and rhabdomyolysis.

Effect and Mechanism of Menispermi Rhizoma Total Alkaloids on Antiviral Infection / 中国实验方剂学杂志

ObjectiveTo investigate the antiviral effect of Menispermi Rhizoma total alkaloids and its relationship with the type Ⅰ interferon （IFN-Ⅰ） signaling pathway. MethodThe effects of Menispermi Rhizoma total alkaloids on the intracellular replication of influenza A virus （H1N1）， vesicular stomatitis virus （VSV）， and cerebral myocarditis virus （EMCV） were detected by fluorescent inverted microscope， flow cytometry， Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）， and Western blot. A mouse model infected with H1N1 was constructed， and the mice were divided into a control group， H1N1 model group， Menispermi Rhizoma total alkaloids groups （10， 20， 30 mg·kg-1）， and oseltamivir group （40 mg·kg-1）， so as to study the effects on the weight and survival rate of infected mice. Real-time PCR was used to detect the activation effect of Menispermi Rhizoma total alkaloids on the IFN-Ⅰ pathway in cells， and the relationship between the antiviral effect of Menispermi Rhizoma total alkaloids in IFNAR1 knockout A549 cells （IFNAR1-/--A549） and IFN-Ⅰ pathway was detected. ResultCompared with the control group， the virus proliferated significantly in the model group （P<0.01）. Compared with the model group， Menispermi Rhizoma total alkaloids could significantly inhibit the replication of H1N1， VSV， and EMCV in vitro （P<0.01）， inhibit the weight loss of the mice infected with the H1N1 in vivo， and improve the survival rate of mice （P<0.05）. In addition， Menispermi Rhizoma total alkaloids activated the IFN-I pathway and relied on this pathway to exert the function of antiviral infection. ConclusionMenispermi Rhizoma total alkaloids exert antiviral effects in vivo and in vitro by activating the IFN-Ⅰ pathway.

Long-term outcomes for epidemic viral pneumonia survivors after discharge from the intensive care unit: a systematic review

ABSTRACT Objective To review the long-term outcomes (functional status and psychological sequelae) of survivors of critical illnesses due to epidemic viral pneumonia before the COVID-19 pandemic and to establish a benchmark for comparison of the COVID-19 long-term outcomes. Methods This systematic review of clinical studies reported the long-term outcomes in adults admitted to intensive care units who were diagnosed with viral epidemic pneumonia. An electronic search was performed using databases: MEDLINE®, Web of Science™, LILACS/IBECS, and EMBASE. Additionally, complementary searches were conducted on the reference lists of eligible studies. The quality of the studies was assessed using the Newcastle-Ottawa Scale. The results were grouped into tables and textual descriptions. Results The final analysis included 15 studies from a total of 243 studies. This review included 771 patients with Influenza A, Middle East Respiratory Syndrome, and Severe Acute Respiratory Syndrome. It analyzed the quality of life, functionality, lung function, mortality, rate of return to work, rehospitalization, and psychiatric symptoms. The follow-up periods ranged from 1 to 144 months. We found that the quality of life, functional capacity, and pulmonary function were below expected standards. Conclusion This review revealed great heterogeneity between studies attributed to different scales, follow-up time points, and methodologies. However, this systematic review identified negative long-term effects on patient outcomes. Given the possibility of future pandemics, it is essential to identify the long-term effects of viral pneumonia outbreaks. This review was not funded. Prospero database registration: (www.crd.york.ac.uk/prospero) under registration ID CRD42021190296.

Advances in animal models of influenza A virus infection / 中华微生物学和免疫学杂志

Influenza has caused high morbidity and mortality worldwide, seriously endangering human health and life. The continuous mutation of influenza virus has brought new challenges to the prevention and treatment of influenza. Animal models provide convenience for a comprehensive understanding of influenza virus pathogenesis, transmission mechanism, vaccine development, and evaluation of therapeutic effects. The construction and use of animal models of influenza virus infection vary in different studies, and the application of different animal models also has its own characteristics. This article reviewed the current status of the construction and use of various animal models, and summarized the advantages and limitations of animal models in evaluating the efficacy of antibodies, drugs and vaccines, with the aim of providing reference for the selection and optimization of animal models in the future.

Progress in development of bivalent vaccines against influenza A virus and SARS-CoV-2 / 中华微生物学和免疫学杂志

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants continue to spread around the world, posing a great threat to global economic and public health. Influenza A virus, a major cause of influenza, has a wide host range and evolves rapidly. Influenza pandemics, which occur every 20 to 40 years, annual seasonal influenza epidemics, severe influenza and animal influenza viruses are all serious threats to public health. Clinical manifestations of infections caused by the two pathogens are very similar. It is of great significance to develop an effective bivalent vaccine for controlling alternating epidemics or co-infection of the two pathogens. This article reviewed the progress in the development of bivalent vaccines against SARS-CoV-2 and influenza A virus based on different platforms.

One case of severe pneumonia and death from H3N8 influenza in human / 中华检验医学杂志

A female patient, years of age 56, having no distinct inducement before 5 d but developed fever, coughing, and shortness of breath, presented in People′s Hospital of Zhongshan with community-acquired pneumonia on March 3rd, 2023. Influenza A virus infection was confirmed on March 11th after performing macro transcriptome sequencing with alveolar lavage fluid, and H3N8 was confirmed with influenza typing afterward, having declared dead on March 16th. This case is a patient with refractory multiple myeloma autologous stem cell transplantation and continuous chemotherapy with immune dysfunction. She has a history of chronic upper respiratory tract infection. Imaging showed a widespread distribution of plaques, solid lesions, and other pneumonia manifestations in both lungs, a severe decrease in the counts of white blood cells, platelets, neutrophils, and lymphocytes, and a significant increase in laboratory inflammation indicators. After the clinical consideration was an acute aggravation of chronic respiratory tract infection and poor effect of anti-bacterial treatment, fungal infection was considered, and antibiotic treatment was changed several times according to the condition. Still, the outcome was poor, and the disease progressed rapidly. Medical workers initiated Oseltamivir antiviral therapy immediately after the alveolar lavage fluid etiology confirmed A-H3N8 influenza. However, due to complex and varied systemic symptoms, including inflammatory storm, sepsis, acute respiratory failure, tachycardia, coagulopathy, and other extrapulmonary organ injuries, she died 19 days after signs due to severe respiratory failure and multiple organ failure.

Research Progress on Influenza A Virus and Nervous System Disease of Human and Experimental Animals / 实验动物与比较医学

Influenza is a highly contagious disease that mainly affects the respiratory system and often leads to lung complications. Also it can cause a variety of very rare and serious neurological complications, including Guillain-Barre syndrome, transverse myelitis, meningoencephalitis and others. In recent years, neurological complications caused by influenza A virus have been reported in many countries and regions, and gradually attracted international attention. However, the pathogenesis of this complication remains unclear, and there are few related cases and animal experimental studies,and no specific treatment. Therefore, the authors summarized the study of neurological complications caused by influenza A virus in human and laboratory animals, in order to have a comprehensive understanding of the neurological diseases caused by influenza A virus.

Construction of an mRNA vaccine encoding hemagglutinin of influenza A H1N1 virus and investigation on booster immunization strategy / 上海交通大学学报（医学版）

Objective·To construct an mRNA vaccine encoding hemagglutinin(HA)of influenza A H1N1 virus,and explore the protective effects of different booster vaccination strategies.Methods·Firefly luciferase(Fluc)was used as the reporter gene to construct Fluc mRNA vaccine enveloped in lipid nanoparticles(LNP).The in vivo expression of Fluc mRNA-LNP after intramuscular injection was determined by live imaging assay in mice.Furthermore,M15-HA mRNA-LNP derived from H1N1 subtype(A/Michigan/45/2015)was constructed.Mice were immunized with 20,10,5,or 1 μg doses of M15-HA mRNA-LNP twice(with an interval of 3 weeks)through intramuscular injection.Serum antibody titers were measured by enzyme-linked immunosorbent assay(ELISA)at 2 weeks and 4 weeks after the second immunization,and functional antibody levels were detected by hemagglutination inhibition test.The third booster vaccination was performed 40 d after the second immunization in 1 μg dose group with 1 μg M15-HA mRNA-LNP or 10 μg HA subunit vaccine.The levels of specific antibody and functional antibody were detected by ELISA and hemagglutination inhibition test,respectively 2 weeks and 4 weeks later.Results·Live imaging assay showed that luciferase activity could be detected in mice 1 d after injection of Fluc mRNA-LNP.At 2 weeks and 4 weeks after the second immunization of M1 5-HA mRNA-LNP,HA-specific antibodies were significantly higher than those before the immunization in all vaccination groups at different doses(P=0.000).The hemagglutination inhibition test showed that the levels of functional antibodies in the 20 μg dose and 10 μg dose groups were significantly higher than those in the PBS control group(P＜0.05).After 1 μg dose group mice were immunized with HA protein or M15-HA mRNA-LNP,higher levels of HA-specific antibody and functional antibody were induced and maintained for a long time.There was no significant difference between the two different booster immunization strategies.Conclusion·M15-HA mRNA-LNP vaccine is constructed with immunogenicity and antibody neutralization activity.Low-dose mRNA priming vaccination followed by both homologous mRNA vaccine and heterologous protein subunit vaccine booster vaccination can induce stronger immune recall responses.

Genetic variation characteristics of HA gene of influenza A virus (H3N2) in Guizhou province from 2017 to 2019 / 中国基层医药

Objective:To analyze the genetic variation characteristics of the HA gene of influenza A virus (H3N2) in Guizhou province from 2017 to 2019. Methods:Twenty strains of influenza A virus (H3N2) were randomly selected from 10 network laboratories in Guizhou province for RNA extraction. Reverse transcriptase-polymerase chain reaction and sequencing were performed. The products were analyzed using bioinformatics software.Results:The nucleotide homology of the HA gene of the 20 strains was 97.7%-100%, which was highly homologous to the vaccine strains A/Hong-Kong/4801/2014 recommended by WHO in 2017 and A/Singapore-INFIMH/16-0019/2016 recommended by WHO in 2018, but they were significantly different from the vaccine strain A/Kansas/14/2017 recommended by WHO in 2019. Genetic analysis showed that the 20 strains were divided into two branches, and the strains that were prevalent in 2019 were located in different branches, with marked genetic differences. Key site analysis showed mutations in antigenic determinants A, B, C, and E and mutations in the anterior and posterior walls of receptor binding sites. Key site analysis also showed that there was an increase in the number of glycosylation sites compared with the vaccine strains prevalent in the same year. Genetic distance, antigen sites, and glycosylation sites were slightly different between virus strains prevalent in 2017-2018 and virus strains prevalent in 2019. Conclusion:The HA gene of the influenza A virus subtype H3N2 in Guizhou province from 2017 to 2019 showed heterogeneity and gene mutation, especially in 2019. Therefore, close monitoring of the genetic evolution of the influenza A virus subtype H3N2 is necessary.

Research progress of m 6A methylation modification in respiratory viruses replication and host immune response / 中华临床感染病杂志

N 6-methyladenosine (m 6A) modification is the most prevalent internal modification of eukaryotic mRNA and is dynamically regulated by a variety of m 6A modifying enzymes, including methylation transferases, demethylases and specific binding proteins. Respiratory viral infections have received much attention in recent years, and the process of virus replication and metabolism in host cells is regulated by m 6A. This article reviews the mechanism of m 6A-regulated enzymes, the roles of m 6A modifications in respiratory viruses replication and the host immune response to viruses, including adenovirus, influenza A virus, severe acute respiratory syndrome coronavirus 2, respiratory syncytial virus, and human metapneumovirus. It would provide a reference for exploring the regulatory role of viral episodic transcriptome modifications and antiviral targets or vaccine development.

Polymorphisms of host tropism relating amino acid sites in influenza A virus / 上海预防医学

ObjectiveTo discover and analyze single or several correlative key amino acid sites that influence the host tropism during the influenza A virus （IAV） infection based on complete internal protein gene segments of IAV strains， and to provide evidence for the study of human host-adaptive mutations of IAV. MethodsThe full-length nucleotide sequences of 43 671 IAV strains containing 6 complete internal gene segments were downloaded from the GISAID EpiFluTM database， and 698 human-tropic （HU） and 1 266 avian-tropic （AV） representative strains were included. The consensus coding sequences of the representative strains from the amphitropic category were compared by R script， and the differential amino acid sites and their polymorphisms were then obtained. The multi-site combination analysis of differential sites was conducted with R script. ResultsA total of 49 and 57 conserved differential sites were obtained from the consensus sequence comparison between AV and H1N1 （subtype from HU）， and comparison between AV and H3N2 （another subtype from HU）， separately. 79 and 65 multi-site combinations were found between HU and AV strains through 3 and 4 sites combination analysis， respectively， and a total of 11 conserved sites were involved： site 271 and 684 in PB2； site 336， 486， 581 and 621 in PB1； site 204 and 356 in PA； site 33， 305 and 357 in NP. No eligible differential sites were found in M1 and NS1. ConclusionSeveral conserved amino acid differential sites， between HU and AV strains of IAV， are found in PB2， PB1， PA and NP proteins. Instead of working as single units， these sites may have interactions， forming specific amino acid combinations that determine the host tropism of IAV collectively.

The role of mammalian target of rapamycin inhibitor in virus infection of organ transplant recipients / 器官移植

At present, mammalian target of rapamycin (mTOR) inhibitors are commonly-used immunosuppressive drugs after organ transplantation, including sirolimus (rapamycin) and everolimus. mTOR inhibitors not only exert an immunosuppressive effect by inhibiting T cell proliferation, but also possess multiple potential functions, such as antiaging, anti-tumor and anti-virus infection, etc. Virus infection is one of the most common complications after organ transplantation. Current anti-viral treatments are limited and yield poor efficacy. In this article, the role of mTOR pathway in virus infection, the mechanism of common mTOR inhibitors and the role of mTOR inhibitors in different types of virus infections were reviewed, aiming to provide reference for clinical application and subsequent research of mTOR inhibitors in organ transplant recipients.

Mechanism of Huashi Baidu Prescription in Treating Influenza Viral Pneumonia Based on Transcriptome / 中国实验方剂学杂志

ObjectiveTo clarify the therapeutic effect of Huashi Baidu prescription on pneumonia in mice caused by influenza A （H1N1） virus and explore its mechanism based on the transcriptome. MethodA mouse influenza viral pneumonia model was built by intranasal infection with influenza A virus， and mice were continuously administered the drug for five days， so as to investigate the general condition， lung index， viral load， pathological morphology of lung tissue， survival time， and prolongation rate of survival time of mice and clarify the therapeutic effect of Huashi Baidu prescription on influenza viral pneumonia. Transcriptome technology was used to detect the differentially expressed genes in the lung tissue of mice in the model group and the normal group， as well as the Huashi Baidu prescription group and the model group， and the potential core target of the Huashi Baidu prescription for the treatment of influenza viral pneumonia was screened. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to verify the effect of Huashi Baidu prescription on the mRNA expression level of core target genes. ResultCompared with the normal group， the lung index and viral load in the lung tissue of the model group were significantly increased （P<0.05， P<0.01）. Compared with the model group， the high-dose group of Huashi Baidu prescription significantly prolonged the survival time of mice infected with influenza A virus （P<0.05） and significantly reduced the lung index value of mice （P<0.05） and the viral load of lung tissue. The high-dose， medium-dose， and low-dose groups of Huashi Baidu prescription could significantly reduce lung tissue inflammation， blood stasis， swelling， and other pathological changes in mice （P<0.05， P<0.01）. Transcriptome analysis of lung tissue showed that core genes were mainly enriched in the nuclear transcription factor-κB （NF-κB） signaling pathway， interleukin-17 （IL-17） signaling pathway， cytokine-cytokine receptor interaction， and other pathways after the intervention of Huashi Baidu prescription. TRAF6， NFKBIA， CCL2， CCL7， and CXCL2 were the top five node genes with combined score values. Real-time PCR validation showed that Huashi Baidu prescription significantly downregulated the mRNA expression of key genes TRAF6 and NFKBIA in the NF-κB signaling pathway， as well as chemokines CCL2， CCL7， and CXCL2 （P<0.05， P<0.01）. ConclusionHuashi Baidu prescription has a therapeutic effect on influenza viral pneumonia， possibly by inhibiting the expression of key nodes TRAF6 and NFKBIA in the NF-κB signaling pathway and that of chemokines CCL2， CCL7， and CXCL2， reducing the recruitment of inflammatory cells and viral load， and exerting anti-influenza viral pneumonia effects.

Influenza A(H3N2) infection followed by separate COVID-19 infection / Infección por el virus de la gripe A (H3N2) seguida de infección separada por el virus causante de la COVID-19 / Infecção por influenza A (H3N2) seguida de infecção independente por COVID-19

ABSTRACT This study describes the case of a health professional infected first by influenza virus A(H3N2) and then by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 11 days later. Respiratory samples and clinical data were collected from the patient and from close contacts. RNA was extracted from samples and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to investigate the viruses. The patient presented with two different illness events: the first was characterized by fever, chest and body pain, prostration and tiredness, which ceased on the ninth day; RT-qPCR was positive only for influenza virus A(H3N2). Eleven days after onset of the first symptoms, the patient presented with sore throat, nasal congestion, coryza, nasal itching, sneezing and coughing, and a second RT-qPCR test was positive only for SARS-CoV-2; in the second event, symptoms lasted for 11 days. SARS-CoV-2 sequencing identified the Omicron BA.1 lineage. Of the patient's contacts, one was coinfected with influenza A(H3N2) and SARS-CoV-2 lineage BA.1.15 and the other two were infected only with SARS-CoV-2, one also with Omicron BA.1.15 and the other with BA.1.1. Our findings reinforce the importance of testing for different viruses in cases of suspected respiratory viral infection during routine epidemiological surveillance because common clinical manifestations of COVID-19 mimic those of other viruses, such as influenza.

RESUMEN Este estudio describe el caso de un profesional de la salud que contrajo la infección primero por el virus de la gripe A (H3N2) y a continuación por el coronavirus 2 del síndrome respiratorio agudo grave (SARS-CoV-2) 11 días después. Se recogieron muestras respiratorias y datos clínicos del paciente y sus contactos cercanos. Se extrajo ARN de muestras y se utilizó la reacción en cadena de la polimerasa cuantitativa con transcripción inversa (RT-qPCR, por su sigla en inglés) para investigar los virus. El paciente presentó dos procesos infecciosos distintos: el primero se caracterizó por fiebre, dolor corporal y torácico, postración y cansancio, que cesó en el noveno día. La prueba mediante RT-qPCR solo fue positiva en el virus de la gripe A (H3N2). Once días después del inicio de los primeros síntomas, el paciente manifestó dolor de garganta, congestión nasal, catarro, picazón nasal, estornudos y tos. Una segunda prueba mediante RT-qPCR solo fue positiva para el SARS-CoV-2 y durante este segundo proceso los síntomas duraron 11 días. La secuenciación del SARS-CoV-2 identificó el linaje ómicron BA.1. De los contactos del paciente, uno presentaba una coinfección por el virus de la gripe A (H3N2) y el linaje BA.1.15 del SARS-COV-2, y los otros dos presentaban infecciones únicamente por SARS-CoV-2, uno también del linaje ómicron BA.1.15 y el otro de BA.1.1. Estos hallazgos refuerzan la importancia de realizar pruebas para detectar diferentes virus en casos de sospecha de infección viral respiratoria durante la vigilancia epidemiológica de rutina porque las manifestaciones clínicas comunes de COVID-19 son similares a las de otros virus, como en el caso de la gripe.

RESUMO Este estudo descreve o caso de uma profissional de saúde infectada primeiro pelo vírus influenza A (H3N2) e, 11 dias depois, pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Amostras respiratórias e dados clínicos foram coletados da paciente e de contatos próximos. RNA foi extraído das amostras, e o método de reação em cadeia da polimerase via transcriptase reversa quantitativa (RT-qPCR) foi utilizado para investigar os vírus. A paciente apresentou dois quadros clínicos distintos. O primeiro foi caracterizado por febre, dor no peito e no corpo, prostração e fadiga, que cessou no nono dia. A RT-qPCR foi positiva apenas para o vírus da influenza A (H3N2). Onze dias após o início dos primeiros sintomas, a paciente apresentou dor de garganta, congestão nasal, coriza, prurido nasal, espirros e tosse. Um segundo teste de RT-qPCR foi positivo apenas para SARS-CoV-2. No segundo evento, os sintomas duraram 11 dias. O sequenciamento do SARS-CoV-2 identificou a cepa Ômicron BA.1. Dentre os contatos da paciente, um teve coinfeção por influenza A (H3N2) e SARS-COV-2 (cepa BA.1.15), e os outros dois foram infectados apenas por SARS-CoV-2 (um também pela cepa Ômicron BA.1.15 e o outro pela BA.1.1). Nossos achados reforçam a importância de testes para a detecção de diferentes vírus em casos de suspeita de infecção viral respiratória durante a vigilância epidemiológica de rotina, visto que as manifestações clínicas comuns da COVID-19 imitam as de outros vírus, como o vírus influenza.

Caracterización demográfica y clínica de pacientes críticos con neumonía por influenza A H1N1 / Demographic and clinical characterization of critically ill patients with influenza A H1N1 pneumonia

INTRODUCCIÓN. La epidemia de influenza y sus complicaciones profundizaron el estudio de las neumonías virales en cuidados intensivos. En nuestro país hay pocos datos sobre este tema. OBJETIVOS. Realizar una caracterización demográfica y clínica de pacientes críticos con neumonía por Influenza A H1N1 en un hospital de tercer nivel de complejidad. MATERIALES Y MÉTODOS. Estudio observacional, analítico, retrospectivo, con análisis univariante y multivariante. Población de 293 y muestra de 44 datos de historias clínicas electrónicas de pacientes diagnosticados con A H1N1 ingresados a la Unidad de cuidados intensivos del Hospital de Especialidades Carlos Andrade Marín en el período enero 2016 a diciembre de 2018. Como criterios de inclusión se consideró a todos los pacientes adultos mayores de 18 años que ingresaron a la UCI, con el diagnóstico de neumonía comunitaria grave con confirmación por reacción de cadena de polimerasa en tiempo real para influenza A H1N1 en hisopado nasal o aspirado traqueal. Se excluyó a pacientes embarazadas con diagnóstico de influenza A H1N1, pacientes con más de 48 horas de ingreso hospitalario previo a su ingreso a UCI, pacientes con datos insuficientes en los registros. Los datos se obtuvieron del sistema AS-400. El análisis estadístico se realizó en el programa Statistical Package for Social Sciences, versión 22. El nivel de significación fue una p<0.05. RESULTADOS. La prevalencia en pacientes críticos de neumonía por influenza A H1N1 durante 2016-2018 fue de 16,72%, la mediana de edad fue de 55 años, 25% masculinos, 34% obesos, 34% con hipertensión arterial. Escala "Acute Physiology and Chronic Health Evaluation II" 23,50, "Simplified Acute Physiologic Score III" 54, "Sepsis related Organ Failure Assessment" 11,50, Lactato deshidrogenasa 99,50, Procalcitonina 0,99; 9 días de ventilación mecánica invasiva, 10,50 días de estancia en la unidad. El 91% presentó shock séptico, 59% lesión renal aguda. El 89% tuvo Síndrome de Distrés Respiratorio del Adultos, 69% fue grave, 87% usó ventilación mecánica, 38,50% corticoides, 36% posición prona, Presión parcial de oxígeno/Fracción inspirada de oxígeno 74, volumen tidal/kilogramo de 7 mililitros, presión plateau de 27,50 centímetros de agua. La mortalidad general en la Unidad de Cuidados Intensivos fue de 38,63% y a los 28 días de 63,60%, en shock séptico fue 42,50% y en Síndrome de Distrés Respiratorio del Adultos del 41,02%. El análisis de regresión logística multivariable identificó como factores independientes asociados a mortalidad el incremento de Lactato deshidrogenasa (OR 2,69, 9% IC 1,090-6,642) y Procalcitonina (OR 2,51, IC 1,005-6,272). CONCLUSIONES. Las características, frecuencia y mortalidad de este grupo de pacientes críticos con neumonía por influenza A H1N1 son similares a lo reportado en la literatura mundial.

INTRODUCTION. The influenza epidemic and its complications deepened the study of viral pneumonias in intensive care. In our country there is little data on this subject. OBJECTIVES. To perform a demographic and clinical characterization of critical patients with pneumonia due to pneumonia due to Influenza A H1N1 in a third level hospital. MATERIALS AND METHODS. Observational, analytical, retrospective study, with univariate and multivariate analysis. We compared the groups of dead patients and survivors. The significance level was p<0,05. RESULTS. The prevalence in critically ill patients of influenza A H1N1 pneumonia during 2016-2018 was 16,72%, 44 cases were collected, median age 55 years, 25% male, 34% obese, 34% with arterial hypertension. APACHE II 23,50, SAPS III 54, SOFA 11,50, LDH 99,50, PCT 0,99, 9 days of invasive mechanical ventilation, 10,50 days of unit stay. 91% presented septic shock, 59% with acute kidney injury 89% had ARDS, 69% were severe, 87% used mechanical ventilation, 38,50% corticosteroids, 36% prone position, PaO2/FiO2 74, tidal volume/kg of 7 ml, plateau pressure of 27,50 cmH2O. Overall mortality in the ICU was 38,63% and at 28 days was 63,60%, in septic shock it was 42,50% and in Adult Respiratory Distress Syndrome it was 42,50%. was 42,50% and 41,02% in Adult Respiratory Distress Syndrome. The ultivariate logistic regression analysis identified as independent factors associated with mortality, the increase in LDH (OR 2,69, 9% CI 1,090-6,642) and PCT (OR 2,51, CI 1,005-6,272). CONCLUSIONS. The characteristics, frequency and mortality of this group of critical patients with pneumonia due to influenza A H1N1 are similar to those reported in the world literature.

Use of oral fluids for efficient monitoring of influenza viruses in swine herds in Colombia

Background: Influenza A virus (IAV) surveillance in swine is critical not only due to the direct impact of the disease in the pork industry but also because IAV are prone to interspecies transmission (from human to pigs and vice versa); therefore, its monitoring is fundamental from a public and animal health perspective. Several diagnostic techniques have been used to detect IAV infection from nasal samples in swine, while samples of oral fluids (OF) are in use as novel alternatives for pathogen detection. The OF allow for efficient and feasible low-cost disease detection at the herd level, with low risk of stress for the animals. Objective: To describe a surveillance strategy of IAV at the herd level during respiratory disease outbreaks in swine farms at tropical settings using porcine oral fluids. Methods: An active surveillance strategy was conducted in several farms with past records of respiratory disease. The IAV detection was conducted in five purposively selected swine farms from years 2014 to 2017. We investigated a total of 18 respiratory outbreaks of the disease. Swine OF were collected for IAV testing. An OF sample is described as a pen-based specimen collected from a group of >20 pigs per pen and/or per barn (stall-housed individually with close contact among them). The IAV infection was investigated in OF by rRT-PCR testing and confirmed by viral isolation in cell culture Results: We found 107 (7.4%) positives to IAV by rRT-PCR from a total of 1,444 OF samples tested. Additionally, 9 IAV isolates were all further identified as H1 subtype. Conclusions: Our results demonstrate that OF can be easily implemented as a novel, user-friendly, welfare-friendly, accurate and cost-effective sampling method for active surveillance and monitoring of IAV infections in swine farms in tropical settings.

Antecedentes: La vigilancia del Virus Influenza A (IAV) en los cerdos es fundamental debido al impacto directo de la enfermedad en la industria porcina, pero también porque los IAV son propensos de transmisión entre especies (humanos a cerdos y viceversa), y por lo tanto su monitoreo es crítico desde las perspectivas de salud pública y animal. Actualmente existen varias técnicas de diagnóstico disponibles para detectar la infección por IAV a partir de muestras nasales en cerdos, sin embargo, se han implementado otras muestras como los fluidos orales (OF) como nuevas alternativas para la detección de patógenos. El OF permite una detección eficiente y factible de enfermedades a menor costo a nivel de rebaño, con menor riesgo de estrés para los animales. Objetivo: Describir una estrategia de vigilancia de IAV a nivel de hato por medio de fluidos orales porcinos durante brotes de enfermedades respiratorias en granjas porcinas en entornos tropicales. Métodos: Se llevó a cabo una estrategia de vigilancia activa en cinco granjas porcinas seleccionadas con antecedentes de enfermedades respiratorias. Se recolectaron OF porcinos para la prueba de IAV. Una muestra de OF se describió como una muestra grupal recolectada de un grupo de >20 cerdos por corral y/o por establo (si estaban alojados individualmente, pero tenían un contacto cercano entre ellos). La infección por IAV se investigó probando OF mediante rRT-PCR y la confirmación mediante aislamiento viral en cultivo celular. Resultados: La detección de IAV se llevó a cabo en cinco granjas seleccionadas intencionalmente entre 2014- 2017. Investigamos un total de 18 eventos de brotes de enfermedades respiratorias. Del total de 1.444 OF muestras analizadas, encontramos 107 (7,4%) positivos a IAV mediante rRT-PCR. Además, solo se obtuvieron 9 aislamientos de IAV y todos se identificaron además como subtipo H1. Conclusiones: Los resultados de nuestro estudio demostraron cómo la OF puede implementarse fácilmente como un método de muestreo novedoso, fácil de usar, amigable con el bienestar animal, preciso y rentable para la vigilancia activa y el monitoreo de infecciones por IAV en granjas porcinas en entornos tropicales.

Antecedentes: A vigilância do vírus Influenza A (IAV) em suínos é crítica devido ao impacto direto da doença na indústria de suínos, mas também porque os IAV são propensos a transmissão interespécies (de humanos para porcos e vice-versa) e, portanto, seu monitoramento é crítico do ponto de vista da saúde pública e animal. Atualmente, existem várias técnicas de diagnóstico disponíveis para detectar a infecção por IAV em amostras nasais de suínos, no entanto, outras amostras, como fluidos orais (OF), têm sido implementadas como novas alternativas para a detecção de patógenos. O OF permite uma detecção eficiente e viável de doenças com menor custo em nível de rebanho, com menor risco de estresse para os animais. Objetivo: Descrever uma estratégia de vigilância de IAV em nível de rebanho durante surtos de doenças respiratórias em granjas de suínos em ambientes tropicais por meio de fluidos orais suínos. Métodos: A estratégia de vigilância ativa foi conduzida em cinco granjas de suínos selecionadas com histórico de doenças respiratórias. Suínos OF foram coletados para teste de IAV. Uma amostra OF foi descrita como um espécime baseado em curral coletado de um grupo de >20 porcos por curral e/ou por celeiro (se eles foram alojados individualmente, mas tendo contato próximo entre eles). A infecção IAV foi investigada testando OF por rRT-PCR e confirmada por isolamento em cultura de células. Resultados: A detecção do IAV foi realizada em cinco fazendas selecionadas propositalmente entre 2014-2017. Nós investigamos um total de 18 eventos de surto de doença respiratória. Do total de 1.444 amostras de OF testadas, encontramos 107 (7,4%) positivas para IAV por rRT-PCR. Além disso, apenas 9 isolados de IAV foram obtidos, e todos foram posteriormente identificados como subtipo H1. Conclusão: Os resultados de nosso estudo demonstraram como o OF pode ser facilmente implementado como um método de amostragem novo, amigável, amigável com o bem-estar, preciso e de baixo custo para vigilância ativa e monitoramento de infecções IAV em fazendas de suínos em ambientes tropicais.