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(searched for: doi:10.1111/irv.12470)
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Momoka Tanabe, Kazuho Maeda, Yosuke Usumoto, Hikaru Kuninaka, Moe Mukai, Ayako Nasu, Chiaki Fuke, Yoko Ihama
Published: 1 August 2022
Forensic Science International; https://doi.org/10.1016/j.forsciint.2022.111419

Published: 1 August 2022
Trials, Volume 23, pp 1-11; https://doi.org/10.1186/s13063-022-06564-7

Abstract:
Background: Vaccination is one of the most effective strategies for prevention and eradication of immunopreventable diseases, but community acceptance of vaccination can be influenced by different factors, such as pain and anxiety. The use of high-frequency vibration associated with cryotherapy has been used to manage pain and anxiety during the vaccination process in children, but studies with adults are still scarce. This study aims to evaluate the effect of high-frequency vibration associated with cryotherapy on the levels of self-reported pain and anxiety related to administration of the Influenza vaccine intramuscularly in adults. Methods: A two-arm, parallel, randomized clinical trial conducted in a Brazilian Primary Health Care Unit is proposed. A sample of 350 adults will be randomly assigned to participate in the control group, receiving the vaccine intramuscularly according to the standard protocol of the service, or in the intervention group, receiving the vaccine by the same route and using a portable device of high frequency vibration associated with cryotherapy for 30 s before and during administration. The primary endpoints will be self-reported levels of pain, assessed before and after vaccine administration. Secondary endpoints will be levels of anxiety, satisfaction with vaccine administration, and discomfort caused by high frequency vibration and temperature of the frozen bag in contact with the skin. Self-reported levels of pain and anxiety will be compared before and after vaccination as well as between the control and intervention groups. Discussion: By evaluating the effect of high-frequency vibration associated with cryotherapy on pain and anxiety levels, we expect to find evidence that will support nursing practice, in order to promote greater comfort and safety in the vaccination process and, consequently, greater compliance by the population, by minimizing its undesirable effects. Trial registration: Human Research Ethics Committee Opinion Number: 5.138.564. Approved on December 2, 2021. Brazilian Registry of Clinical Trials (REBEC): Registration number RBR-5zgy25w. Registered on December 09, 2021.
Yingying Peng, Zhe Chen, Huanmin Li, Yaowei Han, Dan Sun, Yanjiao Li, Xiaoxia Wu, Hongxiang Chen, Xinmin Li
Published: 22 July 2022
Frontiers in Pharmacology, Volume 13; https://doi.org/10.3389/fphar.2022.848770

Abstract:
Background: As a cause of respiratory tract infections in humans, influenza remains with high morbidity and mortality, with associated significant healthcare burden and increased financial burden. Traditional Chinese medicine injections (TCMIs) combined with oseltamivir (TCMIs + oseltamivir) are the representative therapeutic strategies for influenza, which is a compliant with clinical applications in China. The aim of this study was to describe the comparative efficacy and safety of TCMIs + oseltamivir in patients with influenza, based on the current evidence.Methods: PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, VIP information resource integration service platform databases, and the Chinese biomedical literature service system were searched to find randomized controlled trials where TCMIs + oseltamivir are the representative therapeutic strategies for influenza, from inception until October 2021, without language restriction. Two investigators independently screened eligibility criteria, extracted data, and appraised the risk of bias with the same criteria. We conducted a network meta-analysis using the Bayesian random method for each outcome and performed the sensitivity analysis, meta-regression, and Egger’s and Begg’s tests for the reliability and robustness of our results.Results: Thirty-one trials including 2,893 participants proved eligible and reported on four TCMIs + oseltamivir versus oseltamivir. Network meta-analysis showed Yanhuning (YHN) +oseltamivir (MD = −1.7, 95% CrI: −2.5 to −0.88; SUCRA = 0.89; low certainty of evidence) in fever disappearance time, Tanreqing (TRQ) +oseltamivir (MD = −1.9, 95% CrI: −2.8 to −1; SUCRA = 0.97; low certainty of evidence) in cough disappearance time, and Xiyanping (XYP) +oseltamivir (OR = 5.9, 95% CrI: 3.1 to 11; SUCRA = 0.82; very low certainty of evidence) in the response rate to be more efficacious than oseltamivir alone with the best SUCRA. Based on the combined SUCRA value for primary outcomes, TRQ + oseltamivir is probably better in cough disappearance time, and XYP + oseltamivir and YHN + oseltamivir may be better in fever disappearance time than others. No significant difference in safety between the treatments.Conclusion: In patients with influenza, TCMIs + oseltamivir only partially improve flu symptoms. Overall therapeutic efficacy and safety are inconclusive, based on low to very low certainty of evidence. However, the safety remains uncertain, and TCMI treatments for influenza should be considered with caution. More high-quality studies examining the efficacy and safety of TCMIs are needed.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021286994
Published: 20 July 2022
by MDPI
Abstract:
This analysis piece will attempt to examine some of the critical pandemic-related measures implemented in the United States from an immunological perspective and pinpoint caveats that should have been considered before their implementation. I also discuss alternative measures grounded in scientific data that were not thoroughly explored and likely could have helped fight the pandemic.
Published: 15 July 2022
by MDPI
Journal of Clinical Medicine, Volume 11; https://doi.org/10.3390/jcm11144123

Abstract:
Myopericarditis is a rare complication of influenza infection. The presentation may range from mild and frequently unrecognized, to fulminant and potentially complicated by cardiogenic and/or obstructive shock (tamponade), which is associated with high mortality. We performed a review of literature on all influenza pericarditis and myopericarditis cases according to PRISMA guidelines using the PubMed search engine of the Medline database. Seventy-five cases of influenza myopericarditis and isolated pericarditis were identified from 1951 to 2021. Influenza A was reported twice as often as influenza B; however, influenza type did not correlate with outcome. Men and elderly patients were more likely to have isolated pericarditis, while women and younger patients were more likely to have myopericarditis. All included patients had pericardial effusion, while 36% had tamponade. Tamponade was more common in those with isolated pericarditis (41.2%) than myopericarditis (13.8%). Cardiogenic shock was more common in patients with myopericarditis (64%), with an overall mortality rate of 14.7%. Nearly 88% of the recovered patients remained without long-term complications reported. Conclusion: Influenza A appears a more common cause of pericarditis and myopericarditis. Isolated pericarditis was more commonly associated with tamponade but without reported deaths, whereas myopericarditis was more commonly associated with cardiogenic shock and death (19%).
Arina A Tamborska, Bhagteshwar Singh, , , Julia Stowe, Taylor Watson-Fargie, Peter M Fernandes, , Jacob Roelofs, Kathryn Brennan, et al.
Published: 12 July 2022
by BMJ
BMJ Neurology Open, Volume 4; https://doi.org/10.1136/bmjno-2022-000309

Abstract:
Objective To investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two. Methods We captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS). Results Between 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50–59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p<0.00001). Facial weakness (63% (n=44/70) vs 36% (n=220/620); p<0.00001) and sensory dysfunction (93% (n=63/68) vs 69% (n=408/588); p=0.00005) were more common but disease severity and outcomes were similar to the IGOS study. Interpretation Most reports of GBS followed the first dose of ChAdOx1 vaccine. While our study cannot confirm or refute causation, this observation, together with the absence of alternative aetiologies, different than expected age distribution and the presence of unusual clinical features support a causal link. Clinicians and surveillance bodies should remain vigilant to the possibility of this very rare adverse event and its atypical variants.
Charles Neu, Philipp Baumbach, André Scherag, Andreas Kortgen, Juliane Götze,
Published: 3 June 2022
Abstract:
Introduction: Severe COVID-19 constitutes a form of viral sepsis. Part of the specific pathophysiological pattern of this condition is the occurrence of cardiovascular events. These include pulmonary embolism, arrhythmias and cardiomyopathy as manifestations of extra-pulmonary organ dysfunction. Hitherto, the prognostic impact of these cardiovascular events and their predisposing risk factors remains unclear. This study aims to explore this question in two cohorts of viral sepsis–COVID-19 and influenza–in order to identify new theragnostic strategies to improve the short- and long-term outcome of these two diseases. Methods and analysis: In this prospective multi-centre cohort study, clinical assessment will take place during the acute and post-acute phase of sepsis and be complemented by molecular laboratory analyses. Specifically, echocardiography and cardiovascular risk factor documentation will be performed during the first two weeks after sepsis onset. Aside from routine haematological and biochemical laboratory tests, molecular phenotyping will comprise analyses of the metabolome, lipidome and immune status. The primary endpoint of this study is the difference in 3-month mortality of patients with and without septic cardiomyopathy in COVID-19 sepsis. Patients will be followed up until 6 months after onset of sepsis via telephone interviews and questionnaires. The results will be compared with a cohort of patients with influenza sepsis as well as previous cohorts of patients with bacterial sepsis and healthy controls. Ethics and dissemination: Approval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (2020-2052-BO). The results will be published in peer-reviewed journals and presented at appropriate conferences. Trial registration: DRKS00024162.
Published: 1 June 2022
by MDPI
Viruses, Volume 14; https://doi.org/10.3390/v14061206

Abstract:
Influenza A viruses (IAV) modulate host antiviral responses to promote viral growth and pathogenicity. The non-structural (NS1) protein of influenza A virus has played an indispensable role in the inhibition of host immune responses, especially in limiting interferon (IFN) production. In this study, random site mutations were introduced into the NS1 gene of A/WSN/1933 (WSN, H1N1) via an error prone PCR to construct a random mutant plasmid library. The NS1 random mutant virus library was generated by reverse genetics. To screen out the unidentified NS1 functional mutants, the library viruses were lung-to-lung passaged in mice and individual plaques were picked from the fourth passage in mice lungs. Sanger sequencing revealed that eight different kinds of mutations in the NS1 gene were obtained from the passaged library virus. We found that the NS1 F9Y mutation significantly enhanced viral growth in vitro (MDCK and A549 cells) and in vivo (BALB/c mice) as well as increased virulence in mice. The NS1 D2I mutation attenuated the viral replication and pathogenicity in both in vitro and in vivo models. Further studies demonstrated that the NS1 F9Y mutant virus exhibited systematic and selective inhibition of cytokine responses as well as inhibited the expression of IFN. In addition, the expression levels of innate immunity-related cytokines were significantly up-regulated after the rNS1 D2I virus infected A549 cells. Collectively, our results revealed that the two mutations in the N-terminal of the NS1 protein could alter the viral properties of IAV and provide additional evidence that the NS1 protein is a critical virulence factor. The two characterized NS1 mutations may serve as potential targets for antiviral drugs as well as attenuated vaccine development.
Zhichao Xu, Xinjin Liu, Xiaoyu Ma, Wenting Zou, Qi Chen, Feifei Chen, Xiaofei Deng, Jinsen Liang, Chune Dong, Ke Lan, et al.
Published: 1 June 2022
, Yi Lee, Katie Latack, Laila Poisson, Dee Dee Wang, Shiyi Song, Dinesh R. Apala, Kiritkumar Patel, Abdul R. Halabi, Geetha Krishnamoorthy, et al.
Published: 1 June 2022
Data in Brief, Volume 42; https://doi.org/10.1016/j.dib.2022.108177

, , Katie Latack, , Dee Dee Wang, Shiyi Song, Dinesh R. Apala, Kiritkumar Patel, Abdul R. Halabi, Geetha Krishnamoorthy, et al.
The American Journal of Cardiology, Volume 173, pp 64-72; https://doi.org/10.1016/j.amjcard.2022.02.051

E. A. Pashkov, M. O. Korotysheva, A. V. Pak, , A. V. Sidorov, , E. P. Bystritskaya, Y. E. Dronina, V. K. Solntseva, T. A. Zaiceva, et al.
Published: 31 May 2022
Fine Chemical Technologies, Volume 17; https://doi.org/10.32362/2410-6593-2022-17-2-140-151

Abstract:
Objectives. Evaluation of changes in the viral activity of influenza A/WSN/33 after complex knockdown of combinations of cellular genes FLT4, Nup98 and Nup205 in human lung cell culture A549.Methods. The work was carried out using the equipment of the Center for Collective Use of the I. Mechnikov Research Institute of Vaccines and Sera, Russia. The authors performed transfection of combinations of small interfering ribonucleic acid (siRNA) complexes that cause simultaneous disruption of the expression of cellular genes FLT4, Nup98, and Nup205. Within three days from the moment of transfection and infection, the supernatant fluid and cell lysate were taken for subsequent viral reproduction intensity determination using the titration method for cytopathic action. The dynamics of changes in the concentration of viral ribonucleic acid (vRNA) was determined by real-time reverse transcription polymerase chain reaction (real-time RT-PCR). The nonparametric Mann–Whitney test was used to calculate statistically significant differences between groups.Results. Using all of the combinations of siRNA complexes, cell viabilitydid not decrease below the threshold level of 70%. In cells treated with complex FLT4.2 + Nup98.1 + Nup205 at the multiplicity of infection (MOI) equal to 0.1, a significant decrease in viral reproduction by 1.5 lg was noted on the first day in relation to nonspecific and viral controls. The use of siRNA complexes at MOI 0.01 resulted in a more pronounced antiviral effect. The viral titer in cells treated with siRNA complexes FLT4.2 + Nup98.1 and Nup98.1 + Nup205 decreased by 1.5 lg on the first day. In cells treated with complexes FLT4.2 + Nup205 and FLT4.2 + Nup98.1 + Nup205, it decreased by 1.8 and 2.0 lg on the first day and by 1.8 and 2.5 lg on the second day, respectively, in relation to nonspecific and viral controls. When conducting real-time RT-PCR, a significant decrease in the concentration of vRNA was noted. At MOI 0.1, a 295, 55, and 63-fold decrease in the viral load was observed with the use of siRNA complexes FLT4.2 + Nup98.1, Nup98.1 + Nup205, and FLT4.2 + Nup98.1 + Nup205, respectively. On the second day, a decrease in vRNA was also observed in cells treated with complex A. A 415-fold decrease in vRNA on the third day was noted in cells treated with complex FLT4.2 + Nup205. At MOI 0.01, the concentration of vRNA decreased 9.5 times when using complex B relative to nonspecific and viral control.Conclusions. The study showed a pronounced antiviral effect of siRNA combinations while simultaneously suppressing the activity of cellular genes (FLT4, Nup98, and Nup205), whose expression products are playing important role in the viral reproduction process, and obtained original designs of siRNA complexes. The results obtained are of great importance for the creation of emergence prophylactic and therapeutic drugs, whose action is based on the mechanism of RNA interference.
Adam D. Kenney, Stephanie L. Aron, Clara Gilbert, , Peng Chen, Adrian Eddy, Lizhi Zhang, Ashley Zani, Nahara Vargas-Maldonado, Samuel Speaks, et al.
Science Advances, Volume 8; https://doi.org/10.1126/sciadv.abm5371

Abstract:
Cardiac dysfunction is a common complication of severe influenza virus infection, but whether this occurs due to direct infection of cardiac tissue or indirectly through systemic lung inflammation remains unclear. To test the etiology of this aspect of influenza disease, we generated a novel recombinant heart-attenuated influenza virus via genome incorporation of target sequences for miRNAs expressed in cardiomyocytes. Compared with control virus, mice infected with miR-targeted virus had significantly reduced heart viral titers, confirming cardiac attenuation of viral replication. However, this virus was fully replicative in the lungs and induced similar systemic inflammation and weight loss compared to control virus. The miR-targeted virus induced fewer cardiac conduction irregularities and significantly less fibrosis in mice lacking interferon-induced transmembrane protein 3 (IFITM3), which serve as a model for influenza-associated cardiac pathology. We conclude that robust virus replication in the heart is required for pathology, even when lung inflammation is severe.
Published: 13 May 2022
by MDPI
Viruses, Volume 14; https://doi.org/10.3390/v14051036

Abstract:
The newest type of influenza virus, influenza D virus (IDV), was isolated in 2011. IDV circulates in several animal species worldwide, causing mild respiratory illness in its natural hosts. Importantly, IDV does not cause clinical disease in humans and does not spread easily from person to person. Here, we review what is known about the host–pathogen interactions that may limit IDV illness. We focus on early immune interactions between the virus and infected host cells in our summary of what is known about IDV pathogenesis. This work establishes a foundation for future research into IDV infection and immunity in mammalian hosts.
Li Zhang, Jing Xu, Xiaoling Qi, Zheying Tao, , Wei Chen, Xiaoli Wang, Tingting Pan, Yunqi Dai, Rui Tian, et al.
Infection and Drug Resistance, pp 2371-2381; https://doi.org/10.2147/idr.s348278

Abstract:
Background: Since the outbreak of coronavirus disease (COVID-19) in December 2019 in Wuhan, it has spread rapidly worldwide. We aimed to establish and validate a nomogram that predicts the probability of coronavirus-associated acute respiratory distress syndrome (CARDS). Methods: In this single-centre, retrospective study, 261 patients with COVID-19 were recruited using positive reverse transcription–polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2 in Tongji Hospital at Huazhong University of Science and Technology (Wuhan, China). These patients were randomly distributed into the training cohort (75%) and the validation cohort (25%). The factors included in the nomogram were determined using univariate and multivariate logistic regression analyses based on the training cohort. The area under the receiver operating characteristic curve (AUC), consistency index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the efficiency of the nomogram in the training and validation cohorts. Results: Independent predictive factors, including fasting plasma glucose, platelet, D-dimer, and cTnI, were determined using the nomogram. In the training cohort, the AUC and concordance index were 0.93. Similarly, in the validation cohort, the nomogram still showed great distinction (AUC: 0.92) and better calibration. The calibration plot also showed a high degree of agreement between the predicted and actual probabilities of CARDS. In addition, the DCA proved that the nomogram was clinically beneficial. Conclusion: Based on the results of laboratory tests, we established a predictive model for acute respiratory distress syndrome in patients with COVID-19. This model shows good performance and can be used clinically to identify CARDS early. Trial Registration: Ethics committee of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (No.:(2020) Linlun-34th).
Jung-Woo Rhim, Jin-Han Kang,
Clinical and Experimental Pediatrics, Volume 65, pp 153-166; https://doi.org/10.3345/cep.2021.01270

Abstract:
During the coronavirus disease 2019 (COVID-19) pandemic, a novel multisystem inflammatory syndrome in children (MIS-C) has been reported worldwide since the first cases were reported in Europe in April 2020. MIS-C is temporally associated with severe acute respiratory syndrome coronavirus 2 infection and shows Kawasaki disease (KD)-like features. The epidemiological and clinical characteristics in COVID-19, KD, and MIS-C differ, but severe cases of each disease share similar clinical and laboratory findings such as a protracted clinical course, multiorgan involvement, and similar activated biomarkers. These findings suggest that a common control system of the host may act against severe disease insult. To solve the enigmas, we proposed the protein-homeostasis-system hypothesis in that every disease involves etiological substances and the host’s immune system controls them by their size and biochemical properties. Also, it is proposed that the etiological agents of KD and MIS-C might be certain strains in the microbiota of human species and etiological substances in severe COVID-19, KD, and MIS-C originate from pathogen-infected cells. Since disease severity depends on the amounts of inflammation-inducing substances and corresponding immune activation in the early stage of the disease, an early proper dose of corticosteroids and/or intravenous immunoglobulin (IVIG) may help reduce morbidity and possibly mortality among patients with these diseases. Corticosteroids are low cost and an analogue of host-origin cortisol among immune modulators. This study’s findings will help clinicians treating severe COVID-19, KD, and MIS-C, especially in developing countries, where IVIG and biologics supplies are insufficient.
, Wanqin Zhang, Peng Yuan, Chunmiao Lu, Jianping Dong,
Published: 1 April 2022
Pharmaceutical Biology, Volume 60, pp 722-728; https://doi.org/10.1080/13880209.2022.2056206

Abstract:
QiShenYiQi pill (QSYQ) is a traditional Chinese medicine with a myocardial protective effect. To explore the effect of QSYQ on myocardial collagen metabolism in rats with autoimmune cardiomyopathy and explore the underlying mechanism from the aspect of apoptosis. We established an autoimmune cardiomyopathy model using Lewis rats. The rats were then randomly divided into six groups (n = 8): control, model, 3-methyladenine (15 mg/kg, intraperitoneal injection), QSYQ low-dose (135 mg/kg, gavage), QSYQ medium dose (270 mg/kg, gavage), and QSYQ high-dose (540 mg/kg, gavage) for four weeks. Van Gieson staining was applied for myocardial pathological characteristics, TUNEL fluorescence for myocardial cell apoptosis, enzyme-linked immunosorbent assay (ELISA) for serum PICP, PIIINP, and CTX-I levels, and western blot analysis for type I/III myocardial collagen, Bcl-2, Bax, and caspase-3 proteins. Results showed that QSYQ (135, 270, or 540 mg/kg) significantly reduced the expression of myocardial type I/III collagen, and concentrations of serum PICP, PIIINP, and CTX-I in rats. Moreover, QSYQ could alleviate myocardial fibrosis more effectively at a higher dose. QSYQ could also inhibit myocardial apoptosis via downregulating Bcl-2 expression, and upregulating Bax and caspase-3 expression levels. The QSYQ can improve myocardial collagen metabolism by inhibiting apoptosis, which provides a potential therapeutic approach for autoimmune cardiomyopathy.
Published: 23 March 2022
by MDPI
Journal of Personalized Medicine, Volume 12; https://doi.org/10.3390/jpm12040520

Abstract:
The purpose of the study was to analyze the relationship between the high-sensitivity troponin T levels in patients with confirmed influenza virus infection and its severity determined by mortality during the care process. In addition, a high-sensitivity troponin T cut-off value was sought to allow us to a safe discharge from the emergency department. An analytical retrospective observational study was designed in which high-sensitivity troponin T is determined as an exposure factor, patients are followed until the resolution of the clinical picture, and the frequency of mortality is analyzed. We included patients ≥ 16 years old with confirmed influenza virus infection and determination of high-sensitivity troponin T. One hundred twenty-eight patients were included (96.9% survivors, 3.1% deceased). Mean and median blood levels of high-sensitivity troponin T of survivors were 26.2 ± 58.3 ng/L and 14.5 ng/L (IQR 16 ng/L), respectively, and were statistically different when compared with those of the deceased patients, 120.5 ± 170.1 ng/L and 40.5 ng/L (IQR 266.5 ng/L), respectively, p = 0.012. The Youden index using mortality as the reference method was 0.76, and the cut-off value associated with this index was 24 ng/L (sensitivity 100%, specificity 76%, NPV 100%, PPV 4%) with AUC of 88,8% (95% CI: 79.8–92.2%), p < 0.001. We conclude that high-sensitivity troponin T levels in confirmed virus influenza infection are a good predictor of mortality in our population, and this predictor is useful for safely discharging patients from the emergency department.
Trinita Roy, Khushal Sharma, , ,
Published: 21 March 2022
Abstract:
Influenza A is a contagious viral disease responsible for four pandemics in the past and a major public health concern. Being zoonotic in nature, the virus can cross the species barrier and transmit from wild aquatic bird reservoirs to humans via intermediate hosts. Virus gradually undergoes host adaptive mutations in their genome and proteins, resulting in different strain s/vari ants which might spread virus from avians/mammals to humans. In this study, we have developed an in-silico models to identify infectious strains of Influenza A virus, which has the potential of getting transmitted to humans, from its whole genome/proteins. Firstly, machine learning based models were developed for predicting infectious strains using composition of 15 proteins of virus. Random Forest based model of protein Hemagglutinin, achieved maximum AUC 0.98 on validation data using dipeptide composition. Secondly, we obtained maximum AUC of 0.99 on validation dataset using one-hot-encoding features of each protein of virus. Thirdly, models build on DNA composition of whole genome of Influenza A, achieved maximum AUC 0.98 on validation dataset. Finally, a web-based service, named “FluSPred”(https://webs.iiitd.edu.in/raghava/fluspred/) has been developed which incorporate best 16 models (15 proteins and one based on genome) for prediction of infectious strains of virus. In addition, we provided standalone software for the prediction and scanning of infectious strains at large-scale (e.g., metagenomics) from genomic/proteomic data. We anticipate this tool will help researchers in prioritize high-risk viral strains of novel influenza virus possesses the capability to spread human to human, thereby being useful for pandemic preparedness and disease surveillance.Key Points: Influenza A is a contagious viral disease responsible for four pandemics. Virus can cross species barrier and infect human beings. In silico models developed for predicting human infectious strains of virus. Models developed were build using 15 proteins and whole genome datasets. Webserver and standalone package for predicting and scanning of high-risk viral strains.
Revista Brasileira de Medicina de Família e Comunidade, Volume 17, pp 2819-2819; https://doi.org/10.5712/rbmfc17(44)2819

Abstract:
Introdução: As informações sobre a presença de doenças crônicas nos idosos não são registradas durante as campanhas de vacinação contra influenza, o que dificulta sua identificação (proporção) nos idosos vacinados. Objetivo: Descrever a prevalência de doenças crônicas autorreferidas em idosos vacinados contra a influenza; verificar a influência da mídia na decisão de tomar a vacina; e se recebeu orientações sobre a importância dela, segundo o tipo de profissional de saúde. Métodos: Estudo transversal descritivo, com dados coletados por meio de entrevistas com idosos vacinados contra influenza (n=798) em um Centro de Saúde de Campinas (SP) em 2019. Resultados: Na amostra estudada, a maioria eram mulheres (58,0%), indivíduos com ensino médio completo ou ensino superior (53,0%) e com plano de saúde (72,3%). As doenças mais prevalentes foram hipertensão arterial (56,9%; intervalo de confiança — IC95% 53,4–60,3), diabetes (24,7%; IC95% 21,8–27,8), doenças cardíacas (13,6%; IC95% 11,4–16,2) e respiratórias (5,6%; IC95% 4,2–7,5). A maioria (58,0%) considerou que a mídia influenciou sua decisão de tomar a vacina. Receberam orientações sobre a importância da vacinação 21,1% dos idosos, fornecidas principalmente por médicos/as (67,4%), enfermeiros/as (18,2%) e agentes de saúde (7,0%). Conclusões: A investigação mostrou que as principais doenças referidas pelos idosos vacinados foram hipertensão arterial, diabetes, cardiopatias e doenças respiratórias. A orientação de profissionais da saúde foi pouco relatada pelos idosos e a maioria referiu influência da mídia na decisão de vacinar-se. Ressaltam-se a necessidade e a relevância de investir em estratégias de comunicação em saúde, a fim de esclarecer a população sobre a importância da vacinação contra a influenza para as pessoas idosas e com doenças crônicas.
, Jun Duan, Chelsea Himsworth, William Hsiao, Natalie A. Prystajecky
Published: 26 February 2022
Abstract:
Background: Sequencing viruses in many specimens is hindered by excessive background material from hosts, microbiota, and environmental organisms. Consequently, enrichment of target genomic material is necessary for practical high-throughput viral genome sequencing. Hybridization probes are widely used for enrichment in many fields, but their application to viral sequencing faces a major obstacle: it is difficult to design panels of probe oligo sequences that broadly target many viral taxa due to their rapid evolution, extensive diversity, and genetic hypervariability. To address this challenge, we created ProbeTools, a package of bioinformatic tools for generating effective viral capture panels, and for assessing coverage of target sequences by probe panel designs in silico. In this study, we validated ProbeTools by designing a panel of 3,600 probes for subtyping the hypervariable haemagglutinin (HA) and neuraminidase (NA) genome segments of avian-origin influenza A viruses (AIVs). Using in silico assessment of AIV reference sequences and in vitro capture on egg-cultured viral isolates, we demonstrated effective performance by our custom AIV panel and ProbeTools’ suitability for challenging viral probe design applications.Results: Based on ProbeTool’s in silico analysis, our panel provided broadly inclusive coverage of 14,772 HA and 11,967 NA reference sequences. 90% of these HA and NA references sequences had 90.8% and 95.1% of their nucleotide positions covered in silico by the panel respectively. We also observed effective in vitro capture on a representative collection of 23 egg-cultured AIVs that included isolates from wild birds, poultry, and humans and representatives from all HA and NA subtypes. 42 of 46 HA and NA segments had over 98.3% of their nucleotide positions significantly enriched by our custom panel. These in vitro results were further used to validate ProbeTools’ in silico coverage assessment algorithm; 89.2% of in silico predictions were concordant with in vitro results.Conclusions: ProbeTools generated an effective panel for subtyping AIVs that can be deployed for genomic surveillance, outbreak prevention, and pandemic preparedness. Effective probe design against hypervariable AIV targets also validated ProbeTools’ design and coverage assessment algorithms, demonstrating their suitability for other challenging viral capture applications.
, Daniel Modin, , Deborah Rudin, Gunnar Gislason, Helen P. Booth, , Rachael Williams, Hilary Shepherd, Eleanor Yelland, et al.
Published: 23 February 2022
npj Vaccines, Volume 7, pp 1-9; https://doi.org/10.1038/s41541-022-00444-6

Abstract:
We estimated the frequency of non-specific influenza-associated clinical endpoints to inform the feasibility of pragmatic randomized controlled trials (RCT) assessing relative vaccine effectiveness (rVE). Hospitalization rates of respiratory, cardiovascular and diabetic events were estimated from Denmark and England’s electronic databases and stratified by age, comorbidity and influenza vaccination status. We included a seasonal average of 4.5 million Danish and 7.2 million English individuals, 17 and 32% with comorbidities. Annually, approximately 1% of Danish and 0.5% of English individuals were hospitalized for selected events, ~50% of them respiratory. Hospitalization rates were 40–50-fold and 2–10-fold higher in those >50 years and with comorbidities, respectively. Our findings suggest that a pragmatic RCT using non-specific endpoints is feasible. However, for outcomes with rates <2.5%, it would require randomization of ~100,000 participants to have the power to detect a rVE difference of ~13%. Targeting selected groups (older adults, those with comorbidities) where frequency of events is high would improve trial efficiency.
Published: 19 February 2022
by MDPI
Abstract:
Background: Obesity is a risk factor for the development of influenza by leading to a chronic inflammatory state and T-cell dysfunction. Based upon preclinical research, metformin has influenza activity by restoring T-cell function and improving the immune response. Objective: We aimed to evaluate the potential drug repurposing of metformin for the management of influenza among patients with obesity utilizing national claims data in an electronic health record database. Methods: The VA Informatics and Computing Infrastructure (VINCI) was utilized to obtain individual-level information on demographics, administrative claims, and pharmacy dispensation. A cohort was created among individuals with laboratory confirmed diagnosis of influenza with a diagnosis of fever, cough, influenza, or acute upper respiratory infection in an outpatient setting. The study outcome was death after diagnosis of influenza. Cohorts were formed using diabetes status and metformin exposure prior to a positive influenza diagnosis. Hazard ratios for mortality were estimated using a cox proportional hazards model adjusting for baseline covariates and a sub-analysis was conducted utilizing propensity score matching. A greedy nearest neighbor algorithm was utilized to match 1 to 1 non-metformin diabetic controls and non-diabetic controls to diabetic patients receiving metformin. Results: A total of 3551 patients met the inclusion criteria and were evaluated in our study. The cohorts consisted of 1461 patients in the non-diabetic cohort, 1597 patients in the diabetic / metformin cohort, and 493 patients in the diabetic no metformin cohort. Compared to non-diabetic patients, diabetic patients with metformin had a lower rate of death (aHR 0.78, 95% CI 0.609–0.999). There was not a statistical difference between the non-diabetic patients and the diabetic patients without metformin (aHR 1.046, 95% CI 0.781–1.400). The propensity score matched cohorts revealed consistent results with the primary analysis. Conclusion: Our results demonstrated patients with obesity and a history of metformin treatment have lower influenza mortality.
Published: 25 January 2022
by MDPI
Abstract:
Influenza A virus (IAV) infection is a global public health burden causing up to 650,000 deaths per year. Yearly vaccination programmes and anti-viral drugs currently have limited benefits; therefore, research into IAV is fundamental. Leukocyte trafficking is a crucial process which orchestrates the immune response to infection to protect the host. It involves several homing molecules and receptors on both blood vessels and leukocytes. A key mediator of this process is the transmembrane glycoprotein L-selectin, which binds to vascular addressins on blood vessel endothelial cells. L-selectin classically mediates homing of naïve and central memory lymphocytes to lymph nodes via high endothelial venules (HEVs). Recent studies have found that L-selectin is essential for homing of activated CD8+ T cells to influenza-infected lungs and reduction in virus load. A disintegrin and metalloproteinase 17 (ADAM17) is the primary regulator of cell surface levels of L-selectin. Understanding the mechanisms that regulate these two proteins are central to comprehending recruitment of T cells to sites of IAV infection. This review summarises the immune response to IAV infection in humans and mice and discusses the roles of L-selectin and ADAM17 in T lymphocyte homing during IAV infection.
, Elliott Bosco, RishiK Manthana, Melissa Eliot, Barbara H. Bardenheier, Joe B.B. Silva, Robertus van Aalst, Ayman Chit, Matthew M. Loiacono, Stefan Gravenstein, et al.
Journal of the American Medical Directors Association; https://doi.org/10.1016/j.jamda.2021.12.036

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Michael Kwan Leung Yu, Cherry Pui Pik Leung, Wilfred Hing Sang Wong, Alvin Chi Chung Ho, Annie Ting Gee Chiu, Helen Hui Zhi, Godfrey Chi Fung Chan, Sophelia Hoi Shan Chan
Published: 20 January 2022
Frontiers in Pediatrics, Volume 9; https://doi.org/10.3389/fped.2021.752816

Abstract:
Background: Influenza is one of the most common causes of acute respiratory tract infections around the world. Influenza viruses can cause seasonal epidemics. There remains limited information on the impact of both seasonal influenza A and influenza B related hospitalisations from neurological complications in paediatric populations in Asia.Objectives: To examine both the clinical spectrum and healthcare burden of influenza-associated neurological complications (IANCs) within the paediatric population of Hong Kong.Methods: We conducted a population-based retrospective study to identify all paediatric patients (<18 years) admitted to a public hospital in Hong Kong with a confirmed influenza A or B infection between 2014 and 2018 using the Clinical Data Analysis and Reporting System of the Hospital Authority. The clinical spectrum of the paediatric patients with IANCs was studied. The clinical burden of paediatric influenza patients with IANCs were compared to paediatric influenza patients without neurological complications.Results: A total of 28,016 children admitted to the paediatric wards diagnosed to have influenza A or B infection were identified, accounting for 5.7% (28,016/489,955) of total paediatric admissions. 67.3% had influenza A and 32.7% had influenza B, and 8.9% had IANCs. The mean annual incidence of IANCs in children was 57 per 100,000 population. The spectrum of IANCs in our paediatric patients included febrile seizures (80.6%), myositis (11.4%), seizures with fever (5.4%), influenza-associated encephalitis/encephalopathy (IAE) (2.6%) and rarely Guillain–Barré syndrome (0.04%). Most paediatric patients with IANCs (85.5%) presented at a young age of <6 years. Paediatric patients with IANCs had significant longer hospital stays (p < 0.001), higher percentages of mechanical ventilation use (p < 0.05) and PICU admissions (p < 0.001), and higher mortality rates (p < 0.001) compared to those without neurological complications. Amongst those with IANCs, IAE was the sole cause of all seven reported mortalities.Conclusions: Seasonal influenza A & B is a common cause of hospitalisation for paediatric patients in Hong Kong. We found neurological complications from influenza A and B caused a significantly higher clinical burden compared to those without neurological complications. Children in younger age groups (<6 years old) are at highest risk and thus increasing vaccination coverage to this age group is recommended.
Mylène Cottet, , José David Arroja, Diego Arroyo
European Heart Journal - Case Reports, Volume 6; https://doi.org/10.1093/ehjcr/ytac026

Abstract:
Background: Acute myocarditis is a common condition, with viral infections being the most common aetiology in North America and Europe. Influenza A myocarditis is however rare. As clinical manifestation may be fulminant, early recognition and management are paramount and may impact overall prognosis by hindering complications such as thromboembolism. A brief review of the literature, diagnostic modalities, work-up and treatment are discussed. Case summary: We present the case of a 42-year-old, previously healthy woman with recent flu-like symptoms, developing decompensated heart failure (HF) and cardiogenic shock within a week, due to Influenza A myocarditis. Biventricular thrombi were identified. Pharmacological haemodynamic support, followed by HF therapy, allowed full recuperation of heart function. Intracavitary thrombi disappeared under unfractionated heparin with bridging to rivaroxaban. Discussion: Fulminant myocarditis due to Influenza A is rare and, to the best of our knowledge, has not been associated with intracardiac thrombi formation. Echocardiography is the essential first-line imaging modality. Cardiac magnetic resonance plays a major role in the diagnosis of myocarditis and may preclude the need for an endomyocardial biopsy in selected cases. Coronary angiography may be required to rule out ischaemic aetiology. First-line therapy in fulminant disease is pharmacological and, if required, mechanical haemodynamic support. Standard HF therapy complete the therapeutic options and should be introduced as soon as possible. Complications such as intracardiac thrombi formation, require targeted treatment. Specific drug therapies targeting Influenza A have no proven benefit in myocarditis.
Rocío Eiros, Manuel Barreiro-Pérez, Ana Martín-García, Julia Almeida, Eduardo Villacorta, Alba Pérez-Pons, Soraya Merchán, Alba Torres-Valle, Clara Sánchez-Pablo, David González-Calle, et al.
Published: 13 January 2022
Revista Española de Cardiología; https://doi.org/10.1016/j.recesp.2021.10.021

The publisher has not yet granted permission to display this abstract.
Suheiry Márquez,
Published: 7 January 2022
Case Reports in Rheumatology, Volume 2022, pp 1-6; https://doi.org/10.1155/2022/9506733

Abstract:
Transverse myelitis (TM) is a rare complication seen in 1–2% of patients with systemic lupus erythematosus (SLE). Viral infections may cause TM in these patients by causing a dysregulation of their immune system. We report a 30-year-old woman with SLE who had influenza A and a few days later developed urinary retention, bilateral lower extremity paralysis, upper extremity weakness, and optic nerve and macular edema. Magnetic resonance imaging showed C4-T12 hyperintense lesions consistent with TM. She was treated with intravenous methylprednisolone 1 g daily for 3 days and then 6 cycles of monthly intravenous cyclophosphamide. This treatment was followed by oral prednisone. She had a remarkable clinical response. Visual acuity improved to her baseline, and muscle strength almost fully recovered. Clinicians should be aware that viral infections, including influenza, may induce TM. This case highlights the importance of early recognition and prompt treatment with immunosuppressive drugs in such cases.
, Erman Ataş, Bülent Ünay,
Journal of Pediatric Infectious Diseases, Volume 17, pp 076-082; https://doi.org/10.1055/s-0041-1741003

Abstract:
Objective Influenza viruses are among the most common respiratory pathogens for all age groups, and may cause seasonal outbreaks. The aim of our study was to describe the clinical characteristics of influenza cases in the 2019–2020 flu season and to study the risk factors for hospital admission and complications. Methods This was a retrospective study in 251 children (group 1: nonhospitalized; group 2: hospitalized) with influenza in the 2019–2020 flu season. Data on demographic features, influenza type, complaints, complications, and hospitalization length were collected and recorded. Results Influenza A was detected in 199 (79.3%) patients, and influenza B was detected in 52 (20.7%); 43.4% of patients were girls and 56.6% were boys. The mean age of the patients was 3.91 ± 3.3 years (16 days to 18 years). A total of 52 (20.7%) patients were hospitalized. The age of the patients in group 2 was lower than that in group 1 (3.1 vs. 4.2 years, p = 0.03). Group 2 patients were more likely to have creatine kinase (CK) elevation, febrile seizures, and physical examination abnormalities. Group 2 patients were also more likely to have influenza A. Patients with febrile seizures, chronic diseases, abnormal physical examination findings, developed complications, and additional drug use apart from oseltamivir in the treatment were also more likely to require hospitalization. Conclusion Infants and children with chronic diseases, history of febrile seizures, complications, and the use of drugs other than antiviral drugs should be carefully evaluated in case they need hospitalization. Increasing vaccination rates, initiation of antiviral treatment for selected patients, and close monitoring of patients in risk groups can decrease morbidity and mortality. Myalgias are a common complaint in patients with acute influenza infection. Previous studies suggest CK measurement be part of the work-up for the hospitalized patient with acute influenza infection.
, P. Jaquet, G. Vellieux, , B. Visseaux
Published: 29 December 2021
Revue Neurologique, Volume 178, pp 48-56; https://doi.org/10.1016/j.neurol.2021.12.002

The publisher has not yet granted permission to display this abstract.
Karine R. Badalyan, Ella Iu. Solovyeva
Published: 15 December 2021
Consilium Medicum, Volume 23, pp 993-999; https://doi.org/10.26442/20751753.2021.12.201347

Abstract:
Several studies have recently been conducted showing persistent COVID-19 symptoms in patients recovering after the acute phase of the disease. Energy imbalance plays a leading role in the pathogenesis of post-COVID syndrome. The choice of a metabolic cytoprotection drug with anti-asthenic activity will be decisive for the further tactics of managing the patient not only in the hospital, but also during the entire further period of recovery after the infection.
Guillermo Mena, , Cristina Casañ, Mario Auñón, Lurdes Matas, Josep-Maria Mòdol, María Esteve
Published: 2 December 2021
Abstract:
Introduction: Influenza vaccination rates in risk groups remain suboptimal. Evidence supporting a significant association between influenza vaccination and severe illness is limited. Methods: We retrospectively analyzed the epidemiological characteristics of out- and inpatients with laboratory-confirmed influenza infection attended during the 2018–19 epidemic season. Influenza vaccination coverage by indication was analyzed. Logistic regression was used to compare the odds of vaccination between severe and non-severe influenza-positive patients. Severe cases were defined as presenting pneumonia, admission to critical care units and/or death. Results: The overall vaccination coverage among influenza-positive patients was 30.4%. In subjects with ≥ 1 indication for vaccination, the vaccination coverage was 42.4%. By indication, coverage rates were: 52.5% in patients aged ≥ 59 years, 42.2% in obese patients, 29.2% in immunosuppressed subjects and 6.5% in pregnant women. In patients with underlying chronic diseases, a higher coverage was found in patients with cognitive impairment (77%), muscular dystrophy (63.6%) and renal disease (60.4%). The multivariate logistic regression model showed severe influenza-related illness was associated with a lack of influenza vaccination before seeking care during the 2018–2019 season [0.59 (95%CI 0.36–0.97); p = 0.038], older age [1.01 (95%CI 1.00–1.02); p = 0.009] and current or former smoking status [1.63 (95%CI 0.84–3.18) and 2.03 (95%CI 1.16–3.57); p = 0.031], adjusted by underlying disease. Conclusion: Adjusting by age, smoking status and underlying disease, a moderate association between the influenza vaccine and severe laboratory-confirmed influenza-related illness was found in an epidemic season in which there was matching between the vaccine and circulating strains. Protection against complications, especially in older subjects and in those with underlying disease is postulated as one of the strengths of annual influenza vaccination. However, influenza vaccination is a pending issue in these groups, especially in pregnant women and obese people. To avoid suboptimal vaccination coverages, health professionals should recommend the seasonal influenza vaccination according to the annual instructions of the health authorities.
, Penny Post, Deborah Rudin
Published: 2 December 2021
npj Vaccines, Volume 6, pp 1-8; https://doi.org/10.1038/s41541-021-00403-7

Abstract:
The influenza vaccine field has been constantly evolving to improve the speed, scalability, and flexibility of manufacturing, and to improve the breadth and longevity of the protective immune response across age groups, giving rise to an array of next generation vaccines in development. Among these, the recombinant influenza vaccine tetravalent (RIV4), using a baculovirus expression vector system to express recombinant haemagglutinin (rHA) in insect cells, is the only one to have reached the market and has been studied extensively. We describe how the unique structural features of rHA in RIV4 improve protective immune responses compared to conventional influenza vaccines made from propagated influenza virus. In addition to the sequence integrity, characteristic of recombinant proteins, unique post-translational processing of the rHA in insect cells instills favourable tertiary and quaternary structural features. The absence of protease-driven cleavage and addition of simple N-linked glycans help to preserve and expose certain conserved epitopes on HA molecules, which are likely responsible for the high levels of broadly cross-reactive and protective antibodies with rare specificities observed with RIV4. Furthermore, the presence of uniform compact HA oligomers and absence of egg proteins, viral RNA or process impurities, typically found in conventional vaccines, are expected to eliminate potential adverse reactions to these components in susceptible individuals with the use of RIV4. These distinct structural features and purity of the recombinant HA vaccine thus provide a number of benefits in vaccine performance which can be extended to other viral targets, such as for COVID-19.
N. V. Orlova, V. V. Lomaychikov
Meditsinskiy sovet = Medical Council; https://doi.org/10.21518/2079-701x-2021-18-86-93

Abstract:
Influenza remains one of the most common respiratory viral diseases with a high risk of complications. In the context of the COVID-19 pandemic, there is a possibility of simultaneous circulation of two viruses, which makes it necessary to conduct a differential diagnosis. Influenza and COVID-19 have common pathways of transmission of the pathogen and similar symptoms, so the optimal differential diagnosis is the use of test systems for both viruses. Against the background of influenza and COVID-19, complications from various organs and systems can develop. The article describes in detail the complications of influenza from the cardiovascular system. After infection with the flu virus, there is a 6-to 10-fold increase in the risk of acute myocardial infarction and a 3 - to 8-fold increase in the risk of stroke. COVID-19 is associated with arterial hypertension, diabetes mellitus, cardiac arrhythmias, myocarditis, high risk of acute myocardial infarction, and heart failure. The article presents the data of our own research, indicating that the transferred COVID-19 disease increases the risk of acute coronary syndrome, regardless of the presence of risk factors for cardiovascular events. Prevention of the development of influenza complications is the early administration of etiotropic antiviral therapy. Numerous studies confirm the effectiveness of the neuraminidase inhibitor oseltamivir in the treatment of influenza. The use of oseltamivir reduces the severity of clinical manifestations, reduces the duration of the disease, reduces the risk of complications and death. The most effective measure to prevent influenza and COVID-19 is specific immunization. In some cases, chemoprophylaxis can be used. The article discusses studies on the effectiveness of influenza chemoprophylaxis with the use of neuraminidase inhibitors.
Xiao-Xin Wu, Song-Jia Tang, Shu-Hao Yao, Yu-Qin Zhou, Lan-Lan Xiao, Lin-Fang Cheng, Fu-Ming Liu, Nan-Ping Wu, ,
Published: 29 November 2021
Virology Journal, Volume 18, pp 1-11; https://doi.org/10.1186/s12985-021-01709-7

Abstract:
Background: The highly pathogenic Influenza H7N9 virus is believed to cause multiple organ infections. However, there have been few systematic animal experiments demonstrating the virus distribution after H7N9 virus infection. The present study was carried out to investigate the viral distribution and pathological changes in the main organs of mice after experimental infection with highly pathogenic H7N9 virus. Methods: Infection of mice with A/Guangdong/GZ8H002/2017(H7N9) virus was achieved via nasal inoculation. Mice were killed at 2, 3, and 7 days post infection. The other mice were used to observe their illness status and weight changes. Reverse transcription polymerase chain reaction and viral isolation were used to analyse the characteristics of viral invasion. The pathological changes of the main organs were observed using haematoxylin and eosin staining and immunohistochemistry. Results: The weight of H7N9 virus-infected mice increased slightly in the first two days. However, the weight of the mice decreased sharply in the following days, by up to 20%. All the mice had died by the 8th day post infection and showed multiple organ injury. The emergence of viremia in mice was synchronous with lung infection. On the third day post infection, except in the brain, the virus could be isolated from all organs (lung, heart, kidney, liver, and spleen). On the seventh day post infection, the virus could be detected in all six organs. Brain infection was detected in all mice, and the viral titre in the heart, kidney, and spleen infection was high. Conclusion: Acute diffuse lung injury was the initial pathogenesis in highly pathogenic H7N9 virus infection. In addition to lung infection and viremia, the highly pathogenic H7N9 virus could cause multiple organ infection and injury.
, Ana Paula Sayuri Sato, Priscila Maria Stolses Bergamo Francisco
Published: 8 November 2021
Abstract:
This study aimed to estimate the prevalence of non-vaccination and the reasons for nonadherence to the influenza vaccine among older Brazilians according to sociodemographic characteristics. A cross-sectional study was conducted with data from older people (≥ 60 years of age; n = 23,815) who participated in the 2013 National Health Survey. Frequencies of non-vaccination and the main reasons for nonadherence were calculated with respective 95% confidence intervals. The prevalence of non-vaccination was 26.9% (approximately 7,106,730 older people). The reason rarely gets the flu was the most cited among the men (28.2%), the 60-to-69-year-old age group (29.6%), individuals with higher education (41.9%), and those with health insurance (32.3%). Fear of a reaction was the most cited reason in the northeastern region (25.4%), among women (29.3%), longer-lived individuals (≥70 years; 28.7%), and those who did not know how to read/write (26.7%). A total of 12.1% reported not believing in the vaccine’s protection, and 5.5% did not know that it was necessary to take vaccine. The proportions of the main reasons for non-vaccination varied by sociodemographic characteristics. This study’s findings highlight the need to increase older people’s knowledge regarding influenza and influenza vaccines. Healthcare providers should be encouraged to counsel older people–especially those in subgroups with lower adherence, such as residents in the Northeast region, those aged 60–69 years, those who do not know how to read/write, those without a spouse/companion, and those without health insurance–regarding the different aspects of the vaccine and formally indicate it for groups at risk.
Irene Giacchetta, Chiara Primieri, Riccardo Cavalieri, Alexander Domnich, Chiara Waure
Influenza and Other Respiratory Viruses, Volume 16, pp 351-365; https://doi.org/10.1111/irv.12925

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, , Melissa A. Rolfes, Benjamin Lee, Shreya Chodisetty, Julio A. Ramirez, Alicia M. Fry,
Published: 21 October 2021
Abstract:
Background Experimental studies have shown that vaccination can reduce viral replication to attenuate progression of influenza-associated lower respiratory tract illness (LRTI). However, clinical studies are conflicting, possibly due to use of non-specific outcomes reflecting a mix of large and small airway LRTI lacking specificity for acute lung or organ injury. Methods We developed a global ordinal scale to differentiate large and small airway LRTI in hospitalized adults with influenza using physiologic features and interventions (PFIs): vital signs, laboratory and radiographic findings, and clinical interventions. We reviewed the literature to identify common PFIs across 9 existing scales of pneumonia and sepsis severity. To characterize patients using this scale, we applied the scale to an antiviral clinical trial dataset where these PFIs were measured through routine clinical care in adults hospitalized with influenza-associated LRTI during the 2010–2013 seasons. Results We evaluated 12 clinical parameters among 1020 adults; 210 (21%) had laboratory-confirmed influenza, with a median severity score of 4.5 (interquartile range, 2–8). Among influenza cases, median age was 63 years, 20% were hospitalized in the prior 90 days, 50% had chronic obstructive pulmonary disease, and 22% had congestive heart failure. Primary influencers of higher score included pulmonary infiltrates on imaging (48.1%), heart rate ≥110 beats/minute (41.4%), oxygen saturation 24 breaths/minute (21.0%). Key PFIs distinguishing patients with severity < or ≥8 (upper quartile) included infiltrates (27.1% vs 90.0%), temperature ≥ 39.1°C or 24 breaths/minute (7.9% vs 47.1%), heart rate ≥110 beats/minute (29.3% vs 65.7%), oxygen saturation 15,000 (5.0% vs 27.2%), and need for invasive or non-invasive mechanical ventilation (2.1% vs 15.7%). Conclusion We developed a scale in adults hospitalized with influenza-associated LRTI demonstrating a broad distribution of physiologic severity which may be useful for future studies evaluating the disease attenuating effects of influenza vaccination or other therapeutics.
Carlo De Intinis, Margherita Bodini, Denise Maffione, Laurane De Mot, Margherita Coccia, Duccio Medini, Emilio Siena
Published: 21 October 2021
Scientific Reports, Volume 11, pp 1-13; https://doi.org/10.1038/s41598-021-99870-0

Abstract:
Gene expression data is commonly used in vaccine studies to characterize differences between treatment groups or sampling time points. Group-wise comparisons of the transcriptional perturbations induced by vaccination have been applied extensively for investigating the mechanisms of action of vaccines. Such approaches, however, may not be sensitive enough for detecting changes occurring within a minority of the population under investigation or in single individuals. In this study, we developed a data analysis framework to characterize individual subject response profiles in the context of repeated measure experiments, which are typical of vaccine mode of action studies. Following the definition of the methodology, this was applied to the analysis of human transcriptome responses induced by vaccination with a subunit influenza vaccine. Results highlighted a substantial heterogeneity in how different subjects respond to vaccination. Moreover, the extent of transcriptional modulation experienced by each individual subject was found to be associated with the magnitude of vaccine-specific functional antibody response, pointing to a mechanistic link between genes involved in protein production and innate antiviral response. Overall, we propose that the improved characterization of the intersubject heterogeneity, enabled by our approach, can help driving the improvement and optimization of current and next-generation vaccines.
G. L. Habib, H. Yousuf, J. Narula,
Published: 14 October 2021
Netherlands Heart Journal, Volume 29, pp 545-550; https://doi.org/10.1007/s12471-021-01637-9

Abstract:
The COVID-19 pandemic has spurred clinical and scientific interest in the cardiology community because of the significantly enhanced vulnerability of patients with underlying cardiac diseases. COVID-19 vaccination is therefore of vital importance to the patients we see in our clinics and hospitals every day and should be promoted by the medical community, especially cardiologists. In view of vaccine-preventable diseases, the association between influenza and cardiovascular complications has been widely investigated. Several studies have found a substantially elevated risk of hospital admission for acute myocardial infarction in the first 7 days after laboratory-confirmed influenza, with incidence ratios ranging from 6.05–8.89. The effectiveness of the influenza vaccine to protect against acute myocardial infarction is about 29%. This effectiveness is comparable to or even better than that of existing secondary preventive therapies, such as statins (prevention rate approximately 36%), antihypertensives (prevention rate approximately 15–18%), and smoking cessation (prevention rate approximately 26%). As the influenza season is rapidly approaching, this Point of View article serves as a call to action: Cardiologists should promote influenza vaccination and actively advice their patients to get the seasonal influenza vaccination.
, Saskia Klein, Hans-Martin Schuldt, Micha Löbermann, Kerstin Köller, Jan Däbritz, Emil Christian Reisinger
Published: 28 September 2021
Wiener Medizinische Wochenschrift pp 1-6; https://doi.org/10.1007/s10354-021-00884-0

Abstract:
Summary: Background: The influenza season 2017–2018 of the northern hemisphere was the highest since 2001 and was caused predominantly by influenza B virus. Methods: We performed a retrospective analysis of all patients in a university hospital in northern Germany with laboratory-confirmed influenza during the winter season 2017–2018 and analyzed underlying conditions, complications, and outcome. Results: A total of 272 cases of influenza were diagnosed: 70 influenza A (25.7%), 201 influenza B (73.9%), and 1 co-infection. Of 182 adults, 145 were hospitalized, 73 developed pneumonia, 11 developed myocardial infarction, two a transient ischemic attack, one a stroke, and one perimyocarditis. Eleven of the 145 hospitalized adult patients (7.6%) died, ten of them because of pneumonia. All of them had preexisting diseases. Pneumonia was associated with a mortality of 13.7%. Underlying cardiac insufficiency was correlated with higher mortality (7/51 with versus 4/126 patients without cardiac insufficiency; p< 0.05). Ninety cases of influenza were diagnosed in 89 children (30 A, 60 B), one child had first influenza B, then influenza A. Twenty-eight children (31%) were hospitalized, 15 children developed one or more complications (lower respiratory tract infections, meningeal irritations, febrile seizures, otitis media, myositis). No child died. Influenza vaccination status was known in 149 adult patients, pneumonia occurred more frequently in non-vaccinated individuals (43/90; 47.8%) than in vaccinated patients (18/59; 30.5%, p< 0.05). Conclusion: Patients with influenza should be monitored for secondary pneumonia and myocardial infarction, and vaccination should be enforced especially in patients with coronary heart disease and cardiac insufficiency.
, Ian A York, Arnold S Monto, Mark G Thompson, Alicia M Fry
Published: 24 September 2021
The Lancet Microbe, Volume 2; https://doi.org/10.1016/s2666-5247(21)00180-4

The publisher has not yet granted permission to display this abstract.
, F. Ortega-Valín, González Quintanilla, J. García-Poza, M. Feo-González, S. Marcos-González, M. Rollán-Martínez-Herrera
Published: 21 September 2021
Clinical Neurology and Neurosurgery, Volume 210; https://doi.org/10.1016/j.clineuro.2021.106956

The publisher has not yet granted permission to display this abstract.
Shahnoor Amin, Marcin Wozniak, Lidija Barbaric, Shanel Pickard, Rahul S. Yerrabelli, Anton Christensen,
Journal of Healthcare Informatics Research, Volume 6, pp 48-71; https://doi.org/10.1007/s41666-021-00106-7

The publisher has not yet granted permission to display this abstract.
Margaret McCartney, Richard Byng
Published: 20 August 2021
by BMJ
Abstract:
Multidisciplinary care is not magically beneficial and can exclude patients from decisions
Valentin Sencio, Alexandre Gallerand, Marina Gomes Machado, Lucie Deruyter, Séverine Heumel, Daphnée Soulard, Johanna Barthelemy, Céline Cuinat, Angelica T. Vieira, Adeline Barthelemy, et al.
Infection and Immunity, Volume 89; https://doi.org/10.1128/iai.00734-20

Abstract:
Along with respiratory tract disease per se , viral respiratory infections can also cause extrapulmonary complications with a potentially critical impact on health. In the present study, we used an experimental model of influenza A virus (IAV) infection to investigate the nature and outcome of the associated gut disorders.
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