Reintroduction of highly pathogenic avian influenza A H7N9 virus in southwestern China.

Highly pathogenic (HP) avian influenza A H7N9 virus has emerged in China since 2016. In recent years, it has been most prevalent in northern China. However, several strains of HP H7N9 reappeared in southwestern China (Yunnan Province) in 2021. As a result, we are wondering if these viruses have re-emerged in situ or been reintroduced. Here, we present phylogenetic evidence that the HP H7N9 viruses isolated in Yunnan emigrated from northern to southwestern China in 2020. The northern subregion of China has become a novel epicenter in HP H7N9 dissemination. Meanwhile, a cleavage motif re-emerged due to the T341I mutation, implying a parallel evolution. This cross-region transmission, which originated in non-adjacent provinces and traveled a great geographic distance in an unknown way, indicates that HP H7N9 dissemination did not halt in 2020, even under the shadow of the COVID-19 pandemic. Additional surveillance studies in poultry are required to determine the HP H7N9 virus's geographic distribution and spread.

Comparison of clinical characteristics between COVID-19 and H7N9 fatal cases: An observational study.

Objective: The outbreak of COVID-19 in 2020 is reminiscent of the H7N9 outbreak in 2013, which poses a huge threat to human health. We aim to compare clinical features and survival factors in fatal cases of COVID-19 and H7N9. Methods: Data on confirmed COVID-19 and H7N9 fatal cases identified in mainland China were analyzed to compare demographic characteristics and clinical severity. Survival curves were estimated by the Kaplan-Meier method and compared using log-rank tests and a restricted mean survival time model. A Cox regression model was used to identify survival factors in fatal cases of COVID-19 and H7N9. Results: Similar demographic characteristics were observed in fatal cases of COVID-19 and H7N9. The proportion of fatal cases of H7N9 receiving antibiotics, antiviral drugs, and oxygen treatment was higher than that of COVID-19. The potential protective factors for fatal COVID-19 cases were receiving antibiotics (HR: 0.37, 95% CI: 0.22-0.61), oxygen treatment (HR: 0.66, 95% CI: 0.44-0.99), and corticosteroids (HR: 0.46, 95% CI: 0.35-0.62). In contrast, antiviral drugs (HR: 0.21, 95% CI: 0.08-0.56) and corticosteroids (HR: 0.45, 95% CI: 0.29-0.69) were the protective factors for H7N9 fatal cases. Conclusion: The proportion of males, those having one or more underlying medical condition, and older age was high in COVID-19 and H7N9 fatal cases. Offering antibiotics, oxygen treatment, and corticosteroids to COVID-19 cases extended the survival time. Continued global surveillance remains an essential component of pandemic preparedness.

Antigenic Characterization of Human Monoclonal Antibodies for Therapeutic Use against H7N9 Avian Influenza Virus.

Since 2013, H7N9 avian influenza viruses (AIVs) have caused more than 1,500 human infections and the culling of millions of poultry. Despite large-scale poultry vaccination, H7N9 AIVs continue to circulate among poultry in China and pose a threat to human health. Previously, we isolated and generated four monoclonal antibodies (mAbs) derived from humans naturally infected with H7N9 AIV. Here, we investigated the hemagglutinin (HA) epitopes of H7N9 AIV targeted by these mAbs (L3A-44, K9B-122, L4A-14, and L4B-18) using immune escape studies. Our results revealed four key antigenic epitopes at HA amino acid positions 125, 133, 149, and 217. The mutant H7N9 viruses representing escape mutations containing an alanine-to-threonine substitution at residue 125 (A125T), a glycine-to-glutamic acid substitution at residue 133 (G133E), an asparagine-to-aspartic acid substitution at residue 149 (N149D), or a leucine-to-glutamine substitution at residue 217 (L217Q) showed reduced or completely abolished cross-reactivity with the mAbs, as measured by a hemagglutination inhibition (HI) assay. We further assessed the potential risk of these mutants to humans should they emerge following mAb treatment by measuring the impact of these HA mutations on virus fitness and evasion of host adaptive immunity. Here, we showed that the L4A-14 mAb had broad neutralizing capabilities, and its escape mutant N149D had reduced viral stability and human receptor binding and could be neutralized by both postinfection and antigen-induced sera. Therefore, the L4A-14 mAb could be a therapeutic candidate for H7N9 AIV infection in humans and warrants further investigation for therapeutic applications. IMPORTANCE Avian influenza virus (AIV) H7N9 continues to circulate and evolve in birds, posing a credible threat to humans. Antiviral drugs have proven useful for the treatment of severe influenza infections in humans; however, concerns have been raised as antiviral-resistant mutants have emerged. Monoclonal antibodies (mAbs) have been studied for both prophylactic and therapeutic applications in infectious disease control and have demonstrated great potential. For example, mAb treatment has significantly reduced the risk of people developing severe disease with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition to the protection efficiency, we should also consider the potential risk of the escape mutants generated by mAb treatment to public health by assessing their viral fitness and potential to compromise host adaptive immunity. Considering these parameters, we assessed four human mAbs derived from humans naturally infected with H7N9 AIV and showed that the mAb L4A-14 displayed potential as a therapeutic candidate.

Chemically Modified Bovine ß-Lactoglobulin as a Broad-Spectrum Influenza Virus Entry Inhibitor with the Potential to Combat Influenza Outbreaks.

Frequent outbreaks of the highly pathogenic influenza A virus (AIV) infection, together with the lack of broad-spectrum influenza vaccines, call for the development of broad-spectrum prophylactic agents. Previously, 3-hydroxyphthalic anhydride-modified bovine ß-lactoglobulin (3HP-ß-LG) was proven to be effective against human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it has also been used in the clinical control of cervical human papillomavirus (HPV) infections. Here, we show its efficacy in potently inhibiting infection by divergent influenza A and B viruses. Mechanistic studies suggest that 3HP-ß-LG binds, possibly through its negatively charged residues, to the receptor-binding domain in the hemagglutinin 1 (HA1) subunit in the HA of the influenza virus, thus inhibiting the attachment of the HA to sialic acid on host cells. The intranasal administration of 3HP-ß-LG led to the protection of mice against challenges by influenza A(H1N1)/PR8, A(H3N2), and A(H7N9) viruses. Furthermore, 3HP-ß-LG is highly stable when stored at 50 °C for 30 days and it shows excellent safety in vitro and in vivo. Collectively, our findings suggest that 3HP-ß-LG could be successfully repurposed as an intranasal prophylactic agent to prevent influenza virus infections during influenza outbreaks.

Rapid and universal detection of SARS-CoV-2 and influenza A virus using a reusable dual-channel optic fiber immunosensor.

Establishment of rapid on-site detection technology capable of concurrently detecting SARS-Cov-2 and influenza A virus is urgent to effectively control the epidemic from these two types of important viruses. Accordingly, we developed a reusable dual-channel optical fiber immunosensor (DOFIS), which utilized the evanescent wave-sensing properties and tandem detection mode of the mobile phase, effectively accelerating the detection process such that it can be completed within 10 min. It could detect the nucleoprotein of multiple influenza A viruses (H1N1, H3N2, and H7N9), as well as the spike proteins of the SARS-CoV-2 Omicron and Delta variants, and could respond to 20 TCID50 /ml SARS-CoV-2 pseudovirus and 100 TCID50 /ml influenza A (A/PR/8/H1N1), presenting lower limit of detection and wider linear range than enzyme-linked immunosorbent assay. The detection results on 26 clinical samples for SARS-CoV-2 demonstrated its specificity (100%) and sensitivity (94%), much higher than the sensitivity of commercial colloidal gold test strip (35%). Particularly, DOFIS might be reused more than 80 times, showing not only cost-saving but also potential in real-time monitoring of the pathogenic viruses. Therefore, this newly-developed DOFIS platform is low cost, simple to operate, and has broad spectrum detection capabilities for SARS-CoV-2 mutations and multiple influenza A strains. It may prove suitable for deployment as a rapid on-site screening and surveillance technique for infectious disease.

Comparison of acute respiratory distress syndrome in patients with COVID-19 and influenza A (H7N9) virus infection.

OBJECTIVES: We aimed to compared the clinical features of acute respiratory distress syndrome (ARDS) induced by COVID-19 and H7N9 virus infections. METHODS: Clinical data of 100 patients with COVID-19 and 46 patients with H7N9 were retrospectively analyzed. RESULTS: Elevated inflammatory indices and coagulation disorders were more common in COVID-19-ARDS group than in the H7N9-ARDS group. The median interval from illness onset to ARDS development was shorter in H7N9-ARDS. The PaO2/FiO2 level was lower in H7N9-ARDS, whereas the Sepsis-related Organ Failure Assessment score was higher in COVID-19-ARDS. The proportion of patients with disseminated intravascular coagulation and liver injury in COVID-19-ARDS and H7N9-ARDS was 45.5% versus 3.1% and 28.8% versus 50%, respectively (P <0.05). The mean interval from illness onset to death was shorter in H7N9-ARDS. A total of 59.1% patients with H7N9-ARDS died of refractory hypoxemia compared with 28.9% with COVID-19-ARDS (P = 0.014). Patients with COVID-19-ARDS were more likely to die of septic shock and multiple organ dysfunction compared with H7N9-ARDS (71.2% vs 36.4%, P = 0.005). CONCLUSION: Patients with H7N9 were more susceptible to develop severe ARDS and showed a more acute disease course. COVID-19-ARDS was associated with severe inflammatory response and coagulation dysfunction, whereas liver injury was more common in H7N9-ARDS. The main causes of death between patients with the two diseases were different.

Post-viral mental health sequelae in infected persons associated with COVID-19 and previous epidemics and pandemics: Systematic review and meta-analysis of prevalence estimates.

AIMS: Post-viral mental health problems (MHP) in COVID-19 patients and survivors were anticipated already during early stages of this pandemic. We aimed to synthesize the prevalence of the anxiety, depression, post-traumatic and general distress domain associated with virus epidemics since 2002. METHODS: In this systematic review and meta-analysis, we searched PubMed, PsycINFO, and Embase from 2002 to April 14, 2021 for peer-reviewed studies reporting prevalence of MHP in adults with laboratory-confirmed or suspected SARS-CoV-1, H1N1, MERS-CoV, H7N9, Ebolavirus, or SARS-CoV-2 infection. We included studies that assessed post-viral MHP with validated and frequently used scales. A three-level random-effects meta-analysis for dependent effect sizes was conducted to account for multiple outcome reporting. We pooled MHP across all domains and separately by severity (above mild or moderate-to-severe) and by acute (one month), ongoing (one to three months), and post-illness stages (longer than three months). A meta-regression was conducted to test for moderating effects, particularly for exploring estimate differences between SARS-Cov-2 and previous pandemics and epidemics. PROSPERO registration: CRD42020194535. RESULTS: We identified 59 studies including between 14 and 1002 participants and providing 187 prevalence estimates. MHP, in general, decreased from acute to post-illness from 46.3% to 38.8% and for mild and moderate-to-severe from 22.3% to 18.8%, respectively. We found no evidence of moderating effects except for non-random sampling and H1N1 showing higher prevalence. There was a non-significant trend towards lower MHP for SARS-CoV-2 compared to previous epidemics. CONCLUSIONS: MHP prevalence estimates decreased over time but were still on a substantial level at post-illness. Post-viral mental health problems caused by SARS-CoV-2 could have been expected much earlier, given the previous post-viral sequelae.

A Single Vaccine Protects against SARS-CoV-2 and Influenza Virus in Mice.

The ongoing SARS-CoV-2 pandemic poses a severe global threat to public health, as do influenza viruses and other coronaviruses. Here, we present chimpanzee adenovirus 68 (AdC68)-based vaccines designed to universally target coronaviruses and influenza. Our design is centered on an immunogen generated by fusing the SARS-CoV-2 receptor-binding domain (RBD) to the conserved stalk of H7N9 hemagglutinin (HA). Remarkably, the constructed vaccine effectively induced both SARS-CoV-2-targeting antibodies and anti-influenza antibodies in mice, consequently affording protection from lethal SARS-CoV-2 and H7N9 challenges as well as effective H3N2 control. We propose our AdC68-vectored coronavirus-influenza vaccine as a universal approach toward curbing respiratory virus-causing pandemics. IMPORTANCE The COVID-19 pandemic exemplifies the severe public health threats of respiratory virus infection and influenza A viruses. The currently envisioned strategy for the prevention of respiratory virus-causing diseases requires the comprehensive administration of vaccines tailored for individual viruses. Here, we present an alternative strategy by designing chimpanzee adenovirus 68-based vaccines which target both the SARS-CoV-2 receptor-binding-domain and the conserved stalk of influenza hemagglutinin. When tested in mice, this strategy attained potent neutralizing antibodies against wild-type SARS-CoV-2 and its emerging variants, enabling an effective protection against lethal SARS-CoV-2 challenge. Notably, it also provided complete protection from lethal H7N9 challenge and efficient control of H3N2-induced morbidity. Our study opens a new avenue to universally curb respiratory virus infection by vaccination.

Competitive Endogenous RNA Network Activates Host Immune Response in SARS-CoV-2-, panH1N1 (A/California/07/2009)-, and H7N9 (A/Shanghai/1/2013)-Infected Cells.

The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still ongoing, as is research on the molecular mechanisms underlying cellular infection by coronaviruses, with the hope of developing therapeutic agents against this pandemic. Other important respiratory viruses such as 2009 pandemic H1N1 and H7N9 avian influenza virus (AIV), influenza A viruses, are also responsible for a possible outbreak due to their respiratory susceptibility. However, the interaction of these viruses with host cells and the regulation of post-transcriptional genes remains unclear. In this study, we detected and analyzed the comparative transcriptome profiling of SARS-CoV-2, panH1N1 (A/California/07/2009), and H7N9 (A/Shanghai/1/2013) infected cells. The results showed that the commonly upregulated genes among the three groups were mainly involved in autophagy, pertussis, and tuberculosis, which indicated that autophagy plays an important role in viral pathogenicity. There are three groups of commonly downregulated genes involved in metabolic pathways. Notably, unlike panH1N1 and H7N9, SARS-CoV-2 infection can inhibit the m-TOR pathway and activate the p53 signaling pathway, which may be responsible for unique autophagy induction and cell apoptosis. Particularly, upregulated expression of IRF1 was found in SARS-CoV-2, panH1N1, and H7N9 infection. Further analysis showed SARS-CoV-2, panH1N1, and H7N9 infection-induced upregulation of lncRNA-34087.27 could serve as a competitive endogenous RNA to stabilize IRF1 mRNA by competitively binding with miR-302b-3p. This study provides new insights into the molecular mechanisms of influenza A virus and SARS-CoV-2 infection.

Comparative study of hematological and radiological feature of severe/critically ill patients with COVID-19, influenza A H7N9, and H1N1 pneumonia.

OBJECTIVES: This study aimed to explore clinical indexes for management of severe/critically ill patients with COVID-19, influenza A H7N9, and H1N1 pneumonia by comparing hematological and radiological characteristics. METHODS: Severe/critically ill patients with COVID-19, H7N9, and H1N1 pneumonia were retrospectively enrolled. The demographic data, clinical manifestations, hematological parameters, and radiological characteristics were compared. RESULTS: In this study, 16 cases of COVID-19, 10 cases of H7N9, and 13 cases of H1N1 who met severe/critically ill criteria were included. Compared with COVID-19, H7N9 and H1N1 groups had more chronic diseases (80% and 92.3% vs. 25%, p < 0.05), higher APACHE Ⅱ scores (16.00 ± 8.63 and 15.08 ± 6.24, vs. 5.50 ± 2.58, p < 0.05), higher mortality rates (40% and 46.2% vs. 0%, p < 0.05), significant lymphocytopenia (0.59 ± 0.31 × 109 /L and 0.56 ± 0.35 × 109 /L vs. 0.97 ± 0.33 × 109 /L, p < 0.05), and elevated neutrophil-to-lymphocyte ratio (NLR; 14.67 ± 6.10 and 14.64 ± 10.36 vs. 6.29 ± 3.72, p < 0.05). Compared with the H7N9 group, ground-glass opacity (GGO) on chest CT was common in the COVID-19 group (p = 0.028), while pleural effusion was rare (p = 0.001). CONCLUSIONS: The NLR can be used as a clinical parameter for the predication of risk stratification and outcome in COVID-19 and influenza A pneumonia. Manifestations of pleural effusion or GGO in chest CT may be helpful for the identification of different viral pneumonia.

Risk of Environmental Exposure to H7N9 Influenza Virus via Airborne and Surface Routes in a Live Poultry Market in Hebei, China.

Environmental transmission of viruses to humans has become an early warning for potential epidemic outbreaks, such as SARS-CoV-2 and influenza virus outbreaks. Recently, an H7N9 virus, A/environment/Hebei/621/2019 (H7N9), was isolated by environmental swabs from a live poultry market in Hebei, China. We found that this isolate could be transmitted by direct contact and aerosol in mammals. More importantly, after 5 passages in mice, the virus acquired two adaptive mutations, PB1-H115Q and B2-E627K, exhibiting increased virulence and aerosol transmissibility. These results suggest that this H7N9 virus might potentially be transmitted between humans through environmental or airborne routes.

Binding affinities of 438 HLA proteins to complete proteomes of seven pandemic viruses and distributions of strongest and weakest HLA peptide binders in populations worldwide.

We report detailed peptide-binding affinities between 438 HLA Class I and Class II proteins and complete proteomes of seven pandemic human viruses, including coronaviruses, influenza viruses and HIV-1. We contrast these affinities with HLA allele frequencies across hundreds of human populations worldwide. Statistical modelling shows that peptide-binding affinities classified into four distinct categories depend on the HLA locus but that the type of virus is only a weak predictor, except in the case of HIV-1. Among the strong HLA binders (IC50 ≤ 50), we uncovered 16 alleles (the top ones being A*02:02, B*15:03 and DRB1*01:02) binding more than 1% of peptides derived from all viruses, 9 (top ones including HLA-A*68:01, B*15:25, C*03:02 and DRB1*07:01) binding all viruses except HIV-1, and 15 (top ones A*02:01 and C*14:02) only binding coronaviruses. The frequencies of strongest and weakest HLA peptide binders differ significantly among populations from different geographic regions. In particular, Indigenous peoples of America show both higher frequencies of strongest and lower frequencies of weakest HLA binders. As many HLA proteins are found to be strong binders of peptides derived from distinct viral families, and are hence promiscuous (or generalist), we discuss this result in relation to possible signatures of natural selection on HLA promiscuous alleles due to past pathogenic infections. Our findings are highly relevant for both evolutionary genetics and the development of vaccine therapies. However they should not lead to forget that individual resistance and vulnerability to diseases go beyond the sole HLA allelic affinity and depend on multiple, complex and often unknown biological, environmental and other variables.

Early Surveillance and Public Health Emergency Responses Between Novel Coronavirus Disease 2019 and Avian Influenza in China: A Case-Comparison Study.

Background: Since the novel coronavirus disease (COVID-19) has been a worldwide pandemic, the early surveillance and public health emergency disposal are considered crucial to curb this emerging infectious disease. However, studies of COVID-19 on this topic in China are relatively few. Methods: A case-comparison study was conducted using a set of six key time nodes to form a reference framework for evaluating early surveillance and public health emergency disposal between H7N9 avian influenza (2013) in Shanghai and COVID-19 in Wuhan, China. Findings: A report to the local Center for Disease Control and Prevention, China, for the first hospitalized patient was sent after 6 and 20 days for H7N9 avian influenza and COVID-19, respectively. In contrast, the pathogen was identified faster in the case of COVID-19 than in the case of H7N9 avian influenza (12 vs. 31 days). The government response to COVID-19 was 10 days later than that to avian influenza. The entire process of early surveillance and public health emergency disposal lasted 5 days longer in COVID-19 than in H7N9 avian influenza (46 vs. 41 days). Conclusions: The identification of the unknown pathogen improved in China between the outbreaks of avian influenza and COVID-19. The longer emergency disposal period in the case of COVID-19 could be attributed to the government's slower response to the epidemic. Improving public health emergency management could lessen the adverse social effects of emerging infectious diseases and public health crisis in the future.

Universal influenza vaccine based on conserved antigens provides long-term durability of immune responses and durable broad protection against diverse challenge virus strains in mice.

Current influenza vaccines rely on inducing antibody responses to the rapidly evolving hemagglutinin (HA) and neuraminidase (NA) proteins, and thus need to be strain-matched. However, predictions of strains that will circulate are imperfect, and manufacturing of new vaccines based on them takes months. As an alternative, universal influenza vaccines target highly conserved antigens. In proof of concept studies of universal vaccine candidates in animal models challenge is generally conducted only a short time after vaccination, but protective immunity lasting far longer is important for the intended public health impact. We address the challenge of providing long-term protection. We demonstrate here broad, powerful, and long-lasting immune protection for a promising universal vaccine candidate. A single intranasal dose of recombinant adenoviruses (rAd) expressing influenza A nucleoprotein (A/NP) and matrix 2 (M2) was used. Extending our previous studies of this type of vaccine, we show that antibody and T-cell responses persist for over a year without boosting, and that protection against challenge persists a year after vaccination and remains broad, covering both group 1 and 2 influenza A viruses. In addition, we extend the work to influenza B. Immunization with influenza B nucleoprotein (B/NP)-rAd also gives immune responses that last a year without boosting and protect against challenge with influenza B viruses of mismatched HA lineages. Despite host immunity to adenoviral antigens, effective readministration is possible a year after primary vaccination, as shown by successful immunization to a transgene product the animals had not seen before. Protection against challenge with divergent and highly pathogenic A/H7N9 virus was weaker but was enhanced by a second dose of vaccine. Thus, this mucosal vaccination to conserved influenza antigens confers very long-lasting immune protection in animals against a broad range of influenza A and B viruses.

The Impact of Epidemics and Pandemics on the Mental Health of Healthcare Workers: A Systematic Review.

BACKGROUND: There is increasing evidence that healthcare workers (HCWs) experience significant psychological distress during an epidemic or pandemic. Considering the increase in emerging infectious diseases and the ongoing COVID-19 pandemic, it is timely to review and synthesize the available evidence on the psychological impact of disease outbreaks on HCWs. Thus, we conducted a systematic review to examine the impact of epidemics and pandemics on the mental health of HCWs. METHOD: PubMed, PsycInfo, and PsycArticles databases were systematically searched from inception to June-end 2020 for studies reporting the impact of a pandemic/epidemic on the mental health of HCWs. RESULTS: Seventy-six studies were included in this review. Of these, 34 (45%) focused on SARS, 28 (37%) on COVID-19, seven (9%) on MERS, four (5%) on Ebola, two (3%) on H1N1, and one (1%) on H7N9. Most studies were cross-sectional (93%) and were conducted in a hospital setting (95%). Common mental health symptoms identified by this review were acute stress disorder, depression, anxiety, insomnia, burnout, and post-traumatic stress disorder. The associated risk factors were working in high-risk environments (frontline), being female, being a nurse, lack of adequate personal protective equipment, longer shifts, lack of knowledge of the virus, inadequate training, less years of experience in healthcare, lack of social support, and a history of quarantine. CONCLUSION: HCWs working in the frontline during epidemics and pandemics experience a wide range of mental health symptoms. It is imperative that adequate psychological support be provided to HCWs during and after these extraordinary distressful events.

Intra-species sialic acid polymorphism in humans: a common niche for influenza and coronavirus pandemics?

The ongoing COVID-19 pandemic has led to more than 159 million confirmed cases with over 3.3 million deaths worldwide, but it remains mystery why most infected individuals (∼98%) were asymptomatic or only experienced mild illness. The same mystery applies to the deadly 1918 H1N1 influenza pandemic, which has puzzled the field for a century. Here we discuss dual potential properties of the 1918 H1N1 pandemic viruses that led to the high fatality rate in the small portion of severe cases, while about 98% infected persons in the United States were self-limited with mild symptoms, or even asymptomatic. These variations now have been postulated to be impacted by polymorphisms of the sialic acid receptors in the general population. Since coronaviruses (CoVs) also recognize sialic acid receptors and cause severe acute respiratory syndrome epidemics and pandemics, similar principles of influenza virus evolution and pandemicity may also apply to CoVs. A potential common principle of pathogen/host co-evolution of influenza and CoVs under selection of host sialic acids in parallel with different epidemic and pandemic influenza and coronaviruses is discussed.

Avian influenza A (H7N9) virus: from low pathogenic to highly pathogenic.

The avian influenza A (H7N9) virus is a zoonotic virus that is closely associated with live poultry markets. It has caused infections in humans in China since 2013. Five waves of the H7N9 influenza epidemic occurred in China between March 2013 and September 2017. H7N9 with low-pathogenicity dominated in the first four waves, whereas highly pathogenic H7N9 influenza emerged in poultry and spread to humans during the fifth wave, causing wide concern. Specialists and officials from China and other countries responded quickly, controlled the epidemic well thus far, and characterized the virus by using new technologies and surveillance tools that were made possible by their preparedness efforts. Here, we review the characteristics of the H7N9 viruses that were identified while controlling the spread of the disease. It was summarized and discussed from the perspectives of molecular epidemiology, clinical features, virulence and pathogenesis, receptor binding, T-cell responses, monoclonal antibody development, vaccine development, and disease burden. These data provide tools for minimizing the future threat of H7N9 and other emerging and re-emerging viruses, such as SARS-CoV-2.

Experiences and management of physician psychological symptoms during infectious disease outbreaks: a rapid review.

BACKGROUND: Prior to the COVID-19 pandemic, physicians experienced unprecedented levels of burnout. The uncertainty of the ongoing COVID-19 pandemic along with increased workload and difficult medical triage decisions may lead to a further decline in physician psychological health. METHODS: We searched Medline, EMBASE, and PsycINFO for primary research from database inception (Medline [1946], EMBASE [1974], PsycINFO [1806]) to November 17, 2020. Titles and abstracts were screened by one of three reviewers and full-text article screening and data abstraction were conducted independently, and in duplicate, by three reviewers. RESULTS: From 6223 unique citations, 480 articles were reviewed in full-text, with 193 studies (of 90,499 physicians) included in the final review. Studies reported on physician psychological symptoms and management during seven infectious disease outbreaks (severe acute respiratory syndrome [SARS], three strains of Influenza A virus [H1N1, H5N1, H7N9], Ebola, Middle East respiratory syndrome [MERS], and COVID-19) in 57 countries. Psychological symptoms of anxiety (14.3-92.3%), stress (11.9-93.7%), depression (17-80.5%), post-traumatic stress disorder (13.2-75.2%) and burnout (14.7-76%) were commonly reported among physicians, regardless of infectious disease outbreak or country. Younger, female (vs. male), single (vs. married), early career physicians, and those providing direct care to infected patients were associated with worse psychological symptoms. INTERPRETATION: Physicians should be aware that psychological symptoms of anxiety, depression, fear and distress are common, manifest differently and self-management strategies to improve psychological well-being exist. Health systems should implement short and long-term psychological supports for physicians caring for patients with COVID-19.

[Practice and thinking of acute respiratory infection surveillance for the response of emerging respiratory diseases in Shanghai].

Shanghai Municipal Center for Disease Control and Prevention has implemented an active comprehensive surveillance project of acute respiratory infections in adults in Shanghai, including influenza like illness (ILI) and severe acute respiratory infection (SARI). By testing and identifying a variety of respiratory pathogens, it was found that influenza viruses were the main pathogens in 172 ILI cases in 2019. The positive rates of influenza A (H1N1) pdm09 virus, influenza A (H3N2) virus and influenza B virus Victoria lineage were 30.81%, 14.53% and 30.55%, respectively. The positive detection of influenza A (H1N1) pdm09 virus peaked in the first quarter. The positive rate of enterovirus/human rhinovirus was 6.40%, with a positive detection peak in the third quarter, while the positive rate of adenovirus was 4.65% with a positive detection peak in the second quarter of the year. Two human coronavirus (HCoV)-OC43 positive samples, 1 HCoV-HKU1 positive sample and 1 HCoV-NL63 positive sample were detected, respectively, and no HCoV-229E positive sample was detected. The detection rate of Staphylococcus aureus was 17.44%, and the detection rate of Klebsiellapneumoniae was 9.88%. Influenza viruses were also the main pathogens in 1 447 SARI cases. The positive rates of influenza A (H1N1) pdm09 virus, influenza A (H3N2) virus and influenza B virus Victoria lineage were 5.46%, 1.73% and 0.30%, respectively. The positive detection of influenza A (H1N1) pdm09 virus (17.50%) peaked in the first quarter. The total positive detection rate of enterovirus/human rhinovirus was 2.97%, the positive detection peaked in the first quarter. The positive rate of Mycoplasma pneumoniae was 3.25% and the positive rate of Legionella was 1.04%. 5 HCoV-229E positive samples, 10 HCoV-OC43 positive samples, 7 HCoV-HKU1 positive samples and 6 HCoV-NL63 positive samples were detected. Eight strains of Staphylococcus aureus, 4 strains of Pseudomonas aeruginosa and 3 strains of Klebsiella pneumoniae were detected after cultures. By implementing the active surveillance, we not only detected a case of human infection with avian influenza A(H7N9) virus in time, but also preliminary understood the pathogenic spectrum characteristics and seasonality of ILI and SARI in Shanghai. In recent years, the surveillance methods have been continuously improved and the number of sentinel hospitals has increased gradually. In particular, for the response to COVID-19, the Surveillance Information Reporting System of Acute Respiratory Infection based on HIS system has been promoted to cover the whole city, which might lay a foundation for the active surveillance and early warning of emerging infectious diseases in the future.

H7N9 pandemic preparedness: A large-scale production of a split inactivated vaccine.

In March 2013 it was reported by the World Health Organization (WHO) the first cases of human infections with avian influenza virus A (H7N9). From 2013 to December 2019, 1568 cases have been reported with 616 deaths. H7N9 infection has been associated with high morbidity and mortality rates, and vaccination is currently the most effective way to prevent infections and consequently flu-related severe illness. Developing and producing vaccines against pandemic influenza viruses is the main strategy for a response to a possible pandemic. This study aims to present the production of three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to produce the pandemic influenza vaccine candidate against A(H7N9). These batches were characterized and evaluated for quality standards and tested for immunogenicity in mice. The average yield was 173.50 ± 7.88 µg/mL of hemagglutinin and all the preparations met all the required specifications. The formulated H7N9 vaccine is poorly immunogenic and needs to be adjuvanted with an oil in water emulsion adjuvant (IB160) to achieve a best immune response, in a prime and in a boost scheme. These data are important for initial production planning and preparedness in the case of a H7N9 pandemic.