Background: Following the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country. Methods: Nasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases, and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PVR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory confirmed cases were mapped and six genomes of viruses were fully sequenced. Results: Overall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2 positive patients, the median age was 39 years (CI95%: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A, and 20B in favour of several independent introduction of viruses. Conclusions. Our study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.

Background Claims of influenza vaccination increasing COVID-19 risk are circulating. Within the I-MOVE-COVID-19 primary care multicentre study, we measured the association between 2019–20 influenza vaccination and COVID-19. Methods We conducted a multicentre test-negative case-control study at primary care level, in study sites in five European countries, from March–August 2020. Patients presenting with acute respiratory infection were swabbed, with demographic, 2019–20 influenza vaccination and clinical information documented. Using logistic regression we measured the adjusted odds ratio (aOR), adjusting for study site and age, sex, calendar time, presence of chronic conditions. The main analysis included patients swabbed ≤7 days after onset from the three countries with <15% of missing influenza vaccination. In secondary analyses, we included five countries, using multiple imputation with chained equations to account for missing data. Results We included 257 COVID-19 cases and 1631 controls in the main analysis (three countries). The overall aOR between influenza vaccination and COVID-19 was 0.93 (95% CI: 0.66–1.32). The aOR was 0.92 (95% CI: 0.58–1.46) and 0.92 (95%CI: 0.51–1.67) among those aged 20–59 and ≥60 years, respectively. In secondary analyses, we included 6457 cases and 69272 controls. The imputed aOR was 0.87 (95% CI: 0.79–0.95) among all ages and any delay between swab and symptom onset. Conclusions There was no evidence that COVID-19 cases were more likely to be vaccinated against influenza than controls. Influenza vaccination should be encouraged among target groups for vaccination. I-MOVE-COVID-19 will continue documenting influenza vaccination status in 2020-21, in order to learn about effects of recent influenza vaccination.

Background: Although the burden of influenza is well characterized, the burden of community-onset non-influenza respiratory viruses has not been systematically assessed. Understanding the severity and seasonality of non-influenza viruses, including human coronaviruses, will provide a better understanding of the overall disease burden from respiratory viruses that could better inform resource utilization for hospitals and highlight the value of preventative strategies, including vaccines. Methods: From October 2017 to September 2019, a retrospective study was performed in a pre-defined catchment area to estimate the population-based incidence of community-onset respiratory viruses associated with hospitalization. Included patients were >18 years old, resided in New York City, were hospitalized for >24 hours, and had a respiratory virus detected within 3 calendar-days of admission. Disease burden was measured by hospital length of stay (LOS), intensive care unit (ICU) admissions, and in-hospital mortality and compared among those with laboratory-confirmed influenza versus those with laboratory-confirmed non-influenza viruses (human coronaviruses, parainfluenza viruses, respiratory syncytial virus, human metapneumovirus, and adenovirus). Results: During the study period, 4,232 eligible patients were identified of whom 50.9% were >65 years of age. For each virus, the population-based incidence was highest for those >80 years of age. When compared to those with influenza viruses detected, those with non-influenza respiratory viruses detected (combined) had higher population-based incidence, significantly more ICU admissions, and higher in-house mortality. Conclusions: The burden of non-influenza respiratory viruses for hospitalized adults is substantial. Prevention and treatment strategies are needed for non-influenza respiratory viruses, particularly for older adults.

Global influenza virus circulation declined and has been below traditional seasonal levels during the COVID-19 pandemic.1-3 We reviewed WHO influenza surveillance outputs from May 1-December 31, 2020 (epidemiologic weeks 18-53) from tropical Asian countries. For each country we report influenza surveillance specimens tested, and the percentage positive for influenza, by type and subtype. We compared current data to historical data from 2015-2019 in order to place the current season in historical context. Twelve included countries tested 17,407 surveillance specimens, with 592 (3.4%) testing positive for influenza viruses. From April 27-July 26, 2020 (epidemiologic weeks 18-30), specimens tested decreased from an average of 14,102 per year in 2015-2019 to 3,969 (71.9% decrease) and influenza positivity from 22% to <1%. During weeks 31-53, specimens tested decreased from an average of 24,782 per year in 2015-2019 to 13,438 (45.8% decrease) and influenza positivity from 18% to 4%. In six countries that maintained testing of surveillance specimens for >90% of weeks, influenza circulation was unseasonably low, or absent, during weeks 18-30, 2020. However, during weeks 31-53, the percentage of surveillance specimens testing positive for influenza approached or reached positivity rates of 2015-2019 in Bangladesh and Cambodia; and increased but remained lower than historical positivity in Lao PDR and Viet Nam. The data presented here are a reminder that the low levels of influenza circulation in the northern hemisphere in summer 2020 may not necessarily persist into the upcoming influenza season, and influenza surveillance and prevention strategies should continue as planned and not be delayed.

Background: Acute lower respiratory tract infections (ALRI) are one leading cause of morbidity and mortality among people of all ages worldwide, particularly in low- and middle-income countries (LMICs). The purpose of this study was to determine epidemiological characteristics of respiratory viruses in ARI patients during the SARS-CoV-2 pandemic in Yaoundé, Cameroon. Methods: Patients were monitored for respiratory symptoms as part of surveillance of SARS-CoV-2 and other respiratory viral infections. Patients of all ages with respiratory symptoms less than 5 days were considered. Sociodemographic and clinical data as well as nasopharyngeal samples was collected from patients. Nasopharyngeal samples were tested for SARS-CoV-2, Influenza and Respiratory Syncytial Virus (RSV) using real-time reverse-transcription polymerase chain reaction methods. Virus distribution and demographic data were analyzed with R version 2.15.1. Results: From July 2020 to October 2021, 1120 patients were included. The overall viral detection rate was 32.5%, including 9.5 % for RSV (Respiratory Syncytial Virus), 12.6 % for influenza virus and 12.8 % for SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Co-infections were detected in 6.9% of positive cases. While RSV and influenza virus showed seasonal trends, SARS-CoV-2 was detected throughout the study period. Conclusion: We found that during SARS-CoV-2 pandemic, respiratory viruses play an important role in aetiology of influenza-like illness in Cameroon, and this observation was true for patients of all ages.

Background: Tens of thousands of Australians become ill with influenza annually, causing thousands of severe infections that require hospitalisation. However, only 40% of adults receive the annual influenza vaccine. We surveyed Australian adults to provide up-to-date data on the predictors and barriers of seasonal influenza vaccination. Methods: We administered an online survey to a nationally representative sample of Australian adults. We designed survey questions using the constructs of the health belief model. Using simple and multivariable Poisson regression, we identified attitudes and beliefs associated with influenza vaccination in 2019. Results: Among 1,444 respondents, 51.7% self-reported influenza vaccination in 2019. We estimated vaccine coverage to be 44% for adults under 45, 46% for adults aged 45 to 64, and 77% for adults aged 65 and over. The strongest individual predictors of self-reported vaccination were believing the vaccine is effective at preventing influenza (APR = 3.71; 95% CI = 2.87-4.80), followed by recalling their doctor recommending the vaccine (APR = 2.70; 95%CI = 2.31-3.16). Common perceived barriers that predicted self-reported vaccination included believing the vaccine could give you influenza (APR = 0.59; 95% CI = 0.52-0.67), believing the vaccine can make you ill afterwards (APR = 0.68; 95% CI = 0.62-0.74), and preferring to develop immunity “naturally” (APR = 0.38; 95% CI = 0.32-0.45). Conclusion: Although vaccine uptake in 2019 appears to be higher than previous years, there are perceived barriers which may limit uptake among Australians. Tailored interventions are needed to combat widespread influenza vaccine hesitancy, particularly among high risk grou

Title: Age-related risk of household transmission of COVID-19 in SingaporeRachael Pung1, Minah Park2,3, Alex R Cook2,3, Vernon J Lee1,21 Ministry of Health, Singapore2 Saw Swee Hock School of Public Health, National University of Singapore3 National University Health System

Background Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few studies have evaluated Coronavac vaccine effectiveness (VE), particularly in eastern Europe, where the vaccine has been widely used. Methods We conducted a prospective cohort study among HCWs in seven hospitals in Baku, Azerbaijan between May 17 to December 1, 2021, to evaluate primary series (two-dose) CoronaVac VE against symptomatic SARS-CoV-2 infection. Participants completed weekly symptom questionnaires, provided nasal swabs for SARS-CoV-2 RT-PCR testing when symptomatic, and provided serology samples at enrolment that were tested for anti-spike and anti-nucleocapsid antibodies. We estimated VE as (1 – hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying covariate. Results We enrolled 1582 HCWs. At enrolment, 1040 (66%) had received two doses of CoronaVac; 421 (27%) were unvaccinated. During the study period, 72 PCR-positive SARS-CoV-2 infections occurred; 36/39 (92%) sequenced samples were classified as delta variant. The adjusted primary series VE against COVID-19 illness was 29% (95% CI:-51%;67%). For the delta-predominant period, adjusted primary series VE was 19% (95% CI:-81%;64%). For the entire analysis period, adjusted primary series VE was 39% (95% CI:-40%;73%) for HCW vaccinated within 14–149 days, and 19% (95%CI:-81;63) for those vaccinated ≥150 days. Conclusions During a delta-predominant period in Azerbaijan, point estimates suggest that primary series CoronaVac protected nearly 1 in 3 HCWs against COVID-19, but this finding was not statistically significant. Our findings underscore the need to consider booster doses in individuals who have received primary series CoronaVac.

Objectives: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection in young children. We aimed to analyze the factors affecting the estimation of RSV-related disease burden, and furthermore, to provide evidence to help establish a surveillance system. Methods: We searched for literature published in English or Chinese between 1 January, 2010 and 2 June, 2022. The quality of the included articles was assessed using the Agency for Healthcare Research and Quality scale. Random-effects models were used for data synthesis and subgroup analyses. This review was registered in the Prospective Register of Systematic Reviews (PROSPERO: CRD42022372972). Results: We included 44 studies (149,321,171 participants), all of which were of medium or high quality. The pooled RSV-associated disease incidence, hospitalization rate, in-hospital mortality, and overall mortality rates in children aged 5 years and younger were 9.0% (95% confidence interval [CI]: 7.0–11.0%), 1.68% (95% CI: 1.30–2.05%), 0.45% (95% CI: 0.38–0.52%), and 0.05% (95% CI: 0.04–0.06%), respectively. Age, economics, surveillance types, case definition, and data source were all influencing factors. Conclusions: A standardized and unified RSV surveillance system is required. Case definition and surveillance types should be fully considered for surveillance of different age groups.

Background: After the detection of the first case of coronavirus disease 2019 (COVID-19) in South Korea on January 20, 2019, it has triggered three major outbreaks. To decrease the disease burden of COVID-19, social distancing and active mask wearing were encouraged, reducing the number of patients with influenza-like illness and altering the detection rate of influenza and respiratory viruses in the Korea Influenza and Respiratory Viruses Surveillance System (KINRESS). We examined the changes in respiratory viruses due to COVID-19 in South Korea and virological causes of the high detection rate of human rhinovirus (hRV) in 2020. Methods: We collected 52,684 oropharyngeal or nasopharyngeal swab samples from patients with influenza-like illness in cooperation with KINRESS from 2016 to 2020. Influenza virus and other respiratory viruses were confirmed using real-time RT-PCR. The weekly detection rate was used to compare virus detection patterns. Results: Non-enveloped virus (hRV, human bocavirus, and human adenovirus) detection rates during the COVID-19 pandemic were maintained. The detection rate of hRV significantly increased in 2020 compared with that in 2019 and was negatively correlated with number of COVID-19-confirmed cases in 2020. The distribution of strains and genetic characteristics in hRV did not differ between 2019 and 2020. Conclusions: The extremely low detection rate of enveloped viruses resulted from efforts to prevent the spread of COVID-19 in South Korea. The high detection rate of hRV may be related to resistance against environmental conditions as a non-enveloped virus and the long period of viral shedding from patients.

Background: reliable country-specific data on influenza burden play a crucial role in informing prevention and control measures. Our purpose was to provide a comprehensive summary of the available evidence on the burden of seasonal influenza in Italy. Methods: we performed a sys-tematic literature review of articles published until 31 July 2020. PubMed, Embase and Web of Science were searched using terms related to burden, influenza, and Italian population. We in-cluded studies investigating seasonal influenza-related complications, hospitalizations and/or mortality. Results: sixteen studies were included: eight (50%) analyzed influenza-related compli-cations, eight (50%) hospitalizations, while seven (43.8%) influenza-related deaths. Only three studies (19.7%) concerned pediatric age. The synthesis of results showed that patients with chron-ic conditions have an increased risk for complications up to almost three times as compared to healthy people. Hospitalizations due to influenza can occur in as much as 5% of infected people depending on the study setting. Excess deaths rates were over six-fold higher in the elderly as compared to the rest of population. Conclusions: although there are still gaps in existing data, there is evidence of the significant burden that influenza places each year especially on high-risk groups. These data should be used to inform public health decision-making.

Background: Human respiratory syncytial virus (RSV) is one of the leading causes of respiratory infections, especially in infants and young children. Previous RSV sequencing studies have primarily focused on partial sequencing of G gene (200-300 nucleotides) for genotype characterization or diagnostics. However, the genotype assignment with G gene has not recapitulated the phylogenetic signal of other genes and there is no consensus on RSV genotype definition. Methods: We conducted Maximum Likelihood phylogenetic analysis with 10 RSV individual genes and whole-genome sequence (WGS) that are published in GenBank. RSV genotypes were assigned by the statistical support monophyletic clusters with at least 10-year detection time from the WGS phylogeny. Results: In this study, we first statistically examined the phylogenetic incongruence, rate variation for each RSV gene sequence and WGS. We then proposed a new RSV genotyping system based on a comparative analysis of WGS and the spatial and temporal distribution of each lineage. We also provided an RSV classification tool to perform RSV genotype assignment. Conclusions: This revised RSV genotyping system will provide important information for disease surveillance, epidemiology, and vaccine development.

Background. Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods. This was a phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In part 1 patients (n=24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In part 2 patients (n=48) were randomized 2:1 to receive AK0529 at 0.5, 1 or 2 mg/kg bid or placebo for five days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, signs and symptoms were assessed daily during treatment. Results. No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurred in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 hours was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in RSV signs and symptom score from baseline to 96 hours was observed in the 2 mg/kg group, compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions. AK0529 was well tolerated in hospitalized RSV-infected infants. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and clinical signs and symptoms.

A document by J. Kevin Yin. Click on the document to view its contents.

Background: Respiratory syncytial virus (RSV) is understood to be a cause of significant disease in older adults and children. Further analysis of RSV in younger adults may reveal further insight into its role as an important pathogen in all age groups. Methods: We identified, through laboratory data, adults who tested positive for either influenza or RSV between January 2017 and June 2019 at a single Australian hospital. We compared baseline demographics, testing patterns, hospitalisations and outcomes between these groups. Results: Of 1128 influenza and 193 RSV patients, the RSV cohort was older (mean age 54.7 vs. 64.9, p<0.001) and were more comorbid as determined by the Charlson Comorbidity Index (2.4 vs. 3.2, p<0.001). Despite this, adults under 65 with RSV were equally likely to be admitted compared with their influenza counterparts (70.3% vs. 77.3%, p=0.174). Testing occurred later in RSV hospitalisations as measured by the proportion tested in the emergency department (80.3% vs. 69.2%, p<0.001) and this was strongly associated with differences in presenting phenotype (the presence of fever). RSV was the biggest predictor of 6 month representation, with age and comorbidities predicting this less strongly. Conclusion: RSV is a significant contributor to morbidity and hospitalisation, sometimes outweighing that of influenza, and is not limited to elderly cohorts. Understanding key differences in the clinical syndrome and consequent testing paradigms may allow better detection and potentially treatment of RSV to reduce individual morbidity and health system burden. This growing area of research helps quantify the need for directed therapies for RSV.

Background. Despite the known relatively high disease burden of influenza, data are lacking regarding a critical epidemiological indicator, the case-fatality ratio. Our objective was to infer age-group and influenza (sub)type specific values by combining modelled estimates of symptomatic incidence and influenza-attributable mortality. Methods. The setting was the Netherlands, 2011/12 through 2019/20 seasons. Sentinel surveillance data from general practitioners and laboratory testing were synthesised to supply age-group specific estimates of incidence of symptomatic infection, and ecological additive modelling was used to estimated influenza-attributable deaths. These were combined in an Bayesian inferential framework to estimate case-fatality ratios for influenza A(H3N2), A(H1N1)pdm09 and influenza B, per 5-year age-group. Results. Case-fatality estimates were highest for influenza A(H3N2) followed by influenza B and then A(H1N1)pdm09, and were highest for the 85+ years age-group, at 4.76% (95% credible interval (CrI): 4.52-5.01%) for A(H3N2), followed by influenza B at 4.08% (95% CrI: 3.77-4.39%) and A(H1N1)pdm09 at 2.51% (95% CrI: 2.09-2.94%). For 55-59 through 85+ years, the case-fatality risk was estimated to double with every 3.7 years of age. Conclusions. These estimated case-fatality ratios, per influenza sub(type) and per age-group, constitute valuable information for public health decision-making, for assessing the retrospective and prospective value of preventative interventions such as vaccination, and for health economic evaluations.

Background: Baloxavir marboxil (BXM) is an approved drug that selectively targets cap-dependent endonuclease on PA subunit in the RNA polymerase complex of influenza A and B viruses. Amino acid substitutions at position 38 in the PA subunit were identified as a major pathway for reduced susceptibility to baloxavir acid (BXA), the active form of BXM. Additionally, substitutions found at positions E23, A37, and E199 in the PA subunit impact BXA susceptibility by less than 10-fold. Methods: We comprehensively evaluated the impact of novel amino acid substitutions identified in PA, PB1 and PB2 subunits in BXM clinical trials and influenza sequence databases by means of drug susceptibility and replicative capacity. Results: PA/I38N in A(H1N1) and PA/I38R in A(H3N2) were newly identified as treatment-emergent substitutions in the CAPSTONE-2 study. The I38N substitution conferred reduced susceptibility by 24-fold, whereas replicative capacity of the I38N-substituted virus was impaired compared to the wild-type. The I38R-substituted virus was not viable in cell culture. All other mutations assessed in this extensive study did not significantly affect BXA susceptibility (< 2.4-fold change). Conclusion: These results provide additional information on the impact of amino acid substitutions in the trimeric viral polymerase complex to BXA susceptibility and will further support influenza surveillance.

With the rapid increase of reported COVID-19 cases, German policymakers announced a 4-week “shutdown light” starting on Nov 2, 2020. Applying mathematical models, possible scenarios for the evolution of the outbreak in Germany are simulated. The results indicate that independent of the effectiveness of the current restrictive measures they might not be sufficient to mitigate the outbreak. Repeated shutdown periods or permanently applied measures over the winter could be successful alternatives.