Stringent public health measures imposed across Canada to control the COVID-19 pandemic have nearly suppressed most seasonal respiratory viruses, with the notable exception of human rhinovirus/enterovirus (hRV/EV). Thanks to this unexpected persistence, we highlight that hRV/EV could serve as a sentinel for levels of contact rate in populations to inform on the efficiency¬, or the need of, public health measures to control the subsequent COVID-19 epidemic, but also for future epidemics from other seasonal or emerging respiratory pathogens.

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: The COVID-19 pandemic has highlighted the need for targeted local interventions given substantial heterogeneity within cities and counties. Publicly available case data are typically aggregated to the city or county level to protect patient privacy, but more granular data are necessary to identify and act upon community-level risk factors that can change over time. Methods: Individual COVID-19 case and mortality data from Massachusetts were geocoded to residential addresses and aggregated into two time periods: “Phase 1” (March–June 2020) and “Phase 2” (September 2020–February 2021). Institutional cases associated with long-term care facilities, prisons, or homeless shelters were identified using address data and modeled separately. Census tract sociodemographic and occupational predictors were drawn from the 2015-2019 American Community Survey. We used mixed-effects negative binomial regression to estimate incidence rate ratios (IRRs), accounting for town-level spatial autocorrelation. Results: Case incidence was elevated in census tracts with higher proportions of Black and Latinx residents, with larger associations in Phase 1 than Phase 2. Case incidence associated with proportion of essential workers was similarly elevated in both Phases. Mortality IRRs had differing patterns from case IRRs, decreasing less substantially between Phases for Black and Latinx populations and increasing between Phases for proportion of essential workers. Mortality models excluding institutional cases yielded stronger associations for age, race/ethnicity, and essential worker status. Conclusions: Geocoded home address data can allow for nuanced analyses of community disease patterns, identification of high-risk subgroups, and exclusion of institutional cases to comprehensively reflect community risk.

Introduction: We describe epidemiology and outcomes of confirmed SARS-CoV-2 infection and admissions among children <18 years in South Africa, an upper-middle income setting with high inequality. Methods: Laboratory and hospital COVID-19 surveillance data, 28 January - 19 September 2020 was used. Testing rates were calculated as number of tested for SARS-CoV-2 divided by population at risk; test positivity rates were calculated as positive tests divided by total number of tests. In-hospital case fatality ratio (CFR) was calculated based on hospitalized positive admissions with outcome data who died in-hospital and death was judged SARS-CoV-2 related by attending physician. Findings: 315,570 children aged <18 years were tested for SARS-CoV-2; representing 8.9% of all 3,548,738 tests and 1.6% of all children in the country. Of children tested, 46,137 (14.6%) were positive. Children made up 2.9% (n=2,007) of all SARS-CoV-2 positive admissions to sentinel hospitals. Among children, 47 died (2.6% case-fatality). In-hospital deaths were associated with male sex [adjusted odds ratio (aOR) 2.18 (95% confidence intervals (CI) 1.08 - 4.40)] vs female; age <1 year [aOR 4.11 (95% CI 1.08-15.54)], age 10-14 years [aOR 4.20 (95% CI1.07-16.44)], age 15-17 years [aOR 4.86 (95% 1.28 -18.51)] vs age 1-4 years; admission to a public hospital [aOR 5.07(95% 2.01 -12.76)] vs private hospital and ≥1 underlying conditions [aOR 12.09 (95% CI 4.19-34.89)] vs none Conclusions: Children with underlying conditions were at greater risk of severe SARS-CoV-2 outcomes. Children > 10 years and those with underlying conditions should be considered for increased testing and vaccination.

Background Zanamivir is a neuraminidase inhibitor effective against influenza A and B viruses. In 2009, GlaxoSmithKline (GSK) began clinical development of intravenous (IV) zanamivir, and initiated a global Compassionate Use Program (CUP) in response to the evolving H1N1 global pandemic. The goal of the CUP was to provide zanamivir to critically ill patients with limited treatment options. Methods Zanamivir was administered to patients with suspected or confirmed influenza infection, who were not suitable for other approved antiviral treatments. Reporting of serious adverse events (SAEs) was mandatory and recorded in the GSK safety database. A master summary tracking sheet captured requests and patient characteristics. A case report form was available for detailing medical conditions, dosing, treatment duration, and clinical outcomes. Results In total, 4033 requests were made for zanamivir treatment of hospitalized patients from 38 countries between 2009 and 2019. Europe had the highest number of requests (n=3051) followed by North America (n=713). At least 20 patients were aged ≤6 months, of whom 12 were born prematurely. The GSK safety database included 466 patients with ≥1 SAE, of whom 374 (80%) had a fatal outcome. Drug-related SAEs were reported in 41 (11%) patients, including hepatic failure (n=6 [2%]) and acute kidney injury (n=5 [1%)]. Conclusions The CUP fulfilled the need to provide global access to zanamivir prior to product approval. No new safety concerns were identified in the CUP compared with IV zanamivir clinical studies.

Background. In the United States, infection with SARS-CoV-2 caused 380,000 reported deaths from March to December 2020. Methods. We adapted the Moving Epidemic Method to all-cause mortality data from the United States to assess the severity of the COVID-19 pandemic across age groups and all 50 states. By comparing all-cause mortality during the pandemic with intensity thresholds derived from recent, historical all-cause mortality, we categorized each week from March to December 2020 as either low severity, moderate severity, high severity, or very high severity. Results. Nationally for all ages combined, all-cause mortality was in the very high severity category for 9 weeks. Among people 18 to 49 years of age, there were 29 weeks of consecutive very high severity mortality. Forty-seven states, the District of Columbia, and New York City each experienced at least one week of very high severity mortality for all ages combined. Conclusions. These periods of very high severity of mortality during March through December 2020 are likely directly or indirectly attributable to the COVID-19 pandemic. This method for standardized comparison of severity over time across different geographies and demographic groups provides valuable information to understand the impact of the COVID-19 pandemic and to identify specific locations or subgroups for deeper investigations into differences in severity.

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.

Respiratory Syncytial Virus (RSV) is a common seasonal respiratory virus and an important cause of illness among infants, but the burden of RSV disease is not well described among the older population. The objective of this study was to estimate the age-specific incidence of hospital admission among over 65s due to respiratory illnesses attributable to RSV in England to inform optimal vaccine and therapeutic interventions. We used linear multiple regression to examine the effect of changes in weekly counts of respiratory pathogens on the weekly counts of respiratory hospital admissions. The study population was all patients aged 65 years or over admitted to English hospitals between 2nd August 2010 and 30th July 2017. RSV was estimated to account for a seasonal annual average of 71 (95% CI 52-90) respiratory admissions per 100,000 in adults age 65-74 and 251 (95% CI 186-316) admissions per 100,000 adults age 75+. Pneumococcus was the pathogen responsible for highest annual average respiratory admission with 448 (95% CI 310-587) admissions per 100,000 adults age 65-74 and 1010 (95%CI 527-1493) admissions per 100,000 adults aged 75+. This study shows that RSV continues to exert a significant burden of disease among older adults in England. These findings will support development of policy for the use of RSV therapeutics and vaccines in this age group.

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.

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

Background: Data on influenza incidence during pregnancy in China are limited. Methods: From October 2015–September 2018, we conducted active surveillance for acute respiratory illness (ARI) among women during pregnancy. Nurses conducted twice weekly phone and text message follow-up upon enrollment until delivery to identify new episodes of ARI. Nasal and throat swabs were collected ≤10 days from illness onset to detect influenza. Results: In total, we enrolled 18,724 pregnant women median aged 28yo, 37% in first trimester, 48% in second trimester and 15% in third trimester, with 7 self-reported vaccination during pregnancy. In the 18-week epidemic period during October 2015–September 2016, influenza incidence was 0.7/100 person-months (95% CI:0.5–0.9). In the 29-week epidemic during October 2016–September 2017, influenza incidence was 1.0/100 person-months (95% CI:0.8–1.2). In the 11-week epidemic period during October 2017–September 2018, influenza incidence was 2.1/100 person-months (95% CI:1.9–2.4). Influenza incidence was similar by trimester. More than half of the total influenza illnesses had no elevated temperature and cough. Most influenza-associated ARIs were mild, and <5.1% required hospitalization. Conclusions: Influenza illness in all trimesters of pregnancy was common. These data may help inform decisions regarding the use of influenza vaccine to prevent influenza during pregnancy.

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.

Objectives Possibility of reinfection with SARS-CoV-2 changes our view on herd immunity and vaccination, and can impact worldwide quarantine policies. We performed RT-PCR follow-up studies on recovered patients to assess possible development of reinfections and re-positivity. Method During a 6-month period, 202 PCR-confirmed recovering COVID-19 patients entered this study. Follow-up RT-PCR tests and symptoms assessment were performed one month after the initial Positive results. patients who tested negative were tested again one and three months later. The Serum IgG and IgM levels were measured in the last follow-up session. Results In the first two follow-up sessions, 82 patients continued their participation, of which four patients tasted positive. In the second follow-up 44 patients participated, three of whom tested positive. None of the patients who tested positive in the first and second follow-up session were symptomatic. In the last session, 32 patients were tested and four patients were positive, three of them were mildly symptomatic and all of them were positive for IgG. Conclusion A positive RT-PCR in a recovering patient may represent reinfection. While we did not have the resources to prove reinfection by genetic sequencing of the infective viruses, we believe presence of mild symptoms in the three patients who tested positive over 100 days after becoming asymptomatic, can be diagnosed as reinfection. The IgG may have abated the symptoms of the reinfection, without providing complete protection.

Since the start of the SARS-CoV-2 pandemic, it has been difficult to differentiate between SARS-CoV-2 re-infection and prolonged RNA shedding. In this report, we identified patients with positive rtPCR results for SARS-CoV-2 ≥70 days apart. Clinical and laboratory data were collected and criteria were applied to discern whether the presentation was consistent with SARS-CoV-2 re-infection or prolonged viral RNA shedding. Eleven individuals met the initial testing criteria, of which, seven met at least one criteria for re-infection and four were consistent with prolonged RNA shedding. These data demonstrate the need for criteria to differentiate SARS-CoV-2 re-infection from prolonged RNA shedding.

Background: Standard dose seasonal influenza vaccines often produce modest immunogenic responses in adults ≥65 years old. MF59 is intended to elicit a greater magnitude and increased breadth of immune response. Objective: To determine the effectiveness of seasonal MF59-adjuvanted trivalent/quadrivalent influenza vaccine (aTIV/aQIV) relative to no vaccination or vaccination with standard or high dose egg-based influenza vaccines among people ≥65 years old. Methods: Cochrane methodological standards and PRISMA-P guidelines were followed. Real-world evidence from non-interventional studies published in peer reviewed journals and grey literature from 1997 through to July 15, 2020, including cluster-randomized trials, were eligible. Two reviewers independently extracted data and risk of bias was assessed using the ROBINS-I tool. Results: Twenty-one studies conducted during the 2006/07-2019/20 influenza seasons were included in the qualitative review; 16 in the meta-analyses. Meta-analysis of test-negative studies found that aTIV reduced medical encounters due to lab-confirmed influenza with pooled estimates of 40.7% (95% CI: 21.9, 54.9; I2=0%) for general practitioner visits and 58.5% (40.7, 70.9; I2=52.9%) for hospitalized patients. The pooled estimate of VE from case-control studies was 51.3% (39.1, 61.1; I2=0%) against influenza- or pneumonia-related hospitalization. The pooled estimates for the relative VE of aTIV for the prevention of influenza related medical encounters were 13.9% (4.2, 23.5; I2=95.9%) compared with TIV, 13.7% (3.1, 24.2; I2=98.8%) compared with QIV, and 2.8% (-2.9, 8.5; I2=94.5%) compared with HD TIV. Conclusions: Among adults ≥65 years aTIV demonstrated significant absolute VE, improved relative VE compared to non-adjuvanted standard-dose TIV/QIV, and comparable relative VE to high-dose TIV.

Objective: To determine if children born preterm were at increased risk of influenza hospitalization up to age five. Methods: National registry data on all children born in Norway between 2008 and 2011 was used in Cox regression models to estimate adjusted hazard ratios (aHR) for influenza hospitalizations up to age five in children born preterm (<37 pregnancy weeks). HRs were also estimated separately for very preterm (<32 weeks), early term (37-38 weeks), and post-term (≥42 weeks) children. Results: Among 238 628 children born in Norway from January 2008 to December 2011, 15 086 (6.3%) were born preterm. There were 754 (0.3%) children hospitalized with influenza before age five. The rate of hospitalizations in children born preterm was 1.4 per 10 000 person-years (95% confidence interval [CI]: 1.1-1.7), and 0.6 per 10 000 person-years (95% CI: 0.5-0.6) in children born at term (≥37 weeks). Children born preterm had a higher risk of influenza hospitalization before age 5: aHR 2.33 (95% CI: 1.85-2.93). The risk increased with decreasing gestational age and was highest among those born very preterm; aHR 4.07 (95% CI: 2.63-6.31). Compared to children born at 40-41 weeks, children born early term also had an elevated risk of influenza hospitalization; aHR (37 weeks) 1.89 (95% CI: 1.43-2.40), aHR (38 weeks) 1.43 (95% CI: 1.15-1.78). Conclusion: Children born preterm had a higher risk of influenza hospitalizations before age five. An elevated risk was also present among children born at an early term. Children born preterm would benefit from influenza vaccinations.

Abstract: Objectives: Our work assessed the prevalence of co-infections in patients with SARS-CoV-2. Methods: All patients hospitalized in a Parisian hospital during the first wave of COVID-19 were tested by mPCR if they presented ILI symptoms. Results: A total of 806 patients (21%) were positive for SARS-CoV-2, 755 (20%) were positive for other respiratory viruses. Among the SARS-CoV-2 positive patients, 49 (6%) had viral co-infections. They presented similar age, symptoms, except for fever (p=0.013) and headaches (p=0.048), than single SARS-CoV-2 infections. Conclusions: SARS-CoV-2 infected patients presenting viral co-infections had similar clinical characteristics and prognosis than patients solely infected with SARS-CoV-2.

Background Physical distancing and facemask use are worldwide recognized as effective non-pharmaceutical interventions (NPIs) against the coronavirus disease 2019 (COVID-19). Since January 2020, Taiwan has introduced both NPIs but their effectiveness on non-COVID-19 respiratory viruses (NCRVs) remain underexplored. Methods This retrospective observational study examined electronic records at a tertiary hospital in northern Taiwan from pre-COVID (January–December 2019) to post-COVID period (January–May 2020). Patients with respiratory syndromes were tested for both enveloped (e.g. influenza virus and seasonal coronavirus) and non-enveloped RVs (e.g. enterovirus and rhinovirus) using multiplex reverse-transcription polymerase chain reaction assays. Monthly positivity rates of NCRVs among adult and pediatric patients were analyzed with comparison between pre- and post-COVID periods. Results A total of 9693 patients underwent 12127 multiplex RT-PCR tests. The average positivity rate of NCRVs reduced by 11.2% (25.6% to 14.4%) after nationwide PHIs. Despite the COVID-19 pandemic, the most commonly identified enveloped and non-enveloped viruses were influenza virus and enterovirus/rhinovirus, respectively. Observed reduction in NCRV incidence was predominantly contributed by enveloped NCRVs including influenza viruses. We did not observe epidemiological impacts of NPIs on non-enveloped viruses but an increasing trend in enterovirus/rhinovirus test positivity rate among pediatric patients. Our data were validated using Taiwan’s national notification database. Conclusions Our frontline investigation suggests that the current NPIs in Taiwan might not effectively control the transmission of non-enveloped respiratory viruses, despite their protective effects against influenza and seasonal coronavirus. Hydrogen peroxide or chloride-based disinfectants should be integrated into national preventative strategies against respiratory viral infections in the post-COVID-19 era.