Showing papers in "Influenza and Other Respiratory Viruses in 2021"

COVID-19 vaccine hesitancy and attitudes in Qatar: A national cross-sectional survey of a migrant-majority population.

Abstract: BACKGROUND: Vaccine hesitancy is a global threat undermining control of preventable infections. Emerging evidence suggests that hesitancy to COVID-19 vaccination varies globally. Qatar has a unique population with around 90% of the population being economic migrants, and the degree and determinants of hesitancy are not known. METHODS: This study was carried out to evaluate the degree of vaccine hesitancy and its socio-demographic and attitudinal determinants across a representative sample. A national cross-sectional study using validated hesitancy measurement tool was carried out from October 15, 2020, to November 15, 2020. A total of 7821 adults completed the survey. Relevant socio-demographic data along with attitudes and beliefs around COVID-19 vaccination were collected from the respondents. RESULTS: 20.2% of the respondents stated they would not take the vaccine and 19.8% reported being unsure about taking the prospective COVID-19 vaccine. Citizens and females were more likely to be vaccine hesitators than immigrants and males, respectively. Concerns around the safety of COVID-19 vaccine and its longer-term side effects were the main concerns cited. Personal research around COVID-19 and vaccine were by far the most preferred methods that would increase confidence in accepting the vaccine across all demographic groups. CONCLUSIONS: This study reports an overall vaccine hesitancy of 20% toward the COVID-19 vaccine and the influence of social media on attitudes toward vaccination which is in keeping with emerging evidence. This finding comes at a time that is close to the start of mass immunization and reports from a migrant-majority population highlighting important socio-demographic determinants around vaccine hesitancy.

Increased risk of rhinovirus infection in children during the coronavirus disease-19 pandemic.

Abstract: BACKGROUND: Coronavirus disease (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in Japan in January 2020 and has spread throughout the country. Previous studies have reported that viral interference among influenza virus, rhinovirus, and other respiratory viruses can affect viral infections at the host and population level. METHODS: To investigate the impact of COVID-19 on influenza and other respiratory virus infections, we analyzed clinical specimens collected from 2244 patients in Japan with respiratory diseases between January 2018 and September 2020. RESULTS: The frequency of influenza and other respiratory viruses (coxsackievirus A and B; echovirus; enterovirus; human coronavirus 229E, HKU1, NL63, and OC43; human metapneumovirus; human parainfluenza virus 1, 2, 3, and 4; human parechovirus; human respiratory syncytial virus; human adenovirus; human bocavirus; human parvovirus B19; herpes simplex virus type 1; and varicella-zoster virus) was appreciably reduced among all patients during the COVID-19 pandemic except for that of rhinovirus in children younger than 10 years, which was appreciably increased. COVID-19 has not spread among this age group, suggesting an increased risk of rhinovirus infection in children. CONCLUSIONS: Rhinovirus infections should be continuously monitored to understand their increased risk during the COVID-19 pandemic and viral interference with SARS-CoV-2.

Influenza and COVID-19: What does co-existence mean?

Abstract: The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 continues to have a major impact on healthcare and social systems throughout the world. As the clinical and epidemiological features of COVID-19 have many parallels with influenza, it is important to ensure optimal management of both respiratory diseases as we anticipate their continued co-circulation. In particular, there is a need to ensure that effective surveillance and diagnostic capacities are in place to monitor these and other respiratory viruses, as this will underpin decisions on the appropriate clinical management of the respective diseases. As such, we propose a series of key recommendations for stakeholders, public health authorities, primary care physicians and surveillance bodies that will help mitigate the combined risks of concurrent influenza epidemics and the COVID-19 pandemic. We advocate the judicious use of influenza vaccines and antivirals, particularly among groups at high risk of complications, with healthcare workers also considered a priority for vaccination. It is likely that the increased use of emerging technologies such as telemedicine and contact tracing will permanently change our approach to managing infectious disease. The use of these technologies, alongside existing pharmaceutical strategies, will ensure that we achieve a holistic approach to the global public health measures needed to deal with the combined threat of influenza and COVID-19. Ensuring that this approach is optimal will be key as we move from a reactive pandemic response towards preparing for the long-term management of the remarkable clinical burden associated with these respiratory pathogens.

Evidence for pre-symptomatic transmission of coronavirus disease 2019 (COVID-19) in China.

Abstract: Background Between mid-January and early February, provinces of mainland China outside the epicentre in Hubei province were on high alert for importations and transmission of COVID-19. Many properties of COVID-19 infection and transmission were still not yet established. Methods We collated and analysed data on 449 of the earliest COVID-19 cases detected outside Hubei province to make inferences about transmission dynamics and severity of infection. We analysed 64 clusters to make inferences on serial interval and potential role of pre-symptomatic transmission. Results We estimated an epidemic doubling time of 5.3 days (95% confidence interval (CI): 4.3, 6.7) and a median incubation period of 4.6 days (95% CI: 4.0, 5.2). We estimated a serial interval distribution with mean 5.7 days (95% CI: 4.7, 6.8) and standard deviation 3.5 days, and effective reproductive number was 1.98 (95% CI: 1.68, 2.35). We estimated that 32/80 (40%) of transmission events were likely to have occurred prior to symptoms onset in primary cases. Secondary cases in clusters had less severe illness on average than cluster primary cases. Conclusions The majority of transmissions are occurring around illness onset in an infected person, and pre-symptomatic transmission does play a role. Detection of milder infections among the secondary cases may be more reflective of true disease severity.

Differential COVID-19 case positivity in New York City neighborhoods: socioeconomic factors and mobility

Abstract: Background New York City (NYC) has been one of the hotspots of the COVID-19 pandemic in the United States. By the end of April 2020, close to 165 000 cases and 13 000 deaths were reported in the city with considerable variability across the city's ZIP codes. Objectives In this study, we examine: (a) the extent to which the variability in ZIP code-level case positivity can be explained by aggregate markers of socioeconomic status (SES) and daily change in mobility; and (b) the extent to which daily change in mobility independently predicts case positivity. Methods COVID-19 case positivity by ZIP code was modeled using multivariable linear regression with generalized estimating equations to account for within-ZIP clustering. Daily case positivity was obtained from NYC Department of Health and Mental Hygiene and measures of SES were based on data from the American Community Survey. Changes in human mobility were estimated using anonymized aggregated mobile phone location systems. Results Our analysis indicates that the socioeconomic markers considered together explained 56% of the variability in case positivity through April 1 and their explanatory power decreased to 18% by April 30. Changes in mobility during this time period are not likely to be acting as a mediator of the relationship between ZIP-level SES and case positivity. During the middle of April, increases in mobility were independently associated with decreased case positivity. Conclusions Together, these findings present evidence that heterogeneity in COVID-19 case positivity during NYC's spring outbreak was largely driven by residents' SES.

Effectiveness of the MF59-adjuvanted trivalent or quadrivalent seasonal influenza vaccine among adults 65 years of age or older, a systematic review and meta-analysis.

Abstract: 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 gray literature from 1997 through to July 15, 2020, including cluster-randomized trials, were eligible. Two reviewers independently extracted data; 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 non-emergency outpatient 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.

Which influenza viruses will emerge following the SARS-CoV-2 pandemic?

Abstract: The world has experienced five pandemics in just over one hundred years, four due to influenza and one due to coronavirus (SARS-CoV-2). In each case of pandemic influenza, the pandemic influenza strain has replaced the previous seasonal influenza virus. Notably, throughout the SARS-CoV-2 pandemic, there has been a 99% reduction in influenza isolation globally. It is anticipated that influenza will re-emerge following the SARS-CoV-2 pandemic and circulate again. The potential for which influenza viruses will emerge is examined.

Population Anxiety and Positive Behaviour Change During the COVID-19 Epidemic: Cross-Sectional Surveys in Singapore, China and Italy

Abstract: Background: On 31 December 2019, an epidemic of pneumonia of unknown aetiology was first reported in the city of Wuhan, HubeProvince, People’s Republic of Chi

Admission respiratory status predicts mortality in COVID-19.

Abstract: COVID-19 has significant case fatality. Glucocorticoids are the only treatment shown to improve survival, but only among patients requiring supplemental oxygen. WHO advises patients to seek medical care for "trouble breathing," but hypoxemic patients frequently have no respiratory symptoms. Our cohort study of hospitalized COVID-19 patients shows that respiratory symptoms are uncommon and not associated with mortality. By contrast, objective signs of respiratory compromise-oxygen saturation and respiratory rate-are associated with markedly elevated mortality. Our findings support expanding guidelines to include at-home assessment of oxygen saturation and respiratory rate in order to expedite life-saving treatments patients to high-risk COVID-19 patients.

The immunogenicity and safety of respiratory syncytial virus vaccines in development: A systematic review.

Abstract: BACKGROUND Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infection globally. There are vaccine candidates in development, but a systematic review on immunogenicity and safety of vaccine is lacking. METHODS This systematic review of RSV vaccine clinical trials was undertaken using four databases. Searches were conducted using both controlled vocabulary terms such as "Respiratory Syncytial Virus, Human," "Respiratory Syncytial Virus Infections," "Respiratory Syncytial Virus Vaccines," "Immunization," "Immunization Programs" and "Vaccines" and corresponding text word terms. The included studies were limited to clinical trials published from January 2000 to 31 December 2020. RSV infection case was defined as RSV-associated medically attended acute respiratory illness (MAARI) or RSV infection by serologically confirmed test (Western blot) during the RSV surveillance period. We calculated the relative risk of each vaccine trial with RSV infection case. RESULTS Of 6306 publications, 38 were included and data were extracted covering four major types of RSV vaccine candidates, these being live-attenuated/chimeric (n = 14), recombinant-vector (n = 6), subunit (n = 12) and nanoparticle vaccines (n = 6). For RSV infection cases, nine trials were involved and none of them showed a vaccine-related increased MAARI during RSV surveillance season. CONCLUSION LID ∆M2-2, MEDI M2-2, RSVcps2 and LID/∆M2-2 /1030s (live-attenuated) were considered the most promising vaccine candidates in infant and children. In the elderly, a nanoparticle F vaccine candidate and Ad26.RSV.preF were considered as two potential effective vaccines. A promising maternal vaccine candidate is still lacking.

Healthcare workers in Singapore infected with COVID-19: 23 January-17 April 2020.

Abstract: OBJECTIVE: To describe the characteristics of healthcare workers (HCWs) infected with COVID-19 and to examine their sources of exposure. METHODS: A descriptive cross-sectional study using data extracted from the centralized disease notification system comprising individuals confirmed with COVID-19 in Singapore between 23 January and 17 April 2020. Occupation of HCWs was categorized into six categories. Their job nature was classified into "frontline" or "back-end" based on the frequency of direct patient contact, and source of exposure was classified as family/household, social interaction or workplace. Chi-square and median tests were used to identify differences between categorical groups and sample medians, respectively. RESULTS: A total of 88 (1.7%) HCWs were identified from 5,050 cases. Their median age was 35 years. Chinese and Indians constituted 42.0% and 31.8%, respectively, and 43.2% were foreigners. The majority (63.6%) was serving at frontlines handling patient-facing duties, 15.9% were doctors, 11.4% were nurses and 44.3% were ancillary staff. About 81.8% acquired the infection locally, of which 40.3% did not have a clearly identifiable source of exposure. Exposure from the family/household was most common (27.8%), followed by workplace (16.7%) and social interaction (15.3%). All HCWs were discharged well with no mortality; three (3.4%) were ever admitted to intensive care unit and required increased care. CONCLUSION: Healthcare workers accounted for a small proportion of COVID-19 cases in Singapore with favourable outcomes. The possibility of transmission resulting from family/household exposure and social interactions highlights the need to maintain strict vigilance and precautionary measures at all times beyond the workplace.

Early epidemiological investigations: World Health Organization UNITY protocols provide a standardized and timely international investigation framework during the COVID-19 pandemic.

Abstract: BACKGROUND: The declaration of Coronavirus disease 2019 (COVID-19) as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 required rapid implementation of early investigations to inform appropriate national and global public health actions. METHODS: The suite of existing pandemic preparedness generic epidemiological early investigation protocols was rapidly adapted for COVID-19, branded the 'UNITY studies' and promoted globally for the implementation of standardized and quality studies. Ten protocols were developed investigating household (HH) transmission, the first few cases (FFX), population seroprevalence (SEROPREV), health facilities transmission (n = 2), vaccine effectiveness (n = 2), pregnancy outcomes and transmission, school transmission, and surface contamination. Implementation was supported by WHO and its partners globally, with emphasis to support building surveillance and research capacities in low- and middle-income countries (LMIC). RESULTS: WHO generic protocols were rapidly developed and published on the WHO website, 5/10 protocols within the first 3 months of the response. As of 30 June 2021, 172 investigations were implemented by 97 countries, of which 62 (64%) were LMIC. The majority of countries implemented population seroprevalence (71 countries) and first few cases/household transmission (37 countries) studies. CONCLUSION: The widespread adoption of UNITY protocols across all WHO regions indicates that they addressed subnational and national needs to support local public health decision-making to prevent and control the pandemic.

The impact of the 2009 influenza pandemic on the seasonality of human respiratory syncytial virus: A systematic analysis.

Abstract: Background Several local studies showed that the 2009 influenza pandemic delayed the RSV season. However, no global-level analyses are available on the possible impact of the 2009 influenza pandemic on the RSV season. Objectives We aim to understand the impact of the 2009 influenza pandemic on the RSV season. Methods We compiled data from published literature (through a systematic review), online reports/datasets and previously published data on global RSV seasonality and conducted a global-level systematic analysis on the impact of the 2009 influenza pandemic on RSV seasonality. Results We included 354 seasons of 45 unique sites, from 26 countries. Globally, the influenza pandemic delayed the onset of the first RSV season by 0.58 months on average (95% CI: 0.42, 0.73; maximum delay: 2.5 months) and the onset of the second RSV season by a lesser extent (0.25 months; 95% CI: 0.12, 0.39; maximum delay: 3.4 months); no delayed onset was observed for the third RSV season. The delayed onset was most pronounced in the northern temperate, followed by the southern temperate, and was least pronounced in the tropics. Conclusions The 2009 influenza pandemic delayed the RSV onset on average by 0.58 months and up to 2.5 months. This suggests evidence of viral interference as well as the impact of public health measures and has important implications for preparedness for RSV season during the ongoing COVID-19 pandemic and future pandemics.

Defining the seasonality of respiratory syncytial virus around the world: National and subnational surveillance data from 12 countries.

Abstract: Background Respiratory syncytial virus (RSV) infections are one of the leading causes of lower respiratory tract infections and have a major burden on society. For prevention and control to be deployed effectively, an improved understanding of the seasonality of RSV is necessary. Objectives The main objective of this study was to contribute to a better understanding of RSV seasonality by examining the GERi multi-country surveillance dataset. Methods RSV seasons were included in the analysis if they contained ≥100 cases. Seasonality was determined using the "average annual percentage" method. Analyses were performed at a subnational level for the United States and Brazil. Results We included 601 425 RSV cases from 12 countries. Most temperate countries experienced RSV epidemics in the winter, with a median duration of 10-21 weeks. Not all epidemics fit this pattern in a consistent manner, with some occurring later or in an irregular manner. More variation in timing was observed in (sub)tropical countries, and we found substantial differences in seasonality at a subnational level. No association was found between the timing of the epidemic and the dominant RSV subtype. Conclusions Our findings suggest that geographical location or climatic characteristics cannot be used as a definitive predictor for the timing of RSV epidemics and highlight the need for (sub)national data collection and analysis.

Epidemiology and burden of illness of seasonal influenza among the elderly in Japan: A systematic literature review and vaccine effectiveness meta-analysis

Abstract: BACKGROUND Elderly populations are particularly vulnerable to influenza and often require extensive clinical support. In Japan, nationwide passive surveillance monitors seasonal influenza but does not capture the full disease burden. We synthesized existing evidence on the epidemiology, vaccine effectiveness (VE), and economic burden of seasonal influenza in the elderly population. METHODS PubMed, EMBASE, and ICHUSHI were searched for articles on seasonal influenza in Japan, published between 1997 and 2018, in English or Japanese. Grey literature was also assessed. A random-effects meta-analysis characterized VE of influenza vaccines among studies reporting this information. RESULTS Of 1,147 identified articles, 143 met inclusion criteria. Reported incidence rates varied considerably depending on study design, season, study setting and, most importantly, case definition. In nursing homes, the maximum reported attack rate was 55.2% and in the 16 articles reporting mortality rates, case fatality rates varied from 0.009% to 14.3%. Most hospitalizations were in people aged >60; healthcare costs were partially mitigated by vaccine administration. Meta-analysis estimated overall VE of 19.1% (95% CI: 2.3% - 33.0%) with a high proportion of heterogeneity (I2 : 89.1%). There was a trend of lower VE in older people (40.1% [-57.3-77.2] in the <65 group; 12.9% [-8.0-29.8] in those 65; P = .21). CONCLUSIONS Despite differences between studies that make comparisons challenging, the influenza burden in elderly Japanese is significant. While vaccines are effective, current vaccination programs offer suboptimal protection. Health economic data and cost-effectiveness analyses were limited and represent areas for policy-relevant future research.

Impact of coronavirus disease 2019 on respiratory surveillance and explanation of high detection rate of human rhinovirus during the pandemic in the Republic of Korea.

Abstract: 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 COVID-19 pandemic impacted the respiratory virus detection rate. 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.

The COVID-19 epidemic in Madagascar: clinical description and laboratory results of the first wave, march-september 2020.

Abstract: Author(s): Randremanana, Rindra Vatosoa; Andriamandimby, Soa-Fy; Rakotondramanga, Jean Marius; Razanajatovo, Norosoa Harline; Mangahasimbola, Reziky Tiandraza; Randriambolamanantsoa, Tsiry Hasina; Ranaivoson, Hafaliana Christian; Rabemananjara, Harinirina Aina; Razanajatovo, Iony; Razafindratsimandresy, Richter; Rabarison, Joelinotahiana Hasina; Brook, Cara E; Rakotomanana, Fanjasoa; Rabetombosoa, Roger Mario; Razafimanjato, Helisoa; Ahyong, Vida; Raharinosy, Vololoniaina; Raharimanga, Vaomalala; Raharinantoanina, Sandratana Jonhson; Randrianarisoa, Mirella Malala; Bernardson, Barivola; Randrianasolo, Laurence; Randriamampionona, Lea Bricette Nirina; Tato, Cristina M; DeRisi, Joseph L; Dussart, Philippe; Vololoniaina, Manuela Christophere; Randriatsarafara, Fidiniaina Mamy; Randriamanantany, Zely Arivelo; Heraud, Jean-Michel | Abstract: BackgroundFollowing 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.MethodsNasopharyngeal 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-PCR. 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.ResultsOverall, 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 39nyears (IQR: 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 49nyears and more. Viral strains sequenced belong to clades 19A, 20A and 20B indicative of several independent introduction of viruses.ConclusionsOur 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.

Population-based assessment of risks for severe COVID-19 disease outcomes.

Abstract: Among approximately 4.6 million members of Kaiser Permanente Northern California, we examined associations of severe COVID-19 with demographic factors and comorbidities. As of July 23, 2021, 16 182 had been hospitalized, 2416 admitted to an ICU, and 1525 died due to COVID-19. Age was strongly associated with hospitalization, ICU admission, and death. Black persons and Hispanic ethnicity had higher risk of death compared with Whites. Among the comorbidities examined, Alzheimer's disease was associated with the highest risk for hospitalization (aHR 3.19, CI: 2.88-3.52) and death (aHR 4.04, CI: 3.32-4.91). Parkinson's disease had the second highest risk of death (aHR = 2.07, CI: 1.50-2.87).

Household transmission of COVID-19 among the earliest cases in Antananarivo, Madagascar.

Abstract: Background Households are among the highest risk for the transmission of SARS-CoV-2. In sub-Saharan Africa, very few studies have described household transmission during the COVID-19 pandemic. Our work aimed to describe the epidemiologic parameters and analyze the secondary attack rate (SAR) in Antananarivo, Madagascar, following the introduction of SARS-CoV-2 in the country in March 2020. Methods A prospective case-ascertained study of all identified close contacts of laboratory-confirmed COVID-19 infections was conducted in Antananarivo from March to June 2020. Cases and household contacts were followed for 21 days. We estimated epidemic parameters of disease transmission by fitting parametric distributions based on infector-infected paired data. We assessed factors influencing transmission risk by analyzing the SAR. Findings Overall, we included 96 index cases and 179 household contacts. Adjusted with the best-fit normal distribution, the incubation period was 4.1 days (95% CI 0.7-7.5]). The serial interval was 6.0 days (95% CI [2.4-9.6]) after adjusting with the best-fit Weibull distribution. On average, each index case infected 1.6 family members (95%CI [0.9-2.3]). The mean SAR among close contacts was 38.8% (95% CI [19.5-58.2]) with the best-fit gamma distribution. Contacts older than 35 years old were more likely to be infected, and the highest SAR was found among them. Conclusion The results of our study provide key insights into the epidemiology of the first wave of SARS-CoV-2 in Madagascar. High rates of household transmission were found in Antananarivo, emphasizing the need for preventive measures to reduce community transmission.

Comprehensive assessment of amino acid substitutions in the trimeric RNA polymerase complex of influenza A virus detected in clinical trials of baloxavir marboxil.

Abstract: 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)pdm09 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 with 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.

Factors associated with COVID-19 related hospitalisation, critical care admission and mortality using linked primary and secondary care data.

Abstract: BACKGROUND: It is important that population cohorts at increased risk of hospitalisation and death following a COVID-19 infection are identified and protected. OBJECTIVES: We identified risk factors associated with increased risk of hospitalisation, intensive care unit (ICU) admission and mortality in inner North East London (NEL) during the first UK COVID-19 wave. METHODS: Multivariate logistic regression analysis on linked primary and secondary care data from people aged 16 or older with confirmed COVID-19 infection between 01/02/2020 and 30/06/2020 determined odds ratios (OR), 95% confidence intervals (CI) and P-values for the association between demographic, deprivation and clinical factors with COVID-19 hospitalisation, ICU admission and mortality. RESULTS: Over the study period, 1781 people were diagnosed with COVID-19, of whom 1195 (67%) were hospitalised, 152 (9%) admitted to ICU and 400 (23%) died. Results confirm previously identified risk factors: being male, or of Black or Asian ethnicity, or aged over 50. Obesity, type 2 diabetes and chronic kidney disease (CKD) increased the risk of hospitalisation. Obesity increased the risk of being admitted to ICU. Underlying CKD, stroke and dementia increased the risk of death. Having learning disabilities was strongly associated with increased risk of death (OR = 4.75, 95% CI = [1.91, 11.84], P = .001). Having three or four co-morbidities increased the risk of hospitalisation (OR = 2.34, 95% CI = [1.55, 3.54], P < .001; OR = 2.40, 95% CI = [1.55, 3.73], P < .001 respectively) and death (OR = 2.61, 95% CI = [1.59, 4.28], P < .001; OR = 4.07, 95% CI = [2.48, 6.69], P < .001 respectively). CONCLUSIONS: We confirm that age, sex, ethnicity, obesity, CKD and diabetes are important determinants of risk of COVID-19 hospitalisation or death. For the first time, we also identify people with learning disabilities and multi-morbidity as additional patient cohorts that need to be actively protected during COVID-19 waves.

Adenovirus infection in children hospitalized with pneumonia in Guangzhou, China.

Abstract: BACKGROUND HAdV infection can cause a variety of diseases. Although infections with HAdVs often are mild, life-threatening respiratory disease can occur. Pneumonia is one of the more serious types of HAdV-induced respiratory disease in children. In this study, we determined the prevalence and genotype of HAdVs among children hospitalized with pneumonia in Guangzhou, China. METHODS Nasopharyngeal swabs (NPSs) were collected from children hospitalized with pneumonia in Guangzhou, China, from January 2013 to June 2019. HAdVs were detected by real-time polymerase chain reaction assay, and hexon, fiber, and penton gene were amplified and used for phylogenetic analysis. Epidemiological data were analyzed using SPSS16.0 software. RESULTS AND CONCLUSIONS A total of 1778 children hospitalized with pneumonia were enrolled. The overall HAdV detection rate was 3.26%. And the yearly detection rate varied from around 2.5% in 2013-2017 to around 6% in 2018-2019. Children >5 years had the highest HAdV infection rate. 92.86% of HAdV sequences obtained in this study were belonged to species B, and no recombination was observed. HAdV-B7 and HAdV-B3 were the common types detected in the study period, with the predominant HAdV genotype shifted from HAdV-B3 in 2015-2016 to HAdV-B7 in 2017-2018. The discrepancies in HAdV detection rates in different study period and changes of HAdV predominant types over time highlighted the importance of continued surveillance.

Using the health belief model to identify barriers to seasonal influenza vaccination among Australian adults in 2019.

Abstract: Background Each year tens of thousands of Australians become ill with influenza, resulting in 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, population-specific 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 theoretical 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 groups.

Transmission of SARS-CoV-2 during a 2-h domestic flight to Okinawa, Japan, March 2020.

Abstract: Background Coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), has rapidly spread globally. Potentially infected individuals travel on commercial aircraft. Thus, this study aimed to investigate and test the association between the use of face masks, physical distance, and COVID-19 among passengers and flight attendants exposed to a COVID-19 passenger in a domestic flight. Methods This observational study investigated passengers and flight attendants exposed to COVID-19 on March 23, 2020, on board a flight to Naha City, Japan. Secondary attack rates were calculated. Whole-genome sequencing of SARS-CoV-2 was used to identify the infectious linkage between confirmed cases in this clustering. The association between confirmed COVID-19 and proximity of passengers' seats to the index case and/or the use of face masks was estimated using logistic regression. Results Fourteen confirmed and six probable cases were identified among passengers and flight attendants. The secondary attack rate was 9.7%. Twelve of 14 SARS-CoV-2 genome sequences in confirmed cases were identical to that of the index case or showed only one nucleotide mutation. Risk factors for infection included not using a face mask (adjusted odds ratio [aOR]: 4.6, 95% confidence interval [95% CI]: 1.28-16.6), partial face mask use (aOR: 2.46, 95% CI: 0.75-8.09), and being seated within two rows from the index patient (aOR: 4.8, 95% CI: 1.46-15.8). Conclusion SARS-CoV-2 was transmitted on the airplane. Nonuse of face masks was identified as an independent risk factor for contracting COVID-19 on the airplane.

Risk factors for outbreaks of COVID-19 in care homes following hospital discharge: A national cohort analysis.

Abstract: BACKGROUND: The population of adult residential care homes has been shown to have high morbidity and mortality in relation to COVID-19 METHODS: We examined 3115 hospital discharges to a national cohort of 1068 adult care homes and subsequent outbreaks of COVID-19 occurring between 22 February and 27 June 2020 A Cox proportional hazards regression model was used to assess the impact of time-dependent exposure to hospital discharge on incidence of the first known outbreak, over a window of 7-21 days after discharge, and adjusted for care home characteristics, including size and type of provision RESULTS: A total of 330 homes experienced an outbreak, and 544 homes received a discharge over the study period Exposure to hospital discharge was not associated with a significant increase in the risk of a new outbreak (hazard ratio 115, 95% CI 089, 147, P = 29) after adjusting for care home characteristics Care home size was the most significant predictor Hazard ratios (95% CI) in comparison with homes of <10 residents were as follows: 340 (199, 580) for 10-24 residents; 825 (493, 1381) for 25-49 residents; and 1735 (965, 3119) for 50+ residents When stratified for care home size, the outbreak rates were similar for periods when homes were exposed to a hospital discharge, in comparison with periods when homes were unexposed CONCLUSION: Our analyses showed that large homes were at considerably greater risk of outbreaks throughout the epidemic, and after adjusting for care home size, a discharge from hospital was not associated with a significant increase in risk

Absence of association between 2019-20 influenza vaccination and COVID-19: Results of the European I-MOVE-COVID-19 primary care project, March-August 2020.

Abstract: 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 to 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 69 272 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.

Diagnostic performance of COVID-19 serological assays during early infection: A systematic review and meta-analysis of 11 516 samples.

Abstract: OBJECTIVE: The use of coronavirus disease 2019 (COVID-19) serological testing to diagnose acute infection or determine population seroprevalence relies on understanding assay accuracy during early infection. We aimed to evaluate the diagnostic performance of serological testing in COVID-19 by providing summary sensitivity and specificity estimates with time from symptom onset. METHODS: A systematic search of Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed was performed up to May 13, 2020. All English language, original peer-reviewed publications reporting the diagnostic performance of serological testing vis-a-vis virologically confirmed SARS-CoV-2 infection were included. RESULTS: Our search yielded 599 unique publications. A total of 39 publications reporting 11 516 samples from 8872 human participants met eligibility criteria for inclusion in our study. Pooled percentages of IgM and IgG seroconversion by Day 7, 14, 21, 28 and after Day 28 were 37.5%, 73.3%, 81.3%, 72.3% and 73.3%, and 35.4%, 80.6%, 93.3%, 84.4% and 98.9%, respectively. By Day 21, summary estimate of IgM sensitivity was 0.872 (95% CI: 0.784-0.928) and specificity 0.973 (95% CI: 0.938-0.988), while IgG sensitivity was 0.913 (95% CI: 0.823-0.959) and specificity 0.960 (95% CI: 0.919-0.980). On meta-regression, IgM and IgG test accuracy was significantly higher at Day 14 using enzyme-linked immunosorbent assay (ELISA) compared to other methods. CONCLUSIONS: Serological assays offer imperfect sensitivity for the diagnosis of acute SARS-CoV-2 infection. Estimates of population seroprevalence during or shortly after an outbreak will need to adjust for the delay between infection, symptom onset and seroconversion.

Home collection of nasal swabs for detection of influenza in the Household Influenza Vaccine Evaluation Study.

Abstract: Background Community-based studies of influenza and other respiratory viruses (eg, SARS-CoV-2) require laboratory confirmation of infection. During the current COVID-19 pandemic, social distancing guidelines require alternative data collection in order to protect both research staff and participants. Home-collected respiratory specimens are less resource-intensive, can be collected earlier after symptom onset, and provide a low-contact means of data collection. A prospective, multi-year, community-based cohort study is an ideal setting to examine the utility of home-collected specimens for identification of influenza. Methods We describe the feasibility and reliability of home-collected specimens for the detection of influenza. We collected data and specimens between October 2014 and June 2017 from the Household Influenza Vaccine Evaluation (HIVE) Study. Cohort participants were asked to collect a nasal swab at home upon onset of acute respiratory illness. Research staff also collected nose and throat swab specimens in the study clinic within 7 days of onset. We estimated agreement using Cohen's kappa and calculated sensitivity and specificity of home-collected compared to staff-collected specimens. Results We tested 336 paired staff- and home-collected respiratory specimens for influenza by RT-PCR; 150 staff-collected specimens were positive for influenza A/H3N2, 23 for influenza A/H1N1, 14 for influenza B/Victoria, and 31 for influenza B/Yamagata. We found moderate agreement between collection methods for influenza A/H3N2 (0.70) and B/Yamagata (0.69) and high agreement for influenza A/H1N1 (0.87) and B/Victoria (0.86). Sensitivity ranged from 78% to 86% for all influenza types and subtypes. Specificity was high for influenza A/H1N1 and both influenza B lineages with a range from 96% to 100%, and slightly lower for A/H3N2 infections (88%). Conclusions Collection of nasal swab specimens at home is both feasible and reliable for identification of influenza virus infections.

Viral epidemiology and SARS-CoV-2 co-infections with other respiratory viruses during the first COVID-19 wave in Paris, France.

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 multiplex PCR 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 = .013) and headaches (P = .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.