Publications by authors named "Benjamin J Cowling"

423 Publications

COVID-19 transmission in Hong Kong despite universal masking.

J Infect 2021 Apr 22. Epub 2021 Apr 22.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Laboratory of Data Discovery for Health, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China. Electronic address:

Objectives: mask-wearing outside the home has been almost universal in Hong Kong since late January 2020 with very high compliance. Nevertheless, community spread of COVID-19 has still occurred. We aimed to assess the settings where COVID-19 transmission occurred and determine the fraction of transmission events that occurred in settings where masks are not usually worn.

Methods: we reviewed detailed information provided by the Hong Kong Department of Health on local COVID-19 cases diagnosed up to 30 September 2020 to determine the most likely settings in which transmission occurred. We classified them in probably mask-on or mask-of and compared the prevalence of asymptomatic infections in these settings.

Results: among the 2425 cases (65.3%, 2425/3711) with information on transmission setting, 77.6% of the transmission occurred in household and social settings where face masks are not usually worn. Infections that occurred in mask-on settings were more likely to be asymptomatic (adjusted odds ratio 1.33; 95% confidence interval: 1.04, 1.68).

Conclusions: we conclude that universal mask-wearing can reduce transmission, but transmission can continue to occur in settings where face masks are not usually worn. The higher proportion of asymptomatic cases in mask-on settings could be related to a milder disease presentation or earlier case detection.
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http://dx.doi.org/10.1016/j.jinf.2021.04.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8061183PMC
April 2021

Lack of cross-transmission of SARS-CoV-2 between passenger's cabins on the cruise ship.

Build Environ 2021 Jul 15;198:107839. Epub 2021 Apr 15.

Department of Mechanical Engineering, The University of Hong Kong, Hong Kong, China.

An outbreak of COVID-19 occurred on the cruise ship in January and February 2020 in Japan. We analysed information on the cases of infection to infer whether airborne transmission of SARS-CoV-2, the causative agent of COVID-19, had occurred between cabins. We infer from our analysis that most infections in passengers started on 28 January and were completed by 6 February, except in those who shared a cabin with another infected passenger. The distribution of the infected cabins was random, and no spatial cluster of the infected can be identified. We infer that the ship's central air-conditioning system for passenger's cabins did not play a role in SARS-CoV-2 transmission, i.e. airborne transmission did not occur between cabins during the outbreak, suggesting that the sufficient ventilation was provided. We also infer that the ship's cabin drainage system did not play a role. Most transmission appears to have occurred in the public areas of the cruise ship, likely due to crowding and insufficient ventilation in some of these areas.
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http://dx.doi.org/10.1016/j.buildenv.2021.107839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8046742PMC
July 2021

The impact of childhood pneumococcal conjugate vaccine immunisation on all-cause pneumonia admissions in Hong Kong: A 14-year population-based interrupted time series analysis.

Vaccine 2021 May 12;39(19):2628-2635. Epub 2021 Apr 12.

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; Centre for Mathematical Modelling of Infectious Diseases, Department of Infectious Disease Epidemiology, London School of Hygiene & Tropical Medicine, London, UK.

Background: Nine years after the introduction of pneumococcal conjugate vaccine (PCV) in the United States, Hong Kong (HK) introduced the vaccine to its universal childhood immunisation programme in 2009. We aimed to assess the impact of childhood PCV immunisation on all-cause pneumonia (ACP) admissions among the overall population of HK.

Methods: In this population-based interrupted time series analysis, we used territory-wide population-representative electronic health records in HK to evaluate the vaccine impact. We identified hospitalised patients with a diagnosis of pneumonia from any cause between 2004 and 2017. We applied segmented Poisson regression to assess the gradual change in the monthly incidence of ACP admissions between pre- and post-vaccination periods. Negative outcome control, subgroup and sensitivity analyses were used to test the robustness of the main analysis.

Findings: Over the 14-year study period, a total of 587,607 ACP episodes were identified among 357,950 patients. The monthly age-standardised incidence of ACP fluctuated between 33.42 and 87.44 per 100,000-persons. There was a marginal decreasing trend in pneumonia admissions after PCV introduction among overall population (incidence rate ratio [IRR]: 0·9965, 95% confidence interval [CI]: 0·9932-0·9998), and older adults (≥65 years, IRR: 0·9928, 95% CI: 0·9904-0·9953) but not in younger age groups.

Interpretation: There was a marginally declining trend of overall ACP admissions in HK up to eight years after childhood PCV introduction. The significance disappeared when fitting sensitivity analyses. The results indicate the complexities of using non-specific endpoints for measuring vaccine effect and the necessity of enhancing serotype surveillance systems for replacement monitoring.

Funding: Health and Medical Research Fund, Food and Health Bureau of the Government of Hong Kong (Reference number: 18171272).
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http://dx.doi.org/10.1016/j.vaccine.2021.03.090DOI Listing
May 2021

Diagnostic performance of different sampling approaches for SARS-CoV-2 RT-PCR testing: a systematic review and meta-analysis.

Lancet Infect Dis 2021 Apr 12. Epub 2021 Apr 12.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address:

Background: The comparative performance of different clinical sampling methods for diagnosis of SARS-CoV-2 infection by RT-PCR among populations with suspected infection remains unclear. This meta-analysis aims to systematically compare the diagnostic performance of different clinical specimen collection methods.

Methods: In this systematic review and meta-analysis, we systematically searched PubMed, Embase, MEDLINE, Web of Science, medRxiv, bioRxiv, SSRN, and Research Square from Jan 1, 2000, to Nov 16, 2020. We included original clinical studies that examined the performance of nasopharyngeal swabs and any additional respiratory specimens for the diagnosis of SARS-CoV-2 infection among individuals presenting in ambulatory care. Studies without data on paired samples, or those that only examined different samples from confirmed SARS-CoV-2 cases were not useful for examining diagnostic performance of a test and were excluded. Diagnostic performance, including sensitivity, specificity, positive predictive value, and negative predictive value, was examined using random effects models and double arcsine transformation.

Findings: Of the 5577 studies identified in our search, 23 studies including 7973 participants with 16 762 respiratory samples were included. Respiratory specimens examined in these studies included 7973 nasopharyngeal swabs, 1622 nasal swabs, 6110 saliva samples, 338 throat swabs, and 719 pooled nasal and throat swabs. Using nasopharyngeal swabs as the gold standard, pooled nasal and throat swabs gave the highest sensitivity of 97% (95% CI 93-100), whereas lower sensitivities were achieved by saliva (85%, 75-93) and nasal swabs (86%, 77-93) and a much lower sensitivity by throat swabs (68%, 35-94). A comparably high positive predictive value was obtained by pooled nasal and throat (97%, 90-100) and nasal swabs (96%, 87-100) and a slightly lower positive predictive value by saliva (93%, 88-97). Throat swabs have the lowest positive predictive value of 75% (95% CI 45-96). Comparably high specificities (range 97-99%) and negative predictive value (range 95-99%) were observed among different clinical specimens. Comparison between health-care-worker collection and self-collection for pooled nasal and throat swabs and nasal swabs showed comparable diagnostic performance. No significant heterogeneity was observed in the analysis of pooled nasal and throat swabs and throat swabs, whereas moderate to substantial heterogeneity (I ≥30%) was observed in studies on saliva and nasal swabs.

Interpretation: Our review suggests that, compared with the gold standard of nasopharyngeal swabs, pooled nasal and throat swabs offered the best diagnostic performance of the alternative sampling approaches for diagnosis of SARS-CoV-2 infection in ambulatory care. Saliva and nasal swabs gave comparable and very good diagnostic performance and are clinically acceptable alternative specimen collection methods. Throat swabs gave a much lower sensitivity and positive predictive value and should not be recommended. Self-collection for pooled nasal and throat swabs and nasal swabs was not associated with any significant impairment of diagnostic accuracy. Our results also provide a useful reference framework for the proper interpretation of SARS-CoV-2 testing results using different clinical specimens.

Funding: Hong Kong Research Grants Council.
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http://dx.doi.org/10.1016/S1473-3099(21)00146-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041361PMC
April 2021

Decreased use of broad-spectrum antibiotics during COVID-19 epidemic in South Korea.

J Infect Dis 2021 Apr 15. Epub 2021 Apr 15.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Background: Early in the COVID-19 pandemic, there was a concern over possible increase in antibiotic use due to co-infections among COVID-19 patients in the community. Here, we evaluate the changes in nationwide use of broad-spectrum antibiotics during the COVID-19 epidemic in South Korea.

Methods: We obtained national reimbursement data on the prescription of antibiotics, including penicillin with beta-lactamase inhibitors, cephalosporins, fluoroquinolones, and macrolides. We examined the number of antibiotic prescriptions compared with the previous three years in the same period from August to July. To quantify the impact of the COVID-19 epidemic on antibiotic use, we developed a regression model adjusting for changes of viral acute respiratory tract infections (ARTIs) which are an important factor driving antibiotic use.

Results: During the COVID-19 epidemic in South Korea, the broad-spectrum antibiotic use dropped by 15%-55% compared to the previous 3 years. Overall reduction in antibiotic use adjusting for ARTIs was estimated to be 14%-30%, with a larger impact in children.

Conclusions: Our study found that broad-spectrum antibiotic use was substantially reduced during the COVID-19 epidemic in South Korea. This reduction can be in part due to reduced ARTIs as a result of stringent public health interventions including social distancing measures.
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http://dx.doi.org/10.1093/infdis/jiab208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083342PMC
April 2021

The Causal Interpretation of "Overall Vaccine Effectiveness" in Test-Negative Studies.

Am J Epidemiol 2021 Apr 8. Epub 2021 Apr 8.

Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Test-negative studies are commonly used to estimate influenza vaccine effectiveness (VE). In a typical study, an "overall VE" estimate may be reported based on data from the entire sample. However, there may be heterogeneity in VE, particularly by age. We therefore discuss the potential for a weighted average of age-specific VE estimates to provide a more meaningful measure of overall VE. We illustrate this perspective first using simulations to evaluate how overall VE would be biased when certain age groups are over-represented. We found unweighted overall VE estimates tended to be higher than weighted VE when children were over-represented and lower when elderly were over-represented. Then we extracted published estimates from the US Flu VE network, in which children are overrepresented, and some discrepancy between unweighted and weighted overall VE was observed. Differences in weighted versus unweighted overall VE could translate to substantial differences in the interpretation of individual risk reduction in vaccinated persons, and the total averted disease burden at the population level. Weighting overall estimates should be considered in VE studies in future.
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http://dx.doi.org/10.1093/aje/kwab101DOI Listing
April 2021

Assessing asymptomatic, pre-symptomatic and symptomatic transmission risk of SARS-CoV-2.

Clin Infect Dis 2021 Mar 27. Epub 2021 Mar 27.

Division of Infectious disease, Key Laboratory of Surveillance and Early Warning on Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China.

Background: The relative contributions of asymptomatic, pre-symptomatic and symptomatic transmission of SARS-CoV-2 have not been clearly measured although control measures may differ in response to the risk of spread posed by different types of cases.

Methods: We collected detailed information on transmission events and symptom status based on laboratory-confirmed patient data and contact tracing data from four provinces and one municipality in China. We estimated the variation in risk of transmission over time, and the severity of secondary infections, by symptomatic status of the infector.

Results: There were 393 symptomatic index cases with 3136 close contacts and 185 asymptomatic index cases with 1078 close contacts included into the study. The secondary attack rate among close contacts of symptomatic and asymptomatic index cases were 4.1% (128/3136) and 1.1% (12/1078), respectively, corresponding to a higher transmission risk from symptomatic cases than from asymptomatic cases (OR: 3.79, 95% CI: 2.06, 6.95). Approximately 25% (32/128) and 50% (6/12) of the infected close contacts were asymptomatic from symptomatic and asymptomatic index cases, respectively, while more than one third (38%) of the infections in the close contacts of symptomatic cases were attributable to exposure to the index cases before symptom onset. Infected contacts of asymptomatic index cases were more likely to be asymptomatic and less likely to be severe.

Conclusions: Asymptomatic and pre-symptomatic transmission play an important role in spreading infection, although asymptomatic cases pose a lower risk of transmission than symptomatic cases. Early case detection and effective test-and-trace measures are important to reduce transmission.
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http://dx.doi.org/10.1093/cid/ciab271DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083716PMC
March 2021

Risk for International Importations of Variant SARS-CoV-2 Originating in the United Kingdom.

Emerg Infect Dis 2021 05 24;27(5):1527-1529. Epub 2021 Mar 24.

A fast-spreading severe acute respiratory syndrome coronavirus 2 variant identified in the United Kingdom in December 2020 has raised international alarm. We analyzed data from 15 countries and estimated that the chance that this variant was imported into these countries by travelers from the United Kingdom by December 7 is >50%.
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http://dx.doi.org/10.3201/eid2705.210050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084518PMC
May 2021

Probable airborne transmission of SARS-CoV-2 in a poorly ventilated restaurant.

Build Environ 2021 Jun 13;196:107788. Epub 2021 Mar 13.

Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, China.

Although airborne transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been recognized, the condition of ventilation for its occurrence is still being debated. We analyzed a coronavirus disease 2019 (COVID-19) outbreak involving three families in a restaurant in Guangzhou, China, assessed the possibility of airborne transmission, and characterized the associated environmental conditions. We collected epidemiological data, obtained a full video recording and seating records from the restaurant, and measured the dispersion of a warm tracer gas as a surrogate for exhaled droplets from the index case. Computer simulations were performed to simulate the spread of fine exhaled droplets. We compared the in-room location of subsequently infected cases and spread of the simulated virus-laden aerosol tracer. The ventilation rate was measured using the tracer gas concentration decay method. This outbreak involved ten infected persons in three families (A, B, C). All ten persons ate lunch at three neighboring tables at the same restaurant on January 24, 2020. None of the restaurant staff or the 68 patrons at the other 15 tables became infected. During this occasion, the measured ventilation rate was 0.9 L/s per person. No close contact or fomite contact was identified, aside from back-to-back sitting in some cases. Analysis of the airflow dynamics indicates that the infection distribution is consistent with a spread pattern representative of long-range transmission of exhaled virus-laden aerosols. Airborne transmission of the SARS-CoV-2 virus is possible in crowded space with a ventilation rate of 1 L/s per person.
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http://dx.doi.org/10.1016/j.buildenv.2021.107788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7954773PMC
June 2021

An investigation of prevalence in an Endemic County in Guangxi Zhuang Autonomous Region, China, 2016.

Food Waterborne Parasitol 2021 Mar 8;22:e00109. Epub 2021 Jan 8.

Key Laboratory of Surveillance and Early Warning on Infectious Disease, Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China.

To effectively promote the implementation of interventions, the identification of high-risk groups and the characteristics of infection in endemic regions are needed. In a clonorchiasis-endemic area, local residents were randomly enrolled for helminth egg examination in June 2016. The prevalence in subpopulations as well as the knowledge, attitudes, and behaviours and the factors influencing clonorchiasis in egg-positive populations were analysed. A total of 2282 local residents participated in the survey; the prevalence was 48.6% (1109 persons). A higher prevalence was found in males (62.6%) than in females (29.7%). People older than 30 years had the highest prevalence (52.7%-57.6%). Among the 888 persons who were infected with and participated the questionnaire investigation, 19.0% (169/888) knew that it could cause cancer. In addition, 60.6% of people reported that they intended to keep eating raw fish despite knowing the risk of infection. The two primary reasons for continuing to eat raw fish were the disease being regarded as not serious (38.3%) and the belief that anti-parasite medications are effective (39.6%). A total of 94.4% (797/844) of responders reported eating raw fish more frequently in the home than outside of the home. Our study revealed a notably high prevalence in the study area. Awareness of clonorchiasis disease severity should be increased among high-risk individuals and families in highly endemic areas.
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http://dx.doi.org/10.1016/j.fawpar.2020.e00109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930122PMC
March 2021

Clinical outcomes of different therapeutic options for COVID-19 in two Chinese case cohorts: A propensity-score analysis.

EClinicalMedicine 2021 Feb 13;32:100743. Epub 2021 Feb 13.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.

Background: The timing of administration of agents and use of combination treatments in COVID-19 remain unclear. We assessed the effectiveness of therapeutics in cohorts in Hong Kong SAR and Anhui, China.

Methods: We conducted propensity-score analysis of 4771 symptomatic patients from Hong Kong between 21st January and 6th December 2020, and 648 symptomatic patients from Anhui between 1st January and 27th February 2020. We censored all observations as at 13st December 2020. Time from hospital admission to discharge, and composite outcome of death, invasive mechanical ventilation or intensive care unit admission across 1) all therapeutic options including lopinavir-ritonavir, ribavirin, umifenovir, interferon-alpha-2b, interferon-beta-1b, corticosteroids, antibiotics, and Chinese medicines, and 2) four interferon-beta-1b combination treatment groups were investigated.

Findings: Interferon-beta-1b was associated with an improved composite outcome (OR=0.55, 95%CI 0.38, 0.80) and earlier discharge (-8.8 days, 95%CI -9.7, -7.9) compared to those not administered interferon-beta-1b. Oral ribavirin initiated within 7 days from onset was associated with lower risk of the composite outcome in Hong Kong (OR=0.51, 95%CI 0.29, 0.90). Lopinavir-ritonavir, intravenous ribavirin, umifenovir, corticosteroids, interferon-alpha-2b, antibiotics or Chinese medicines failed to show consistent clinical benefit. Interferon-beta-1b co-administered with ribavirin was associated with improved composite outcome (OR=0.50, 95%CI 0.32, 0.78) and earlier discharge (-2.35 days, 95%CI -3.65, -1.06) compared to interferon-beta-1b monotherapy.

Interpretation: Our findings support the early administration of interferon-beta-1b alone or in combination with oral ribavirin for COVID-19 patients.

Funding: Hong Kong Health and Medical Research Fund; Hong Kong Innovation and Technology Commission; Chinese Fundamental Research Funds for the Central Universities.
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http://dx.doi.org/10.1016/j.eclinm.2021.100743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881744PMC
February 2021

Upper Respiratory Infections in Schools and Childcare Centers Reopening after COVID-19 Dismissals, Hong Kong.

Emerg Infect Dis 2021 05 17;27(5):1525-1527. Epub 2021 Feb 17.

A large number of common cold outbreaks in Hong Kong schools and childcare centers during October-November 2020 led to territorywide school dismissals. Increased susceptibility to rhinoviruses during prolonged school closures and dismissals for coronavirus disease and varying effectiveness of nonpharmaceutical interventions may have heightened transmission of cold-causing viruses after school attendance resumed.
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http://dx.doi.org/10.3201/eid2705.210277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084506PMC
May 2021

Immunogenicity of standard, high-dose, MF59-adjuvanted, and recombinant-HA seasonal influenza vaccination in older adults.

NPJ Vaccines 2021 Feb 16;6(1):25. Epub 2021 Feb 16.

HKU-Pasteur Research Pole, School of Public Health, The University of Hong Kong, Hong Kong SAR, China.

The vaccine efficacy of standard-dose seasonal inactivated influenza vaccines (S-IIV) can be improved by the use of vaccines with higher antigen content or adjuvants. We conducted a randomized controlled trial in older adults to compare cellular and antibody responses of S-IIV versus enhanced vaccines (eIIV): MF59-adjuvanted (A-eIIV), high-dose (H-eIIV), and recombinant-hemagglutinin (HA) (R-eIIV). All vaccines induced comparable H3-HA-specific IgG and elevated antibody-dependent cellular cytotoxicity (ADCC) activity at day 30 post vaccination. H3-HA-specific ADCC responses were greatest following H-eIIV. Only A-eIIV increased H3-HA-IgG avidity, HA-stalk IgG and ADCC activity. eIIVs also increased polyfunctional CD4+ and CD8+ T cell responses, while cellular immune responses were skewed toward single-cytokine-producing T cells among S-IIV subjects. Our study provides further immunological evidence for the preferential use of eIIVs in older adults as each vaccine platform had an advantage over the standard-dose vaccine in terms of NK cell activation, HA-stalk antibodies, and T cell responses.
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http://dx.doi.org/10.1038/s41541-021-00289-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886864PMC
February 2021

Comparative cost-effectiveness of SARS-CoV-2 testing strategies in the USA: a modelling study.

Lancet Public Health 2021 03 5;6(3):e184-e191. Epub 2021 Feb 5.

The University of Texas at Austin, Austin, TX, USA; Santa Fe Institute, Santa Fe, NM, USA. Electronic address:

Background: To mitigate the COVID-19 pandemic, countries worldwide have enacted unprecedented movement restrictions, physical distancing measures, and face mask requirements. Until safe and efficacious vaccines or antiviral drugs become widely available, viral testing remains the primary mitigation measure for rapid identification and isolation of infected individuals. We aimed to assess the economic trade-offs of expanding and accelerating testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the USA in different transmission scenarios.

Methods: We used a multiscale model that incorporates SARS-CoV-2 transmission at the population level and daily viral load dynamics at the individual level to assess eight surveillance testing strategies that varied by testing frequency (from daily to monthly testing) and isolation period (1 or 2 weeks), compared with the status-quo strategy of symptom-based testing and isolation. For each testing strategy, we first estimated the costs (incorporating costs of diagnostic testing and admissions to hospital, and salary lost while in isolation) and years of life lost (YLLs) prevented under rapid and low transmission scenarios. We then assessed the testing strategies across a range of scenarios, each defined by effective reproduction number (R), willingness to pay per YLL averted, and cost of a test, to estimate the probability that a particular strategy had the greatest net benefit. Additionally, for a range of transmission scenarios (R from 1·1 to 3), we estimated a threshold test price at which the status-quo strategy outperforms all testing strategies considered.

Findings: Our modelling showed that daily testing combined with a 2-week isolation period was the most costly strategy considered, reflecting increased costs with greater test frequency and length of isolation period. Assuming a societal willingness to pay of US$100 000 per YLL averted and a price of $5 per test, the strategy most likely to be cost-effective under a rapid transmission scenario (R of 2·2) is weekly testing followed by a 2-week isolation period subsequent to a positive test result. Under low transmission scenarios (R of 1·2), monthly testing of the population followed by 1-week isolation rather than 2-week isolation is likely to be most cost-effective. Expanded surveillance testing is more likely to be cost-effective than the status-quo testing strategy if the price per test is less than $75 across all transmission rates considered.

Interpretation: Extensive expansion of SARS-CoV-2 testing programmes with more frequent and rapid tests across communities coupled with isolation of individuals with confirmed infection is essential for mitigating the COVID-19 pandemic. Furthermore, resources recouped from shortened isolation duration could be cost-effectively allocated to more frequent testing.

Funding: US National Institutes of Health, US Centers for Disease Control and Prevention, and Love, Tito's.
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http://dx.doi.org/10.1016/S2468-2667(21)00002-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862022PMC
March 2021

International risk of the new variant COVID-19 importations originating in the United Kingdom.

medRxiv 2021 Jan 15. Epub 2021 Jan 15.

A fast-spreading SARS-CoV-2 variant identified in the United Kingdom in December 2020 has raised international alarm. We estimate that, in 16 out of 19 countries analyzed, there is at least a 50% chance the variant was imported by travelers from the United Kingdom byDecember 7th.

Article Summary Line: The new variant COVID-19 has likely been introduced by travelers from the UK and spreading undetected for months in many countries.
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http://dx.doi.org/10.1101/2021.01.09.21249384DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814837PMC
January 2021

Changing disparities in COVID-19 burden in the ethnically homogeneous population of Hong Kong through pandemic waves: an observational study.

Clin Infect Dis 2021 Jan 6. Epub 2021 Jan 6.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Background: Disparities were marked in previous pandemics, usually with higher attack rates reported for those in lower socioeconomic positions and for ethnic minorities.

Methods: We examined characteristics of laboratory-confirmed COVID-19 cases in Hong Kong, assessed associations between incidence and population-level characteristics at the level of small geographic areas, and evaluated relations between socioeconomics and work-from-home (WFH) arrangements.

Results: The largest source of COVID-19 importations switched from students studying overseas in the second wave to foreign domestic helpers in the third. The local cases were mostly individuals not in formal employment (retirees and homemakers) and production workers who were unable to WFH. For every 10% increase in the proportion of population employed as executives or professionals in a given geographic region, there was an 84% (95% confidence interval (CI): 1% to 97%) reduction in the incidence of COVID-19 during the third wave. In contrast, in the first two waves, the same was associated with 3.69 times (95% CI: 1.02 to 13.33) higher incidence. Executives and professionals were more likely to implement WFH and experienced frequent changes in WFH practice, compared to production workers.

Conclusions: Consistent findings on the reversed socioeconomic patterning of COVID-19 burden between infection waves in Hong Kong at both individual and population level analyses indicated that risks of infections may be related to occupations involving high exposure frequency and WFH flexibility. Contextual determinants should be taken into account in policy planning aiming at mitigating such disparities.
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http://dx.doi.org/10.1093/cid/ciab002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929139PMC
January 2021

Neutralizing antibody titres in SARS-CoV-2 infections.

Nat Commun 2021 01 4;12(1):63. Epub 2021 Jan 4.

School of Public Health, The University of Hong Kong, Special Administrative Region of Hong Kong, Hong Kong, China.

The SARS-CoV-2 pandemic poses the greatest global public health challenge in a century. Neutralizing antibody is a correlate of protection and data on kinetics of virus neutralizing antibody responses are needed. We tested 293 sera from an observational cohort of 195 reverse transcription polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 infections collected from 0 to 209 days after onset of symptoms. Of 115 sera collected ≥61 days after onset of illness tested using plaque reduction neutralization (PRNT) assays, 99.1% remained seropositive for both 90% (PRNT) and 50% (PRNT) neutralization endpoints. We estimate that it takes at least 372, 416 and 133 days for PRNT titres to drop to the detection limit of a titre of 1:10 for severe, mild and asymptomatic patients, respectively. At day 90 after onset of symptoms (or initial RT-PCR detection in asymptomatic infections), it took 69, 87 and 31 days for PRNT antibody titres to decrease by half (T) in severe, mild and asymptomatic infections, respectively. Patients with severe disease had higher peak PRNT and PRNT antibody titres than patients with mild or asymptomatic infections. Age did not appear to compromise antibody responses, even after accounting for severity. We conclude that SARS-CoV-2 infection elicits robust neutralizing antibody titres in most individuals.
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http://dx.doi.org/10.1038/s41467-020-20247-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7782739PMC
January 2021

Influenza Virus: Tracking, Predicting, and Forecasting.

Annu Rev Public Health 2021 Apr 21;42:43-57. Epub 2021 Dec 21.

World Health Organization Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; email:

Influenza is a common respiratory infection that causes considerable morbidity and mortality worldwide each year. In recent years, along with the improvement in computational resources, there have been a number of important developments in the science of influenza surveillance and forecasting. Influenza surveillance systems have been improved by synthesizing multiple sources of information. Influenza forecasting has developed into an active field, with annual challenges in the United States that have stimulated improved methodologies. Work continues on the optimal approaches to assimilating surveillance data and information on relevant driving factors to improve estimates of the current situation (nowcasting) and to forecast future dynamics.
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http://dx.doi.org/10.1146/annurev-publhealth-010720-021049DOI Listing
April 2021

Face masks and COVID-19: don't let perfect be the enemy of good.

Euro Surveill 2020 12;25(49)

Laboratory of Data Discovery for Health, Hong Kong Science and Technology Park, Hong Kong Special Administrative Region, China.

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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.49.2001998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730488PMC
December 2020

Serological evidence of human infections with highly pathogenic avian influenza A(H5N1) virus: a systematic review and meta-analysis.

BMC Med 2020 12 2;18(1):377. Epub 2020 Dec 2.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, 200032, China.

Background: Highly pathogenic avian influenza A(H5N1) virus poses a global public health threat given severe and fatal zoonotic infections since 1997 and ongoing A(H5N1) virus circulation among poultry in several countries. A comprehensive assessment of the seroprevalence of A(H5N1) virus antibodies remains a gap and limits understanding of the true risk of A(H5N1) virus infection.

Methods: We conducted a systematic review and meta-analysis of published serosurveys to assess the risk of subclinical and clinically mild A(H5N1) virus infections. We assessed A(H5N1) virus antibody titers and changes in titers among populations with variable exposures to different A(H5N1) viruses.

Results: Across studies using the World Health Organization-recommended seropositive definition, the point estimates of the seroprevalence of A(H5N1) virus-specific antibodies were higher in poultry-exposed populations (range 0-0.6%) and persons exposed to both human A(H5N1) cases and infected birds (range 0.4-1.8%) than in close contacts of A(H5N1) cases or the general population (none to very low frequencies). Seroprevalence was higher in persons exposed to A(H5N1) clade 0 virus (1.9%, range 0.7-3.2%) than in participants exposed to other clades of A(H5N1) virus (range 0-0.5%) (p < 0.05). Seroprevalence was higher in poultry-exposed populations (range 0-1.9%) if such studies utilized antigenically similar A(H5N1) virus antigens in assays to A(H5N1) viruses circulating among poultry.

Conclusions: These low seroprevalences suggest that subclinical and clinically mild human A(H5N1) virus infections are uncommon. Standardized serological survey and laboratory methods are needed to fully understand the extent and risk of human A(H5N1) virus infections.
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http://dx.doi.org/10.1186/s12916-020-01836-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7709391PMC
December 2020

Meteorological drivers of respiratory syncytial virus infections in Singapore.

Sci Rep 2020 11 24;10(1):20469. Epub 2020 Nov 24.

Department of Neonatology, KK Women's and Children's Hospital, Singapore, Singapore.

Meteorological drivers are known to affect transmissibility of respiratory viruses including respiratory syncytial virus (RSV), but there are few studies quantifying the role of these drivers. We used daily RSV hospitalization data to estimate the daily effective reproduction number (R), a real-time measure of transmissibility, and examined its relationship with environmental drivers in Singapore from 2005 through 2015. We used multivariable regression models to quantify the proportion of the variance in R explained by each meteorological driver. After constructing a basic model for RSV seasonality, we found that by adding meteorological variables into this model we were able to explain a further 15% of the variance in RSV transmissibility. Lower and higher value of mean temperature, diurnal temperature range (DTR), precipitation and relative humidity were associated with increased RSV transmissibility, while higher value of maximum wind speed was correlated with decreased RSV transmissibility. We found that a number of meteorological drivers were associated with RSV transmissibility. While indoor conditions may differ from ambient outdoor conditions, our findings are indicative of a role of ambient temperature, humidity and wind speed in affecting RSV transmission that could be biological or could reflect indirect effects via the consequences on time spent indoors.
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http://dx.doi.org/10.1038/s41598-020-76888-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7686497PMC
November 2020

Influenza vaccination effectiveness in preventing influenza hospitalization in children, Hong Kong, winter 2019/20.

Vaccine 2020 12 6;38(51):8078-8081. Epub 2020 Nov 6.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

The winter influenza season 2019/20 in Hong Kong was predominated by influenza A(H1N1)pdm09. We analysed an on-going test-negative design study consisting of 1227 children admitted for febrile acute respiratory illness from 3 November 2019 (week 45) to 21 March 2020 (week 12). We estimated influenza vaccine effectiveness of 65% (95% CI: 46 - 78) against hospitalization due to influenza A and B combined, and 74% (95% CI: 54 - 85) against hospitalization due to influenza A(H1N1)pdm09.
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http://dx.doi.org/10.1016/j.vaccine.2020.10.081DOI Listing
December 2020

Variation by lineage in serum antibody responses to influenza B virus infections.

PLoS One 2020 9;15(11):e0241693. Epub 2020 Nov 9.

World Health Organization Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, The University of Hong Kong, Hong Kong, China.

Two lineages of influenza B virus currently co-circulate and have distinct antigenicity, termed Victoria and Yamagata after the B/Victoria/2/87 and B/Yamagata/16/88 strains, respectively. We analyzed antibody titer dynamics following PCR-confirmed influenza B virus infection in a longitudinal community-based cohort study conducted in Hong Kong from 2009-2014 to assess patterns in changes in antibody titers to B/Victoria and B/Yamagata viruses following infections with each lineage. Among 62 PCR-confirmed cases, almost half had undetectable hemagglutination inhibition (HAI) antibody titers to the lineage of infection both pre-infection and post-infection. Among those infected with influenza B/Victoria who showed an HAI titer response after infection, we found strong rises to the lineage of infection, positive but smaller cross-lineage HAI titer boosts, a small dependence of HAI titer boosts on pre-infection titers, and a shorter half-life of HAI titers in adults. Our study is limited by the low HAI sensitivity for non-ether-treated IBV antigen and the incapacity of performing other assays with higher sensitivity, as well as the mismatch between the B/Yamagata lineage circulating strain and the assay strain in one of the study seasons.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0241693PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652285PMC
January 2021

Enterovirus genomic load and disease severity among children hospitalised with hand, foot and mouth disease.

EBioMedicine 2020 Dec 6;62:103078. Epub 2020 Nov 6.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China. Electronic address:

Background: Examining associations between viral genomic loads of enteroviruses and clinical severity is important for promoting and improving development of antiviral drugs related to hand, foot and mouth disease (HFMD).

Methods: Throat swabs were collected from HFMD cases at acute phase of illness using a standardized technique in a prospective study. The viral genomic load was categorized into low, medium, and high groups using parameters of real-time reverse transcription-polymerase chain reaction. The clinical severities were assessed with four indicators, respectively.

Findings: We analysed 1109 HFMD cases, including 538 children with CV-A6, 231 with CV-A16, 156 with EV-A71, 78 with CV-A10, 59 with CV-A4, and 47 with CV-A2. EV-A71 genomic load categories were associated with risks of diagnoses of CNS complications (p = 0.016), requiring systemic corticosteroids or IVIG (p = 0.011), intensive care unit admission (p = 0.002) and length of hospital stay over 5 days (p = 0.048). In the multivariate analyses, point estimates of adjusted odds ratio (OR) tended to increase with viral genomic loads for all four severe outcomes and ORs of highest viral genomic load were all significantly larger than one for EV-A71.

Interpretation: HFMD clinical severities positively associate with viral genomic loads of EV-A71 in throat swabs. Specific antiviral drugs should be developed to reduce enterovirus load and to alleviate the clinical severities for HFMD cases.

Funding: National Science Fund for Distinguished Young Scholars.
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http://dx.doi.org/10.1016/j.ebiom.2020.103078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653080PMC
December 2020

Serological evidence of human infection with avian influenza A(H7N9) virus: a systematic review and meta-analysis.

J Infect Dis 2020 Oct 29. Epub 2020 Oct 29.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China.

Background: The extent of human infections with avian influenza A(H7N9) virus, including mild and asymptomatic infections, is uncertain.

Methods: We performed a systematic review and meta-analysis of serosurveys for avian influenza A(H7N9) virus infections in humans published during 2013-2020. Three seropositive definitions were assessed to estimate pooled seroprevalence, seroconversion rate and seroincidence by types of exposures. We applied a scoring system to assess the quality of included studies.

Results: Of 31 included studies, pooled seroprevalence of A(H7N9)-virus antibodies from all participants was 0.02%, with poultry workers, close contacts, and general populations having seroprevalence of 0.1%, 0.2% and 0.02% based on the WHO-recommended definition, respectively. Although most infections were asymptomatic, evidence of infection was highest in poultry workers (5% seroconversion, 19.1% seroincidence per 100 person-years). Use of different virus clades did not significantly affect seroprevalence estimates. Most serological studies were of low to moderate quality and did not follow standardized seroepidemiological protocols or WHO-recommended laboratory methods.

Conclusions: Human infections with avian influenza A(H7N9) virus have been uncommon, especially for general populations. Workers with occupational exposures to poultry and close contacts of A(H7N9) human cases had low risks of infection.
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http://dx.doi.org/10.1093/infdis/jiaa679DOI Listing
October 2020

Different transmission dynamics of COVID-19 and influenza suggest the relative efficiency of isolation/quarantine and social distancing against COVID-19 in China.

Clin Infect Dis 2020 Oct 20. Epub 2020 Oct 20.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou, P.R. China.

Background: Non-pharmaceutical interventions (NPIs) against Coronavirus Disease 2019 (COVID-19) are vital to reducing the transmission risks. However, the relative efficiency of social distancing against COVID-19 remains controversial, since social distancing and isolation/quarantine were implemented almost at the same time in China.

Methods: In this study, surveillance data of COVID-19 and seasonal influenza in the year 2018-2020 were used to quantify the relative efficiency of NPIs against COVID-19 in China, since isolation/quarantine was not used for the influenza epidemics. Given that the relative age-dependent susceptibility to influenza and COVID-19 may vary, an age-structured Susceptible-Infected-Recovered model was built to explore the efficiency of social distancing against COVID-19 under different population susceptibility scenarios.

Results: The mean effective reproductive number, Rt, of COVID-19 before NPIs was 2.12 (95% confidential interval (CI): 2.02-2.21). By March 11, 2020, the overall reduction in Rt of COVID-19 was 66.1% (95% CI: 60.1%-71.2%). In the epidemiological year 2019/20, influenza transmissibility reduced by 34.6% (95% CI: 31.3%-38.2%) compared with that in the epidemiological year 2018/19. Under the observed contact patterns changes in China, social distancing had similar efficiency against COVID-19 in three different scenarios. By assuming same efficiency of social distancing against seasonal influenza and COVID-19 transmission, isolation/quarantine and social distancing could lead to a 48.1% (95% CI: 35.4%-58.1%) and 34.6% (95% CI: 31.3%-38.2%) reduction of the transmissibility of COVID-19.

Conclusions: Though isolation/quarantine is more effective than social distancing, given that typical basic reproductive number of COVID-19 is 2-3, isolation/quarantine alone could not contain the COVID-19 pandemic effectively in China.
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http://dx.doi.org/10.1093/cid/ciaa1584DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665384PMC
October 2020

Anxiety levels, precautionary behaviours and public perceptions during the early phase of the COVID-19 outbreak in China: a population-based cross-sectional survey.

BMJ Open 2020 10 8;10(10):e040910. Epub 2020 Oct 8.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China

Objective: To investigate psychological and behavioural responses to COVID-19 among the Chinese general population.

Design, Setting And Participants: We conducted a population-based mobile phone survey between 1 February and 10 February 2020 via random digit dialling. A total of 1011 adult residents in Wuhan (n=510), the epicentre and quarantined city, and Shanghai (n=501) were interviewed. Proportional quota sampling and poststratification weighting were used. Multivariable logistic regression models were used to investigate perception factors associated with the public responses.

Primary Outcome Measures: We measured anxiety levels using the 7-item Generalised Anxiety Disorder Scale (GAD-7) and asked respondents to report their precautionary behaviours before and during the outbreak.

Results: The prevalence of moderate or severe anxiety was significantly higher (p<0.001) in Wuhan (32.8%) than Shanghai (20.5%). Around 79.6%-88.2% residents reported always wearing a face mask when they went out and washing hands immediately when they returned home, with no discernible difference across cities. Only 35.5%-37.0% of residents reported a handwashing duration above 40 s as recommended by the WHO. The strongest predictor of moderate or severe anxiety was perceived harm of the disease (OR 1.8, 95% CI 1.5 to 2.1), followed by confusion about information reliability (OR 1.7, 95% CI 1.5 to 1.9). None of the examined perception factors were associated with odds of handwashing duration above 40 s.

Conclusions: Prevalence of moderate or severe anxiety and strict personal precautionary behaviours was generally high, regardless of the quarantine status. Our results support efforts for handwashing education programmes with a focus on hygiene procedures in China and timely dissemination of reliable information.
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http://dx.doi.org/10.1136/bmjopen-2020-040910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545627PMC
October 2020

The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother-neonate cohort study.

Lancet Infect Dis 2021 03 5;21(3):418-426. Epub 2020 Oct 5.

School of Public Health, Fudan University, Key Laboratory of Public Health Safety, Ministry of Education, Shanghai, China; Key Laboratory of Surveillance and Early Warning on Infectious Disease, Division of Infectious Disease, Chinese Center for Disease Control and Prevention, Beijing, China. Electronic address:

Background: Since 1997, epidemics of hand, foot, and mouth disease associated with enterovirus A71 (EV-A71) have affected children younger than 5 years in the Asia-Pacific region, including mainland China. EV-A71 vaccines have been licensed for use in children aged 6-71 months in China, but not for infants younger than 6 months. We aimed to assess the dynamics of maternal EV-A71 antibodies to inform choice of potential vaccination strategies to protect infants younger than 6 months, because they have a substantial burden of disease.

Methods: We did a longitudinal cohort study with mother-neonate pairs in local hospitals in southern China during 2013-18. We collected cord blood from neonates and venous blood from mothers at delivery. We followed up and collected blood samples from the children at ages 2, 4, 6, 12, 24, and 36 months and tested for the presence of neutralising antibodies against EV-A71 with virus neutralisation assays. Seropositivity, or protective titre, was defined as a neutralisation antibody titre of 16 or higher. We estimated the seroprevalence, geometric mean titre (GMT), and transfer ratio of maternal antibodies. We used a binomial distribution to derive the 95% CIs of seroprevalence. Seropositivity between mothers and neonates was compared by use of an agreement (κ), while GMTs were compared by use of paired Student's t tests.

Findings: Between Sept 20, 2013, and Oct 14, 2015, 1054 mothers with 1066 neonates were enrolled. The EV-A71 GMT was similar among pairs of neonates (22·7, 95% CI 20·8-24·9) and mothers (22·1, 95% CI 20·2-24·1; p=0·20). The mean transfer ratio of maternal antibodies was 1·03 (95% CI 0·98-1·08). Although 705 (66%) of 1066 neonates acquired protective concentrations of EV-A71 antibodies from mothers, these declined rapidly, with a half-life of 42 days (95% CI 40-44). The time to loss of protective immunity was extended to 5 months in neonates with mothers who had titres of 128 or higher. By age 30 months, 28% of children had become seropositive because of natural infection.

Interpretation: EV-A71 maternal antibodies were efficiently transferred to neonates, but declined quickly to below the protective threshold, particularly among those whose mothers had low antibody titres. Our findings suggest that maternal vaccination could be explored to provide neonatal protection against EV-A71 through maternal antibodies. Catch-up vaccination between ages 6 months to 5 years could provide protection to the approximately 30-90% of children that have not had natural EV-A71 infection by that age.

Funding: National Science Fund for Distinguished Young Scholars, National Natural Science Foundation of China.
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http://dx.doi.org/10.1016/S1473-3099(20)30480-1DOI Listing
March 2021

Human Influenza Epidemiology.

Cold Spring Harb Perspect Med 2020 Sep 28. Epub 2020 Sep 28.

WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.

Influenza virus infections are common in people of all ages. Epidemics occur in the winter months in temperate locations and at varying times of the year in subtropical and tropical locations. Most influenza virus infections cause mild and self-limiting disease, and around one-half of all infections occur with a fever. Only a small minority of infections lead to serious disease requiring hospitalization. During epidemics, the rates of influenza virus infections are typically highest in school-age children. The clinical severity of infections tends to increase at the extremes of age and with the presence of underlying medical conditions, and impact of epidemics is greatest in these groups. Vaccination is the most effective measure to prevent infections, and in recent years influenza vaccines have become the most frequently used vaccines in the world. Nonpharmaceutical public health measures can also be effective in reducing transmission, allowing suppression or mitigation of influenza epidemics and pandemics.
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http://dx.doi.org/10.1101/cshperspect.a038356DOI Listing
September 2020