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Resurgence of influenza virus activity during COVID-19 pandemic in Shanghai, China

  • Pengcheng Liu
    Affiliations
    Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China
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  • Jin Xu
    Correspondence
    Corresponding author at: Department of Clinical Laboratory, Children's Hospital of Fudan University, 399 Wanyuan Rd, Minhang District, Shanghai 201102, China.
    Affiliations
    Department of Clinical Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai 201102, China

    Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, China
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Published:September 29, 2022DOI:https://doi.org/10.1016/j.jinf.2022.09.025
      Dear editor,
      Recent study by Han et al., reported the dramatic impact of nonpharmaceutical interventions (NPIs) introduced during the coronavirus disease 2019 (COVID-19) pandemic on influenza and other common respiratory virus detections among children in Hangzhou, China.
      • Han X.
      • Xu P.
      • Wang H.
      • Mao J.
      • Ye Q.
      Incident changes in the prevalence of respiratory virus among children during COVID-19 pandemic in Hangzhou, China.
      Their results demonstrated that the influenza virus activity had apparent seasonality before COVID-19 pandemic, while it was suppressed and the seasonality was not fully highlighted during COVID-19 pandemic (From February 2020 to October 2021). Besides, a study conducted in Singapore also reported that although rhinoviruses, parainfluenza, respiratory syncytial viruses and other common respiratory viruses have returned, the activity of influenza remains absent in circulation during COVID-19 pandemic.
      • Chan H.C.
      • Tambyah P.A.
      • Tee N.
      • Somani J.
      Return of other respiratory viruses despite the disappearance of influenza during COVID-19 control measures in Singapore.
      Herein, we presented a resurgence of influenza virus activity among children during COVID-19 pandemic in Shanghai, China.
      In this cross-sectional study, pediatric patients with respiratory disease symptoms (fever, cough, rhinitis, sore throat or myalgia) in the outpatient clinic at Children's Hospital of Fudan University from Jan 1, 2014 to Aug 31, 2022 were enrolled. Nasopharyngeal swabs were collected from all enrolled outpatients and tested by chromatographic immunoassay for influenza A/B virus (Standard Diagnostics, Yongin, Republic of Korea). Time series models of seasonal autoregressive integrated moving average (SARIMA) were trained using data from Jan 2014 to Jan 2020 (pre-COVID-19) to forecast the monthly positive rates of influenza A/B virus from February 2020 to August 2022 (COVID-19 pandemic). Goodness-of-fit tests of models were performed by comparing Akaike's information criterion (AIC) and Schwarz Bayesian Criterion (SBC). Smaller AIC and SBC indicate the better fitting model.
      • Benvenuto D.
      • Giovanetti M.
      • Vassallo L.
      • Angeletti S.
      • Ciccozzi M.
      Application of the ARIMA model on the COVID-2019 epidemic dataset.
      For comparisons between different periods, Chi-squared test was used for categorical data and Mann-Whitney U test for numeric data.
      A total of 452,552 patients were enrolled in the study, including 328,220 (72.5%) patients in the pre-COVID-19 period and 124,332 (27.5%) patients in the COVID-19 pandemic period. The median age of patients in the pandemic period (6 years) was older than in the pre-pandemic period (4 years), and no qualitative difference was found between the two sexes (Table 1). A significant decline in influenza A/B activity was observed in the pandemic period compared to the pre-COVID-19 period from a positive rate of 20.3 to 6.8% (Table 1). The usual bimodal peaks of influenza A activity, in summer (June to August) and winter (December to February) were present in the pre-COVID-19 period. However, the seasonality of influenza A was interrupted after the introduction of tight nationwide NPIs in February 2020. The peaks disappeared completely in the year of 2020 and 2021. Whereas, a resurgence of influenza A activity was observed in the summer of 2022, and the actual activity significantly exceeded model-projected levels in the hypothetical scenario without COVID-19 related NPIs (Fig. 1A).
      Table 1Comparison of demographics and positive rates (%) of influenza viruses between pre-COVID-19 and COVID-19 pandemic.
      Whole study period
      Whole study period: Jan 1, 2014 to Aug 31, 2022; pre-COVID-19: Jan 1, 2014 to Jan 31, 2020; COVID-19 pandemic: Feb 1, 2020 to Aug 31, 2022.
      pre-COVID-19
      Whole study period: Jan 1, 2014 to Aug 31, 2022; pre-COVID-19: Jan 1, 2014 to Jan 31, 2020; COVID-19 pandemic: Feb 1, 2020 to Aug 31, 2022.
      COVID-19 pandemic
      Whole study period: Jan 1, 2014 to Aug 31, 2022; pre-COVID-19: Jan 1, 2014 to Jan 31, 2020; COVID-19 pandemic: Feb 1, 2020 to Aug 31, 2022.
      P value
      Comparison between pre-COVID-19 and COVID-19 pandemic; Abbreviations: y, years; m, months.
      Demographics
       Total patients452,552328,220124,332
       Male sex, n (%)244,946 (54.1)177,467 (54.1)67,479 (54.3)0.221
       Age, median5y (16m-9y)4y (7m-8y)6y (3m-10y)<0.001
      Virus detections, n (%)
       Influenza A42,293 (9.3)39,950 (12.2)2343 (1.9)<0.001
       Influenza B32,634 (7.2)26,519 (8.1)6115 (5.9)<0.001
       Total74,927 (16.6)66,469 (20.3)8458 (6.8)<0.001
      low asterisk Whole study period: Jan 1, 2014 to Aug 31, 2022; pre-COVID-19: Jan 1, 2014 to Jan 31, 2020; COVID-19 pandemic: Feb 1, 2020 to Aug 31, 2022.
      # Comparison between pre-COVID-19 and COVID-19 pandemic;Abbreviations: y, years; m, months.
      Fig 1
      Fig. 1Observed and model-fitted time series of monthly influenza activity between Jan, 2014 and Aug, 2022. (A) influenza A virus; (B) influenza B virus. Hypothetical positive rates during Feb, 2020-Agu, 2022 (blue) in the absence of NPIs was projected using the SARIMA model based on Jan 2014-Jan 2020. Gray block represents the period of the “COVID-19 pandemic” when NPIs were implemented. NPIs, nonpharmaceutical interventions; SARIMA, seasonal autoregressive integrated moving average.
      The annual peak of influenza B activity occurred in winter or early spring (January to March) in the pre-COVID-19 period and it was also flattened or suppressed after the implementation of NPIs. However, the resurgence of influenza B was earlier than influenza A. The activity increased from July 2021 and peaked in January 2022, which was almost in agreement with the model-projected seasonality (Fig. 1B).
      Early studies conducted in both Southern Hemisphere and Northern Hemisphere reported that influenza seasons were entirely suppressed during the COVID-19 pandemic.
      • Olsen S.J.
      • Azziz-Baumgartner E.
      • Budd A.P.
      • et al.
      Decreased influenza activity during the COVID-19 pandemic-United States, Australia, Chile, and South Africa, 2020.
      • Sohn S.
      • Hong K.
      • Chun B.C.
      Decreased seasonal influenza during the COVID-19 pandemic in temperate countries.
      • Lagace-Wiens P.
      • Sevenhuysen C.
      • Lee L.
      • Nwosu A.
      • Smith T.
      Impact of nonpharmaceutical interventions on laboratory detections of influenza A and B in Canada.
      Likewise, the activity of influenza declined sharply and was reduced to near zero during the early stage of pandemic in our study. Influenza virus can be transmitted by contact, droplet, or aerosol.
      • Brankston G.
      • Gitterman L.
      • Hirji Z.
      • Lemieux C.
      • Gardam M.
      Transmission of influenza A in human beings.
      Leung et al. reported that surgical face masks significantly reduced the detection of influenza virus RNA in respiratory droplets, indicating that surgical face masks could prevent the transmission of influenza viruses from symptomatic individuals.
      • Leung N.
      • Chu D.
      • Shiu E.
      • et al.
      Respiratory virus shedding in exhaled breath and efficacy of face masks.
      These results demonstrated that the current NPIs, including international mobility restriction and mask-wearing, social distancing, increased hand hygiene, could be highly effective against influenza activity. This positive effect in the short term is welcome. However, the lack of immune stimulation due to the reduced circulation of influenza and the related reduced vaccine uptake may induce an "immunity debt" which could have negative consequences and may render the population more vulnerable in the following season.
      • Cohen R.
      • Ashman M.
      • Taha M.K.
      • et al.
      Pediatric Infectious Disease Group (GPIP) position paper on the immune debt of the COVID-19 pandemic in childhood, how can we fill the immunity gap?.
      Unsurprisingly, after a relative absence during the pandemic period, a large resurgence of influenza activity was observed in July 2021 for influenza B and June 2022 for influenza A in Shanghai, China. These findings raise concerns for influenza control. The eventual cancelation of COVID-19 related NPIs may herald a more significant rise in influenza activity. Vaccination is one of the most effective measures in influenza control. Identifying and developing universal vaccines, as well as increasing the vaccination coverage are of primary importance after influenza's long-term absence. Additionally, further studies are still needed to better understand the circulation patterns change of influenza viruses during COVID-19 pandemic in the different stages and regions.

      Funding

      This study was funded by Key Development Program of Children's Hospital of Fudan University (No: EK2022ZX05).

      Declaration of Competing Interest

      All authors claim no conflict of interest.

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