Coinfection of SARS-CoV-2 and multiple respiratory pathogens in children

Shupeng Jianghttp://orcid.org/https://orcid.org/0000-0001-6401-4127 1 , Panpan Liu 2 , Ge Xiong 1 , Zhaohui Yang 3 , Ming Wang 1 , Yan Li 1 ,  and Xue-jie Yu 2
  • 1 Department of Laboratory Medicine, Renmin Hospital of Wuhan University, Wuhan, P.R. China
  • 2 State Key Laboratory of Virology, School of Health Sciences, Wuhan University, Wuhan, P.R. China
  • 3 Department of Radiology, Renmin Hospital of Wuhan University, Wuhan, P.R. China
Shupeng JiangORCID iD: https://orcid.org/0000-0001-6401-4127, Panpan Liu
  • State Key Laboratory of Virology, School of Health Sciences, Wuhan University, Wuhan, P.R. China
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, Ge Xiong
  • Department of Laboratory Medicine, Renmin Hospital of Wuhan University, Wuhan, P.R. China
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, Zhaohui Yang, Ming Wang
  • Corresponding author
  • Department of Laboratory Medicine, Renmin Hospital of Wuhan University, Wuhan, P.R. China
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, Yan Li
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  • Department of Laboratory Medicine, Renmin Hospital of Wuhan University, Wuhan, P.R. China
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and Xue-jie Yu
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  • State Key Laboratory of Virology, School of Health Sciences, Wuhan University, Wuhan, P.R. China
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To the Editor,

The COVID-19 outbreak occurred in Wuhan City of China in December 2019. Within 3 months, the disease has swept the world resulting in 191,127 confirmed cases and 7807 deaths in more than 150 countries and territories [1]. COVID-19 has been reported predominantly in adults, particularly in those with chronic comorbidities [2], [3]. A small number of cases of COVID-19 have been reported in children; therefore, children are widely believed to be not susceptible to COVID-19 [4], [5]. Here we report two cases of COVID-19 in children who were coinfected with human respiratory viruses and Mycoplasma pneumoniae (MP) in China.

A total of 161 hospitalized children (≤14 years of age) with positive respiratory virus polymerase chain reaction (PCR) were enrolled in a retrospective study of respiratory infections in the pediatric ward of a class A tertiary comprehensive hospital in Wuhan, China from December 1, 2019 to January 16, 2020. Nasopharyngeal swab, sputum or bronchoalveolar lavage fluid specimens were tested for respiratory viruses by real-time PCR (RT-PCR) or multiplex PCR combined with capillary electrophoresis. Clinical presentation, laboratory findings and radiological features were collected from electronic medical records. The study was approved by the Ethics Committee of the Renmin Hospital of Wuhan University.

A total of 239 positive targets of pathogens were detected in 161 children. The highest proportion of pathogens were human respiratory syncytial virus (HRSV) (in 76 patients [31.80%]) and influenza A virus (in 72 patients [30.13%]). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, was detected in two patients and accounted for 0.84%.

SARS-COV-2, HRSV and human metapneumovirus (HMPV) were found in the bronchoalveolar lavage fluid of patient 1, and SARS-COV-2, MP and HMPV were found in the bronchoalveolar lavage fluid of patient 2. The two patients stayed in different pediatric wards. Clinical characteristics of these two children with COVID-19 are shown in Table 1.

Table 1:

Clinical characteristics of the two children with COVID-19.

CharacteristicPatient 1Patient 2
Age, years6Y8M3Y6M
GenderFemaleFemale
Top temperature40.0 °C40.0 °C
Respiratory symptomsFever, coughFever, cough, wheeze
Pharyngeal symptomsSwollen pharynx, large tonsilsSwollen pharynx
Gastrointestinal symptomsVomitingVomiting
CT findingsPatchy shadowsNA
PathogensSARS-COV-2, HRSV, HMPVSARS-COV-2, MP, HMPV
Treatments
 OseltamivirYesNo
 GlucocorticoidsNoYes
 Antibiotic treatmentYesYes
 Intravenous immune globulinYesNo
 Supplemental oxygenYesYes
 Bronchoalveolar lavageYesYes
Clinical course
 ICU admissionYesNo
 Duration of hospitalization14D11D

COVID-19, coronavirus disease 2019; CT, computed tomography; HMPV, human metapneumovirus; HRSV, human respiratory syncytial virus; ICU, intensive care unit; MP, Mycoplasma pneumoniae; NA, not available; SARS-COV-2, severe acute respiratory syndrome coronavirus 2.

Patient 1 was admitted to the hospital on December 28, 2019, for fever and dry cough that occurred a few hours ago. Routine blood tests revealed a leukocyte count of 16.81×109 cells/L (reference range 3.5–9.5×109 cells/L), neutrophil count of 14.02×109 cells/L (reference range 1.8–6.3×109 cells/L) and lymphocyte count of 2.05×109 cells/L (reference range 1.1–3.2×109 cells/L). Inflammatory factor investigations revealed elevated C-reactive protein (CRP) level (46.92 mg/L, normal: 0–10 mg/L) and procalcitonin (PCT) level (0.11 ng/mL, reference range 0–0.10 ng/mL). Blood culture and sputum culture were all negative. Chest computed tomography revealed a ground-glass opacity in the lung. Due to her oxygen saturation of 70% in ambient air, this patient was diagnosed with severe pneumonia and was admitted to the intensive care unit (ICU). After 2 weeks of treatment with antiviral agents, antibiotic agents and supportive therapies, she was discharged smoothly with no residual symptoms.

Patient 2 was admitted to the hospital on December 29, 2019, for fever, cough and vomiting the day before. Laboratory investigations showed the leukocyte, neutrophil and lymphocyte counts were in the normal range. Serum amyloid A was increased (41.20 mg/L, normal: 0–10 mg/L), but PCT and CRP levels were normal. After 11 days of treatment with supportive therapies and antibiotic agents, she was on the mend and was re-examined for all inflammatory indexes and all showed normal, and she was discharged from the hospital.

In this retrospective study, we demonstrate that children are not only susceptible to SARS-CoV-2 infection, but they can be coinfected with SARS-CoV-2 and multiple respiratory viruses and bacterial pathogens including HRSV, HMPV and MP in China. Children were reported to have milder illnesses and shorter durations compared to adults [5]. Our study indicated that one of the two children needed ICU, indicating the child had severe symptoms. Because the number of cases of coinfection is small, we cannot determine whether coinfection of SARS-CoV-2 with other viruses or bacteria aggravates the condition. Our study indicated that coinfection of SARS-CoV-2 and HRSV, HMPV or MP in children occurs, suggesting that children with respiratory infection should be screened for SARS-CoV-2 and other respiratory viral and bacterial pathogens during the COVID-19 pandemic to prevent missed diagnosis and transmission of SARS-CoV-2. The prevalence of SARS-CoV-2 coinfection with other pathogens is also unclear in adult COVID-19 patients, as there has only been a case report of a 69-year-old man who was coinfected with SARS-CoV-2 and influenza A virus in China [3]. Our study indicates that COVID-19 patients should be investigated for coinfection with other respiratory viruses and bacterial pathogens.

Research funding: This study was supported by a grant from National Natural Science Funds of China (Grant No. 81971939).

Author contributions: Drs. Li, Wang and Yu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Jiang and Liu contributed equally to the study. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

Competing interests: Authors state no conflict of interest.

Informed consent: Informed consent was obtained from all individuals included in this study.

Ethical approval: The study was approved by the Ethics Committee of the Renmin Hospital of Wuhan University.

References

  • 1.

    World Health Organization. Coronavirus disease (COVID-2019) situation reports. at https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/.

  • 2.

    Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England) 2020;395:497–506.

    • Crossref
    • PubMed
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  • 3.

    Wu X, Cai Y, Huang X, Yu X, Zhao L, Wang F, et al. Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China. Emerg Infect Dis 2020;26. doi: 10.3201/eid2606.200299. [Epub ahead of print].

    • PubMed
    • Export Citation
  • 4.

    Liu W, Zhang Q. Detection of Covid-19 in children in early January 2020 in Wuhan, China. New Engl J Med 2020;382:1370–71..

    • Crossref
    • Export Citation
  • 5.

    Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel coronavirus infection in hospitalized infants under 1 year of age in China. J Am Med Assoc 2020;323:1313–14.

    • Crossref
    • Export Citation

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  • 1.

    World Health Organization. Coronavirus disease (COVID-2019) situation reports. at https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports/.

  • 2.

    Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet (London, England) 2020;395:497–506.

    • Crossref
    • PubMed
    • Export Citation
  • 3.

    Wu X, Cai Y, Huang X, Yu X, Zhao L, Wang F, et al. Co-infection with SARS-CoV-2 and influenza A virus in patient with pneumonia, China. Emerg Infect Dis 2020;26. doi: 10.3201/eid2606.200299. [Epub ahead of print].

    • PubMed
    • Export Citation
  • 4.

    Liu W, Zhang Q. Detection of Covid-19 in children in early January 2020 in Wuhan, China. New Engl J Med 2020;382:1370–71..

    • Crossref
    • Export Citation
  • 5.

    Wei M, Yuan J, Liu Y, Fu T, Yu X, Zhang ZJ. Novel coronavirus infection in hospitalized infants under 1 year of age in China. J Am Med Assoc 2020;323:1313–14.

    • Crossref
    • Export Citation
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