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COVID-19 croup: Solitary infections and a coinfection case – author reply to a letter

  • Paul C. Mullan
    Correspondence
    Corresponding author at: Department of Pediatrics, Children's Hospital of the King's Daughters, 601 Children's Lane, Norfolk, VA 23507, USA.
    Affiliations
    Children's Hospital of the King's Daughters, 601 Children's Lane, Norfolk, VA, 23507, USA

    Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501-1980, USA
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  • April M.R. Venn
    Affiliations
    Children's Hospital of the King's Daughters, 601 Children's Lane, Norfolk, VA, 23507, USA

    Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501-1980, USA

    Department of Emergency Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York Presbyterian Hospital, 630 W. 168th St, New York, NY 10032, USA
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  • James M. Schmidt
    Affiliations
    Children's Hospital of the King's Daughters, 601 Children's Lane, Norfolk, VA, 23507, USA

    Eastern Virginia Medical School, P.O. Box 1980, Norfolk, VA 23501-1980, USA
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Published:February 22, 2021DOI:https://doi.org/10.1016/j.ajem.2021.02.027

      Keywords

      Thank you for sharing your institution's recent data and experience with a case of croup who was seen in your emergency department (ED), admitted on oxygen after dexamethasone treatment, and was found to be co-infected with both SARS-CoV-2 and enterovirus. I am glad your patient had a swift recovery. In our three reported cases of croup associated with SARS-CoV-2 infection over a two-month period, all three patients were positive for a single virus and had a negative viral panel (Biofire® FilmArray Respiratory Panel) (CR) for nineteen other viruses, including the ones most commonly associated with croup [
      • Venn A.M.R.
      • Schmidt J.M.
      • Mullan P.C.
      A case series of pediatric croup with COVID-19.
      ]. Two other case reports have also described solitary infection of SARS-CoV-2 associated with presentations of croup [
      • Pitstick C.E.
      • Rodriguez K.M.
      • Smith A.C.
      • Herman H.K.
      • Hays J.F.
      • Nash C.B.
      A curious case of croup: laryngotracheitis caused by COVID-19.
      ,
      • Jagadish K.
      Croup: a rare manifestation of COVID-19.
      ]; your description is the first case of croup that we are aware of that had a SARS-CoV-2 infection with a second virus. Other solitary and co-infection cases of croup will likely be reported in the literature as the pandemic progresses.
      From your description, sixteen patients presented to your ED in 2020 with croup and only the aforementioned patient tested positive for SARS-CoV-2. To help understand this data more fully, it would be helpful to know when you had SARS-CoV-2 added to your multiplex RT-PCR viral testing platform and exclude any of the 16 cases that were done before that time. Our hospital's multiplex RT-PCR panel added the SARS-CoV-2 to their panel in April 2020. It would also be helpful to know how many of the remaining cases were tested at all with your multiplex viral panel, as most of the cases were probably discharged and might not have been tested. Prior studies on patients with croup suggest approximately 80% of cases are positive for a virus [
      • Rihkanen H.
      • Rönkkö E.
      • Nieminen T.
      • Komsi K.L.
      • Räty R.
      • Saxen H.
      • et al.
      Respiratory viruses in laryngeal croup of young children.
      ,
      • Miller E.K.
      • Gebretsadik T.
      • Carroll K.N.
      • Dupont W.D.
      • Mohamed Y.A.
      • Morin L.L.
      • et al.
      Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years.
      ]. If your positivity rates for these cases that you did perform viral testing on were significantly lower, this potentially could be an issue with inadequate sampling collection.
      Given the novelty of the SARS-CoV-2 virus, multi-center studies will need to be performed to determine the true rate of co-infection with other viruses. Regarding the three studies you cited, you mentioned that “most often, co-infections were found” and that “single infections [with coronaviruses] are rare.” [
      • Rihkanen H.
      • Rönkkö E.
      • Nieminen T.
      • Komsi K.L.
      • Räty R.
      • Saxen H.
      • et al.
      Respiratory viruses in laryngeal croup of young children.
      ,
      • Miller E.K.
      • Gebretsadik T.
      • Carroll K.N.
      • Dupont W.D.
      • Mohamed Y.A.
      • Morin L.L.
      • et al.
      Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years.
      ,
      • Sung J.Y.
      • Lee H.J.
      • Eun B.W.
      • Kim S.H.
      • Lee S.Y.
      • Lee J.Y.
      • et al.
      Role of human coronavirus NL63 in hospitalized children with croup.
      ] In three those studies, co-infections were relatively infrequent, found in 19% (6 of 31 coronavirus infections in Sung JY, et al.), 100% (1 of 1 cases in Miller EK, et al.), and 0 to 100% (unknown number of 3 coronavirus infections in Rihkanen, et al.; Personal Communication) of cases; in aggregate, these studies showed co-infection in only 7 to 10 (20 to 29%) of the 35 cases [
      • Rihkanen H.
      • Rönkkö E.
      • Nieminen T.
      • Komsi K.L.
      • Räty R.
      • Saxen H.
      • et al.
      Respiratory viruses in laryngeal croup of young children.
      ,
      • Miller E.K.
      • Gebretsadik T.
      • Carroll K.N.
      • Dupont W.D.
      • Mohamed Y.A.
      • Morin L.L.
      • et al.
      Viral etiologies of infant bronchiolitis, croup and upper respiratory illness during 4 consecutive years.
      ,
      • Sung J.Y.
      • Lee H.J.
      • Eun B.W.
      • Kim S.H.
      • Lee S.Y.
      • Lee J.Y.
      • et al.
      Role of human coronavirus NL63 in hospitalized children with croup.
      ].
      After excluding any of the 16 cases that were diagnosed during a time without SARS-CoV-2 PCR testing capacity or not tested for SARS-CoV-2 infection, how many of the remaining patients were admitted to the hospital? Admissions for croup are a relatively infrequent event in our hospital and historically elsewhere as well [].. In a recent large database study, reviewing the NEDS and NHAMCS databases over an eight year period, there were 2.8 million ED visits for croup, of which only 3% were admitted to the hospital and their data showed a significant decreasing trend in admission rates over time over the study period (p < 0.001) [
      • Hanna J.
      • Brauer P.R.
      • Morse E.
      • Berson E.
      • Mehra S.
      Epidemiological analysis of croup in the emergency department using two national datasets.
      ].. How many of the remaining patients were admitted with an oxygen requirement? In two recent studies, with a total of 1096 admitted patients for croup, only 14 (1.3%) of the 1096 children had an oxygen requirement [
      • Asmundsson A.S.
      • Arms J.
      • Kaila R.
      • Roback M.G.
      • Theiler C.
      • Davey C.S.
      • et al.
      Hospital course of croup after emergency department management.
      ,
      • Hester G.
      • Barnes T.
      • O'Neill J.
      • Swanson G.
      • McGuinn T.
      • Nickel A.
      Rate of airway intervention for croup at a tertiary children's hospital 2015-2016.
      ]. While your patient thankfully had a brief (12h) inpatient admission, his need for both an admission and his oxygen requirement do place him at the higher severity end of the spectrum of croup disease when compared to these aforementioned studies. Our three cases were also atypical in their need for admission and other interventions. As mentioned in our paper, there might have been other cases of croup in our ED that were milder in severity and subsequently not tested for SARS-CoV-2 infection.
      The absence of reported croup symptoms with SARS-CoV-2 infections in children in the three studies you cited is noteworthy [
      • Liguoro I.
      • Pilotto C.
      • Bonanni M.
      • Ferrari M.E.
      • Pusiol A.
      • Nocerino A.
      • et al.
      SARS-COV-2 infection in children and newborns: a systematic review.
      ,
      • Ludvigsson J.F.
      Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults.
      ,
      • Swann O.V.
      • Holden K.A.
      • Turtle L.
      • Pollock L.
      • Fairfield C.J.
      • Drake T.M.
      • et al.
      Clinical characteristics of children and young people admitted to hospital with covid-19 in United Kingdom: prospective multicentre observational cohort study.
      ].. This could have been influenced by the retrospective nature of their study designs in that their symptom screening tools for recording data might not have included stridor or barky cough. Additionally, most patients with croup have mild symptoms and are discharged without being tested for any virus. Our three cases were tested primarily due to their need for admission, which prompted viral testing due to infectious control reasons for bed placement. It is also possible that SARS-CoV-2 infection associated with croup is a relatively rare presentation compared to the more common pediatric presentation of a flu-like illness. Multi-centered or database studies will likely be required to further characterize the nature of this association. Given the pandemic nature of this virus, we certainly hope that this emerging association of SARS-CoV-2 infection and severe cases of croup is a rare one.

      Contributor CRediT Author Statement

      April Venn: Conceptualization, investigation, writing-review & editing. James Schmidt: Conceptualization, investigation, writing-review & editing. Paul Mullan: Conceptualization, investigation, writing-original draft, writing-review & editing, supervision. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
      Patient consent from parents was obtained from all three cases in this case series. In addition, parents have reviewed the reports for accuracy and have provided verbatim follow-up outcome quotes in descriptions of each case.

      Funding/support

      No funding was secured for this study.

      Declaration of Competing Interest

      None.

      Acknowledgments

      Thank you to Kari Ausherman, Pharm.D. and Stacey Lynn English, Pharm.D., for your help in pulling the pharmaceutical data report. Thanks to Faiqa Qureshi, MD for reviewing the manuscript.

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