Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children

Jianling Xie¹, Nathan Kuppermann², Todd A Florin³, Daniel J Tancredi², Anna L Funk¹, Kelly Kim¹, Marina I Salvadori⁴, Adriana Yock-Corrales⁵, Nipam P Shah⁶, Kristen A Breslin⁷, Pradip P Chaudhari⁸, Kelly R Bergmann⁹, Fahd A Ahmad¹⁰, Jasmine R Nebhrajani¹¹, Santiago Mintegi¹², Iker Gangoiti¹², Amy C Plint¹³, Usha R Avva¹⁴, Michael A Gardiner¹⁵, Richard Malley¹⁶, Yaron Finkelstein¹⁷, Stuart R Dalziel¹⁸, Maala Bhatt¹⁹, Nirupama Kannikeswaran²⁰, Kerry Caperell²¹, Carmen Campos²², Vikram J Sabhaney²³, Shu-Ling Chong²⁴, Maren M Lunoe²⁵, Alexander J Rogers²⁶, Sarah M Becker²⁷, Meredith L Borland²⁸, Laura F Sartori²⁹, Viviana Pavlicich³⁰, Pedro B Rino³¹, Andrea K Morrison³², Mark I Neuman¹⁶, Naveen Poonai³³, Norma-Jean E Simon³⁴, April J Kam³⁵, Maria Y Kwok³⁶, Claudia R Morris³⁷, Laura Palumbo³⁸, Lilliam Ambroggio³⁹, Nidhya Navanandan³⁹, Michelle Eckerle⁴⁰, Terry P Klassen⁴¹, Daniel C Payne⁴², Jonathan C Cherry⁴³, Muhammad Waseem⁴⁴, Andrew C Dixon⁴⁵, Isabel Beneyto Ferre⁴⁶, Stephen B Freedman¹

Affiliations

¹ University of Calgary, Calgary, Alberta, Canada.
² Davis School of Medicine, University of California, Sacramento, California, USA.
³ Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
⁴ Public Health Agency of Canada, Ottawa, Ontario, Canada.
⁵ Hospital Nacional de Niños ¨Dr. Carlos Sáenz Herrera", CCSS, San José, Costa Rica.
⁶ University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁷ Children's National Hospital, Washington, DC, USA.
⁸ University of Southern California, Los Angeles, California, USA.
⁹ Children's Minnesota, Minneapolis, Minnesota, USA.
¹⁰ Washington University School of Medicine, St.Louis, Missouri, USA.
¹¹ St.Mary's Medical Center, West Palm Beach, Florida, USA.
¹² University of the Basque Country, UPV/EHU Bilbao, Basque Country, Spain.
¹³ University of Ottawa, Ottawa, Ontario, Canada.
¹⁴ Montefiore-Nyack Hospital, Nyack, NewYork, New York, USA.
¹⁵ University of California San Diego, San Diego, California, USA.
¹⁶ Harvard Medical School, Boston, Massachusetts, USA.
¹⁷ Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁸ University of Auckland, Auckland, Auckland, New Zealand.
¹⁹ Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
²⁰ Central Michigan University, Detroit, Michigan, USA.
²¹ University of Louisville, Louisville, Kentucky, USA.
²² Hospital Universitario Miguel Servet, Zaragoza, Spain.
²³ University of British Columbia, Vancouver, British Columbia, Canada.
²⁴ Duke-NUS Medical School, SingHealth Duke-NUS Global Health Institute, Singapore.
²⁵ UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²⁶ University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
²⁷ Primary Children's Hospital, Intermountain Healthcare, Salt Lake City, Utah, USA.
²⁸ University of Western Australia, Perth, Western Australia, Australia.
²⁹ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
³⁰ Universidad Privada del Pacífico, San Lorenzo, Paraguay.
³¹ Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," RIDEPLA, Buenos Aires, Argentina.
³² Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
³³ Schulich School of Medicine & Dentistry, London, Ontario, Canada.
³⁴ Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
³⁵ McMaster Children's Hospital, Hamilton, Ontario, Canada.
³⁶ Columbia University Irving Medical Center, NewYork, New York, USA.
³⁷ Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.
³⁸ ASST Spedali Civili di Brescia-Pronto Soccorso Pediatrico, Brescia, Italy.
³⁹ University of Colorado, Aurora, Colorado, USA.
⁴⁰ University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁴¹ University of Manitoba, Winnipeg, Manitoba, Canada.
⁴² Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁴³ Dalhousie University, Halifax, Nova Scotia, Canada.
⁴⁴ Lincoln Medical Center, Bronx NewYork, New York, USA.
⁴⁵ University of Alberta, Edmonton, Alberta, Canada.
⁴⁶ Hospital Francesc de Borja, Gandia, Spain.

PMID: 37869403
PMCID: PMC10588618
DOI: 10.1093/ofid/ofad485

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children

Jianling Xie et al. Open Forum Infect Dis. 2023.

. 2023 Oct 3;10(10):ofad485.

doi: 10.1093/ofid/ofad485. eCollection 2023 Oct.

Authors

Affiliations

¹ University of Calgary, Calgary, Alberta, Canada.
² Davis School of Medicine, University of California, Sacramento, California, USA.
³ Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University, Chicago, Illinois, USA.
⁴ Public Health Agency of Canada, Ottawa, Ontario, Canada.
⁵ Hospital Nacional de Niños ¨Dr. Carlos Sáenz Herrera", CCSS, San José, Costa Rica.
⁶ University of Alabama at Birmingham, Birmingham, Alabama, USA.
⁷ Children's National Hospital, Washington, DC, USA.
⁸ University of Southern California, Los Angeles, California, USA.
⁹ Children's Minnesota, Minneapolis, Minnesota, USA.
¹⁰ Washington University School of Medicine, St.Louis, Missouri, USA.
¹¹ St.Mary's Medical Center, West Palm Beach, Florida, USA.
¹² University of the Basque Country, UPV/EHU Bilbao, Basque Country, Spain.
¹³ University of Ottawa, Ottawa, Ontario, Canada.
¹⁴ Montefiore-Nyack Hospital, Nyack, NewYork, New York, USA.
¹⁵ University of California San Diego, San Diego, California, USA.
¹⁶ Harvard Medical School, Boston, Massachusetts, USA.
¹⁷ Hospital for Sick Children, Toronto, Ontario, Canada.
¹⁸ University of Auckland, Auckland, Auckland, New Zealand.
¹⁹ Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
²⁰ Central Michigan University, Detroit, Michigan, USA.
²¹ University of Louisville, Louisville, Kentucky, USA.
²² Hospital Universitario Miguel Servet, Zaragoza, Spain.
²³ University of British Columbia, Vancouver, British Columbia, Canada.
²⁴ Duke-NUS Medical School, SingHealth Duke-NUS Global Health Institute, Singapore.
²⁵ UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
²⁶ University of Michigan School of Medicine, Ann Arbor, Michigan, USA.
²⁷ Primary Children's Hospital, Intermountain Healthcare, Salt Lake City, Utah, USA.
²⁸ University of Western Australia, Perth, Western Australia, Australia.
²⁹ Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
³⁰ Universidad Privada del Pacífico, San Lorenzo, Paraguay.
³¹ Hospital de Pediatría "Prof. Dr. Juan P. Garrahan," RIDEPLA, Buenos Aires, Argentina.
³² Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
³³ Schulich School of Medicine & Dentistry, London, Ontario, Canada.
³⁴ Ann and Robert H Lurie Children's Hospital of Chicago, Chicago, Illinois, USA.
³⁵ McMaster Children's Hospital, Hamilton, Ontario, Canada.
³⁶ Columbia University Irving Medical Center, NewYork, New York, USA.
³⁷ Children's Healthcare of Atlanta, Emory University School of Medicine, Atlanta, Georgia, USA.
³⁸ ASST Spedali Civili di Brescia-Pronto Soccorso Pediatrico, Brescia, Italy.
³⁹ University of Colorado, Aurora, Colorado, USA.
⁴⁰ University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
⁴¹ University of Manitoba, Winnipeg, Manitoba, Canada.
⁴² Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
⁴³ Dalhousie University, Halifax, Nova Scotia, Canada.
⁴⁴ Lincoln Medical Center, Bronx NewYork, New York, USA.
⁴⁵ University of Alberta, Edmonton, Alberta, Canada.
⁴⁶ Hospital Francesc de Borja, Gandia, Spain.

PMID: 37869403
PMCID: PMC10588618
DOI: 10.1093/ofid/ofad485

Abstract

Background: To assist clinicians with identifying children at risk of severe outcomes, we assessed the association between laboratory findings and severe outcomes among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected children and determined if SARS-CoV-2 test result status modified the associations.

Methods: We conducted a cross-sectional analysis of participants tested for SARS-CoV-2 infection in 41 pediatric emergency departments in 10 countries. Participants were hospitalized, had laboratory testing performed, and completed 14-day follow-up. The primary objective was to assess the associations between laboratory findings and severe outcomes. The secondary objective was to determine if the SARS-CoV-2 test result modified the associations.

Results: We included 1817 participants; 522 (28.7%) SARS-CoV-2 test-positive and 1295 (71.3%) test-negative. Seventy-five (14.4%) test-positive and 174 (13.4%) test-negative children experienced severe outcomes. In regression analysis, we found that among SARS-CoV-2-positive children, procalcitonin ≥0.5 ng/mL (adjusted odds ratio [aOR], 9.14; 95% CI, 2.90-28.80), ferritin >500 ng/mL (aOR, 7.95; 95% CI, 1.89-33.44), D-dimer ≥1500 ng/mL (aOR, 4.57; 95% CI, 1.12-18.68), serum glucose ≥120 mg/dL (aOR, 2.01; 95% CI, 1.06-3.81), lymphocyte count <1.0 × 10⁹/L (aOR, 3.21; 95% CI, 1.34-7.69), and platelet count <150 × 10⁹/L (aOR, 2.82; 95% CI, 1.31-6.07) were associated with severe outcomes. Evaluation of the interaction term revealed that a positive SARS-CoV-2 result increased the associations with severe outcomes for elevated procalcitonin, C-reactive protein (CRP), D-dimer, and for reduced lymphocyte and platelet counts.

Conclusions: Specific laboratory parameters are associated with severe outcomes in SARS-CoV-2-infected children, and elevated serum procalcitonin, CRP, and D-dimer and low absolute lymphocyte and platelet counts were more strongly associated with severe outcomes in children testing positive compared with those testing negative.

Keywords: C-reactive protein; COVID-19; SARS-CoV-2; child; lymphopenia; procalcitonin.

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Conflict of interest statement

Potential conflicts of interest. All authors: no reported conflicts.

Figures

**Figure 1.**
Study participants, SARS-CoV-2 test result, hospitalization status, laboratory tests performed, and occurrence of severe outcomes. Abbreviations: CBC, complete blood count; ED, emergency department; MIS-C, multisystem inflammatory syndrome in children; PCR, polymerase chain reaction; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

See this image and copyright information in PMC

References

1. UNICEF . Child mortality and COVID-19. Available at: https://data.unicef.org/topic/child-survival/covid-19/. Accessed December 16, 2022.
1. Sumner MW, Kanngiesser A, Lotfali-Khani K, et al. . Severe outcomes associated with SARS-CoV-2 infection in children: a systematic review and meta-analysis. Front Pediatr 2022; 10:916655. - PMC - PubMed
1. Funk AL, Florin TA, Kuppermann N, et al. . Outcomes of SARS-CoV-2-positive youths tested in emergency departments: the global PERN-COVID-19 study. JAMA Netw Open 2022; 5:e2142322. - PMC - PubMed
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Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children

Affiliations

Impact of SARS-CoV-2 Infection on the Association Between Laboratory Tests and Severe Outcomes Among Hospitalized Children

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources

Research Materials

Miscellaneous