COVID-19: Publications

Summaries of the latest pediatric literature and guidelines regarding COVID-19.

The following summaries have been produced by medical students at The Warren Alpert Medical School of Brown University and reviewed by pediatric infectious disease specialists at Hasbro Children's Hospital

Pediatric Literature

Can SARS-CoV-2 Infection Be Acquired In Utero?

David Kimberlin, Sergio Stagno

Lan Dong, Jinhua Tian, Songming He

  • Case study of mother with COVID-19 and infant delivered on 2/22/20 in Wuhan, China
    • 29 year-old 34 weeks 2 days of gestation diagnosed with COVID-19 by positive RT-PCR and ground-glass opacities in periphery of both lungs on 1/28/20
    • Infant was delivered by cesarean in negative-pressure room; mother wore N95 mask and did not hold the infant; neonate was immediately quarantined in NICU
    • Infant had elevated IgG, IgM, IL-6, IL-10 , WBC at 2 hours of age with normal chest CT and 5 negative RT-PCR tests from 2 hours to 16 days of age
  • Antibodies in Infants Born to Mothers With COVID-19 Pneumonia

Hui Zeng, Chen Xu, Junli Fan

  • Case study of 6 pregnant women with COVID-19 from 2/16/20-3/6/20 in Wuhan 
    • Pregnant women diagnosed by symptoms, chest CT, and positive RT-PCR
    • All had cesarean deliveries in negative pressure isolation rooms; all mothers wore masks, and all medical staff wore protective suits and double masks; infants were isolated from mothers immediately after delivery
    • All infants had negative RT-PCR results, 5 had elevated IgG concentrations, 2 had elevated IgM
  • Authors conclude that data is not conclusive and does not prove in utero transmission 
    • IgM assays are prone to false-positive and false-negative results, cross-reactivity, and testing challenges
    • IgM assays are less reliable than molecular diagnostic tests based on nucleic acid amplification and detection
  • Authors suggest more definitive evidence is needed before findings can be used to counsel pregnant women
  • #editorial #pregnancy #verticaltransmission

Clinical and epidemiological features of 36 children with coronavirus disease 2019 (COVID-19) in Zhejiang, China: an observational cohort study

Haiyan Qiu, Junhua Wu, Liang Hong, Yunling Luo, Qifa Sng, Dong Chen

  • Retrospective cohort study of 36 children infected with COVID-19 in three hospitals in Zhejiang, China from Jan 17 to March 1, 2020
    • Symptoms: pneumonia with ground-glass opacities (19; 53%), fever (13; 36%), dry cough (7; 19%), asymptomatic (10; 28%)
    • Labs: elevated creatine kinase MB (11; 31%), decreased lymphocytes (11; 31%), leucopenia (7; 19%), elevated procalcitonin (6; 17%)
    • Management: all received interferon alfa by aerosolization 2x/day, 14 (39%) received lopinavir-ritonavir syrup 2x/day, 6 (17%) needed oxygen inhalation
    • Mean time in hospital was 14 days (SD 3 days) and all patients had full recovery
  • In the commentary to this article (COVID-19 in children: the link in the transmission chain, Alyson Kelvin, Scott Halperin)
    • Authors point out that there is clear evidence that are susceptible to COVID-19 but often do not have notable disease
    • Raises possibility of that children could be facilitators of transmission
  • #retrospectivecohort #treatment

Clinical Characteristics of Children with Coronavirus Disease 2019 in Hubei, China.

Fang Zheng, Chun Liao, Qi-hong Fan et al.

  • 25 hospitalized pediatric COVID-19 cases in Hubei province (Wuhan-centric)
    • Demographics - 14 male/11 female. Median 3 yo., range 3 mo-14 yo. 23/25 previously healthy with no underlying disease. 1 8mo M with CHD s/p op, malnutrition, suspected hereditary metabolic disease; 1 1 yo M with CHD s/p op.
    • Epidemiology - 84% (21) w/known contact hx. Highest infection incidence in children < 3 yo (40% of 25).
    • Symptoms - most common fever (52%/13) > dry cough (44%), diarrhea (12%), nasal congestion (8%), dyspnea (8%), abd pain (8%), vomiting (8%)
      • Mostly mild presentations--mild upper respiratory infection, PNA
    • Lab trends - 10/25 lymphopenia. Critical cases (2--the previous underlying conditions listed above) had elevated Cr, PT, and serum LDH. (1) critical case complicated by hyponatremia.
    • Imaging - 24/25 chest CT obtained. 33.3% nl, 20.8% unilateral involvement, 45.8% bilateral. Findings usually bilateral patchy shadows or consolidation.
      • Bilateral involvement in 70% children < 3 yo. Unilateral and nl CTs more common in children ≥ 6 yo.
    • Treatment
      • 48% received antiviral(s) (IFN most common; also oseltamivir, lopinavir/litonavir, and/or umifenovir [Arbidol])
      • 56% empiric abx (1 pt showed efficacy). 
      • 2 critical cases (8%) received IFN + oseltamivir, broad-spec abx, invasive mechanical ventilation, systemic steroids, IVIG
        • 1 critical case on CVVHDF (continuous veno-venous hemodiafiltration) and plasma exchange in addition with sig. Improvement of sx
        • Other critical case with partial improvement
    • Outcomes - all cases with improvement of sx; 1 discharge at 2/15/20
      • Compared to adults, less severe sx in children with lower ICU utilization rates (see Wang et al which had 26% adult COVID-19 pts requiring ICU care with 4.3% mortality vs. this study with 2/25 (8%) ICU care and 0 mortality)
        • Theory - reports that children had milder and shorter courses than adults in past SARS outbreak; fewer children infected with MERS
  • #retrospectivestudy

Clinical features in pediatric COVID-19

Sora Yasri, Viroj Wiwanitkit

  • Brief letter to the editor on presentation of pediatric COVID-19 cases in Thailand (COVID present since January 2020) in the authors’ experience
  • 2/48 Thai COVID-19 patients were pediatric--3 yo F, 7 yo M
    • Both with hx of fever and close familial infected contact w/n 3 days
    • Both hospitalized with full recovery after cases were early detected by close contact screening of known COVID-19 cases
    • Theorize that early diagnosis of cases may have contributed to mild presentation with no serious lung pathology or infiltration on chest CT 
  • #lettertotheeditor

Clinical features of severe pediatric patients with coronavirus disease 2019 in Wuhan: a single center's observational study

Dan Sun, Hui Li, Xiao-Xia Lu, et al.

  • Observational study of 8 pediatric COVID-19 cases in Wuhan Children’s Hospital ICU 1/24-2/24/20
  • Definition of severe: ≥ 1 of 3 criteria: (1) RR > 30/min, (2) SaO2 < 93% resting, (3) arterial O2 partial pressure (PaO2) / oxygen concentration (FiO2) ≤ 300 mmHg
    • Definition of critical: ≥ 1 of 3 criteria: (1) respiratory failure requiring mechanical ventilation, (2) septic shock, (3) any other organ failure requiring ICU level of care
  • Demographics: age range 2 mo-15 yo. 6/8 male. 5 severe, 3 critical.
    • Epidemiology: 5 family cluster; 1 nosocomial (8 yo M PMH of ALL hospitalized for blood transfusion); 2 unknown. Incubation 5-10 days.
  • Symptomatology: Most common polypnea (8/8) > fever, cough (6/8)
    • Also sputum production, N/V, diarrhea, fatigue, myalgias, headache, constipation
  • Physical exam: Rales or crackles in lower lung lobes
  • Lab trends: Nl/increased WBCs (⅞ except for ALL pt); increased CRP, procalcitonin, LDH (6/8); elevated ALT (4/8)
    • Evidence of cytokine storm on TBNK lymphocyte marker test and cytokine assays (increased CD3 (2/8), CD4 (4/8) and CD8 (1/8), IL-6 (2/8), IL-10 (5/8) and IFN-γ (2/8) with decreased CD16 + CD56 (4/8) and Th/Ts*(1/8))
  • Imaging: chest CT with multiple patchy shadows (⅞), ground-glass opacities (6/8).
  • Treatment: All received supportive/respiratory care and ribavirin, oseltamivir, and IFN. 2/8 intubated, 6/8 high-flow O2. Some received abx, IV steroids, IVIG, TCM. 
  • Course/prognosis: ⅝ recovered and discharged home; ⅜ still in ICU 2/24/20
    • Duration of disease > 10 days; > 20 d. if critical
    • Complications: Most commonly septic shock and MODS in critical cases
  • #observationalstudy #ICU

Accepted March 19
SARS-CoV2 Infection in children

Xiaoxia Lu, Liqiong Zhang, Hui Du, Jinging Zhang, Yuan Y. Li, Jingyu Qu, Wenxin Zhang, Youjie Wang, Shuangshuang Bao, Ying Li, Chuansha Wu, Hongxia Liu, Di Liu, Jianbo Shao, Xuehua Peng, Yonghong Yang, Zhisheng Liu, Yun Xiang, Furong Zhang, Rona M. Silva, Kent E. Pinkerton, Kunling Shen, Han Xiao, Shunqing Xu, Gary W. K. Wong

  • Analysis of evaluated children infected with COVID-19 and treated at Wuhan Children’s Hospital (n=1391), 171 (12.3%) tested positive for infection
  • Median age: 6.7 years, Male: 60.8%
  • Symptoms: Fever in 41.5%, Cough in 48.5%, PNA in 64.9%, pharyngeal erythema in 46.2%
  • 3 patients with comorbidities required ICU level of care, 1 death
  • Most children appear mildly asymptomatic

Epidemiological Characteristics of 2143 Pediatric Patients With 2019 Coronavirus Disease in China.

Yuanyuan Dong, Xi Mo, Yabin Hu, Xin Qi, Fang Jiang, Zhongyi Jiang, Shilu Tong 

  • Children at all ages were susceptible to COVID-19, but no significant gender difference was found
  • Clinical manifestations of pediatric patients were generally less severe than those of adults’ patients
  • For the severity of patients (including both confirmed and suspected cases), 94 (4.4 %), 1091 (50.9 %) and 831 (38.8 %) patients were diagnosed as asymptomatic, mild or moderate cases, respectively, totally accounted for 94.1 % of all cases.
  • Young children, particularly infants, were vulnerable to 2019-nCoV infection: the proportion of severe and critical cases was 10.6 %, 7.3%, 4.2%, 4.1% and 3.0% for the age group of <1, 1-5, 6-10, 11-15 and ≥16 years, respectively.
  • As of 8 February 2020, of the 2143 pediatric patients included in this study, only one child died
  • #retrospectiveanalysis
  • In the commentary to this article (March 16, 2020, COVID-19 in Children: Initial Characterization of the Pediatric Disease, Andrea T. Cruz, MD, MPH1 and Steven L. Zeichner, MD, PhD2):
    • Cruz and Zeichner point out that subpopulations of children are at increased risk for severe illness including younger age, existing lung pathology, and immunocompromised status
    • Attributable risk for severe disease from COVID-19 in children is challenging to discern due to lacking data on co-infection
    • Children may play a large role in community transmission: concerns include different symptoms than adults, asymptomatic patients, & fecal viral shedding
    • No reports yet of vertical transmission
    • #commentary #summarypaper

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women:a retrospective review of medical records

Huijun Chen, Juanjuan Guo, Chen Wang, Fan Luo, Xuechen Yu, Wei Zhang, Jiafu Li, Dongchi Zhao, Dan Xu, Qing Gong, Jing Liao, Huixia Yang,Wei Hou, Yuanzhen Zhang

  • No vertical transmission for mothers with virus 
  • Retrospective review of 9 patients with 3rd trimester C sections with +COVID
  • #pregnancy

Clinical and CT features in pediatric patients with COVID‐19 infection: Different points from adults

Wei Xia MD  Jianbo Shao MD  Yu Guo MD Xuehua Peng MD  Zhen Li MD Daoyu Hu MD

  • Unlike adults, pediatric CT’s have consolidation with surrounding halo signs as well as elevated prolactin rates
  • CT consolidation
    • Early stage: consolidation with surrounding halo signs, ground-glass opacity
    • Advanced stage: increased density
    • Critical stage: white lung
    • Recovery stage: absorbed, ground-glass, or residual fiber strip
  • Retrospective study on non-contrast CT scans on 20 pediatric patients with +COVID nucleic acid test and 8/20 coinfected with another virus from 1/23/20-2/28/20
  • #radiology 

Clinical analysis of 31 cases of 2019 novel coronavirus infection in children from six provinces (autonomous region) of northern China

Wang Duan, Ju Xiuli, Xie Feng, et al.

  • Note: Article is in Mandarin Chinese. Abstract available in English.
  • Retrospective study of 31 pediatric COVID-19 cases dx’d 1/25-2/21/20
    • Demographics: Mean age 7 yr, 1 mo; range 6 mo-17 yo.
    • Epidemiology: 29% imported from other parts of country; 68% with confirmed adult COVID-19 contacts; 3% (1 case) with asymptomatic Wuhan returnees contact 
      • 90% family cluster cases
    • Clinical severity: 13% asymptomatic; 42% mild; 45% moderate; no severe/critical
    • Symptomatology
      • Most common = fever (65% or 20 cases) - 1 high, 9 moderate, 10 low
        • Duration of fever: 1-9 days; 15 cases ≤ 3 d., 5 > 3 d.
      • Other common = cough (45% or 14 cases), fatigue (10% or 3), diarrhea (10% or 3)
    • Lab trends
      • Rare leukopenia (2/31), lymphopenia (“), thrombocytosis (“)
      • Relatively more common elevated CRP (3/30 tested), ESR (4/21), procalcitonin (1/28), LFTs (6/27), muscle enzymes (4/27)
    • Imaging - 14 with chest CT changes (9 patchy ground-glass opacities and nodules, predominantly BL lower lung lobe near pleura)
    • Prognosis - 24/31 (77%) recovered and discharged; no deaths
      • Time for viral nucleic acid to return negative = 7-23 days (25/31 cases)
  • #retrospectivestudy

Clinical strategies for treating pediatric cancer during the outbreak of 2019 novel coronavirus infection

Chao Yang, Changchun Li, Shan Wang

  • Letter to the editor from Chinese pediatric oncologists on treatment recommendations for balancing anticancer therapy and infection prevention based on data from adult cases
    • Preadmission - Screen for COVID-19 in all patients, their family, and caregivers. T > 37.3 C should be screened in a fever clinic. If clinical suspicion, also obtain chest CT &/or nucleic acid testing with isolation precautions and supportive care.
    • Strict infection control strategies to prevent hospital-acquired infection
    • Chemotherapy - Stable disease = consider moderate chemo reduction or prolonged cycle interval. Normal physical status = individual risk/benefit decision. Conduct chemo at local hospital to minimize mov’t.
    • Radiotherapy - Can continue RT as before for existing RT patients. Consider moderately delaying subsequent chemo and RT initiation for new patients.
    • Surgery - Suspected/confirmed COVID-19 case - preop in isolation ward, special transport channels, disinfect OR after op. Can delay f/u if no urgent need.
  • #lettertotheeditor #treatment #cancer

Novel Coronavirus Infection in Hospitalized Infants Under 1 Year of Age in China

Min Wei, Jingping Yuan, Yu Liu et al.

  • 9 infected infants, 7 female/2 male, ages 1-11 mo.
  • Symptoms - 4 fever, 2 mild upper respiratory sx, 1 no sx, 2 no info
    • No ICU/mechanical ventilation/severe complications
  • Epidemiology - all 9 had ≥ 1 infected family member (family cluster cases)
  • #retrospectivestudy #infant

Diagnosis and treatment recommendations for pediatric respiratory infection caused by the 2019 novel coronavirus

Zhi-Min Chen, Jun-Fen Fu, Qiang Shu, et al

  • Diagnosis - incubation 2-14 d. (average 3-7)
    • Common symptoms - fever, fatigue, dry cough; also nasal congestion, rhinorrhea, sputum production, diarrhea, headache. Can have no fever.
      • Severe, progressive symptoms - dyspnea, cyanosis; systemic signs (malaise, restlessness, poor feeding/appetite, decreased activity)
      • Severe complications - respiratory failure, septic shock, metabolic acidosis, bleeding/coagulatory dysfunction
    • Suspicion should be raised by:
      • Travel/residence in areas with persistent local transmission w/n 14 d of sx onset
      • Hx of contact with patients w/fever or respiratory sx w/travel/residence in areas with persistent local transmission w/n 14 d of sx onset
      • Hx of contact w/suspected or confirmed COVID-19 cases w/n 14 d of sx onset
      • Related to cluster outbreak
      • Newborns of suspected or confirmed COVID-19 mothers (?)
    • DDx - other viral respiratory infection, bacterial PNA, mycoplasma PNA
  • Clinical classification
    • Mild - asymptomatic, URI, mild PNA. Fever, cough, sore throat, fatigue, myalgias, headache. May have PNA signs on chest imaging.
    • Severe - any of the following: (1) RR ≥ 70/min (≤ 1 yo) or ≥ 50/min (> 1 yo), (2) SpO2 ≤ 93% (< 90% if premature infant) or signs of respiratory distress (ex: nasal flaring, suprasternal/intercostal/subcostal retractions, grunting, etc.), (3) PaO2 < 60 mmHg, PaCO2 > 50 mmHg, (4) change in consciousness (ex: restlessness, lethargy, coma), (5) poor feeding/appetite/dehydration, (6) signs of end-organ damage (coagulatory abnormalities, heart damage, GI dysfunction, abnormal LFTs, rhabdomyolysis)
    • Critical - (1) respiratory failure requiring mechanical ventilation, (2) septic shock, (3) other organ failure requiring ICU level of care
  • Prognosis - usually family cluster cases with good prognosis, mild sx, recovery 1-2 wks. after onset
  • Lab trends - nl/low WBCs (lymphopenia), nl/increased CRP, nl procalcitonin
    • Occasional elevated LFTs, CK, myoglobin, D-dimer esp severe cases
  • Testing - nucleic acid test via RT-PCR or viral gene sequencing from throat swab, sputum, stool, blood sample
    • Not widely available at publication: viral culture, viral Ag, viral Ab testing
  • Imaging
    • CXR - early - multiple small patchy shadows, interstitial changes, esp in periphery. Severe - BL ground-glass opacities, infiltrating shadows, pulmonary consolidation, rare pleural effusion
    • Chest CT - BL ground-glass opacity, segmental consolidation esp in periphery.
  • Management
    • 4 principles - (1) early identification, (2) early isolation, (3) early diagnosis, (4) early treatment
    • General treatment - bed rest, supportive, adequate calorie/water intake, maintain electrolyte balance, “strengthening psychotherapy” (?)
    • Antivirals - nothing effective/evidence-based for children. Consider the following (off-label, no proven efficacy or safety):
      • IFN-a2b neb 100,000-200,000 IU/kg (mild) and 200,000-400,000 IU/kg for severe BID x5-7 days
      • Lopinavir/litonavir (7-15 kg) 12/3 mg/kg, (15-40 kg) 10/2.5/kg, (> 40 kg) 400/100 mg BID x1-2 wks
    • Mild cases - avoid broad-spectrum abx and steroids
    • Severe/critical cases - options include abx, steroids, IVIG, bronchoalveolar lavage, mechanical ventilation, blood purification, ECMO based on clinical judgment
  • Discharge criteria - nl body temp ≥ 3 days, sig. Improved respiratory sx, ≥ 2 consecutive negative COVID-19 nucleic acid test. Can home isolate x14 days.
  • #treatment #diagnosis