COVID-19 associated pediatric complications

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Harmeet Kharoud M.D.[2]; Abdelrahman Ibrahim Abushouk, MD[3]; Asra Firdous, M.B.B.S.[4] Neepa Shah, M.B.B.S.[5]

Overview

  • Pediatric cases of COVID-19 have been reported in children. It ranges from asymptomatic mild cases to Multisystem Inflammatory Syndrome in Children (MIS-C). There are less cases of SARS CoV 2 in children compared to adults.[1][2][3]

Epidemiology and Demographics [1]

  • Less than 2% of the confirmed positive cases of COVID 19 comprise of children less than 19 years of age.[4]
  • Among the 1,761,503 aggregate cases reported to CDC from January 22–May 30, the incidence of confirmed cases was 403.6 cases per 100,000 population.
  • Data of children age 1-9 years with the total number of cases 20,458 reported by CDC for a period of January 22 to May 30
  • Lowest cumulative incidence being in the group of children less than 9 years. (51.1)
Data of children with different comorbidities as reported by the CDC for a period of January 22 to May 30
Age
Different comorbidities <9 10-19
Underlying medical condition 2896(14.2%) 7123(14.5%)
Cardiovascular disorders 78(2.7%) 164(2.3%)
Chronic lung disease 363(12.5%) 1285(18%)
Renal disease 21(0.7%) 34(0.5%)
Diabetes 12(0.4%) 34(0.5%)
Liver disease 5(0.2%) 19(0.3%)
Immunicompromised 61(2.1%) 146(2.0%)
Neurological disease 41(1.4%) 113(1.6%)
Total cases in the population 1,320,488 20458 49245


Data of children with hospitalized children and ICU admissions as reported by CDC for a period of January 22 to May 30
Age All admissions in the hospital and ICU divided according to associated comorbidity
<9 years (20458 cases) All patients (20458) Among all patients with reported underlying disease (619) Among all patients with no reported underlying disease (2277)
All admissions in the hospital including ICU ICU admissions All admissions in the hospital including ICU ICU admissions All admissions in the hospital including ICU ICU admissions
848/20458 (4.1%) 141/20458 (0.7%) 138/619 (22.3%) 31/619 (5%) 84/2277(3.7%) 116/2277 (0.7%)
10-19 years (49245 cases) All patients (49245) Among all patients with reported

underlying disease (2076)

Among all patients with no reported underlying disease (5047)
All admissions in the hospital including ICU ICU admissions All admissions in the hospital including ICU (2076) ICU admissions All admissions in the hospital including ICU (5047) ICU admissions
1234/49245 (2.5%) 216/49245 (0.4%) 309/2076 (14.9%) 72/2076 (3.5%) 115/5047 (2.3%) 17/5047 (0.3%)

Mode of transmission

  • Most children who were found to be COVID positive were found to have acquired infection from parents and other household contacts.
  • For newborn babies testing positive for the COVID 19 could be infected via vertical transmission, breastfeeding, or contact with virus-contaminated surfaces[5]
  • Breastfeeding - According to the CDC there is no transmission of the SARS CoV 2 virus from infected mother to the newborn while breastfeeding. However limited studies are available to yet decide if there is a true transmission risk while breastfeeding.
  • CDC advises all mothers who are positive or suspected to be COVID positive to practice precaution like covering the mouth with a face mask, washing hands with soap and water before and after washing hands.
  • Bulk RNA-seq profiles from two public databases including The Cancer Genome Atlas (TCGA) and Functional Annotation of The Mammalian Genome Cap Analysis of Gene Expression (FANTOM5 CAGE) dataset were collected. Ace- 2 receptors are used by the coronavirus to gain entry into the cells. The RNA Sequence database found ACE-2 expression in the breast tissue similar to the expression in the lung tissue.[6]
  • However, the current data suggest there is one isolated case reported where the breast milk sample was found to be positive for COVID 19 sample on Day 1 and subsequently negative in the day 3 sample. More research needs to be done to conclude if there is any transmission vis breastfeeding.

Presentations

  • Presentation of COVID-19 is less severe in children as compared to adults.
  • According to CDC, as of April 2, 2020, 1.7% confirmed cases of COVID-19 were reported in children aged <18 years age among the total number of confirmed cases of COVID-19.
  • Illness severity of COVID-19 in children ranges from asymptomatic to critical.

Symptoms

Clinical Course of COVID-19 in children.

  • Asymptomatic presentation-
    • Children present with no clinical signs or symptoms with normal chest imaging.
    • Among 2143 children with COVID-19 infection 4% of children were asymptomatic.
    • According to one study 14.2% of children were asymptomatic. Another study showed 18% of asymptomatic children with COVID-19.
  • Mild Disease
    • Children present with mild symptoms including fever, fatigue, myalgia, cough.
    • Among 2143 children with COVID-19 infection 51% of children had a mild disease of COVID-19.
    • A study showed 36.3% of children present with a mild form of the disease.
  • Severe
    • Children present with dyspnea, central cyanosis, hypoxia.[7]
    • Among 2143 children with COVID-19 infection 5% of children had a severe presentation.[7]
    • 2.1% of children present with a severe form of COVID-19 disease.
    • Children with underlying comorbidities are more susceptible to getting severe COVID-19 disease.
  • Critical

Complications

Some of the complications associated with COVID-19 pediatric population are

Multisystem Inflammatory Syndrome in Children (MIS-C)

  • It is a condition that causes inflammation of some parts of the body like heart, blood vessels, kidneys, digestive system, brain, skin, or eyes.
  • According to recent evidence, it is suggested that children with MISC had antibodies against COVID-19 suggesting children had COVID-19 infection in the past.

Pathophysiology

  • Exact cause of MIS-C is unclear. It is suspected that it is caused by a delayed immune response to the SARS-CoV-2, causing inflammation of organs."Multisystem Inflammatory Syndrome in Children (MIS-C) | Boston Children's Hospital".
  • It is also suspected that it is occurring due to antibody-mediated reaction."Multisystem Inflammatory Syndrome in Children (MIS-C) | Boston Children's Hospital".

Symptoms

Emergency Warning Signs

Diagnosis

Preliminary WHO case definition: Children and adolescents

  • 0–19 years of age with fever >3 days

AND

  • Two of the following:
  1. Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet)
  2. Hypotension or shock
  3. Features of myocardial dysfunction, pericarditis, valvulitis, or coronary abnormalities (including ECHO findings or elevated Troponin/NT-proBNP)
  4. Evidence of coagulopathy (by PT, PTT, elevated D-Dimers)
  5. Acute gastrointestinal problems (diarrhea, vomiting, or abdominal pain)

AND

AND

AND

  • Evidence of COVID-19 (RT-PCR, antigen test or serology-positive), or likely contact with patients with COVID-19

Prevention of MIS-C

  • MIS-C can be prevented by reducing the risk of child exposure to COVID-19 infection.

Acute Heart Failure

Diagnosis


Most of the children with SARS-CoV-2 infection are either asymptomatic or produce mild symptoms. As asymptomatic patients do not get tested for COVID-19 and are potential carriers for viral transmission, high clinical suspicion is required to prevent such transmissions to a population at risk of developing severe disease. A pediatrician should be cautious to eliminate other causes of respiratory illnesses like seasonal influenza before any diagnostic tests. No diagnostic test is required for a kid with mild illness and no history of exposure to SARS-CoV-2.

Reverse-Transcriptase Polymerase Chain Reaction

U.S. Food and Drug Administration (FDA) has approved real-time Reverse-Transcription Polymerase Chain Reaction (RT-PCR) as the preferred test for diagnosing COVID-19 in children

Lab abnormalities

Studies reportedly showed following lab abnormalities in pediatric patients with COVID-19

Co-infections

Co-infection with other pathogens were reported in 27% of cases. Some common microorganisms associated with SARS-CoV-2 infection in children are:

Radiological findings

CT chest is an important diagnostic modality in pediatric patients with COVID-19. Chest CT scans has reportedly shown higher positive rates in suspected patients than RT-PCR. It has better sensitivity. CT chest and a series of chest X-rays can be used to monitor the progression of the disease. Imaging findings reported in the studies are

Children are at increased risk of radiation and its effects, so CT scans and X-rays should be judiciously used in them. It is advised to perform Pulmonary Ultrasonography (USG) in newborns. It has better sensitivity and is safer than CT scans and Chest X-rays.

Management

Management of COVID-19 in pediatric patients depends on the severity of symptoms.

  • Hospital admission and level of care depend on the clinical presentation, supportive care requirement, underlying comorbidities, and availability of health care facilities at home
  • Suspected patients must be isolated at a hospital or home until the diagnosis is excluded
  • After confirming the diagnosis, they should be hospitalized and isolated in the wards maintained for pediatric patients with COVID-19
  • Critical and severe cases require Intensive Care Unit (ICU) admission and management

As no effective treatment has been approved by the FDA yet, the main goal of managing patients with COVID-19 is to treat the symptoms, provide supportive care, prevent and treat complications, treat underlying diseases and secondary infections, and provide organ function support. Following measures are reported to be crucial in the management of COVID-19[9]

Symptomatic treatment and Supportive Care

Fever should be treated with physical cooling and antipyretics. If the body temperature exceeds 38.5C, antipyretic drugs should be started. Drugs that can be used in children are acetaminophen 10-15 mg/kg and ibuprofen 5-10 mg/kg orally.[9]

Respiratory support

Mechanical Ventilation

Low tidal volume mechanical ventilation is preferred to prevent ventilation related lung injury. Criteria for starting mechanical ventilation[9]

OR

OR

Antibiotics

Antibiotics and antifungals help in reducing symptoms and preventing complications of secondary infections[11]

Corticosteroids

Steroids are used in severe cases and to prevent complications[11]. Any of the following criteria must be met before starting corticosteroid therapy in patients with COVID-19[9]. Intravenous methylprednisolone 1-2mg/kg/day used for 3-5 days. Long-term usage is highly discouraged.

  • Rapid progression of the disease as documented from chest imaging and development of ARDS

OR

OR

OR

Anticoagulation therapy

Convalescent plasma therapy

Evidence suggests the use of plasma therapy in children with exacerbations and severe and critical disease.

Immunoglobulin therapy

  • Intravenous immunoglobulins (IVIG) can be used in severe cases[11]
  • Dose of 1g/kg/day for 2days or 400mg/kg/day for 8 days is recommended for children
  • More studies are required to support its efficacy and safety in children with COVID-19

Antiviral therapy

Following are the experimental drugs that are being considered to treat children with COVID-19[12]. Various clinical trials are being conducted on the efficacy and safety of these drugs in children with COVID-19.

Interferon-alpha

Inhaled interferon-alpha was the most commonly used antiviral in patients with COVID-19. Reports suggest that it helps in decreasing the viral load, alleviating symptoms and shortening the disease course.[13][14]

Remdesivir

Favipiravir


Prevention

  • Re-opening of schools:
    • The pandemic which started in China in January 2020 and now is all over the world has had a tremendous effect on the everyday life of many however children are the most affected.
    • With the peak of the coronavirus cases being over in many countries like the USA and Europe, there is a dilemma for the school officials about when to reopen schools for children.
    • According to the data collected by the CDC[1] and other articles[20][21] children are affected less compared to adults with asymptomatic to mild COVID-19 symptoms.
    • The challenge faced by the school committees around the world is to decide between the pros and cons of whether to reopen the school with children facing the emotional toll of the lockdown and quarantine. [22]
    • Negative effects of lockdown in children [23]
      • Children less than 10 years in the school develop very important language, social and developmental traits with the mitigation in place these kids are at risk to develop anxiety, anger, and post-traumatic stress disorder.
      • Children whose parents have either suffered economically or have mental health issues are more prone to physical ad mental abuse.
      • With the schools using digital media to continue classes during mitigation, those kids who are not able to get these devices are suffering from little to no education in this period of lockdown.
      • Children of healthcare workers are facing a great deal with change in the environment with a new baby sitter to not being able to interact and hug the parents working in the frontline.
  • The CDC guidelines for re-opening schools are as follows [24]
    • These guidelines are to be followed by schools by coordinating with the local health department to know the level of mitigation in your community as the coronavirus cases are increasing.
    • Educate the teachers and the parents on signs of coronavirus like dry cough, cold, high fever, and other flu-like symptoms.
    • If the child has the above-mentioned symptoms or is in contact with an adult at home having these symptoms or the adult at home has tested positive the child should stay home.
    • Teachers, children, and other staff members with the immunocompromised state should be given the option to work from home virtually as they are in the high-risk group.
    • Hand hygiene- Soap and water should be provided by the school for students to wash hands frequently for 20 seconds
    • If soap and water are not available provide hand sanitizer with at least 60% alcohol.
    • Use a tissue to cover cough/sneeze and wash hands after discarding the tissue safely.
    • Cloth face mask is advised for all the school staff and the children except kids younger than 2 years of age or kids with a breathing problem who needs assistance in removing the face mask.
    • Signs about COVID 19 should be placed in places frequently visited like the school entrance, cafeteria, and the bathroom.
    • Avoid sharing objects and if possible give kids individual supplies.
    • Ensure proper ventilation systems are in place, open windows when its safe and possible.
    • Identify small groups of children and try to keep them together with the same teacher.
    • Food brought from home is advisable. If not then food should be distributed in the classroom, not the cafeteria.
    • Advise students and teachers to limit their exposure to the news stories. It can be overwhelming for the students.
    • Encourage the students to talk to anyone they trust or to reach out to teachers to talk when overwhelmed.
    • To seek help the national distress hotline: 1-800-985-5990, or text TalkWithUsto 66746 should be provided by the school to all the students.
    • If a child tests positive or is suspected to have COVID 19 the school should arrange special transport for the student separately.
    • Inform the local health care department and close contacts if the student tests positive.
    • Proper contact tracing, isolation, disinfecting the common places frequently used by the students should be made a priority.
  • Domestic violence in children:
    • In this lockdown even though children are affected less compared to adults with COVID -19 that however is not the case when it comes to mental health and safety.
    • As reported by this study by Silvia Bressan et all [25] reported a sharp increase in pediatric emergency visit due to domestic violence with majority of limb fractures, facial fracture, subdural hematoma and ingestion of caustic cleaning product.
    • Increased measures for children's safety and frequent disinfection should be encouraged.

References

  1. ↑ 1.0 1.1 1.2 Stokes EK, Zambrano LD, Anderson KN, Marder EP, Raz KM, El Burai Felix S; et al. (2020). "Coronavirus Disease 2019 Case Surveillance - United States, January 22-May 30, 2020". MMWR Morb Mortal Wkly Rep. 69 (24): 759–765. doi:10.15585/mmwr.mm6924e2. PMC 7302472 Check |pmc= value (help). PMID 32555134 Check |pmid= value (help).
  2. ↑ <Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in children and adolescents - a systematic review. JAMA Pediatr Rev. 2020. 10.1001/jamapediatrics.2020.1467>
  3. ↑ <Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020. 10.1542/peds.2020-0702>
  4. ↑ Fariña LA, Iglesias JM, Hocsman H, Vicente R (1990). "[Cancer of the prostate with rectal invasion]". Arch Esp Urol. 43 (9): 1010–2. PMID 2091533.
  5. ↑ Mahyuddin AP, Kanneganti A, Wong J, Dimri PS, Su LL, Biswas A; et al. (2020). "Mechanisms and evidence of vertical transmission of infections in pregnancy including SARS-CoV-2". Prenat Diagn. doi:10.1002/pd.5765. PMC 7307070 Check |pmc= value (help). PMID 32529643 Check |pmid= value (help).
  6. ↑ Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X; et al. (2020). "High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa". Int J Oral Sci. 12 (1): 8. doi:10.1038/s41368-020-0074-x. PMC 7039956 Check |pmc= value (help). PMID 32094336 Check |pmid= value (help).
  7. ↑ 7.0 7.1 7.2 7.3 Eastin, Carly; Eastin, Travis (2020). "Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China". The Journal of Emergency Medicine. 58 (4): 712–713. doi:10.1016/j.jemermed.2020.04.006. ISSN 0736-4679.
  8. ↑ 8.0 8.1 Belhadjer, Zahra; Méot, Mathilde; Bajolle, Fanny; Khraiche, Diala; Legendre, Antoine; Abakka, Samya; Auriau, Johanne; Grimaud, Marion; Oualha, Mehdi; Beghetti, Maurice; Wacker, Julie; Ovaert, Caroline; Hascoet, Sebastien; Selegny, Maëlle; Malekzadeh-Milani, Sophie; Maltret, Alice; Bosser, Gilles; Giroux, Nathan; Bonnemains, Laurent; Bordet, Jeanne; Di Filippo, Sylvie; Mauran, Pierre; Falcon-Eicher, Sylvie; Thambo, Jean-Benoît; Lefort, Bruno; Moceri, Pamela; Houyel, Lucile; Renolleau, Sylvain; Bonnet, Damien (2020). "Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic". Circulation. doi:10.1161/CIRCULATIONAHA.120.048360. ISSN 0009-7322.
  9. ↑ 9.0 9.1 9.2 9.3 Shen K, Yang Y, Wang T, Zhao D, Jiang Y, Jin R; et al. (2020). "Diagnosis, treatment, and prevention of 2019 novel coronavirus infection in children: experts' consensus statement". World J Pediatr. doi:10.1007/s12519-020-00343-7. PMC 7090771 Check |pmc= value (help). PMID 32034659 Check |pmid= value (help).
  10. ↑ Sankar J, Dhochak N, Kabra SK, Lodha R (2020). "COVID-19 in Children: Clinical Approach and Management". Indian J Pediatr. 87 (6): 433–442. doi:10.1007/s12098-020-03292-1. PMC 7183927 Check |pmc= value (help). PMID 32338347 Check |pmid= value (help).
  11. ↑ 11.0 11.1 11.2 Zhang L, Peres TG, Silva MVF, Camargos P (2020). "What we know so far about Coronavirus Disease 2019 in children: A meta-analysis of 551 laboratory-confirmed cases". Pediatr Pulmonol. doi:10.1002/ppul.24869. PMC 7300763 Check |pmc= value (help). PMID 32519809 Check |pmid= value (help).
  12. ↑ Deniz M, Tapısız A, Tezer H (2020). "Drugs being investigated for children with COVID-19". Acta Paediatr. doi:10.1111/apa.15399. PMC 7300686 Check |pmc= value (help). PMID 32506621 Check |pmid= value (help).
  13. ↑ Wang BX, Fish EN (2019). "Global virus outbreaks: Interferons as 1st responders". Semin Immunol. 43: 101300. doi:10.1016/j.smim.2019.101300. PMC 7128104 Check |pmc= value (help). PMID 31771760.
  14. ↑ Chen L, Shi M, Deng Q, Liu W, Li Q, Ye P; et al. (2020). "Correction: A multi-center randomized prospective study on the treatment of infant bronchiolitis with interferon α1b nebulization". PLoS One. 15 (4): e0231911. doi:10.1371/journal.pone.0231911. PMC 7147733 Check |pmc= value (help). PMID 32275690 Check |pmid= value (help).
  15. ↑ Grein J, Ohmagari N, Shin D, Diaz G, Asperges E, Castagna A; et al. (2020). "Compassionate Use of Remdesivir for Patients with Severe Covid-19". N Engl J Med. 382 (24): 2327–2336. doi:10.1056/NEJMoa2007016. PMC 7169476 Check |pmc= value (help). PMID 32275812 Check |pmid= value (help).
  16. ↑ Dörnemann J, Burzio C, Ronsse A, Sprecher A, De Clerck H, Van Herp M; et al. (2017). "First Newborn Baby to Receive Experimental Therapies Survives Ebola Virus Disease". J Infect Dis. 215 (2): 171–174. doi:10.1093/infdis/jiw493. PMC 5583641. PMID 28073857.
  17. ↑ Campbell CH (1967). "Effect of incubation temperature and serum content in agar overlay on plaque production by foot-and-mouth disease virus". Can J Comp Med Vet Sci. 31 (10): 251–5. PMC 1494743. PMID 04292899.
  18. ↑ 18.0 18.1 Cai Q, Yang M, Liu D, Chen J, Shu D, Xia J; et al. (2020). "Experimental Treatment with Favipiravir for COVID-19: An Open-Label Control Study". Engineering (Beijing). doi:10.1016/j.eng.2020.03.007. PMC 7185795 Check |pmc= value (help). PMID 32346491 Check |pmid= value (help).
  19. ↑ 19.0 19.1 Bouazza N, Treluyer JM, Foissac F, Mentré F, Taburet AM, Guedj J; et al. (2015). "Favipiravir for children with Ebola". Lancet. 385 (9968): 603–604. doi:10.1016/S0140-6736(15)60232-X. PMID 25706078.
  20. ↑ <Castagnoli R, Votto M, Licari A, et al. Severe acute respiratory syndrome coronavirus 2 (sars-cov-2) infection in children and adolescents - a systematic review. JAMA Pediatr Rev. 2020. 10.1001/jamapediatrics.2020.1467>
  21. ↑ <Dong Y, Mo X, Hu Y, et al. Epidemiological characteristics of 2143 pediatric patients with 2019 coronavirus disease in China. Pediatrics. 2020. 10.1542/peds.2020-0702>
  22. ↑ Fantini MP, Reno C, Biserni GB, Savoia E, Lanari M (2020). "COVID-19 and the re-opening of schools: a policy maker's dilemma". Ital J Pediatr. 46 (1): 79. doi:10.1186/s13052-020-00844-1. PMC 7280677 Check |pmc= value (help). PMID 32517815 Check |pmid= value (help).
  23. ↑ <Posttraumatic stress disorder in parents and youth after health-related disasters. Sprang G, Silman M Disaster Med Public Health Prep. 2013 Feb; 7(1):105-10.>
  24. ↑ <https://www.cdc.gov/coronavirus/2019-ncov/community/schools-childcare/schools.html>
  25. ↑ Bressan S, Gallo E, Tirelli F, Gregori D, Da Dalt L (2020). "Lockdown: more domestic accidents than COVID-19 in children". Arch Dis Child. doi:10.1136/archdischild-2020-319547. PMID 32487724 Check |pmid= value (help).
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