Interim Recommendation on Clinical Management of Paediatric Patients of COVID 19infection.pdf

Ref No.
CCIDER-COVID19-002(v1)
HA Central Committee on Infectious Diseases  Issue Date
13 March 2020
and Emergency Response (CCIDER)
Review Date
13 March 2023
Interim Recommendation on Clinical Management of
Approved by
CCIDER
Paediatric Patients of Coronavirus Disease 2019
Page
Page 3 of 8
  (COVID-19) Infection

1.
Background
1.1  For  paediatric  patients  infected  with  COVID-19,  cases  reported  in  the  current
literature  are  mild  in  clinical  severity,  and  there  is  no  evidence-based  treatment
regimen.  The  present  treatment  recommendations  take  reference  from  the  adult
interim  management  guideline  and  the  WHO  interim  guideline.  Specifically,  the
Hong  Kong  adult  interim  management  guideline  from  Ad  hoc  Task  Force  on
Clinical  Management  (TFCM)  on  Infection  recommend  consideration  for  specific
anti-novel  coronavirus  treatment  while  WHO  only  recommended  supportive
treatment.  Both  TFCM  on  Infection  and  our  group  recognized  that  the  proposed
regimens  are  based  on  evidence  extrapolated  from  research  on  other
coronaviruses,  expert  opinion,  as  well  as  the  availability  of  therapeutics  in  Hong
Kong.

2.
Infection of COVID-19 in paediatrics
2.1  Infection with SARS-CoV was much milder in paediatrics when compared to adults,
and from limited information to date appears to be the similar with COVID-19.

3.
Anti-viral treatment
3.1  Taking  reference  that  paediatric  infection  with  SARS-CoV  was  associated  with
more  severe  disease  (although  no  mortality)  in  children  ≥12  years  of  age,  an
age-stratified approach for specific anti-viral treatment may be considered.

3.2  Age <12 years old and stable clinical condition:
3.2.1
Investigation after admission
(i)  CBP D/C, ESR, CRP, LRFT, LDH, ABG (if indicated);
(ii)  Chest X-ray (CXR) +/- High Resolution Computed Tomography
(HRCT) of thorax (if indicated);
(iii)  Prescription of empirical antibiotics treatment will be at the discretion
of in charge paediatrician;
3.2.2
Close monitor vital signs and organ functions and recognize signs for
clinical deterioration
(i)  If clinically stable, continue monitoring as in 4.
(ii)  If clinically deteriorated e.g. increase oxygen requirement,

Ref No.
CCIDER-COVID19-002(v1)
HA Central Committee on Infectious Diseases  Issue Date
13 March 2020
and Emergency Response (CCIDER)
Review Date
13 March 2023
Interim Recommendation on Clinical Management of
Approved by
CCIDER
Paediatric Patients of Coronavirus Disease 2019
Page
Page 4 of 8
  (COVID-19) Infection

progressive CXR infiltrates, extensive pulmonary involvement in
HRCT thorax. Consider anti-viral treatment. Proceed to 3.3.

3.3  Age  ≥  12  years  old,  Age  <  12  year  old  with  unstable  clinical  condition  or  severe
pneumonia  on  admission;  clinical  deterioration  during  hospitalization.  Anti-viral
treatment may be considered.
3.3.1  Pre-treatment  laboratory  tests:  Blood  for:  CBC  D/C,  ESR,  CRP,  LRFT,
random  glucose,  clotting  profile,  LDH,  HBsAg,  Anti-HCV,  Anti-HIV,  (+/-
arterial blood gas if indicated);
3.3.2  Chest  X-ray  +/-  High  Resolution  Computed  Tomography  of  thorax  (if
indicated);
3.3.3  Baseline  Electrocardiogram  (if  pre-existing  cardiac  abnormalities  or
disease).  For  patients  with  underlying  pre-existing  cardiac  disorders,
follow-up monitoring of the cardiac condition is recommended;
3.3.4  Consider specific treatment when the diagnosis of COVID-19 is made:
(i)  Kaletra (Lopinavir / Ritonavir) BD for 14 days
Plus or minus
(ii)  Interferon  beta-1b*  (Betaferon)  8  million  IU  (equivalent  to
250micrograms)  subcutaneous  (SC)  every  alternate  day  for  3  doses
{i.e. on D 1-2, D2-3 & D5-6}

*Interferon beta-1b not licensed for <12 year old

To  achieve  adequate  efficacy,  no  dose  titration  is  recommended  in
treatment  of  COVID-19  infection.  However  patient  should  be  closely
monitored for severe side effects.
3.3.5  Dosage of Kaletra (Lopinavir/Ritonavir, LPV/r):
(i)  Do not administer Kaletra to neonates before postmenstrual age of 42
weeks and a postnatal age of at least 14 days
(ii)  Three preparations available in HA:

Oral solution: [Kaletra] Lopinavir 80 mg/ml and ritonavir 20 mg/ml
  Reserve  syrup  formulation  of  Kaletra  for  patients  in  PICU  or
patients with swallowing difficulty.

Tablets: (LPV/r tablets must be swallowed whole. Do not crush or split
tablets)
  [Kaletra] Lopinavir 200 mg/ritonavir 50 mg
  [Kaletra] Lopinavir 100 mg/ritonavir 25 mg

Ref No.
CCIDER-COVID19-002(v1)
HA Central Committee on Infectious Diseases  Issue Date
13 March 2020
and Emergency Response (CCIDER)
Review Date
13 March 2023
Interim Recommendation on Clinical Management of
Approved by
CCIDER
Paediatric Patients of Coronavirus Disease 2019
Page
Page 5 of 8
  (COVID-19) Infection

(iii)  Dosage:

Infant (Aged 14 Days–12 Months) Dose:
  LPV/r  300  mg/75  mg  per  m2  BD.  This  approximates  LPV/r  16
mg/4 mg (both per kg) BD.

Child and Adolescent Dose (Aged >12 Months to 18 Years):
  LPV/r  300  mg/75  mg  per  m2  BD  (maximum  dose  LPV/r  400
mg/100 mg BD).
  For patients weighing <15 kg, this approximates LPV/r 13 mg/3.25
mg (both per kg) BD.
  For  patients  weighing  ≥15  kg  to  45  kg,  this  dose  approximates
LPV/r 11 mg/2.75 mg (both per kg) BD.
3.3.6  Omission of Interferon beta-1b:
(i)  To  omit  the  remaining  dose  of  Interferon  beta-1b  when  the  symptom
onset  is  approaching  7  days,  e.g.  if  the  patient  presents  on  day  6  of
symptoms onset, only one dose of interferon should be given;
(ii)  If the patient presents with symptoms more than 7 days, only Kaletra
should be given.
3.3.7  Pre-treatment check-list:
(i)  Check presence of any drug interaction with concomitant medications
(especially with ritonavir);
(ii)  Pregnancy  test  for  adolescent  girls  before  initiating  interferon
(contraindication);
(iii)  Obtain consent for treatment:

Unlicensed  indication  and  the  treatment  is  experimental,  treatment
may improve or worsen infection,

The patient and/or parents should be explained on the side effects of
treatments,

Contraindications:
  Interferon  beta-1b:  history  of  hypersensitivity  to  interferon  beta,
albumin; pregnancy, decompensated liver disease, current severe
depression and/or suicidal ideation
  Kaletra: history of hypersensitivity to Lopinavir, Ritonavir. Avoid in
patients  with  congenital  long  QT  syndrome  and  cautious  use  in
patients using other drugs that prolong QT interval.

Ref No.
CCIDER-COVID19-002(v1)
HA Central Committee on Infectious Diseases  Issue Date
13 March 2020
and Emergency Response (CCIDER)
Review Date
13 March 2023
Interim Recommendation on Clinical Management of
Approved by
CCIDER
Paediatric Patients of Coronavirus Disease 2019
Page
Page 6 of 8
  (COVID-19) Infection

4.
Monitoring during treatment
4.1  Blood for CBP D/C, LRFT, LDH, CRP

4.2  Stool for RT-PCR nCoV-2019 if having GI symptoms

4.3  Repeat NPS + Throat swab (pooled specimens) OR NPA for RT-PCR COVID-19
(release of isolation order requires 2 negative specimens taken 24 hours apart).

4.4  2  negative  stool  specimens  for  RT-PCR  COVID-19  are  required  for  release  of
isolation order if the initial specimen(s) on admission tested positive.

4.5  Side effects from treatment.
4.5.1  Interferon beta-1b:
Most frequently observed side effects are a flu-like symptom complex e.g.
fever,  chills,  arthralgia,  malaise,  sweating,  headache,  or  myalgia;  which  is
mainly  due  to  the  pharmacological  effects  of  the  medicinal  product,  and
injection  site  reactions.  Other  side  effects  include  neutropenia,
thrombocytopenia,  hepatotoxicity,  thyroid  dysfunction  and  drug-induced
lupus.  Severe  adverse  reactions  manifested  as  acute  anaphylaxis  and
psychiatric disorders were also reported.
4.5.2  Kaletra:
(i)  Most common side effects include gastrointestinal upset (diarrhea, nausea
and  vomiting),  liver  function  derangement,  hypertriglyceridemia  and
hypercholesterolemia.  Serious  adverse  reaction  including  prolonged  QT
interval, torsade de pointes and anaphylaxis reaction.
(ii)  KALETRA  oral  solution  contains  approximately  42%  (v/v)  ethanol  and
approximately  15%  (w/v)  propylene  glycol.  Ethanol  competitively  inhibits
propylene  glycol  metabolism,  which  may  lead  to  propylene  glycol  toxicity
due to impaired elimination in neonates. In neonates and infants 14 days to
6  months  of  age,  especially  for  those  with  renal  impairment,  the  total
amounts  of  ethanol  and  propylene  glycol  delivered  from  all  medications
should be considered to avoid toxicity. They should be monitored for signs
and  symptoms  of  propylene  glycol  toxicity  (e.g.,  increase  in  serum
creatinine,  seizures,  cardiac  arrhythmias,  lactic  acidosis,  hyperosmolarity,
stupor, and hemolysis).

Ref No.
CCIDER-COVID19-002(v1)
HA Central Committee on Infectious Diseases  Issue Date
13 March 2020
and Emergency Response (CCIDER)
Review Date
13 March 2023
Interim Recommendation on Clinical Management of
Approved by
CCIDER
Paediatric Patients of Coronavirus Disease 2019
Page
Page 7 of 8
  (COVID-19) Infection

5.
Use of Corticosteroids
5.1  Routine use of corticosteroid is not recommended;

5.2  Stress  dose  steroids  for  refractory  septic  shock  may  be  used  for  short  period  or
other indications at the discretion of the in-charge paediatrician.

6.
Use of adjunct treatment
6.1  There is no adjunct treatment recommended at this moment.

7.
Psychological support
7.1  The  patients  are  more  prone  to  have  symptoms  of  anxiety  and/or  depression,
proactive psychological counselling and early intervention are needed.

8.
Release of isolation order
8.1  To liaise with Medical Control Officer (MCO) of Centre for Health Protection (CHP)
for release of isolation order when the patient is clinically ready for discharge and
result of specimens on 4.3 & 4.4 tested negative

9.
References
1.  Report  of  clustering  pneumonia  of  unknown  etiology  in  Wuhan  City.  Wuhan
Municipal Health Commission, 2019.
http://wjw.wuhan.gov.cn/front/web/showDetail/2019123108989
2.  N  Zhu,  et.  al.  A  Novel  Coronavirus  from  Patients  with  Pneumonia  in  China,
2019. NEJM 24 Jan 2020. DOI: 10.1056/NEJMoa2001017.
3.  K Shen, et. al. Diagnosis, treatment, and prevention of 2019 novel coronavirus
infection  in  children:  experts’  consensus  statement.  World  Journal  of
Paediatrics 29 Jan 2020. https://doi.org/10.1007/s12519-020-00343-7.
4.  The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus
Disease  (COVID-19) –  China,  2020.  Chinese  Center for  Disease  Control  and
Prevention. China CDC Weekly; Vol 2 (x): Page 1-10.
5.  CM  Chu,  et  al.  Role  of  lopinavir/ritonavir  in  the  treatment  of  SARS:  initial

Ref No.
CCIDER-COVID19-002(v1)
HA Central Committee on Infectious Diseases  Issue Date
13 March 2020
and Emergency Response (CCIDER)
Review Date
13 March 2023
Interim Recommendation on Clinical Management of
Approved by
CCIDER
Paediatric Patients of Coronavirus Disease 2019
Page
Page 8 of 8
  (COVID-19) Infection

virological and clinical findings. Thorax 2004; 59: 252–256.
6.  JFW  Chan,  et.  al.  Treatment  With  Lopinavir/Ritonavir  or  Interferon-β1b
Improves Outcome  of  MERS  CoV  Infection  in  a  Nonhuman  Primate  Model of
Common Marmoset. J Infect Dis 2015; 12; 1904-13.
7.  ML Holshue, et. al. First Case of 2019 Novel Coronavirus in the United States.
31 Jan 2020 NEJM. DOI: 10.1056/NEJMoa2001191.
8.  新型冠状病毒肺炎诊疗方案（试行第六版）.  国家卫生健康委办公厅,  国家中医
药管理局办公室. 2020 年 2 月 18 日
http://www.nhc.gov.cn/xcs/zhengcwj/202002/8334a8326dd94d329df351d7da8
aefc2/files/b218cfeb1bc54639af227f922bf6b817.pdf.
9.  儿童新型冠状病毒感染诊断、治疗和预防专家共识(第一版).  中华医学会儿科分会.
中华实用儿科临床杂志,2020,35(02):81-85.
http://rs.yiigle.com/yufabiao/1180110.htm
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Coronavirus  Disease  2019  (COVID  19),  HA  Central  Committee  on  Infectious
Diseases and Emergency Response (CCIDER). Effective since 13 February.
11.  Clinical  management  of  severe  acute  respiratory  infection  when  novel
coronavirus  (2019-nCoV)  infection  is  suspected  Interim  guidance  28  January
2020. WHO.
12.  Kaletra drug information, https://www.rxabbvie.com/pdf/kaletratabpi.pdf
13.  Betaferon drug information, summary of product characteristics updated 23 Oct
2019. https://www.medicines.org.uk/emc/product/1121/smpc/print