for UG and PG teaching

1. COVID 19 IN CHILDREN
Dr M SANJEEVAPPA
Designated Associate Professor
Dept of Pediatrics
GMC ,Anantapuramu

2. SARS-CoV-2
 The current pandemic caused by SARS -CoV-2
emerged initially in Wuhan, China in the month of
December 2019.
 So far affected 216 countries with 2,15,16,760
confirmed cases and 7,66,663 deaths as on
17.8.2020
 Closely related to two bat-derived SARS-like
coronaviruses collected in 2018 in eastern China
(bat-SL-CoVZC45 and bat-SLCoVZXC21) and
genetically distinct from SARS-CoV and MERS-CoV.

3. SARS-CoV-2
 Viral RNA load from upper respiratory samples:
Peak on day 4 : 7.11 × 108 copies/swab
Average till day 5 : 6.76 × 105 copies/swab
Average after day 5 : 3.4×105 copies/swab
 Viral load from lower respiratory samples (sputum)
Maximum viral load : 2.35×109 copies/ml
Average : 7.00×106 copies/ml

4. SARS-CoV-2
INFECTIVITY AND REPLICATION SITES :
 Presence of viral sub-genomic mRNA indicates actively
infected cells.
 presence of high viral load indicates active viral
replication.
 Active viral replication was noted till day 5 of onset of
symptoms.
 active viral replication from sputum was obvious from
Day 4 to Day 9.
 Decline in viral load occurred from Day 10 to Day 11.

5. SARS-CoV-2
INFECTIVITY AND REPLICATION SITES :
 SARS-CoV-2 infect the ciliated, mucus-secreting, club
cells of bronchial epithelium and alveolar cells in the
lung.
 It replicates more effectively in the bronchi similar to
MERS.
 SARS-CoV-2 infection and replication also takes place in
conjunctiva and gastrointestinal tract.

6. SARS-CoV-2
BASIC REPRODUCTIVE NUMBER - R0
 To calculate the degree of contagiousness or
transmissibility of the coronavirus.
 It is defined as the average number of new infections
generated by an infectious person in a totally uninfected
population.
 If R0 is >1, the number of people infected is likely to
increase and if R0 is <1transmission is likely to die out.
 R0 for SARS-CoV-2 is 2.79

7. SARS-CoV-2
HOUSEHOLD TRANSMISSION OF SARS-COV-2 :
 Secondary attack rate is 30% among household
members.
 Among the close contacts, infection rate is
38% for household with 1 contact.
50% for household with 2 contacts.
31% for households with 3 contacts.

8. SARS-CoV-2
VIRUS STABILITY ON SURFACES
(21 to 230C with 40% humidity for 7 days)
Surfaces Time for significant reduction
in viral titres.
Plastic 72 hours
Stainless steel 48 hours
Copper 4 hours
Card board 24 hours
Aerosol 3 hours

9. SARS-CoV-2
IMMUNOGENICITY :
 IgM and IgG antibodies against SARS-CoV -2 internal
nucleoprotein (NP) and surface spike protein receptor
binding domain (RBD) correlate with neutralising
activity.
 Factors which affect the antibody production :
age, nutritional status, severity of the disease, certain
medications or infections like HIV.
 Seroconversion occurs after 7 days in 50% and by day 14
in majority of the patients.
 Because of the variable sensitivity and specificity,
antibody testing cannot be used to diagnose COVID-19.

10. SARS-CoV-2
HERD IMMUNITY :
 Herd immunity is a form of indirect protection from
infectious disease that occurs when a large
percentage of a population has become immune to an
infection.
 COVID-19 (COVID-19 pandemic)
R0 is 1.4-3.9
HIT is 29-74%

11. PATHOPHYSIOLOGY OF COVID-19
SPECIFIC FEATURES OF SARS-COV-2 :
 A novel mutation increasing susceptibility.
 An easy transmissibility.
 An unusual pathophysiology with involvement of
many systems of the body beyond the respiratory
tract.

12. PATHOPHYSIOLOGY OF COVID-19
STAGE I. ENTRY OF THE VIRUS AND EARLY REPLICATION :
 The route of infection is through the mucosa, mainly
upper respiratory tract, may be conjunctiva also.
 Gain entry by attachment to ACE2 receptor.
 SARS-CoV-2 virus has a 10-20 times higher affinity to
ACE2 receptor.
 ACE2 receptors are in high amounts in the oral and
nasal mucosa and the gastro-intestinal epithelium.

13. PATHOPHYSIOLOGY OF COVID-19
 ACE2 protein also seen on lung alveolar epithelial
cells and in the endothelial cells of arteries and
veins in all organs.
 The testis is another particular organ with high
levels of ACE2 receptors.
 This period lasts from 2 to 7 days with a mean of 4-5
days.
 The symptoms then start and consist of fever,
constitutional symptoms like headache, body ache,
dry cough, throat pain, anosmia, ageusia and
diarrhoea.

14. PATHOPHYSIOLOGY OF COVID-19
STAGE II. SPREAD TO LUNGS AND OTHER SYSTEMS :
 second week - pneumonia is the most common.
 Alveolar type II cells functions include production of
pulmonary surfactant, airway epithelial barrier
stabilization, immune defence and airway
regeneration in response to injury.
 Old age - Poor muco-ciliary clearance.
 Smokers - Chronic damage to the ciliary lining of the
respiratory tract.
 Children have a robust muco-ciliary action and are
therefore less likely to have COVID pneumonia unless
they have pre-existing conditions.

15. PATHOPHYSIOLOGY OF COVID-19
STAGE II. SPREAD TO LUNGS AND OTHER SYSTEMS :
 The pathological result of COVID-19 is diffuse
alveolar damage with fibrin rich hyaline membranes
and a few multinucleated giant cells.
 Aberrant healing of alveolar lining leads to scarring
and fibrosis that may present as ARDS.
 A productive cough is not common and the only
symptom may be a progressive shortness of breath
with general lethargy and fatigue from the slowly
increasing hypoxia.
 Recovery requires a vigorous innate and acquired
immune response and epithelial regeneration.

16. PATHOPHYSIOLOGY OF COVID-19
STAGE II. SPREAD TO LUNGS AND OTHER SYSTEMS :
 Spread of the virus to other organs like liver, kidney
and brain may start in the second week.
 Hepatic involvement is common and leads to elevated
liver transaminases.
 Neurological symptoms like altered sensorium,
seizures and neurological deficit are also seen but not
common.
 Renal dysfunction as a result of circulatory problems.

17. PATHOPHYSIOLOGY OF COVID-19
STAGE III. HYPERIMMUNE RESPONSE PHASE :
 The host immune system comes into play by the end of
the second week.
 Vasculopathy/Coagulopathy: Virchow’s triad:
a) reduction in blood flow (stasis),
b) vascular endothelial injury (leading to triggering
of the coagulation cascade)
c) hypercoagulable state due to alterations in the
blood constituents.

18. PATHOPHYSIOLOGY OF COVID-19
 The laboratory evidence for the onset of the
coagulopathy is the elevation of D-dimer levels.
 Intravascular clots in COVID-19 can essentially occur
in any vessel, arterial or venous.
 In children, vasculitis/coagulopathy changes are more
often in the peripheral circulation like the tips of the
toes and fingers.

19. PATHOPHYSIOLOGY OF COVID-19
CYTOKINE STORM :
 PIMS : IL-2, IL-6, IL-7, IL-10, GCSF and TNF-α are
elevated.
 PIMS presents with features similar to Kawasaki
disease with constitutional features.
 ESR, pro-calcitonin, CRP, IL-6 and ferritin are
elevated. troponin and NT-pro-BNP may also be
elevated.

20. PATHOPHYSIOLOGY OF COVID-19
EXPLANATIONS LOWER MORBIDITY AND MORTALITY IN
CHILDREN :
 expression level of ACE2 may differ and ACE2
expression may be lower in pediatric population.
 Qualitatively different response to the SARS-CoV-2.
 Simultaneous presence of other viruses in the mucosa
of lungs and airways in young children compete with
SARS-CoV-2 virus and limit its growth.

21. DIAGNOSIS OF COVID-19 IN CHILDREN
COMMON MANIFESTATIONS OF COVID-19 IN CHILDREN:
• Any acute illness with no other explainable cause
• Fever with or without associated respiratory/
gastrointestinal manifestations
• Runny nose, sore throat, cough, loss of sense of taste or
smell
• Myalgia, fatigue.
• Abdominal pain, diarrhea and vomiting.
• Irritability, drowsiness, seizures, stroke.
• Breathlessness, tachypnea, hypoxia.
• Manifestations of pediatric multi system inflammatory
syndrome including fever, conjunctivitis, rash, hypotension

22. DIAGNOSIS OF COVID-19 IN CHILDREN
MOLECULAR TESTS (NAAT) :
 The most common NAAT assays in commercial use are
the RT-PCR tests.
 The first screening gene is the generic coronavirus
gene coding for
spike protein (S),
nucleocapsid protein (N),
envelope protein (E) or
membrane protein (M).
 The second target is the gene specific to COVID-19
RNA dependent RNA polymerase or
Spike protein (S) or
ORF 1 or 2

23. DIAGNOSIS OF COVID-19 IN CHILDREN
common kits used in India :
 Altona Real star CoV-2 real-time PCR kit,
 Thermo TaqPATH COVID-19
 Indigenous Mylab PathoDirect COVID-19 kit
 Xpert Xpress SARS-CoV-2

24. DIAGNOSIS OF COVID-19 IN CHILDREN
 The tests are semi quantitative in nature.
 the viral load can be estimated from the cycle threshold (Ct)
the number of cycles that need to be run to amplify the RNA.
 The usual cut off for most test kits is 40
(for the Xpert Xpress kit it is 45).
 If the cycle threshold is above the cut off, test is negative.
 The lower the Ct, the higher is the viral load.
 The Ct values also tend to correlate with infectivity. High Ct
values are associated with non viable virus and low risk of
transmission.

25. DIAGNOSIS OF COVID-19 IN CHILDREN
COLLECTION OF SAMPLES :
 Upper respiratory tract :
nasal swab.
oropharyngeal swab.
nasopharyngeal swab.
 Lower respiratory tract:
sputum.
endotracheal aspirate.
bronchoalveolar lavage.
 If the samples are not processed immediately, they
should be frozen at -20o C.

26. DIAGNOSIS OF COVID-19 IN CHILDREN
HEMATOLOGIC AND BIOCHEMICAL PARAMETERS :
 The WBC count is usually normal or low with lymphopenia
and elevated absolute neutrophil: lymphocyte ratio.
 The platelet counts are normal or mildly decreased.
 Elevation of C reactive protein.
 In patients with severe disease there is elevation of
creatine phosphokinase (CPK), lactate dehydrogenase
(LDH), D-dimer, ferritin and interleukin-6 (IL-6).

27. DIAGNOSIS OF COVID-19 IN CHILDREN
POOR PROGNOSTIC MARKERS IN ADULTS :
 Absolute lymphocyte count of < 1000.
 Neutrophil: lymphocyte count ratio of > 3.5
 Elevation of CRP beyond 100 mg/ L.

 Increase in D-dimer to more than 6 times normal.
 Levels of IL-6 beyond 7-10 times normal.

28. DIAGNOSIS OF COVID-19 IN CHILDREN
RADIOLOGICAL FINDINGS :
 CxR :
usually normal in mild/ early disease.
In severe cases, it is abnormal with bilateral
infiltrates and sometimes complete white out of
the lungs.
 CT Chest :
Infinitely more sensitive than CxR.
Disease could be bilateral/ unilateral.
Predominant involvement of lower lobes
Lesions more peripheral than central.
 The most common radiologic finding is ground glass
opacity

29. MANAGEMENT OF COVID-19 IN CHILDREN

30. MANAGEMENT OF COVID-19 IN CHILDREN
PIMS – TS : Case definition for PIMS – TS:
1. A child presenting with fever, laboratory evidence of
inflammation, and evidence of single or multi-organ
dysfunction (shock, cardiac, respiratory, renal,
gastrointestinal or neurological disorder) with
additional features. This may include children fulfilling
full or partial criteria for KD.
2. Exclusion of other plausible diagnoses (e.g. bacterial
sepsis, staphylococcal or streptococcal shock
syndromes etc.).
3. SARS-CoV-2 PCR testing may be positive or negative.

31. MANAGEMENT OF COVID-19 IN CHILDREN
Clinical features of PIMS-TS:
 Persistent fever ≥ 380C.
 Abdominal symptoms: Abdominal pain, diarrhoea, vomiting.
 Skin and mucous membrane changes: Conjunctivitis, rash,
erythematous changes in lips and oral cavity, extremity
edema/induration etc.
 Cardiovascular: Shock, myocardial dysfunction, arrhythmias &
other features of myocarditis.
 Respiratory: Cough, sore throat, tachypnea, oxygen requirement.
Respiratory failure is uncommon.
 Neurological: Meningeal signs, confusion, lethargy, syncope,
headache.
 Hepatosplenomegaly, lymphadenopathy.
 Acute kidney Injury.
 Serositis.

32. MANAGEMENT OF COVID-19 IN CHILDREN
Laboratory and imaging abnormalities in PIMS-TS:
 CBC: Anemia, neutrophilia, lymphopenia, thrombocytopenia.
 Elevated biomarkers of Inflammation: CRP, ESR, PCT,
fibrinogen, ferritin, D-dimer, LDH, IL-6, TGL.
 Deranged organ function tests: Elevated transaminases,
Coagulopathy Hypoalbuminemia ,Hyponatremia , Elevated
Troponin/BNP
 ECHO: Myocardial dysfunction, coronary dilatation/aneurysm.
 ECG: Cardiac conduction abnormalities
 Chest Xray: Usually normal, may show patchy
consolidation/effusions/atelectasis

33. MANAGEMENT OF COVID-19 IN CHILDREN

34. MANAGEMENT OF COVID-19 IN CHILDREN
Treatment : For all categories
 Supportive care: O2 to maintain SaO2 >94%, ventilation, judicious fluids, vasoactives as
needed.
 Monitor and support other organ functions (Liver, Renal etc.)
 Empiric antibiotics as per local sepsis protocols.
Immunomodulatory therapies:
 Children with no/mild symptoms (Category 1 &2) may require only close monitoring
without immunomodulatory treatment.
 IVIG (2g /kg) in all patients who meet criteria for complete or incomplete KD (Category 3)
and those who have moderate to severe PIMS-TS with shock and cardiac involvement
(Category 4).
 Methylprednisolone (1-2mg/kg/day) for treatment of children with PIMS-TS
with KD phenotype who continue to have fever.

35. MANAGEMENT OF COVID-19 IN CHILDREN
Immunomodulatory therapies:
 Consider other immunomodulators such as Tocilizumab, Anakinra
or Infliximab if IVIG and steroid refractory/severe disease/rapid
clinical decline, in consultation with other specialists.
Antiplatelet and anticoagulation therapy in PIMS -TS:
 Low dose aspirin (3-5 mg/kg/day; max 81 mg/day) should be
used in patients with PIMS –TS and KD-like features and/or
thrombocytosis and continued until normalization of platelet
count and confirmed normal coronary arteries at ≥4 weeks after
diagnosis.
 Treatment with aspirin should be avoided in patients with a
platelet count ≤80,000/𝜇L.

36. MANAGEMENT OF COVID-19 IN CHILDREN
 PIMS-TS patients with coronary artery aneurysms and a
maximal z-score of 2.5-10.0 should be treated with low
dose aspirin.
 Patients with a z-score ≥10.0 should be treated with low
dose aspirin and therapeutic anticoagulation with
enoxaparin (anti factor Xa level 0.5-1.0) or warfarin.
 Patients with PIMS-TS and documented thrombosis or an
LV Ejection Fraction <35% should receive therapeutic
anticoagulation with enoxaparin until at least 2 weeks
after discharge from the hospital.

37. THANK YOU