COVID AND CHILDREN

COVID AND CHILDREN/MINORS

May 18, 2021

Please don’t panic, take heart

Any parent reading this will get alarmed, but please remember that the worldwide experience has been, and all the papers from which this note has been sourced have emphasized, that Covid is mild for the overwhelming majority of children. Severe Covid, though serious, is rare. And the kids getting it are overwhelmingly recovering. Talk to your pediatrician after reading this, they will be able to reassure you as to the likelihood of severe Covid in children, even in the anticipated third wave.  

Purpose 

Since some experts in India are saying that  a third wave is imminent and infections will be more severe than in the past for children, this note collects information on the pattern of severe Covid, and Multisystem Inflammatory Syndrome in Children (MIS-C), and their diagnosis and treatment so that:

(i)              Parents know what to look out for

(ii)            Arrangements can be made for doctors, medicines and medical equipment

Sources

Covid Treatment Guidelines, Special Considerations in Children, National Institutes of Health, USA, last updated April 21, 2020 https://www.covid19treatmentguidelines.nih.gov/special-populations/children/

Clinical Guidance for Podiatric Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with SARS-CoV-2 and Hyperinflammation in COVID-19, American College of Rheumatology, last updated November 2020 https://www.rheumatology.org/Portals/0/Files/ACR-COVID-19-Clinical-Guidance-Summary-MIS-C-Hyperinflammation.pdf

Multisystem inflammatory syndrome in children: A systematic review Ahmed, M., Advani, S, Moreira, A. et al Lancet Sept 2020 covers period January 2020 to July 2020 https://www.thelancet.com/action/showPdf?pii=S2589-5370(20)30271-6&fbclid=IwAR0lxS5viqOe3evaZ830EwzPBlCiAy43e_14vJXZOmtcnuMHA9t_6rMF_Fg

Coronavirus disease 2019 in children: clinical and epidemiological implications, Kuttiatt, V.S., Abraham, P.R., Menon, R.P. et al, Indian J Med Res 152, July & August 2020, pp 21-20, received June 2020 https://www.ijmr.org.in/article.asp?issn=0971-5916;year=2020;volume=152;issue=1;spage=21;epage=40;aulast=Kuttiatt

Definitions of medical terms taken from Google search.

WARNING

THIS IS NOT MEDICAL ADVICE. DO NOT TAKE OR GIVE ANY TREATMENT EXCEPT ON A DOCTOR’S ADVICE. THIS NOTE IS PREPARED BY A LAYPERSON WITH NO QUALIFICATION IN MEDICINE WHATSOEVER.

In Brief 

What is Severe Covid

Severe Covid manifests in a number of ways, all starting as mild and even asymptomatic Covid, these are:

1.     The child is infected with Covid and progresses to an acute case (Acute Covid).

2.     The child gets symptoms that mimic another disease known as Kawasaki Disease (KD) or they get Toxic Shock Syndrome (TSS)

3.     The child gets Covid, recovers or is asymptomatic, tests negative for Covid and 3 to 4 weeks after getting Covid suddenly develops Multisystem Inflammatory Syndrome in Children (MIS-C).  

In Acute Covid upper respiratory symptoms are more common, while in MIS-C vomiting diarrhoea and rash are more common.

Covid typically involves the lungs while MIS-C typically does not involve the respiratory system, but the heart and severe diarrhoea. Sometimes liver and renal (kidney) involvement is seen. It shows up with a persistent fever and gets very bad in 4 to 5 days.

KD shows up with very high fever, red eyes, rash, swollen and red hands and feet followed by peeling skin and even bleeding. TSS involves shock: defined as hypotension (low blood pressure, fainting, dizziness) requiring intravenous fluid rehydration and/or initiation of vasoactive medicines (medicines to raise blood pressure).

There is a spectrum of severity even with MIS-C. One US study recommends hospitalization for MIS-C if there are any of these:

(i) Abnormal vitals; (ii) Tachycardia (heart beating very fast); (iii) Trachypnea (over-rapid breathing); (iv) Severe respiratory distress; (v) Even slight mental deficit or change in mental status; (vi) Even mild renal or hepatic injury; (vii) CRP over 10.00mg/dl; (viii) Abnormal electrocardiogram, Brain Natriuretic Peptide levels or Troponin levels; (ix) Shock (low BP, fainting, dizziness); (x) Dehydration; (xi) Features of Kawasaki Disease (see below for symptoms)

What can we give our kids at home, assuming a repeat of hospitals getting jammed in a third wave

The big question is how to avoid descending into severe Covid and associated syndromes; how to detect them early and what treatment to start at home. This is what we need pediatricians to start a discussion on.

We can’t just rely on asking for more hospital beds. Whatever arrangement is made, the possibility of beds falling short like happened in Delhi in the second wave is very real…perhaps inevitable, if there is a third wave that affects children with severe disease (which it may not, this note is not meant to panic anyone).

So we have to think of what we can do for our kids assuming no hospital and only tele-consult doctor. The foreign journals and guidance say Intravenous Immunoglobulin Therapy (IVIG) with corticosteroids is the first line of treatment. We need to be advised on oral substitutes for that which can be started at home if laboratory work shows Acute Covid or MIS (see below for the relevant markers).

One US study says that patients with milder forms of MIS-C having persistent fever or other symptoms despite a dose of IVIG can be given low-moderate does steroids of 1 to 2 mg/kg/day. Another says to start with glucocorticoids and if that does not work to give Anakinra, an interleukin anagonist that is used to reduce certain types of pain and swelling, brands of this medicine in India are here https://www.medindia.net/doctors/drug_information/anakinra.htm. If Anakinra is given, closely monitor liver function test.

For non-hospitalised high risk patients of 12 years and above, weighing 40 kg and above, treatment with monoclonal antibodies: bamlanivimab plus etesevimab and casirivimab plus imdevima, US authorities have given Emergency Use Authorisation.

All this may be considered by pediatricians here for coming up with a protocol for non-hospitalised patients given realities of hospital bed scarcity when Covid outbreaks peak.

What medicines and equipment we need to stock up on

For details of what medicine is used for what symptoms see below. This is just a list extrapolated from the detailed discussion that follows:

Hospitals and equipment

Hospitals, oxygen, children’s ventilators (non-invasive, mechanical and extra corporeal membrane oxygenation), oxygen concentrators suitable for children of all ages, pulse oximeters and other oxygen saturation measuring equipment suitable for infants and small children, nebulisers, digital thermometers, Holter monitors or other portable equipment to measure heart function (echo cardiogram and electrocardiogram that can be used at home), all equipment for intravenous drip: IV injection (disposable syringes), IV canulas, saline water, hammer a nail about 6 feet high above a bed on which a hanger can be put for drip at home, arrange for a nurse to administer or get trained in doing it yourself, inhaler with spacer, smart phones to enable video consult, digital thermometers

Doctors

Find and keep handy list of doctors to teleconsult from Day 1 of symptoms (do not waste time waiting for test, that can follow, in the  mean time get clinical diagnosis and start treatment). Expertise required: general pediatrician, pulmonary pediatrician, cardiac pediatrician, pediatric hepatologist, pediatric allergy consultant/dermatologist, rheumatologists

Consult all your trusted homeopaths and traditional remedy practitioners. Discuss the disease pattern described here with them, they will have suggestions.

Nurses

Nurses can give IV at home. This can be a life saver. But they are hesitant to come home. Find nurses willing to come home and lobby the government to assign military nurses. Try to get trained to do it yourself.

Testing Facilities  

Kinds of tests needed (none, some or all may be needed, depending on the patient’s condition, keep a list of home facilities or those near you in advance, book them in advance from Day 1 of symptoms, book for every alternate day for atleast 14 days. See below for detailed discuussion):

(i) Laboratory Markers: blood tests, liver and renal function test; (ii) Echocardiogram; (iii) Electrocardiogram; (iv) Cardiac CT; (v) Imaging of abdomen with ultrasound/computed topography/ MRI (vi) Imaging of central nervous system and lumbar puncture; (vii) ultrasonogram for lungs

Depending on the patient’s symptoms (see below for detailed discussion) you may need to test for:

White Blood Cell Count; Neutrophil count; Lymphocyte count; Hemoglobin; Platelets; Albumin; Creatinine; Alanine transaminase; Aspartate aminotransferase; C-Reactive Protein (CRP); Ferritin; Procalcitonin (PCT); Lactate Dehydrogenase (LDH); Inter leukin 6 (IL6); Creatine kinase; D-Dimer; Fibrinogen; Erythrocyte Sedimentation Rate (ESR); IL 2R, Troponin; Brain Natriuretic Peptide (BNP); Prohormone of BNP; N Terminal -proBNP; IL-1beta, International Normalised Ration (INR), IL-10, IL-13, TNF alpha; echocardiogram; electrocardiogram; abdominal imaging for: ascites – abnormal build-up of fluid in the abdomen; intestinal/colonic inflammation; mesenteric adenopathy – swelling of glands in intestine; test for pancreatitis.

Medicines

(This is only a list; for relevant symptoms/explanation see detailed discussion below)

Intravenous Immunoglobulin Therapy (IVIG); corticosteroids; glucocorticoids (eg prednisone, methylprednisolone or hydrocortisone); anakinra (IV and injection); interleukin-1 antagonists; monoclonal antibodies: bamlanivimab plus etesevimab and casirivimab plus imdevimab; dexamethasone; high titre convalescent plasma; baricitnib with remedisivir; tocilizumab and dexamethasone; antibiotics suitable for children like Azee; eye drops for conjunctivitis; ondem; crocin/calpol; decongestion and cough syrups; anti allergy medication; asthma medications; medicines to be used in nebulisers (ask your pediatrician); inotropes, vasopressors; interleukin 6 inhibitors; immune-modulatory drugs; asprin; anticoagulants with enoxaparin or warfarin; antiseizure medication, if needed; remdesivir, rituximab, aminosalicylate, heperin, hydroxychloroquine, siltuximab, lopinavir, ritonavir, [check with pediatrician about ivermectin],   

Please start making arrangements with your local politicians, Resident Welfare Associations, NGOs, volunteer groups and pharmacies for the medicines, equipment and tests described here to be lined up well in advance.

GENERAL DESCRIPTION OF SYNDROMES ASSOCIATED WITH SEVERE COVID

Severe Covid can manifest in a number of ways:

1.     The child is infected with Covid and progresses to an acute case (Acute Covid).

2.     The child gets symptoms that mimic another disease known as Kawasaki Disease (KD) or they get Toxic Shock Syndrome (TSS).

3.     The child gets Covid, recovers or is asymptomatic, tests negative for Covid and 3 to 4 weeks after getting Covid suddenly develops Multisystem Inflammatory Syndrome in Children (MIS-C).  

In Acute Covid upper respiratory symptoms are more common, while in MIS-C vomiting diarrhoea and rash are more common.

Covid typically involves the lungs while MIS-C typically does not involve the respiratory system, but the heart and severe diarrhoea. Sometimes liver and renal (kidney) involvement is seen. It shows up with a persistent fever and gets very bad in 4 to 5 days.

Risk factors for Acute Covid were pre-existing respiratory, cardiac and other serious conditions, however for MISC-C, though one US study found obesity in half the affected children, there seem to be no risk factors as such.

A large US study found more children in the age of around 9 years to be affected with MIS-C. The NIH Guideline says mortality from MIS-C is higher in the age range of 10 to 20 years, especially in the range of 18 to 20 years.  

KD shows up with very high fever, red eyes, rash, swollen and red hands and feet followed by peeling skin and even bleeding. A good description of KD is here: https://www.mayoclinic.org/diseases-conditions/kawasaki-disease/symptoms-causes/syc-20354598?fbclid=IwAR3GQMjPC0XRy1fagS9i1NWdtFJrik4BiBaT-5kC0LhodlS4uut5Jc4fm4k.

One US study said that KD is more likely to present in kids under 5 years. Older kids show MIS-C. Various US studies say younger kids more likely to present with KD and older ones with myocarditis and shock: defined as hypotension (low blood pressure, fainting, dizziness) requiring fluid resuscitation (replacing lost fluids/rehydrating) and/or initiation of vasoactive medicines (medicines to raise blood pressure) eg. phenylephrine, norepinephrine, epinephrine, dopamine, and vasopressin.

The literature says that KD looks alarming but is mostly easily managed and has a low mortality of 0.01%. It is treated with Intravenous Immunoglobulin Therapy (IVIG) and corticosteroids. In rare cases IL-1 and IL-6 antagonists are given. TSS needs intravenous drip –inotropic support (Intensive care patients often require inotropic support to stabilise circulation and to optimise oxygen supply). Typically used medicines are the catecholamines norepinephrine (noradrenaline), epinephrine (adrenaline), dopamine and dobutamine), treatment for hypotension, volume resuscitation or vasoactive medication (see previous paragraph for definitions). There are established treatment protocols for these which you should look up.

The inflammatory markers (D Dimer, IL6, Ferritin, ProCalcitonin etc.) high in Acute Covid, KD and TSS, but exponentially higher in MIS-C.

This note focuses on Acute Covid and MIS-C.  

MULTISYSTEM INFLAMMATORY SYNDROME IN CHILDREN – SYMPTOMS

Most common

(i) Persistent fever 2 to 6 weeks after Covid infection/exposure

(ii) Stomach pain/diarrhoea

(iii) Vomiting

Frequent (any of these):

(i) Conjunctivitis

(ii) Rash

(iii) Peripheral Edema – fluid collection in arms and legs, appear heavy and swollen

(iv) Chilblains/Dermatological (skin) Lesions

(v) Covid toes

(vi) Dyspnea (difficult or laboured breathing)

(vii) Mesenteric Adenitis (swelling of lymph nodes in abdomen) (can be mistaken for appendicitis)

(viii) Confusion/altered mental state/other mental (neurologic) signs, however mild/epileptic seizure

(ix) Hyporeflexia (deficient response to tappjng)

(x) Tongue swelling

(xi) Neck swelling

(xii) Tongue De-epithelialization (erosion? – not able to find definition)

(xiii) Lymphadenopathy (disease affecting lymph nodes, mostly found in head, neck, armpit, groin and stomach. See here for more https://www.mayoclinic.org/diseases-conditions/swollen-lymph-nodes/symptoms-causes/syc-20353902#:~:text=Your%20lymphatic%20system%20is%20a,your%20armpits%20and%20groin%20area

(xiv) Arthralgia (joint pain)

(xv) Swelling of extremities

(xvi) Leg pain

(xvii) Even mild renal (kidney) or hepatic (liver) injury

(xviii) Mucocutaneous involvement (mucous areas and junctions, mucocutaneous junctions are found at the lips, nostrils, conjunctivae, urethra, vagina (in females), foreskin (in males), and anus

(xix) Petechiae (red/brown/purple spots/rash on skin. More here: https://www.mayoclinic.org/symptoms/petechiae/basics/definition/sym-20050724#:~:text=Petechiae%20are%20pinpoint%2C%20round%20spots,when%20you%20press%20on%20them.

(xx) Melena – black stool (means blood in stool)

(xxii) Hematemesis – vomiting blood

(xxiii) Nuchal Rigidity – stiff neck

(xxiv) Clonus - a rhythmic, oscillating, stretch reflex, the cause of which is not totally known; however, it relates to lesions in upper motor neurons

(xxv) Trismus – lockjaw

(xxvi) Chest/scrotal/neck pain

Tests conducted for MIS-C

(i) For Laboratory Markers: blood tests, liver and renal function test

(ii) Echocardiogram: to include evaluation of ventricular/valvar function, especially left ventricular function, pericardial effusion and coronary artery dimensions.

(iii) Electrocardiogram

(iv) Cardiac CT for patients with suspicion of distal Coronary Artery Aneurisms that are not well seen in echocardiograms

Follow-up Cardiac MRI 2 to 6 months after diagnosis for those with Left Ventricular Dysfunction, including functional assessment, T1/T2 weighing imaging, T1 mapping, Extra Cellular Volume (ECV) quantification and late gadolinium enhancement

(v) Imaging of abdomen with ultrasound/computed topography and MRI

(vi) Imaging of central nervous system and lumbar puncture

(vii) Ultrasonogram for lungs, X ray is less sensitive than CT scan in detecting Covid 19 pulmonary disease

Laboratory Test Findings for MIS-C

These include hematology, liver and renal function, inflammatory markers, co-agulation and cardiac markers. Typical findings:

Hematology (blood work)

(i) White Blood Cell Count is high

(ii) Neutrophil count is high

(iii) Lymphocyte count is down

(iv) Hemoglobin is down

(v) Platelets are down

Liver and Renal Function

(i) Albumin is down

(ii) Creatinine is very low

(iii) Alanine transaminase is high

(iv) Aspartate aminotransferase is high

Inflammatory Markers

(i) C-Reactive Protein (CRP) – through the roof

(ii) Ferritin – ditto

(iii) Procalcitonin  (PCT) – ditto

(iv) Lactate Dehydrogenase (LDH) – ditto

(v) Inter leukin 6 (IL6) – ditto

(vi) Creatine kinase – ditto

Co-agulation Markers

(i) D-Dimer - through the roof

(ii) Fibrinogen – ditto

(iii) Erythrocyte Sedimentation Rate (ESR) - ditto

(iv) Some studies also look at IL 2R,

Cardiac markers

(i) Troponin – through the roof

(ii) BNP (Brain Natriuretic Peptide) – ditto

(iii) Prohormone of BNP – ditto

(iv) N Terminal -proBNP

(v) Some other marker taken: IL-1beta, International Normalised Ration (INR), IL-10, IL-13, TNF alpha

Echo and Electrocardiogram Findings

Echo and/or Electrocardiogram not normal

Any of the following may be seen:

(i) Depressed Ejection Fraction

(ii) Depressed SF (Shortening Fraction)

(iii) Aneurysm of Coronary Arteries

(iv) Coronary dilation/prominence

(v) Pericardial effusion/Pericarditis

(vi) Global/septal hypokinesia

(vii) Mitral valve regurgitation

(viii) Myocarditis

The cardiac injury can be silent, the NIH Guideline says that cardiac imaging showed myocardial injury in athletes with only mild disease. 

Some children’s initial ECG was normal, subsequent ECGs showed abnormalities. Some papers have recommended that children being evaluated for MIS-C should have a baseline echocardiogram, electrocardiogram and repeat imaging to follow cardiac function and artery changes. ECG every 48 hours for children with MIS-C. ECG to be repeated minimum 7 to 14 days and 4 to 6 weeks after presentation.

Abdominal Imaging Findings

(i) Ascites – abnormal build up of fluid in the abdomen

(ii) Intestinal/colonic inflammation

(iii) Mesenteric adenopathy – swelling of glands in intestine

Cases of pancreatitis noted

TREATMENT

THIS IS NOT MEDICAL ADVICE. THE WRITER HAS NO MEDICAL QUALIFICATION. DO NOT TAKE OR GIVE ANY MEDICATION EXCEPT UNDER A DOCTOR’S ADVICE. 

Treatment for Acute Covid

For Acute Covid in children the literature says to extrapolate from treatment of adult Covid with antivirals, antibiotics and steroids. Hospitals and doctors are reported to have used these, but there is no information on their safety, efficacy or long term effects. Medicines mentioned include hydroxychloroquine (for 12 yrs and above), oseltamivir, lopinavir, ritnovir, remedisivir, dexamethasone and other steroids, tocilizumab, ventilation – non-invasive, mechanical and ECMO (Extra Corporeal Membrane Oxygenation). Some children may not be able to take non-invasive ventilation because of discomfort or panic, so they will need to be mechanically ventilated.

Adults in India are being given ivermectin with doxycycline or azithral at onset of symptoms to control viral replication. Children in India with mild Covid and fever are being given the antibiotic Azee, if needed. Eye drops for conjunctivitis. Ondem for nausea. Crocin/Calpol for fever. Decongestion and cough syrups as need. Anti allergy medication as needed.

First line of therapy: Intravenous Immunoglobulin Therapy (IVIG) and/or corticosteroids

Anakinra for those not responding to glucocorticoids. Monitor for liver function test abnormalities

Interleukin-1 antagonists for cases that don’t respond to above

For non-hospitalised high risk patients of 12 years and above, weighing 40 kg and above, treatment with monoclonal antibodies: bamlanivimab plus etesevimab and casirivimab plus imdevimab, US authorities have given Emergency Use Authorisation (NIH says Panel don’t recommend for or a/g) 

Dexamethasone: 0.15 mg/ng/dose, once daily for 10 days, maximum dose 6 mg

If dexamethasone cannot be given, glucocorticoids to be given eg prednisone, methylprednisolone or hydrocortisone

High titre convalescent plasma for hospitalized children meeting Emergency Use Criteria, not recommended for those on mechanical ventilation

Baricitnib with remedisivir for whom corticosteroids cannot be used (insuff, data for or a/g)

Tocilizumab (insuff, data for or a/g), if used to be used with dexamethasone, NIH recommends against sarilumab

Treatment for MIS-C

The National Institutes of Health, USA published a guideline for Covid Treatment – Special Considerations for Children. They are positively recommending very few medicines, many of the doses stated etc are either under Emergency Use Authorisation for hospitalized kids or given with the caveat that there is “insufficient evidence for or against” but this is a good road map for pediatricians here to think about a home treatment protocol.

First line of therapy: Intravenous Immunoglobulin Therapy (IVIG) and corticosteroids. A European observational study got better results combining IVIG with methylprednisolone.

NOTE 1: cardiac function and fluids to be assessed before starting IVIG. Children with depressed cardiac function may require close monitoring and diuretics along with IVIG administration. For such patients, may consider dividing IVIG dose into 1 gm per kg daily over 2 days.

NOTE 2: For patients with shock or organ threatening disease give low-moderate gluco-corticosteroids 1 to 2 mg per kg per day with IVIG.

NOTE 3:Patient needing inotropes (defined above) or vasopressors (defined above)  can be given high dose IV pulse glucocorticoids – 10 to 30 mg/kg/day

Interleukin-1 and Interleukin 6 inhibitors

Anakinra (described above) of over 4 mg per kg per day IV or SQ (subcutaneous injection) may be considered in patients with Macrohpage Activation Syndrome (described here: https://www.aboutkidshealth.ca/article?contentid=2310&language=english – do not get alarmed, it says most kids respond to treatment) or those who cannot be given glucocorticoids

Immune-modulatory drugs ot be given 2 to 3 weeks or even longer

For anti-platelet and anti-coagulation therapy:

Low dose asprin (3 to 5 mg per kg per day, maximum dose 8 mg/kg/day, for 4 weeks). Avoid in patients with active bleeding/risk of bleeding/platelet count less than 80,000 ul

For coronary artery aneurism (CAA)

Low dose asprin, if z-score is equal to or greater than 10, add anticoagulants with enoxaparin or warfarin. To continue for atleast 2 weeks after discharge for those with thrombosis or ejection fraction less than 35%.

Holter monitors for follow-up for children with cardiac involvement. Holter monitor is a type of portable electrocardiogram (ECG). It records the electrical activity of the heart continuously over 24 hours or longer while you are away from the doctor's office. A standard or "resting" ECG is one of the simplest and fastest tests used to evaluate the heart.

Antiseizure medication, if needed

Expertise Needed

Besides a regular pediatrician and a pulmonary pediatrician, if suspect MIS-C, immediately consult a pediatric cardiologist, the heart is the most involved here. So keep a list of pediatric cardiologists handy. Also consult a pediatric hepatologist, gastro-enterologist. In the US, some of the most comprehensive advice has come from Rheumatologists, so try to get a list of rheumatologist handy, whether pediatric or adult.     

Don't panic if  you can't find somethinf or anything listed above

You can do this

The body is a wonderful instrument and its own healer. If you can’t find a doctor or a medicine, do not give up. If you are strong in mind and spirit, you can nurse your child out of anything. Do all the home remedies, keep the kids hydrated with salt and sugar liquids, listen to your instincts, keep looking and touching and smelling your kid like you are a search light and sniffer dog combined. Call your friends and family for help. We are here for you. God is with you, and very much with all children.

Questions/suggestions: suranya.aiyar@gmail.com