COVID-19 Disease in Children with Medical Complexity in a Pediatric Long-term Care Facility: A Case Series.

To the Editors:

At the onset of the coronavirus disease 2019 (COVID-19) pandemic, nursing homes were hard-hit as epicenters of outbreaks with roughly one-fifth of cases linked to adult long-term care facilities (LTCF) by 2021.[1] This statistic caused concern among pediatric LTCFs that children with medical complexity (CMC), who comprise the 7000 children living in the United States pediatric LTCFs, might suffer morbidity similar to geriatric LTCF residents.

CMC living in long-term care typically have physical disabilities, severe neurological impairment and medical technology dependence. Historically, CMC fares worse than typical children with common viral illnesses.[2] Nevertheless, reports on COVID-19 in children have demonstrated a milder clinical course and better hospital outcomes versus adults, regardless of risk factors.[3] Data on COVID-19 disease in CMC remains limited. We describe the clinical characteristics, outcomes and immunologic response following COVID-19 infection and vaccination of 5 CMC.

Between September 2020 and March 2021 5 residents of a 76-bed pediatric LTCF tested positive for COVID-19 infection during weekly facility-wide surveillance testing and were enrolled in our descriptive study. Following institutional review board approval (IRB#21.0789) we performed a retrospective review of hospital and facility records to evaluate the disease course 2 weeks post-COVID diagnosis. Blood samples were collected for serologic testing following COVID-19 infection and vaccination. Serologic tests performed include enzyme-linked immunosorbent assays (ELISA), microneutralization assays and activation-induced marker assay to evaluate T cell responses. Signed informed consent was obtained from participant guardians.

Despite underlying comorbidities, participants did not suffer significant morbidity from their COVID-19 infection (Table 1). One patient (case 1) was treated with remdesivir and steroids for a mild oxygen requirement, but on review of his records, intermittent oxygen use is consistent with his baseline. One participant (case 4) had increased seizure activity and mild daytime hypoxia (oxygen use at night is his baseline). Three participants remained asymptomatic.

TABLE 1.

Clinical and Laboratory Characteristics of 5 Medically Complex Children in Long-Term Care with COVID-19 Infection

	Case 1	Case 2	Case 3	Case 4	Case 5
Age	1 year	13 years	12 years	21 years	8 years
Gender	Male	Male	Male	Male	Male
Comorbidities/PMH	Cerebral palsy due to brain injurySevere neurologic impairmentTracheostomySubglottic stenosisChronic lung disease gastrostomy tubeEpilepsyAutonomic instability	Cerebral palsy due to L1 syndromeSevere neurologic impairmentChronic lung disease TracheostomyChronic mechanical ventilationVP shuntaortic insufficiencygastrostomy tubeEpilepsy	VARS2-relatedmitochondrial neurodegenerative disorderSevere neurologic impairmentGastrostomy tubeEpilepsyHistory of stroke	Cerebral palsySevere neurologic impairmentGastrostomy tubeEpilepsyChronic lung disease vesicostomy	Cerebral palsy due to septo-optic dysplasiaSevere neurologic impairmentAdrenal insufficiencyHypothyroidismG-tubeEpilepsy
BMI (kg/m2)	21.1	18	19.1	24.9	22.1
25-OH-Vitamin D level (ng/mL)	28.5	47.7	50.3	32.2	47.3
Melatonin use (mg/night)	0	6	10	0	6
Probiotic use	No	No	No	Florastor	No
COVID-19 symptoms	Hypoxia requiring supplemental oxygen.Increased secretions and respiratory rate. Has baseline waxing and waning of oxygen need and secretions.	None	Fever	Hypoxia requiring supplemental oxygen.Increased seizures.	Bradycardia
Relevant laboratories at presentation:
WBC (4.5–13.5 10*3/uL)	7.94	N/A	7.68	5.89	N/A
Abs lymphocytes (1000–4800cell/uL)	3,790	N/A	2,400	1,360	N/A
LDH (313–618 U/L)	N/A	N/A	N/A	436	N/A
Ferritin (17.9–464 ng/mL)	N/A	N/A	N/A	15.1	N/A
D-dimer (<500 ng/mL)	N/A	N/A	N/A	253	N/A
CRP (<1.0 mg/dL)	<0.5	0.7	0.9	4.8	N/A
Serology at diagnosis	N/A	IgM and IgG Abnegative.	N/A	IgM and IgG Ab negative.	N/A
Chest radiograph at initialCOVID-19 presentation	Chronic lung disease, consistent with prior films. No acute disease.	Consistent with prior chest radiographs.	Peripheral airway infiltrates consistent with viral process.	Retrocardiac infiltrate versus atelectasis.	No acute disease.
COVID-19 treatment	Remdesivir, IV Steroids, Lovenox, Oxygen, Bronchodilators, and Chest physiotherapy	None	Chest physiotherapy (vest therapy)	Oxygen,Bronchodilator,Chest physiotherapy	None
Duration of symptoms	14 days	0 days	1 day	9 days	3 days
COVID-19 infection	9/16/2020	11/9/2020	11/12/2020	11/19/2020	3/8/2021
COVID-19 first vaccination	N/A	N/A	6/2/2021	1/11/2021	N/A
Date of COVID-19 second vaccination	N/A	N/A	6/23/2021	2/1/2021	N/A
Date of first study blood draw	6/1/2021	N/A	6/1/2021	6/1/2021	6/1/2021
Date of second study blood draw	N/A	N/A	7/13/2021	N/A	N/A
BMI indicates body mass index; COVID-19, coronavirus disease 2019; CRP, c-reactive protein; LDH, lactate dehydrogenase; PMH, past medical history; VARS2, valyl-tRNA synthetase 2; VP, ventriculoperitoneal; WBC, white blood cell.

None of our patients had measurable IgG or IgA titers to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens 3–9 months after infection, but vaccination induced a robust antibody response (Table 2, ELISA). Neutralization assays were performed to detect functional systemic antibodies. All participants were able to neutralize the SARS-CoV-2 Washington strain following illness. Only vaccinated patients were able to neutralize the Delta variant, which correlates with the presence of high antibody titers in these participants following vaccination. T cell data indicate variable (weak to none) activation of SARS-CoV-2-specific CD4+ and CD8+ T cells following infection, but vaccination induced strong activation of SARS-CoV-2-specific CD4+ T cells.

TABLE 2.

Virus Neutralization, B cell, and CD4+ and CD8+ T cell Responses to COVID-19 Infection and Vaccination

Patients	MicroneutralizationAssay		Serology					AIM Assay Marker				Fold Change (+ Pep/No Pep)		T Cell Re-activity
	WA	Delta	Spike IgG	Spike IgA	RBD IgG	RBD IgA	Nucleo-capsid IgG	CD4+ T		CD8+ T
								+ Pep	No Pep	+ Pep	No Pep	CD4	CD8
Case 19 months post-COVID	1:1024	<1:128	<1:100	<1:100	<1:100	<1:100	<1:100	2.6	1.56	3.12	0.33	1.67	9.45	Activation (CD8 only)
Case 27 months post-COVID	1:2048	<1:128	<1:100	<1:100	<1:100	<1:100	<1:100	2.73	1.71	5.06	3.03	1.6	1.67	-
Case 37 months post-COVID	1:2580	<1:128	<1:100	<1:100	<1:100	<1:100	<1:100	0.87	0.56	0.63	0.3	1.55	2.1	-
Case 37 months post-COVID1 month post vaccination	1:10,321	1:1024	1:81,000	1:900	1:2700	1:100	<1:100	6.3	0.59	1.13	0.12	10.68	9.42	Activation (CD4 & CD8)
Case 47 months post-COVID5 months post vaccination	1:1290	1:2048	1:8100	1:1559	1:900	1:900	<1:100	2.06	0.47	4.31	0.7	4.38	6.16	Activation (CD4 & CD8)
Case 53 months post-COVID	1:1625	<1:128	<1:100	<1:100	<1:100	<1:100	<1:100	6.11	0.55	0.45	1.14	11.11	0.39	Activation (CD4 only)
AIM indicates activation-induced marker.

CMC in our LTCF experienced mild illness with SARS-CoV-2 infection despite comorbidities. This may be because factors hypothesized to explain age-related differences in severity of COVID-19 infection, such as changes in immune function, antibody cross-protection or differences in intensity of initial viral exposure are unrelated to being a CMC.[4] In our small sample, asymptomatic or mild illness did not confer immunity but the immunologic response to vaccination was robust with lasting antibody formation, high virus neutralization titers against the Delta COVID-19 variant and T cell activity. The authors advocate for vaccination for CMC regardless of past COVID-19 illness history.