Ninety-six patients were enrolled and analyzed (50 acute COVID-19 patients and 46 non-COVID-19 participants) after excluding four patients due to incomplete data. Fifty-seven patients (58.3%) were male at birth. No differences were found in baseline characteristics between COVID-19 participants and non-COVID-19 participants (Table 1).
Families were interviewed at a median of 1.89 years (IQR, 1.25-2.07) after hospitalization. The definition of persistent symptoms was met in 34/96 (35%) CYP: 17/50 (34%) COVID-19 participants and 17/46 (37%) non-COVID-19 participants (p=0.767). Symptoms persisted ³12 months in 14/50 (28%) COVID-19 participants and in 7/46 (15%) non-COVID-19 participants (p=0.140).
Non-COVID-19 participants were more likely to present with only one persistent symptom (9/46, 20% vs. 1/50, 2% of COVID-19 participants), but the difference decreased ³12 months after hospitalization (2/46, [4%] vs 1/50, [2%] of COVID-19 participants). Nine out of 50 (18%) COVID-19 participants and 4/46 non-COVID-19 participants (9%) had ³3 persistent symptoms at ³12 months (p=0.174).
Among COVID-19 participants, the most common symptoms at ³12 months were fatigue in 4/50 (8%), and headache, loss of appetite, abdominal pain, and heart rate variability (3/50, 6% each). Among non-COVID-19 participants, the most common persistent symptoms were abdominal pain and poor appetite (3/46, 7% each) (Figure 1).
For emotional and behavioral items, 16/50 (32%) COVID-19 participants reported being worse or much worse after admission than before compared with 16/46 (35%) non-COVID-19 participants (p=0.941). Both groups rated similarly before and after admission on all the specific items related to emotional welfare, social relationships, and current activities (Supplementary Figures 1 and 2).
Among 11/50 (22%) COVID-19 participants, there were 14 new diagnoses including neurological (n=3, 6%), gastrointestinal (n=3, 6%), pulmonary (n=2, 4%) and hematological, osteo-muscular, renal, cardiological, allergy and psychiatric conditions (n=1, 2% each). Among 10/46 (21%) non-COVID-19 participants, there were 10 new diagnoses (one per each participant): gastrointestinal (n=5,11%), skin (n=2, 4%), osteo-muscular, diabetes and neurological conditions (n=1, 2% each). Persistent symptoms 12 months after admission was associated with a new diagnosis (OR 5.16 [95% CI: 1.75; 15.6]. Detailed information on specific diagnoses can be found in Supplementary Table 4.
Readmissions occurred in 11/50 (22%) COVID-19 participants and in 6/46 (13%) non-COVID-19 participants (p=0.267).
22/50 (44%) participants with COVID-19 were re infected with COVID-19 during the follow-up. To assess the role of reinfection in persistent symptoms, we compared the prevalence of persistent symptoms and persistent symptoms 1 year after admission in children with reinfection (4/22 [18%] and 2/22 [9%]) compared to children without re infection (13/28 [46%] and 12/28 [43%]). Children without re infection were less likely to have persistent symptoms (OR 0.27, [95% CI 0.06; 0.96]) or persistent symptoms after 1 year (OR 0.15 [95% CI, 0.02; 0.65]).
In multivariable analysis, no association was found between any of the risk factors analyzed and the development of persistent symptoms: sex (OR: 0.77; 95% CI [0.07;8.59]), age (OR: 1.23; 95% CI [1.00;1.70]), neurologic conditions (OR: 22.0; 95% CI [0.64;27]), respiratory diseases (OR: 0.00; 95% CI [-;-]), eczema (OR: 0.00; 95% CI [-;-]), severe disease (OR: 0.00; 95% CI [-;-]).
We found a weak negative correlation between the number of emotional symptoms and the number of physical symptoms (R=-0.28; β (95% CI) -0.2262 [-0.3844; -0.0680], p=0.005).