The Prevalence, Characteristics and Risk Factors of Persistent Symptoms in Non-Hospitalized and Hospitalized Children with SARS-CoV-2 Infection Followed-Up for up to 12 Months: A Prospective, Cohort Study in Rome, Italy

Abstract

Previous studies assessing the prevalence of COVID-19 sequelae in children have included either a small number of children or a short follow-up period, or have only focused on hospitalized children. We investigated the prevalence of persistent symptoms amongst children and assessed the risk factors, including the impact of variants. A prospective cohort study included children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection. The participants were assessed via telephone and face-to-face visits at 1–5, 6–9 and 12 or more months post-SARS-CoV-2 diagnosis using the ISARIC COVID-19 follow-up survey. Of the 679 children enrolled, 51% were female; 488 were infected during the wild virus wave, and 29 were infected with the Alpha, 42 with the Delta and 120 with the Omicron variants. Fatigue (19%), headache (12%), insomnia (7.5%), muscle pain (6.9%) and confusion with concentration issues (6.8%) were the most common persistent symptoms. Families reported an overall improvement over time, with 0.7% of parents interviewed at 12 months or more of the follow-up period reporting a poor recovery. Patients that had not recovered by 6–9 months had a lower probability of recovering during the next follow-up period. Children infected with a variant or the wild virus had an overall similar rate of persistent symptoms (although the pattern of reported symptoms differed significantly) and recovery rates. Conclusions: Recovery rates after SARS-CoV-2 infection improved as time passed from the initial infection, ranging from 4% of children having poor recovery at 1–5 months’ follow-up to 1.3% at 6–9 months and 0.7% at 12 months. The patterns of persistence changed according to the variants involved at the time of infection. This study reinforces that a subgroup of children develop long-lasting persistent symptoms and highlights the need for further studies investigating the reasons behind the development of PCC.

Sleep disturbance in post COVID-19 conditions: Prevalence and quality of life

“…There was only one study described several types of sleep disturbance and their prevalence, with insomnia at 60%, waking up several times at night at 41%, awakening due to breathing difficulty at 36%, having restless legs syndrome (RLS) at 18%, sleep apnea at 10%, having vivid dreams at 33%, nightmares 26%, and lucid dreams 15% ( 2 ). Another cause for this wide range of prevalence might be due to the variations in evaluation time following the onset of COVID-19 in the studies shown in Table 1 , starting from 2 weeks until 48 weeks or more after discharge or after having a negative COVID-19 test results ( 19 , 27 ).…”

Cognition and Mental Health in Pediatric Patients Following COVID-19

“…Additional difficulties may arise due to the lack of a standardized approach to diagnosing long COVID in pediatrics, inconsistent testing practices, and incorrect timing of examinations. Furthermore, the prevalence of long COVID is underestimated in children because many children may show mild or absence of symptoms during the acute phase of the infection, leading to fewer PCR tests being conducted [ 41 ]. Developing better and more unified guidelines for diagnosis and treatment is necessary.…”

“…Obesity has also been identified as a risk factor for developing cognitive symptoms as part of long COVID, which is apparently because of increased expression of angiotensin converting enzyme-2 and systemic inflammatory state, leading to higher levels of pro-inflammatory cytokines such as IL-6 and tumor necrosis factor-α. These factors contribute to the development of severe and prolonged cognitive symptoms in long COVID-19 syndrome [ 41 ]. Gonzalez-Aumatell et al reported that 66% of the pediatric patients complained of decreased school performance, while only 12% were reported to have positive findings on neurological physical examination by trained physicians [ 23 ].…”

COVID-19: Insights into long-term manifestations and lockdown impacts

“…Regarding affected youth, fatigue (19%), headache (12%), insomnia (7.5%), muscle pain (6.9%), and confusion with concentration issues (6.8%) were the most common symptoms reported in a 12-month follow-up study. 92 Chest pain (3.8%) was also observed, but specific cardiovascular symptoms were not reported as this data was often not recorded. 92 , 93 , 94 , 95 , 96 Therefore, further studies are required to assess cardiovascular outcomes in youth, especially in severely ill pediatric patients (irrespective of MIS-C survivors, as those cardiovascular complications are known; see chapter 2.1).…”

“… 92 Chest pain (3.8%) was also observed, but specific cardiovascular symptoms were not reported as this data was often not recorded. 92 , 93 , 94 , 95 , 96 Therefore, further studies are required to assess cardiovascular outcomes in youth, especially in severely ill pediatric patients (irrespective of MIS-C survivors, as those cardiovascular complications are known; see chapter 2.1). Furthermore, the immune response to mild infections was similar in children and adults (reviewed by Chou et al 45 ); thus, similar cardiovascular outcomes for children could be expected.…”