key: cord-0297723-3bl597iz
authors: Borel, M.; Xie, L.; Mihalcea, A.; Kahn, J.; Messiah, S. E.
title: Long Term Physical, Mental and Social Health Effects of COVID-19 in the Pediatric Population: A Scoping Review
date: 2021-09-21
journal: nan
DOI: 10.1101/2021.09.17.21263743
sha: f00f9b1db36a626360d680460b307cb83446188b
doc_id: 297723
cord_uid: 3bl597iz

Background. The majority of COVID-19 symptom presentations in adults and children appear to run their course within a couple of weeks. However, a subgroup of adults has started to emerge with effects lasting several months or more after initial infection. However, little is known about long term physical, mental and social health effects of COVID-19 in the pediatric population. The purpose of this review was to determine these impacts well into the second year of the pandemic. Methods. A search was conducted using PUBMED, Web of Science, Science Direct, and COCHRANE between 11/1/2019 and 9/1/2021. Search inclusion criteria were as follows: (1) COVID-19 illness and symptoms in children; (2) SARS-COv2 in children; (3) English language; and (4) human studies only. Results. The few studies that have documented long-term physical symptoms in children show that fatigue, difficulty in concentrating (brain fog), sleep disturbances, and sensory problems are the most reported outcomes. Most studies examining the impact of COVID-19 in pediatric populations have focused on initial clinical presentation, and symptoms, which are similar to those in adult populations. Additionally, COVID-19 has had a moderate impact on children and adolescents social environment, which may exacerbate current and future physiological, psychological, behavioral, and academic outcomes. Conclusions. There are limited studies reporting long physical symptoms of COVID-19 in the pediatric population. However, pediatric COVID-19 cases are underreported due to low rates of testing and symptomatic infection, which calls for more longitudinal studies. Children who have experienced COVID-19 illness should be monitored for long physiological, psychological, behavioral, and academic outcomes.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the novel coronavirus disease 2019 and as of September 9, 2021, there have been 5.3 million reported cases among children in the United States [1] . Early studies from China [2] [3] [4] [5] [6] [7] [8] [9] and Europe [10] have shown that COVID-19 is generally a mild disease in children, including infants. In the US and globally, fewer cases of COVID-19 have been reported in children (age 0-17 years) compared with adults [1] [7] but recent data suggests the delta (B.1.617.2) variant is more transmissible among children compared to the alpha ( B.1.1.7) variant. Specifically, while children comprise 22% of the US population (novel coronavirus) recent data show that 15.5% of all cases of COVID-19 reported to the CDC were among children [3] . Indeed, the true incidence of SARS-CoV-2 infection in children is not known due to lack of widespread testing and the prioritization of testing for adults and those with severe illness. Also, hospitalization rates in children have remained significantly lower than adult rates suggesting that children may have less severe illness from COVID-19 compared to adults [9] . However, a small proportion of children develop severe disease requiring ICU admission and prolonged ventilation [11] , although fatal outcome is rare. Also, reports of a novel Kawasaki disease-like multisystem inflammatory syndrome (MIS-C) necessitate continued surveillance in pediatric patients [12] . This syndrome has also been reported as Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS) [13] [14] .

Common acute symptoms of COVID-19 disease in both adults and children include fever, cough, shortness of breath, chills, muscle pain, headache, sore throat, and loss of taste or smell. The most common physical symptoms reported by adults after a SARS-CoV-2 infection are fatigue/lethargy and shortness of breath, with on average one-third reporting at least one persistent symptom months after recovery [15, 16] . Most patients recover within two weeks of initial symptoms. However, a sub-group of adults has been documented to have longer-lasting symptoms, often termed "long" or "long haulers". One recent study has reported similar long symptoms in children (≤18 years old) previously diagnosed with COVID-19 from the largest hospital in Rome [17] . A questionnaire was delivered by two pediatricians, either online or during outpatient visit, between September 1 st , 2020 and January 1 st , 2020 to the children's caregivers. Symptoms frequently reported up to 120 days after infection included muscle and joint pain, headache, insomnia, respiratory issues, and palpitations [17] . While this study did provide some insight into long COVID-19 symptoms, the findings were limited by a singlecenter design and relatively small sample size.

The COVID-19 pandemic and its associated mitigation strategies are expected to have significant psychosocial, behavioral, socioeconomic, and health impacts, which are exacerbated in populations that experience health disparities and other vulnerable groups. [18] [19] [20] Pediatric populations experiencing health disparities prior to the COVID-19 pandemic are at increased risk of infection and other COVID-19 related consequences (e.g., prolonged school closings, low resources to support online learning, parent job loss, high prevalence of community morbidity and mortality due to COVID-19) [21, 23] . Preliminary reports in the U.S. point consistently to disparities by race and ethnicity, with African Americans, Hispanics/Latinos, American Indians/Alaska Natives, and Native Hawaiians/Other Pacific Islanders experiencing a greater COVID-19 burden than non-Hispanic White populations [24] . Reports by geographic locations indicate that cases are substantially greater in economically disadvantaged census tracts [1] [25] . articles were reported by articles found, those selected for literature review, and those specifically pertaining to or considered as relating to long-term effects, for primary review.

The total number of articles selected for review was 130, with 34 deemed relevant or directly pertaining to long-term effects following a COVID-19 infection and/or effects of the COVID-19 pandemic in the pediatric population. In general, inclusion/exclusion characteristics were not well-defined, but there were five recent studies containing "long" or "long term" in their title.

Studies pertaining to MISC-C, PIMS-TS and/or acute COVID-19 symptoms are included in Table 1 . While all of the common symptoms of COVID-19 such as fever, cough, shortness of breath, chills, muscle pain, headache, sore throat, and loss of taste or smell were reported in the pediatric studies reviewed, the symptoms seen consistently were fever and cough. There were additional respiratory symptoms reported across all pediatric population groups, such as sputum production, along with gastrointestinal (e.g., diarrhea), cardiovascular (e.g., cyanosis), and neurological (e.g., apnea) symptoms. One study examining hospitalized pediatric patients found that a portion demonstrated organ system failure [28] . Non-hospitalized patients in one study reported pain in the pharynx [38] . One study found that a portion of MIS-C pediatric patients reported/displayed (coryza) inflammation of the mucous membrane of the nasal cavity [34] .

Specifically, MIS-C and PIMS-TS patients presented with Kawasaki disease-like features, shock, fatigue, fever and inflammation [11, 12] [42, 43] [44] [45] . PIMS-TS studies consistently reported Myocarditis [13] [46] [47] [48] , with additional PIMS-TS and MIS-C studies All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. reporting cardiovascular findings such as atrioventricular block, coronary artery abnormalities, raised cardiac inflammatory markers, and transient valve regurgitation [11] [40] [49] . One PIMS-TS study from India, suggested that all children are at risk of COVID-19 infection, even if they present with mild symptoms or no symptoms [45] . Table 2 summarizes current studies in the literature focused on the long physical symptoms of COVID-19 illness in the pediatric population. To date, a few studies with limited sample sizes, focusing on the non-hospitalized pediatric population, found that frequently reported physical symptoms were reported on average three to six months after infection including fatigue, muscle and joint pain, headache, insomnia, respiratory problems, palpitations, difficulty in concentration, and sensory problems [17, [70] [71] [72] [73] . Weight gain due to lack of exercise and atopic dermatitis triggered potentially by a lack of exposure to sunlight and the outdoors, have also been reported [51] .

From the many studies examining COVID-19 acute symptoms, a few studies also reported on immunological findings such as long-term viral shedding, or longer duration of viral particle expulsion through daily activities such as talking, exhaling, and eating. Two retrospective studies, one from the U.S. and one from China, both reported long-term viral shedding [38] [50] . There are also many studies regarding IgG levels and immunological responses following COVID-19 infection. For example, one cross-sectional study found that the SARS-CoV-2 IgG rate was double in the children population compared to the adult population [52] . Conversely, another study found similar antibody rates across all age groups [53] .

All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Studies pertaining to the long-term effects on mental health are included in Table 3 . The most common mental health issues reported in the pediatric population throughout the COVID-19 pandemic were anxiety and depression, and these were only reported in papers looking at the COVID-19 pediatric patient groups [54, 55] . From two non-hospitalized cross-sectional studies in China, one examined mental health effects in primary schools and the other in junior and senior high schools, with both studies reporting anxiety and depression during home confinement during the first few months of 2020 [54, 55] . Conversely, a study in the U.S. examined the experiences of children within households identifying as Chinese-American. The authors found poorer mental health statuses as associated with higher levels of perceived racial discrimination [24] .

The daily moods of children were more frequently reported as negative during the pandemic as compared to before [21] . However, children that engaged in more physical activity during the pandemic reported less states of anxiety in a preliminary 2020 study in the U.S. [18] .

A non-hospitalized, cross-sectional study in The Netherlands found significantly worse PROMIS T-scores on all domains, when comparing data from 2017-18 to data collected during April and May 2020 [26] . Mental health effects associated with the COVID-19 pandemic included depressive symptoms, severe anxiety, and patient-specific mental and social health complaints [26] .

Studies pertaining to the long-term effects on social and behavioral health are included in Table 4 . For hospitalized neonates, the only long-term effects on behavioral health reported by parents were feeding, such as difficulties with or refusal to feed [20] . For older children, behavioral symptoms reported included clinginess, distraction, irritability, and fear of asking All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 21, 2021. ;  1 0 questions about the epidemic [19] . Other findings related to mood and emotional status included increases in being affectionate, restless, and frustrated [25] . The behavioral health of nonhospitalized children with COVID-19 had been reported by parents to have been worsening as the pandemic was progressing [56] .

Additionally, a study among adolescents aged 8-18 years in The Netherlands has reported significant worse PROMIS T-scores on all domains including peer relationships, anger, sleeprelated impairment, poor Global Health, social health complaints, effect on atmosphere at home, and negative impacts of the COVID-19 regulations on daily life [26] .

Long-term effects on academic performance and learning outcomes were not found in this review. The majority of articles regarding effects on school/childcare in general, focused primarily on changes in the organizational environment (i.e., in-person, virtual) and differences in COVID-19 infection rates. The locality, setting, duration, and stage of the pandemic that the study was conducted, were all limiting factors when comparing and contrasting the studies. For example, for childcare programs, it was suggested that findings should only be interpreted within the context of transmission rates and the infection mitigation efforts implemented by each program [57] . Throughout 2020, parents reported loss of child care alongside worsening parental mental health and child behavioral health [23] . In schools, there was an increase in the lack of access to technology and internet [22] . There was also an important precedence for developing school reopening plans to protect students who are most vulnerable to learning loss or reduced access to basic needs [22] . All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 21, 2021. ;

Other studies found varying associations in transmission rates among school setting/delivery while some took into account trends before and after school re-openings. A Florida county-level study found a 1.2-fold increase in COVID-19 infection rates among elementary schools, 1.3 in high schools and no effect for virtual learning, after school reopenings [58] . Conversely, a national study in Italy one month after school re-openings found low transmission in schools, mainly among younger students [59] . A U.S. state-level study found an increased prevalence of COVID-19 in adolescents and youth compared to adults in the summer of 2020 [23] .

Studies pertaining to long-term effects on Quality-Of-Life (QOL) and the Social Determinants of Health (SDOH) were not outlined in a table, as these outcomes relate more to parents and changes in environmental settings. Many articles focused on examining quality of life issues such as nutrition, home environment, overall well-being, daily moods, and mental/emotional attitudes toward the pandemic and quarantine measures. They also analyzed effects on social determinants of health such as insurance status, healthcare needs, food insecurity, housing, income status, and caregiving burdens. These outcomes were mostly measured from parental surveys and questionnaires completed by parents or caregivers. In a nonhospital study, authors found an increase in food insecurity, nutrition barriers, homelessness or use of temporary housing [22] . Similarly, another study found an increase in moderate to severe food insecurity, alongside changes in insurance status [23] . One parent survey found an increase in frequency of parent-reported daily negative mood [21] . This article also found that the parents' and children's well-being was strongly associated with the number of reported hardships [21] . Hardships included job loss, income loss, caregiving burden, illnesses, etc. All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Preliminary reports found similar findings in worsening quality-of-life issues and increased health inequities among social determinants of health. Parents experienced anxiety, changes and limitations to healthcare access, and overall "collateral" damage to their well-being as a result of economic impacts and social isolation [60] . A cross-sectional study on children and adolescents in the Netherlands found an increase in mental and social health complaints during the lockdown with the majority reporting a negative impact of COVID-19 on their life [26] .

Families were concerned about the COVID-19 pandemic and quarantine measures, especially towards negative impacts on the economy [61] . These findings also raise concern regarding stability and safety within the home environment. The pandemic's impact on child abuse and claims remains hidden, underscoring the need for further research in this field [62] .

Three hospital studies examined parental opinions and interests regarding COVID-19 and influenza vaccines for their children. One study discussed the overall exacerbation of polarity in COVID-19 vaccination uptake, and those parents who originally chose to not vaccinate their children for influenza, were more likely to commit to this decision than parents who originally chose to vaccinate their children and vice versa [63] . Similarly, one preliminary study found that 60% of parent participants reported that they were likely to vaccinate their children, as well as themselves against COVID-19 [64] . Separately, another study found an increase in willingness to vaccinate against influenza [65] .

To the authors' knowledge, this is one of the first scoping reviews focused on the long physical, psychological, behavioral, academic, and social consequences of COVID-19 disease All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. containing information on long COVID-19 in children [66] . They also included findings from their case report on five patients, who all presented with the primary persisting symptom of fatigue 6-8 months following a clinical COVID-19 diagnosis [66] .

As of March 2021 and within the scope of our review search parameters, one study has now been published reporting physical long symptoms in children. These symptoms which commonly persist following a normal infection recovery include standard symptoms such as fever, cough, shortness of breath, muscle pain, and a headache. Some additional physical long symptoms observed in children were insomnia and heart palpitations. The persistence of these symptoms could possibly be attributed to SARS-CoV-2 triggering an abnormal immunological or inflammatory response in specific areas of the body that express the ACE2 receptor [38] [50] [67] . The invasion and persistence of SARS-CoV-2 in the central nervous system could also potentially be associated with the occurrence of mental health issues such as anxiety and depression, with further research needed to understand the mechanisms of action [67] [68] [69] .

However, many long symptoms and their etiologies may be subjective in nature and therefore, All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. 

In contrast to earlier reports suggesting that the outcomes or physical effects of COVID-19 in the pediatric population were milder or less severe in comparison to the adult population, the findings from this review indicate that a subgroup of children are still at risk to develop more severe and long-term presentation of symptoms, even more so for children diagnosed with MIS-C, PIMS-TS and multiple organ system failure. In addition, COVID-19 has had a moderate impact on children and adolescents' social environment, which may exacerbate current and future physiological, psychological, behavioral, and academic outcomes. The relative lack of All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

The copyright holder for this this version posted September 21, 2021. ; 1 5 evidence evaluating the long-term effects of the recent COVID-19 pandemic and infections on the pediatric population, suggests the need for more prospective studies examining the longhauler effects of an initial infection, as compared to retrospective/cross-sectional studies examining symptom presentation. This review serves as a continuum in which further research is needed to thoroughly investigate and understand the complete effects, from acute to long-term, that SARS-CoV-2 induces in the human body, especially for the pediatric population.

All rights reserved. No reuse allowed without permission. preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. Persistent symptoms among which fatigue (53, 10.7%), sleep disturbance (36, 6.9%,) and sensory problems (29, 5 .6%) were the most common. 

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