Post-COVID Condition in Adults and Children Living in the Same Household in Italy: A Prospective Cohort Study Using the ISARIC Global Follow-Up Protocol

Background Emerging evidence shows that both adults and children may develop post-acute sequelae of SARS-CoV-2 infection (PASC). The aim of this study is to characterise and compare long-term post-SARS-CoV-2 infection outcomes in adults and children in a defined region in Italy. Methods A prospective cohort study including children (≤18 years old) with PCR-confirmed SARS-CoV-2 infection and their household members. Participants were assessed via telephone and face-to-face visits up to 12 months post-SARS-CoV-2 diagnosis of household index case, using the ISARIC COVID-19 follow-up survey. Results Of 507 participants from 201 households, 56.4% (286/507) were children, 43.6% (221/507) adults. SARS-CoV-2 positivity was 87% (249/286) in children, and 78% (172/221) in adults. The mean age of PCR positive children was 10.4 (SD = 4.5) and of PCR positive adults was 44.5 years (SD = 9.5), similar to the PCR negative control groups [children 10.5 years (SD = 3.24), adults 42.3 years (SD = 9.06)]. Median follow-up post-SARS-CoV-2 diagnosis was 77 days (IQR 47–169). A significantly higher proportion of adults compared to children reported at least one persistent symptom (67%, 68/101 vs. 32%, 57/179, p < 0.001) at the first follow up. Adults had more frequently coexistence of several symptom categories at both follow-up time-points. Female gender was identified as a risk factor for PASC in adults (p 0.02 at 1–3 months and p 0.01 at 6–9 months follow up), but not in children. We found no significant correlation between adults and children symptoms. In the paediatric group, there was a significant difference in persisting symptoms between those with confirmed SARS-CoV-2 infection compared to controls at 1–3 months follow up, but not at 6–9 months. Conversely, positive adults had a higher frequency of persisting symptoms at both follow-up assessments. Conclusion Our data highlights that children can experience persistent multisystemic symptoms months after diagnosis of mild acute SARS-CoV-2 infection, although less frequently and less severely than co-habitant adults. There was no correlation between symptoms experienced by adults and children living in the same household. Our data highlights an urgent need for studies to characterise PASC in whole populations and the wider impact on families.

[1]  A. Dagens,et al.  Characterising long COVID: a living systematic review , 2021, BMJ Global Health.

[2]  J. Warner,et al.  Setting Priorities to Address Research Gaps in Long-term COVID-19 Outcomes in Children. , 2021, JAMA pediatrics.

[3]  T. Spector,et al.  Illness duration and symptom profile in symptomatic UK school-aged children tested for SARS-CoV-2 , 2021, The Lancet. Child & adolescent health.

[4]  G. Di Sante,et al.  Evidence of lung perfusion defects and ongoing inflammation in an adolescent with post-acute sequelae of SARS-CoV-2 infection , 2021, The Lancet Child & Adolescent Health.

[5]  P. Edison,et al.  Long covid—mechanisms, risk factors, and management , 2021, BMJ.

[6]  M. Puhan,et al.  Long-term Symptoms After SARS-CoV-2 Infection in Children and Adolescents. , 2021, JAMA.

[7]  Ryan J. Low,et al.  Characterizing long COVID in an international cohort: 7 months of symptoms and their impact , 2021, EClinicalMedicine.

[8]  Laura B. Rawlings,et al.  Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study , 2021, The Lancet.

[9]  T. Vos,et al.  Risk factors for post-COVID-19 condition in previously hospitalised children using the ISARIC Global follow-up protocol: a prospective cohort study , 2021, European Respiratory Journal.

[10]  M. VanElzakker,et al.  Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms , 2021, Frontiers in Microbiology.

[11]  W. Lim,et al.  Long Covid in adults discharged from UK hospitals after Covid-19: A prospective, multicentre cohort study using the ISARIC WHO Clinical Characterisation Protocol , 2021, The Lancet Regional Health - Europe.

[12]  D. Brodie,et al.  Post-acute COVID-19 syndrome , 2021, Nature Medicine.

[13]  A. Jenkner,et al.  Virological and immunological features of SARS-CoV-2-infected children who develop neutralizing antibodies , 2021, Cell Reports.

[14]  C. Giaquinto,et al.  Virological and immunological features of SARS‐COV‐2 infected children with distinct symptomatology , 2021, Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology.

[15]  R. Consolini,et al.  Age‐related differences in the immune response could contribute to determine the spectrum of severity of COVID‐19 , 2021, Immunity, inflammation and disease.

[16]  D. Buonsenso,et al.  Preliminary evidence on long COVID in children , 2021, medRxiv.

[17]  James Thomas,et al.  Living Systematic Review , 2021 .

[18]  P. Brodin Immune determinants of COVID-19 disease presentation and severity , 2021, Nature Medicine.

[19]  Ryan J. Low,et al.  Characterizing long COVID in an international cohort: 7 months of symptoms and their impact , 2020, EClinicalMedicine.

[20]  H. Unwin,et al.  Children’s role in the COVID-19 pandemic: a systematic review of early surveillance data on susceptibility, severity, and transmissibility , 2020, Scientific Reports.

[21]  J. Margolick,et al.  Aging in COVID-19: Vulnerability, immunity and intervention , 2020, Ageing Research Reviews.

[22]  Zhènglì Shí,et al.  Characteristics of SARS-CoV-2 and COVID-19 , 2020, Nature Reviews Microbiology.

[23]  T. Greenhalgh,et al.  Management of post-acute covid-19 in primary care , 2020, BMJ.

[24]  Kari C. Nadeau,et al.  Distribution of ACE2, CD147, CD26, and other SARS‐CoV‐2 associated molecules in tissues and immune cells in health and in asthma, COPD, obesity, hypertension, and COVID‐19 risk factors , 2020, Allergy.

[25]  P. Gautret,et al.  Recurrence of positive SARS‐CoV‐2 in patients recovered from COVID‐19 , 2020, Journal of medical virology.

[26]  S. Goebel,et al.  SARS-CoV-2 Shedding from Asymptomatic Patients: Contribution of Potential Extrapulmonary Tissue Reservoirs , 2020, The American journal of tropical medicine and hygiene.

[27]  Denise Thomson,et al.  Standard 6: Age Groups for Pediatric Trials , 2012, Pediatrics.

[28]  W. Lim,et al.  Dexamethasone in Hospitalized Patients with Covid-19 , 2021 .

[29]  J. McCracken,et al.  Somatic Complaints in Anxious Youth , 2014, Child psychiatry and human development.

[30]  V. Preedy,et al.  Prospective Cohort Study , 2010 .

[31]  K. Shadan,et al.  Available online: , 2012 .