Clinical manifestations of COVID‐19 differ by age and obesity status

Abstract Background Age and obesity status are associated with severe outcomes among hospitalized individuals with COVID‐19. It remains unclear whether age and obesity are risk factors for milder COVID‐19 illness. Methods We prospectively enrolled SARS‐CoV‐2‐exposed individuals. Participants recorded symptoms for 28 days and were tested for SARS‐CoV‐2 by reverse transcription polymerase chain reaction (RT‐PCR) and serology. Type, number, and duration of symptoms and SARS‐CoV‐2 laboratory parameters were compared by age and obesity status. Results Of 552 individuals enrolled from June 2020 to January 2021, 470 (85.1%) tested positive for SARS‐CoV‐2 including 261 (55.5%) adults ≥18 years, 61 (13.0%) adolescents 12–17 years, and 148 (31.5%) children <12 years. Children had fewer symptoms (median 2 vs. 3, p < 0.001) lasting fewer days (median 5 vs. 7, p < 0.001) compared with adolescents/adults. Body mass index of 300 (63.8%) individuals classified with overweight or obesity (OWOB). Individuals with OWOB suffered more symptoms compared with individuals without OWOB (median 3 vs. 2, p = 0.037), including more cough and shortness of breath (p = 0.023 and 0.026, respectively). Adolescents with OWOB were more likely to be symptomatic (66.7% vs. 34.2%, p = 0.008) and have longer respiratory symptoms (median 7 vs. 4 days, p = 0.049) compared with adolescents without OWOB. Lower RT‐PCR Ct values were found in children and symptomatic individuals compared with adolescent and adults and asymptomatic individuals, respectively (p = 0.001 and 0.022). Conclusions Adolescents and adults with OWOB experience more respiratory symptoms from COVID‐19 despite similar viral loads. These findings underscore the importance of vaccinating individuals with OWOB.


| INTRODUCTION
Age and obesity status are both major determinants of host response to pathogens, including during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. 1,2 Incidence of coronavirus disease 2019  appears to be increasing in children, paralleling adult trends. 3 Most infected children are asymptomatic or have mild symptoms. However, hospitalization rates have been increasing among children and adolescents starting in the spring of 2021. 4 Obesity is a prevalent comorbidity in both adults and children hospitalized with severe COVID-19. 5,6 The likelihood of hospitalization and risk for severe COVID-19 increases with higher body mass index (BMI) in adults may be associated with chronic inflammation disrupting immune responses and impairing pulmonary function. [7][8][9] The elevated risk of complications in obese individuals was reflected in the Advisory Committee on Immunization Practices (ACIP)'s inclusion of obesity as high-risk condition for COVID-19 vaccine prioritization in the initial guidelines before widespread availability 10 and the Food and Drug Administration (FDA)'s Emergency Use Authorization for receipt of an anti-SARS-CoV-2 monoclonal antibody. 11 Most published data have focused on disease presentation and prognosis of hospitalized individuals, but the majority of COVID-19 infected individuals are managed outside of the hospital. Less data are available on COVID-19 infected non-hospitalized individuals with overweight or obesity (OWOB), and very few studies have focused on COVID-19 in children with OWOB. [12][13][14] This prospective study analyzes differences in symptom types and duration as well as SARS-CoV-2 laboratory parameters by age and obesity status in predominantly outpatient COVID-19-positive patients reflective of the majority of COVID-19 cases in the general population.

| Study design and participants
We enrolled individuals within 2 weeks of exposure to a laboratoryconfirmed COVID-19 household contact into the Household Exposure and Respiratory Virus Transmission and Immunity Study (HEARTS). We recruited household members of individuals who tested positive for SARS-CoV-2 at the Children's Hospital Los Angeles (CHLA) laboratory using a convenience recruitment strategy. Those who have specimens tested at the laboratory include symptomatic and asymptomatic staff and patients of CHLA and network outpatient clinics. Recruitment fliers were also posted at community testing sites near the hospital. At enrollment, individuals answered a questionnaire that included demographic information, comorbidities, and exposure history. Participants logged illness symptoms and symptom severity in a daily symptom diary for 28 days; study staff followed up on the symptom diary over the phone or at in-person follow-up visits every 3-7 days. Parents/guardians completed questionnaires and recorded symptoms for children unable to record for themselves. COVID-19-associated symptoms were defined (and grouped) as experiencing at least one of the following: fever, chills, headache, fatigue, muscle aches (constitutional); runny nose, congestion, sore throat, cough, shortness of breath, wheeze (respiratory); altered smell,

| SARS-CoV-2 RT-PCR
We tested for SARS-CoV-2 using the CDC protocol approved by the Food and Drug Administration for Emergency Use Authorization. 16 Briefly, total nucleic acid was extracted from 200-μl NP swab samples A valid result for SARS-CoV-2 detection was determined by RNP using a cut-off of Ct value <32. An inconclusive result was defined as either N1 or N2 gene detected only with RNP detection.

| SARS-CoV-2 serology
Serum SARS-CoV-2 receptor binding domain (RBD) and spike IgG antibody was measured using an ELISA as previously described. 17

| RESULTS
We enrolled 560 individuals from June 17, 2020 to January 31, 2021; all had exposure to a household member with laboratory-confirmed SARS-CoV-2 infection. Of those, 4 were excluded because they did not present for NP PCR testing; 4 others were excluded due to prior

| DISCUSSION
Nearly two-thirds of our study participants were with overweight or obesity, reflective of worsening obesity trends in the United States and worldwide. 18,19 The effect of the COVID-19 pandemic's lockdown on lifestyle behaviors including increase intake of high fat and high caloric diets, increased screen time, and less physical activities may contribute further to the obesity epidemic. 20,21 This phenomenon F I G U R E 1 Symptoms in adolescents and adults ≥12 years old (yo) versus children <12 yo. Children <12 yo experience more fever and diarrhea, but adolescents and adults have more chills, headache, fatigue, muscle aches, sore throat, cough, shortness of breath, and altered smell and taste (all p < 0.05). Fever and cough lasted longer in adults and adolescents (p = 0.016 and 0.001, respectively) is especially alarming as COVID-19 and its variants continue to circu- Lowest RT-PCR Ct value from nasopharyngeal swabs obtained within the first 7 days from COVID-19 onset. Individuals with specimen collection after 7 days were excluded. b Participants were included if they had PCR positivity end date, defined as the last date of a positive test before a PCR negative or inconclusive result. c Highest spike protein-specific IgG AUC between 14 and 90 days of COVID-19 onset. Specimens obtained out of this range were excluded.