key: cord-0739317-uun7c3zy
authors: DeBiasi, Roberta L.; Song, Xiaoyan; Delaney, Meghan; Bell, Michael; Smith, Karen; Pershad, Jay; Ansusinha, Emily; Hahn, Andrea; Hamdy, Rana; Harik, Nada; Hanisch, Benjamin; Jantausch, Barbara; Koay, Adeline; Steinhorn, Robin; Newman, Kurt; Wessel, David
title: Severe COVID-19 in Children and Young Adults in the Washington, DC Metropolitan Region
date: 2020-05-13
journal: J Pediatr
DOI: 10.1016/j.jpeds.2020.05.007
sha: a58c9956849d0b9b042c42f426072aed34a3d3c4
doc_id: 739317
cord_uid: uun7c3zy

nan

young adults, including 44 hospitalized and 9 critically ill patients, with comparison of patient characteristics between infected hospitalized and non-hospitalized cohorts, as well as critically ill and non-critically ill cohorts. Children <1 year and adolescents /young adults >15 years of age were over-represented among hospitalized patients (P = .07).

Adolescents/young adults were over-represented among the critically ill cohort. (P = .02).

Since the emergence and worldwide spread of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), published summaries have predominantly highlighted that children represent a small proportion (<2%) of COVID-19 cases, including hospitalizations and deaths. [1] [2] [3] Although children and young adults clearly are susceptible to SARS-CoV-2 infection, attention has focused primarily on their potential role in influencing spread and community transmission rather than the potential severity of infection in children and young adults themselves. Reanalyzed data from the epicenter of the Chinese outbreak noted that children represented 12% of infections. 4 To date, reports of severe disease in international pediatric populations have been limited, primarily descriptive, and in the United States, limited only to incomplete public health epidemiologic data. [5] [6] [7] [8] [9] Methods: This observational retrospective cohort study included 177 children and young adults with clinical symptoms and laboratory confirmed (177/1804; 9.8% of tested) SARS-CoV-2 infection treated between March 15 and April 30, 2020 at the Children's National Hospital, a large freestanding medical center located in Washington DC. These 177 patients came to medical attention for clinical evaluation of symptoms to our emergency departments, ambulatory clinics, inpatient units, or by referral for admission from external facilities. From these 177 infected patients, we identified cohorts of non-hospitalized (N=133) and hospitalized (N=44) patients. Of the 44 hospitalized patients, we identified cohorts of non-critically ill (N=35) and critically ill (N=9) patients. The objective of the study was to determine if specific epidemiologic and clinical patient characteristics were more likely to be associated with hospitalization and/or critical care. Data were extracted from medical records and recorded in a RedCap database, including age, sex, presence or absence of underlying medical condition and presence or absence of fever or respiratory symptoms (rhinorrhea, sore throat, cough, shortness of breath), as well as other symptoms (diarrhea/vomiting, myalgia, chest pain, loss of sense of taste or smell, headache). The Fisher exact test was performed to examine differences in the distribution of categorical variables between hospitalized vs. non-hospitalized patients, as well as between hospitalized critically ill patients vs. non-critically ill patients. Continuous variables were evaluated using logistic regression. This project was submitted to the IRB and was determined to be a Quality Improvement initiative and not human subjects research.

Of the 177 pediatric and young adult SARS-CoV-2 infected patients, 44/177 patients (25%) required hospitalization, of which 35/44 (80%) were non-critically ill and 9/44 (20%) were critically ill.

Age: Children and young adults from all age groups were infected by SARS CoV-2, with a median age of 9.6 years (range 0.1-34.2 years of age). The median age of SARS-CoV-2 infected hospitalized patients compared with non-hospitalized patients was not significantly different (9.6 years versus 9.5 years), but the median age of critically ill patients compared with non-critically ill patients was significantly higher (17.3 years versus 3.6 years; P =.04) ( Table I) . We found no overall difference in the representation of different age groups within the hospitalized and non-hospitalized cohorts, nor between the critically ill and non-critically ill cohorts. However, we noted a bimodal distribution of patients less than one year of age and patients >15 years of age representing the largest proportion of patients within the SARS CoV-2 infected hospitalized and critically ill cohorts. Children <1 year of age and children/young adults >15 years of age each represented 32% (14/44) of all hospitalized patients, accounting for a total of 64% of hospitalizations (p=0.07). Adolescents and young adults > 15 years of age represented 66% (6/9) of critical care admissions (p=0.02). (Figure) .

Sex: Males and females were equally represented within the total SARS CoV-2 infected cohort (52% male, 48% female), as well as the infected hospitalized cohort (50% male, 50% female). There was a predominance of males in the critically ill hospitalized cohort (67% male, 33% female); but this was not statistically significant (p=0.26) Underlying Medical Conditions: Underlying medical conditions were also present in 69/177 (39%) of all patients with SARS-CoV-2 infection. The most frequent underlying diagnosis overall was asthma (35/177; 20%), but also included neurologic (6%), diabetes (3%), obesity (2%), cardiac (3%), hematologic (3%) and oncologic (1%) underlying conditions Underlying conditions were more common as a whole in the SARS-CoV2 infected hospitalized cohort (27/44; 63%) compared with the infected nonhospitalized cohort (42/133; 32%; p=0.001). Several specific underlying conditions were more common in the hospitalized as non-hospitalized patients. Specifically, neurological disorders were more common in the hospitalized cohort (8/44; 19%; p<0.001) compared with the non-hospitalized cohort (3/133; 2%; p<0.001). Additionally, cardiac (p=0.004), hematologic (p=0.004), and oncologic (p=0.013) diagnoses were more common in the hospitalized as compared with the non-hospitalized cohort.

Although asthma was the most prevalent underlying condition overall, it was not more common in the hospitalized cohort (7/44; 16%) compared with the non-hospitalized cohort (28/133; 21%; p =0.46), nor more common in the critically ill cohort (2/11; 22%) compared with the non-critically ill cohort (5/35; 14%; p=0.62). Comparing the SARS-CoV-2 infected non-critically ill and critically ill hospitalized patients, there were no significant difference in the presence of underlying conditions overall or any specific underlying diagnosis. Of note, there was no underlying condition present in 96/177 (55%) SARS-CoV-2 infected patients overall, 16/44 (37%) hospitalized patients and 2/9 (22%) critically ill patients.

The majority (134/177; 76%) of SARS-CoV-2 infected patients came to medical attention with respiratory symptoms (rhinorrhea, congestion, sore throat, cough or shortness of breath) with or without fever. However, only 85/177 (48%) had both fever and respiratory symptoms present. Fever was present in 116/177 (66%) of SARS-CoV-2 infected patients but was not more common in the infected hospitalized cohort (34/44, 77%) compared with the infected non-hospitalized cohort (82/133, 62%; p=0.46). Shortness of breath was more common in the hospitalized cohort (11/44, 26%) compared with non-hospitalized (16/133, 12%; p=0.04). However, less severe respiratory symptoms including sore throat/congestion (p=0.004), or cough (p=0.003) as well as headache (p=0.01) were more common in the non-hospitalized cohort. Other symptoms were also present, including diarrhea/vomiting (27/177, 15%), myalgia (25/177, 14%), chest pain (16/177, 9%) and loss of sense of smell or taste (15/177, 9%), but presence of these symptoms did not vary significantly between cohorts.

Patients in the critically ill cohort were not more likely to have fever or any other specific symptom compared with the non-critically ill cohort.

Critically Ill Cohort: Eight (8) Although all age groups were infected with SARs-CoV-2, the youngest (<1 year) and oldest children/young adults (15-25 years of age) were more likely to be hospitalized, and the oldest were the most likely to require critical care. Underlying conditions were also present in 39% of patients with SARS-CoV-2 infection overall but hospitalized and critically ill patients were more likely to have underlying conditions. Conversely, approximately 55% overall, 37% of hospitalized and 22% of critically ill patients had no underlying conditions, reinforcing the concept that social distancing and hygienic measures to avoid infection should be taken seriously in the pediatric age group, as well as adults.

Although asthma was the most common underlying diagnosis present in the overall group of children and young adults with SARS-CoV-2 infection, children and young adults with asthma were not over-represented in the hospitalized cohort or in the critically ill cohort. This suggests that although children and young adults with asthma may commonly experience exacerbation in response to SARS-CoV-2 infection, asthma exacerbation is not the primary determinant of more severe disease requiring hospitalization. Many underlying diagnoses that have been associated with more severe disease in adults were also present in our pediatric and young adult patients.

However, only neurologic, cardiac, hematologic, and oncologic underlying diagnoses were significantly more common in the hospitalized cohort compared with the nonhospitalized cohort, and none was more common in the critically ill compared with the non-critically-ill cohort.

With regard to symptoms, shortness of breath was more common in hospitalized compared with non-hospitalized children/young adults, but other features did not clearly distinguish them from less ill children, including presence of fever. Minor symptoms such as congestion/rhinorrhea, sore throat, cough and headache were also present more commonly in the non-hospitalized cohort. As has been the case in adult reports, fewer than half of the patients had both fever and respiratory symptoms present at the time of their diagnosis, but the majorities have one or the other. Our critically ill cohort includes a previously well child with the newly emerged hyper-inflammatory phenotype of SARS-CoV-2-associated KD-like shock syndrome that has been identified concurrently within the same time frame at other centers internationally. The pathogenesis of this phenotype is not yet fully characterized but it is important to recognize as yet another potential severe presentation in the pediatric population.

Co-infection with other viruses was distinctly uncommon in SARS-CoV-2 infected children and young adults; 94% of those in whom this was assessed had no co-infection detected. Of the 6% who had an additional virus detected, enterovirus/rhinovirus was responsible for half, which is of unclear significance since enteroviruses are known to be shed asymptomatically and detectable for months after initial infection. There was no association between viral co-detection and severity of disease.

The reasons for the observed increased severity of disease in our pediatric and young adult cohort requires additional detailed analysis, but potentially includes the comparatively higher population density in our region compared with the Western United States and/or the higher representation of African American race and/or Latino/Hispanic ethnicity in our patient population, which has recently emerged as a risk factor for more severe disease in adult populations. It recently has been noted that introduction of SARS-CoV-2 to the Eastern United States most likely occurred as a result of importation of European strains, rather than Asian strains. Although no significant mutations conferring increased pathogenicity have yet been described, this is another potential difference that merits further analysis.

Limitations of this study include the retrospective design and the fact that transmission is still ongoing at a steady rate of increase in our region, thus this represents interim data, which will only be augmented further in the coming weeks. We plan to address the role of race and ethnicity after validation of current administrative data and have elected to defer this analysis until completed. One potential bias of this study is our regional role in providing critical care for young adults age 21-35 years of age with COVID-19.

However only two such hospitalized patients were present in this study at the time of this interim report. Our study results would be expected to be generalizable to other regions on the East Coast with similar patient populations and population density, but may differ from other regions in the US that have yet to experience expansion and surge of SARS-CoV2 cases, including rural areas.

In summary, our findings highlight the potential for severe disease in this age group and inform other regions to anticipate and prepare their COVID-19 response to include a significant burden of hospitalized and critically ill children and young adults. As SARS-CoV-2 spreads within the United States, regional differences may be apparent based on virus and host factors that are yet to be identified. 

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