key: cord-0970388-0n04dyzd
authors: Aykac, Kubra; Cura Yayla, Burcu Ceylan; Ozsurekci, Yasemin; Evren, Kubra; Oygar, Pembe Derin; Gurlevik, Sibel Lacinel; Coskun, Tugce; Tasci, Onur; Demirel Kaya, Filiz; Fidanci, Ilknur; Tasar, Medine Aysin; Alp, Alpaslan; Cengiz, Ali Bulent; Karahan, Sevilay; Ceyhan, Mehmet
title: The association of viral load and disease severity in children with COVID‐19
date: 2021-02-16
journal: J Med Virol
DOI: 10.1002/jmv.26853
sha: 49252668714977a0e0af3d2bcde96d928de2645b
doc_id: 970388
cord_uid: 0n04dyzd

It is still not fully understood how to predict the future prognosis of patients at the diagnosis coronavirus disease 2019 (COVID‐19) due to the wide clinical range of the disease. We aimed to evaluate whether severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) viral load could predict the clinical course of pediatric patients. This study was conducted retrospectively with medical records of pediatric patients who were tested for SARS‐CoV2 between April 12 and October 25, 2020 in the University of Health Sciences, Ankara Educating and Training Hospital and Hacettepe University Faculty of Medicine. We evaluated 518 pediatric patients diagnosed with COVID‐19 and classified according to severity as asymptomatic (16.2%), mild (59.6%), moderate (20.2%), and critical/severe (3.9%) cases. We analyzed patients in four groups in terms of ages: <4, 5‐9, 10–14, and 15–17 years. There was no statistically significant difference in terms of ∆C (t) value among age groups, different gender and the existence of underlying diseases in each disease course. The ∆C (t) values were relatively lower in the first 2 days of symptoms than after days in all groups. Our study has indicated that children with COVID‐19 have similar amount of viral load in all disease courses irrespective of the age and underlying disease. It should be taken into account that, regardless of the severity of the disease, pediatric patients may have a role in the transmission chain.

The whole world is still trying to cope with the coronavirus disease 2019 (COVID- 19) pandemic. For doctors in the clinical setting, the first step for an accurate diagnosis is to suspect the disease according to the symptoms and epidemiologic features of patients and secondly to confirm the diagnosis with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA in the nasopharyngeal swabs by reverse transcriptase-polymerase chain reaction (RT-PCR).

Then, the classification of the clinical course and flow up of the patients to predict the future prognosis and decide for the appropriate treatment are of great importance to find the most appropriate management strategy. However, there is still knowledge gap regarding the prognostic marker for patients with COVID-19 besides, vaccines and effective therapies. [1] [2] [3] Even if, SARS-CoV-2 causes less severe disease and progresses better in children than in adults, the clinical manifestations of children's COVID-19 cases ranged from asymptomatic to critical disease course. 4 It is significant for a pediatrician to provide information and predict which patients are at high risk for the deterioration and have severe or critical disease because of the wide clinical range of COVID-19.

The standard molecular method for the diagnosis of COVID-19 is the real-time RT-PCR. 5 Real-time PCR cycle threshold (C t ) values represent the number of amplification cycles required for the target gene to exceed a threshold level. 6 It was assumed that C t values are an appropriate surrogate for viral load. 7 Some studies showed the correlations between SARS-CoV-2 C t values and clinical outcomes of patients. 3, [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] Moreover, the correlation was shown between C t value and the progression to severe disease and even mortality. 9,10 Additionally, some parameters, such as increased lactate dehydrogenase, decreased lymphocytes and increased high-sensitivity troponin showed an association between viral loads in studies. 9, [11] [12] [13] Due to the limited data in pediatric patients regarding the viral load, we aimed to examine whether the diagnostic viral load has any effect or association with disease severity in children. 

Statistical analyses were performed using SPSS for Windows version 20.0. Descriptive statistics used to define baseline characteristics of cases were mean, median, minimum-maximum, and interquartile ranges (IQRs) for continuous variables and percentages besides numbers for categorical variables. χ 2 and Kruskal-Wallis tests were performed to compare categorical and continuous variables, respectively. The Mann-Whitney U test was used to evaluate non-normally distributed data. In all the analyses, all tests were twotailed and p < .05 was considered significant.

A total of 518 pediatric patients with the diagnosis of COVID-19

were included in the study. The median (IQR) age of total patients was 11 years (5-14), 48.3% were male and the median day after onset of the symptom to the diagnosis was 1 day, ranging from 0 to 21 days. We analyzed patients in four groups in terms of ages: <4, Table 1 .

We first analyzed the laboratory parameters and ΔC t value of patients in each clinical course ( Table 2) . Of the asymptomatic group, the median SARS-CoV-2 RNA ΔC t value from nasopharynx samples was 

We then evaluated the ΔC t value of patients in each clinical course and also according to age groups (<4 years, 5-9 years, 10-14 years, and 15-17 years). There was no statistically significant difference among age groups in each clinical course; asymptomatic, mild, moderate, and severe or critical, in terms of ΔC t value (p = .21, p = .69, 

Our findings demonstrate that the ΔC t which was assumed to be inversely related to viral load were similar in all clinical courses and in all age groups in children with COVID-19 in contrast to some previous reports, in which they reported that C t values were However, some studies reported no age correlation with viral load in children. 26, 27 Although the viral load of SARS-CoV-2 might be a useful marker for assessing disease severity and prognosis in adults,

there is no such kind of relation between viral load and disease severity in children with COVID-19 according to the finding of the present study. To the best of our knowledge, our study is also one of the few studies that evaluate the viral load in different clinical courses in a large pediatric population in the English literature.

According to the scientific report of World Health Organization, transmission can also occur from people who are infected and remain asymptomatic. 28 Additionally, SARS-CoV-2 burden in respiratory epithelial cells indicates a risk to transmit this virus, as well. 29 In this situation, we should pay attention the role of children in the spread of COVID-19 due to the fact that most of the children with COVID-19

have asymptomatic or mild disease course as in our study. We also demonstrated that viral load was similar, even in different gender groups and the presence of the underlying disease, besides age and clinical course in pediatric patients. Namely, host factors including underlying disease, gender and age did not impact viral load and the viral load has no effect on the prediction of the clinical course of children. There are many unclear issues regarding the increased risk of severe disease in children with underlying disease, 30 

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The authors declare that there are no conflict of interests. 

The data that support the findings of this study are available from the corresponding author upon reasonable request.

http://orcid.org/0000-0002-0974-4765Yasemin Ozsurekci http://orcid.org/0000-0001-8662-6909Pembe Derin Oygar http://orcid.org/0000-0002-8612-4586