The association of viral load and disease severity in children with COVID‐19

Aykaç, Kübra; Yayla, Burcu Ceylan Cura; Özsürekçi, Yasemin; Evren, Kübra; Oygar, Pembe Derin; Gürlevik, Sibel Laçinel; Coskun, Tugce; Taşçı, Onur; Demirel, Filiz; Fidancı, İlknur; Taşar, Medine Aysin; Alp, Alpaslan; Cengiz, Ali Bülent; Karahan, Sevilay; Ceyhan, Mehmet

doi:10.1002/jmv.26853

Cited by 30 publications

(29 citation statements)

References 30 publications

(71 reference statements)

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“…We identified 9937 potentially relevant records from the literature databases and registers, and 1575 records from the additional searches. After screening the titles, abstracts and full texts, 56 studies (22 cohort studies, 9 case-control studies, and 25 case series) with a total of 79,104 patients were included [ [10] , [11] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [75] , [76] ] ( Fig. 1 ).…”

Section: Resultsmentioning

confidence: 99%

Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis

et al. 2021

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Background This study provides the first systematic review and meta-analysis to identify the predictors of unfavorable prognosis of COVID-19 in children and adolescents. Methods We searched literature databases until July 2021 for studies that investigated risk factors for unfavorable prognosis of children and adolescents with COVID-19. We used random-effects models to estimate the effect size with 95% confidence interval ( CI ). Findings We identified 56 studies comprising 79,104 individuals. Mortality was higher in patients with multisystem inflammatory syndrome (MIS-C) (odds ratio [ OR ]=58.00, 95% CI 6.39–526.79) and who were admitted to intensive care ( OR =12.64, 95% CI 3.42–46.68). Acute respiratry distress syndrme (ARDS) ( OR =29.54, 95% CI 12.69–68.78) and acute kidney injury (AKI) ( OR =55.02, 95% CI 6.26–483.35) increased the odds to be admitted to intensive care; shortness of breath ( OR =16.96, 95% CI 7.66–37.51) increased the need of respiratory support; and neurological diseases ( OR =5.16, 95% CI 2.30–11.60), C-reactive protein (CRP) level ≥80 mg/L ( OR =11.70, 95% CI 4.37–31.37) and D-dimer level ≥0.5ug/mL ( OR =20.40, 95% CI 1.76–236.44) increased the odds of progression to severe or critical disease. Interpretation Congenital heart disease, chronic pulmonary disease, neurological diseases, obesity, MIS-C, shortness of breath, ARDS, AKI, gastrointestinal symptoms, elevated CRP and D-dimer are associated with unfavourable prognosis in children and adolescents with COVID-19.

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Section: Resultsmentioning

confidence: 99%

Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis

et al. 2021

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“…The data available in the pediatric population are controversial. Some studies found higher levels in symptomatic children compared to asymptomatic children (25,31), while other reports found no association of viral load and disease severity (5,32). A recent study, conducted in COVID-19 children within their first week from baseline (symptom onset and/or first positive virus detection) demonstrated an inverse relationship between viral load and nAbs, and the estimation of virus under curve from NPS, collected every 48 h up to undetectable viral load, confirmed the impact of nAbs on virus clearance (15).…”

Section: Differences Of Immunological Profile and Relationship With Prnt At Second Samplingmentioning

confidence: 99%

Asymptomatic and Mild SARS-CoV-2 Infections Elicit Lower Immune Activation and Higher Specific Neutralizing Antibodies in Children Than in Adults

et al. 2021

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BackgroundThe immune response plays a pivotal role in dictating the clinical outcome in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected adults, but it is still poorly investigated in the pediatric population.MethodsOf 209 enrolled subjects, 155 patients were confirmed by PCR and/or serology as having coronavirus disease 2019 (COVID-19). Blood samples were obtained at a median of 2.8 (interquartile, 2.1–3.7) and 6.1 (5.3–7.2) months after baseline (symptom onset and/or first positive virus detection). The immune profiles of activation, senescence, exhaustion, and regulatory cells were analyzed by flow cytometry. Neutralizing antibodies (nAbs) were detected by a plaque reduction neutralization test. In available nasopharyngeal swabs at baseline, SARS-CoV-2 levels were quantified by digital droplet PCR (ddPCR).ResultsOverall, COVID-19 patients had higher levels of immune activation, exhaustion, and regulatory cells compared to non-COVID-19 subjects. Within the COVID-19 group, activated and senescent cells were higher in adults than in children and inversely correlated with the nAbs levels. Conversely, Tregs and Bregs regulatory cells were higher in COVID-19 children compared to adults and positively correlated with nAbs. Higher immune activation still persisted in adults after 6 months of infection, while children maintained higher levels of regulatory cells. SARS-CoV-2 levels did not differ among age classes.ConclusionsAdults displayed higher immune activation and lower production of anti-SARS-CoV-2 nAbs than children. The different immune response was not related to different viral load. The higher expression of regulatory cells in children may contribute to reduce the immune activation, thus leading to a greater specific response against the virus.

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“…Our findings seem to be consistent with the previous results that showed similar viral load irrespective of age and disease severity in children with COVID-19. 22,23) On the other hand, a study in adult patients showed that viral load was correlated with disease severity, 24) and another study in pediatric patients reported that young children under 5 years of age had significantly higher viral load compared with older children and adults. 25) [27][28][29] but not in pediatric patients yet.…”

Section: A C C E P T E D a R T I C L Ementioning

confidence: 99%

Viral load and rebound in children with coronavirus disease 2019 during the first outbreak in Daegu city

et al. 2021

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Background: Viral load and shedding duration are highly associated with the transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, limited studies have reported on viral load or shedding in children and adolescents infected with sudden acute respiratory syndrome coronavirus 2 (SARS-CoV-2).Purpose: This study aimed to investigate the natural course of viral load in asymptomatic or mild pediatric cases.Methods: Thirty-one children (<18 years) with confirmed SARS-CoV-2 infection were hospitalized and enrolled in this study. Viral loads were evaluated in nasopharyngeal swab samples using real-time reverse transcription polymerase chain reaction (E, RdRp, N genes).Ct values were measured when patients met the clinical criteria to be released from quarantine.Results: The mean age of the patients was 9.8 years, 18 (58%) had mild disease, and 13 (42%) were asymptomatic. Most children were infected by adult family members, most commonly by their mothers. The most common symptoms were fever and sputum (26%), followed by cough and runny nose. Nine patients (29%) had a high or intermediate viral load (Ct value≤30) when they had no clinical symptoms. Viral load showed no difference between symptomatic and asymptomatic patients. Viral rebounds were found in 15 cases (48%), which contributed to prolonged viral detection. The mean duration of viral detection was 25.6 days.Viral loads were significantly lower in patients with viral rebounds than in those with no rebound (E, p=0.003; RdRp, p=0.01; N, p=0.02). Conclusion: Our study showed that many pediatric patients with COVID-19 experiencedA c c e p t e d A r t i c l e 3 viral rebound and showed viral detection for more than 3 weeks. Further studies are needed to investigate the relationship between viral rebound and infectiousness in COVID-19.

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The association of viral load and disease severity in children with COVID‐19

Cited by 30 publications

References 30 publications

Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis

Risk factors for poor prognosis in children and adolescents with COVID-19: A systematic review and meta-analysis

Asymptomatic and Mild SARS-CoV-2 Infections Elicit Lower Immune Activation and Higher Specific Neutralizing Antibodies in Children Than in Adults

Viral load and rebound in children with coronavirus disease 2019 during the first outbreak in Daegu city

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