Relationships between Viral Load and the Clinical Course of COVID-19

Tsukagoshi, Hiroyuki; Shinoda, Daisuke; Saito, Mariko; Okayama, Kaori; Sada, Mitsuru; Kimura, Hirokazu; Saruki, Nobuhiro

doi:10.3390/v13020304

Cited by 58 publications

(51 citation statements)

References 25 publications

(25 reference statements)

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“…Nonetheless, the impact of viral load on adults may differ from its effect on children. It is widely reported that viral load is higher in symptomatic than asymptomatic COVID-19 adults ( 30 ). The data available in the pediatric population are controversial.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…An important aspect of these data is whether there are differences between age groups, especially the often-quoted assumption that children and adolescents are more likely to be asymptomatic following infection. Early data suggested that asymptomatic disease was indeed inversely correlated with age 17 . However, the Real-time Assessment of Community Transmission 2 (REACT-2) UK national study considered asymptomatic disease in a large cohort of 106,000 adults sampled by specific antibody tests during the first wave of the pandemic in the UK (March to June 2020); 5,544 tested positive, of whom one-third had reported no symptoms, although this rose to more than half of those older than 65 years 6 .…”

Section: How Common Is Asymptomatic Infection?mentioning

confidence: 99%

The immunology of asymptomatic SARS-CoV-2 infection: what are the key questions?

Boyton

Altmann

2021

Nat Rev Immunol

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An important challenge during the COVID-19 pandemic has been to understand asymptomatic disease and the extent to which this may be a source of transmission. As asymptomatic disease is by definition hard to screen for, there is a lack of clarity about this aspect of the COVID-19 spectrum. Studies have considered whether the prevalence of asymptomatic disease is determined by differences in age, demographics, viral load, duration of shedding, and magnitude or durability of immunity. It is clear that adaptive immunity is strongly activated during asymptomatic infection, but some features of the T cell and antibody response may differ from those in symptomatic disease. Areas that need greater clarity include the extent to which asymptomatic disease leads to persistent symptoms (long COVID), and the quality, quantity and durability of immune priming required to confer subsequent protection.

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“…Specific molecular signatures of immune profiling have indicated that delayed adaptive immune responses are correlated with poorer outcomes from SARS-CoV-2 infection [ 48 , 95 , 96 ]. In addition, high viral titres at a range of sampling sites (mostly naso/oropharyngeal, but also saliva, sputum, blood, plasma, urine and stool) have been associated with disease severity [ 97 , 98 ], although further work is required to better understand the relationship between viral titres, severity, and impaired adaptive immunity. A putative explanation for the pathophysiology of severe COVID-19 is that the immune evasion by SARS-CoV-2 prevents an adequate early adaptive immune response, allowing uncontrolled viral replication.…”

Section: Systemic Immune Responsesmentioning

confidence: 99%