Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies

Buonsenso, Danilo; Martino, Laura; Morello, Rosa; Mariani, Francesco; Fearnley, Kelly; Valentini, Piero

doi:10.1016/s2666-5247(23)00115-5

Cited by 26 publications

(7 citation statements)

References 76 publications

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“…SARS-CoV-2 replication might occur for several months after the initial infection, as evinced by the detection of subgenomic RNA, a marker of recent virus replication; the isolation of replication-competent SARS-CoV-2 from respiratory and non-respiratory tissues [ 226 , 227 , 228 ]; and the existence of viral reservoirs for SARS-CoV-2 [ 229 , 230 ]. More specifically, these studies have demonstrated the persistence of viral antigens, viral RNA, and whole virus in the brain, sinus, adrenal glands, kidneys, gut, lymph nodes, spleen, lungs, heart, and fungiform papillae in taste buds, which can underlie symptoms through direct viral cytopathic effects; regional inflammation; triggering an immune response causing an elevated and prolonged state of generalized inflammation; and prompting autoimmunity in pediatric or adult populations, independently from the severity of acute disease [ 231 , 232 ]. Extracellular coronaviral N could have similar effects as HIV-1 Tat in terms of toxicity to the nervous system or other organs, even though neither virus can infect neurons.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2

Patarca,

Haseltine

2024

IJMS

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Viruses provide vital insights into gene expression control. Viral transactivators, with other viral and cellular proteins, regulate expression of self, other viruses, and host genes with profound effects on infected cells, underlying inflammation, control of immune responses, and pathogenesis. The multifunctional Tat proteins of lentiviruses (HIV-1, HIV-2, and SIV) transactivate gene expression by recruiting host proteins and binding to transacting responsive regions (TARs) in viral and host RNAs. SARS-CoV-2 nucleocapsid participates in early viral transcription, recruits similar cellular proteins, and shares intracellular, surface, and extracellular distribution with Tat. SARS-CoV-2 nucleocapsid interacting with the replication–transcription complex might, therefore, transactivate viral and cellular RNAs in the transcription and reactivation of self and other viruses, acute and chronic pathogenesis, immune evasion, and viral evolution. Here, we show, by using primary and secondary structural comparisons, that the leaders of SARS-CoV-2 and other coronaviruses contain TAR-like sequences in stem-loops 2 and 3. The coronaviral nucleocapsid C-terminal domains harbor a region of similarity to TAR-binding regions of lentiviral Tat proteins, and coronaviral nonstructural protein 12 has a cysteine-rich metal binding, dimerization domain, as do lentiviral Tat proteins. Although SARS-CoV-1 nucleocapsid transactivated gene expression in a replicon-based study, further experimental evidence for coronaviral transactivation and its possible implications is warranted.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2

Patarca,

Haseltine

2024

IJMS

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“…The virus's persistence in tissues post-recovery indicates potential reservoirs in extrapulmonary organs, as seen in adults and children (209,210). This persistence has been observed in extrapulmonary organs, even in immunocompetent individuals and post-mortem subjects, several weeks or months post-infection (211). In autopsies of deceased individuals, the viral RNA was detected in various tissues, including the CNS and endothelium, weeks or months after infection despite being undetectable in plasma (212,213).…”

Section: Damage To Endothelial Barriers and Viral Persistencementioning

confidence: 99%

Pathophysiological, immunological, and inflammatory features of long COVID

Bohmwald,

Diethelm-Varela,

Rodríguez-Guilarte

et al. 2024

Front. Immunol.

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The COVID-19 pandemic continues to cause severe global disruption, resulting in significant excess mortality, overwhelming healthcare systems, and imposing substantial social and economic burdens on nations. While most of the attention and therapeutic efforts have concentrated on the acute phase of the disease, a notable proportion of survivors experience persistent symptoms post-infection clearance. This diverse set of symptoms, loosely categorized as long COVID, presents a potential additional public health crisis. It is estimated that 1 in 5 COVID-19 survivors exhibit clinical manifestations consistent with long COVID. Despite this prevalence, the mechanisms and pathophysiology of long COVID remain poorly understood. Alarmingly, evidence suggests that a significant proportion of cases within this clinical condition develop debilitating or disabling symptoms. Hence, urgent priority should be given to further studies on this condition to equip global public health systems for its management. This review provides an overview of available information on this emerging clinical condition, focusing on the affected individuals’ epidemiology, pathophysiological mechanisms, and immunological and inflammatory profiles.

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“…The virus persists in some tissues of the body, but it is not sufficient to cause typical clinical manifestations and can form viral reservoirs in vivo . In clinical studies in children and adults, viral RNA and protein can still be detected 2 months after acute infection in some patients, and there is a certain correlation with the symptoms of long COVID ( 16 - 19 ). Furthermore, the activation of herpes virus such as Epstein-Barr virus (EBV) from latent state may also be one of the potential mechanisms ( 20 ).…”

Section: Pathogenesis Of Long Covidmentioning

confidence: 99%

Advances in researches on long coronavirus disease in children: a narrative review

Zhang,

Kuang,

Liu

2024

Transl Pediatr

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Background and Objective In the context of the global pandemic of coronavirus disease 2019 (COVID-19), more than 700 million infections and millions of deaths have occurred in countries around the world. Currently, two main sequelae of this disease are considered to occur in children, namely, multi-system inflammatory syndrome in children and long COVID. Among these two, the incidence of long COVID is higher and its impact on the population is more extensive, which is the focus of us. However, due to the lack of relevant studies and the limitations of most studies, the studies on sequelae of COVID-19 infection lag behind those of adults, but they have begun to attract the attention of some clinicians and researchers. We aim to summarize the current knowledge of long COVID in children, helping pediatricians and researchers to better understand this disease and providing guidance on research and clinical treatment of it. Methods We reviewed all the studies on “long COVID”, pediatric, children, adolescent, post-COVID syndrome in PubMed published after 2019. Key Content and Findings This review summarizes the latest researches on epidemiology, pathogenesis, clinical manifestations, prevention and treatment of long COVID in children. Based on the existing research data, we summarized and analyzed the characteristics of long COVID in children, discovering the means to decipher the diagnosis of COVID-19 in children and some potential therapeutic treatments. Conclusions We aim to summarize existing research on long COVID in children and help pediatricians and government agencies quickly understand the disease so that it can be used for clinical diagnosis, treatment and prevention in the population. In addition, providing a research basis for further researches on the cellular and even molecular level to explain the occurrence and development of diseases, and has a guiding role for future research direction.

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Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies

Cited by 26 publications

References 76 publications

Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2

Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2

Pathophysiological, immunological, and inflammatory features of long COVID

Advances in researches on long coronavirus disease in children: a narrative review

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