Understanding the biological consequences of persistent SARS-CoV-2 infection in children

In a study published in lancet microbeResearchers analyzed the current knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen or ribonucleic acid (RNA) persistence in children infected with SARS-CoV-2.

study: Viral Persistence in Children Infected with SARS-CoV-2: Current Evidence and Future Research Strategies. Image credit: FamVeld/Shutterstock.com

Background

Although our knowledge of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its interactions with humans has advanced significantly since its emergence in December 2019, many unanswered questions about this virus remain. can have a significant impact on the health of both children and adults.

Post-COVID-19 (post-coronavirus disease), the prolonged state of COVID-19 in which the virus persists in the body, poses challenges for researchers and patients, including adults and children. It has become one of the biggest hurdles. Prolonged COVID-19 development is associated with many biological abnormalities.

Nevertheless, the exact etiology is still unknown. The current focus is on persistence of the virus or its components in the human body after initial infection.

About research

In this study, the authors explored the potential sustainability of SARS-CoV-2 in pediatric patients, how it might affect patients, and how it might affect the post-COVID-19 situation. Current data were evaluated as to whether the

Investigators conducted a literature review to identify SARS-CoV-1 in children who died from multisystem inflammatory syndrome and COVID-19, or who underwent surgery, biopsy, or autopsy for post-COVID-19 evaluation. Studies on the presence of two antigens and RNA were analyzed. or any other terms of PubMed.

The review included 21 articles after screening and selection of identified studies. The age range of patients undergoing tissue biopsy or autopsy ranged from 1 day to 17 years.

The research team also analyzed why these findings may serve as a basis for future therapeutic and diagnostic research on SARS-CoV-2 infection. The study also included personal experiences of doctors and patients.

Persistence of SARS-CoV-2 in adults

A study assessing viral persistence and immunopathology in patients with COVID-19 who died for some reason weeks to months after initial infection found that some of the virus may persist in the body. evidence was shown.

Recent evidence has revealed a low or low efficiency of SARS-CoV-2 clearance in non-respiratory tissues. Therefore, understanding how SARS-CoV-2 evades immunodetection is crucial to guide future therapies that facilitate viral clearance.

In addition, several immunological and anatomic pathological studies in immunocompetent and immunocompromised adults have demonstrated that SARS-CoV-2 antigen and RNA may persist in pulmonary and extra-pulmonary regions.

These events have been observed in SARS-CoV-2 pleomicron variant-infected patients. Therefore, these results may not apply to patients with Omicron-mutant infections.

Nonetheless, there is evidence that patients infected with Omicron also develop post-COVID-19 symptoms, suggesting that the virus may persist among newly infected patients until disproved. .

Presence of SARS-CoV-2 in pediatric populations

Of the 21 studies included in this review, eight papers focused on postmortem histopathological results and reverse transcription-polymerase chain reaction (RT-PCR) in pediatric tissues undergoing autopsy due to acute lethal disease. It referred to the detection of SARS-CoV-2 RNA by disease complications.

Six publications have demonstrated the presence of viral RNA in the central nervous system (CNS) and other organs and tissues. In addition, no SARS-CoV-2 RNA was identified in blood, cerebrospinal fluid (CSF), lung, or brain tissue samples from pediatric patients who died from acute fulminant cerebral edema associated with COVID-19. .

In three studies, pediatric patients with COVID-19-associated pneumonia showed respiratory tissue viral infection confirmed by RT-PCR testing.

Furthermore, the authors noted that 11 studies in this study showed that the virus, or at least parts thereof, persisted in children’s body fluids and tissues for weeks to months after acute SARS-CoV-2 infection. .

In addition, three papers describe the postmortem discovery of SARS-CoV-2 RNA in pediatric tissues with multisystem inflammatory syndrome. A case report demonstrated the presence of the SARS-CoV-2 nucleocapsid protein in the intestinal lamina propria of a girl with persistent gastrointestinal symptoms 3 months after acute SARS-CoV-2 infection.

Two papers describe that RT-PCR confirmed SARS-CoV-2 persistence in adenoids and palatine tonsils in children with mild or asymptomatic acute infections. In addition, another study showed detection of SARS-CoV-2 RNA by RT-PCR in the CSF of a 17-year-old girl with Guillain-Barré syndrome associated with acute COVID-19.

Two of these included papers investigating the presence of SARS-CoV-2 RNA in the tissues of stillborn infants who died from COVID-19 in their mothers during pregnancy, and viral RNA was detected in their organs. was done. The most frequent anatomic pathological observations were associated with intrauterine hypoxia, asphyxia, hemosiderosis and hepatocellular injury.

A mother of a very preterm infant who died at 4 days of age had severe acute SARS-CoV-2 infection, with viral RNA present in neonatal liver and heart vascular endothelium, and various placental and neonatal samples. Was.

Potential impact of persistence of SARS-CoV-2 or its particles

Although the biological effects of SARS-CoV-2 RNA persistence are unknown, preliminary data indicate that these viral components may stimulate immune responses. Research reveals that CXCR5+ CD8+ T cells may act as SARS-CoV-2 spreaders in different parts of the body, masking viruses and sources of inflammation during long-lasting COVID-19 infections bottom.

In addition, a pilot study documented an impaired ability to switch from nonspecific to adaptive immune responses in a subgroup of children after COVID-19.

In addition, evidence suggests that prolonged SARS-CoV-2 antigenemia can cause hyperinflammatory symptoms and prolonged COVID in multisystem inflammatory syndrome in pediatric populations.

Observational studies found a surge in new-onset immune-mediated diseases in children with a history of COVID-19, similar to type 1 diabetes, but SARS-CoV-2 infection and A clear association or causal relationship with type 1 diabetes is unknown.

Antiviral Considerations in Pharmacological Studies in Long-Term Novel Coronavirus Infection

The oral antiviral drug nilmatrelvir targets the SARS-CoV-2 3-chymotrypsin-like cysteine ​​protease enzyme (Mpro), which is essential for the viral replication cycle. Nilmatrelvir therapy was associated with a lower risk of long-term morbidity with COVID-19. A series of cases in four long-standing COVID-19 patients showed symptomatic improvement after treatment with nilmatrellvir.

Other promising therapeutic options in long-term COVID-19 include immunomodulatory drugs that reduce chronic inflammation, such as the immunoglobulin G4 monoclonal antibody.

Although SARS-CoV-2 vaccination may not be an immunomodulatory therapy, a 2023 systematic review found that rebalancing and strengthening the immune system could be therapeutic for long-term COVID-19. It turns out there is. Nonetheless, no studies have been published investigating similar effects in the pediatric population.

Comparison of long-term COVID-19 and other viral infections

One study compared the symptoms of long-term COVID-19 patients with psychosomatic or psychiatric patients with other infections such as Ebola, Lyme disease, influenza, and chikungunya.

These clinical findings indicate that many people who survive infection may have long-term adverse health effects. Furthermore, no studies have shown that COVID-19 can cause symptoms as severe as post-measles subacute sclerosing panencephalitis.

Conclusion

Current research indicates that SARS-CoV-2 circulates systemically and can persist for weeks or months in children, regardless of disease severity. Viral RNA has been found in pediatric patients who died from severe acute SARS-CoV-2 infection and in children with mild or asymptomatic COVID-19 multisystem inflammatory syndrome.

The authors discuss what is currently known about the biological impact of SARS-CoV-2 persistence on various viral infections, and provide new insights for exploring basic, clinical, and pharmacological research. I outlined the scenario.

Such strategies are useful in managing and understanding postviral syndromes. The persistence of SARS-CoV-2 RNA after infection is well known. Nevertheless, its effects on immunity, health and chronic disease are still not fully understood.

Researchers suggest that the enormous scientific interest in SARS-CoV-2 offers a unique opportunity to learn more about the virus’ persistent biological, therapeutic and clinical effects in humans. .