Thursday, September 29, 2022

Long COVID. studies on the underlying biology of

In a recently published article science translation therapy In the journal, researchers analyzed the long and unique effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in humans and hamsters after recovery.

Study: SARS-CoV-2 infection in hamsters and humans results in permanent and unique systemic disturbances after recovery.  Image credit: Donkey Works / ShutterstockIStudy: SARS-CoV-2 infection in hamsters and humans results in permanent and unique systemic disturbances after recovery. Image credit: donkeyworks/shutterstock

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SARS-CoV-2 is a respiratory ribonucleic acid (RNA) virus, initially discovered in late 2019. SARS-CoV-2 infection has a plethora of clinical phenotypes, including asymptomatic and more severe disease, commonly known as CoV disease 2019 (COVID-19). ,

COVID-19 causes mild flu-like illness in most healthy and young people, with symptoms such as restricted respiratory tract congestion, myalgia, fever, anosmia, and headache. On the other hand, it can cause multi-organ complications, severe respiratory distress and death in old age, especially in men with co-morbidities. SARS-CoV-2 infection is also hypothesized to disrupt host translation and transcriptional mechanisms to enhance replication, regardless of underlying health or age.

Although the extent to which distal tissues are infected in SARS-CoV-2 infection is unknown, widespread inflammation is stable. According to the information now available, the molecular foundation of acute COVID-19 is the result of virus-induced damage and subsequent systemic response. The host response to SARS-CoV-2 infection can result in long-lasting diseases collectively referred to as prolonged COVID or post-COVID-19 (PASC) acute sequence.

about study

In the current study, the scientists selected the golden hamster as the model system to better explain the long-term effects of SARS-CoV-2 infection. Existing studies have shown that the hamster model closely mimics SARS-CoV-2 infection biology without the need for SARS-CoV-2 adaptation and has a penchant for severe lung tropism and morphology similar to those observed in humans. is the trend.

The team studied the host response to SARS-CoV-2 and compared their findings to previous influenza A virus (IAV) pandemic virus infections. They investigated long- and short-term systemic responses in golden hamsters following IAV and SARS-CoV-2 infection to better understand the mechanisms underpinning the biology of prolonged COVID-19.

The researchers adopted previous investigation-based SARS-CoV-2 and IAV vaccination doses to achieve similar viral loads and kinetics in these two experimental models. In addition, they analyzed lung, heart and kidney cross-sections in hamsters three days after infection, using several histological methods to compare the pathology caused by SARS-CoV-2 against IAV .

Scientists matched RNA-seq analyzes of lung RNA-seq analyzes of SARS-CoV-2-infected hamsters with published data from lungs of COVID-19 deceased patients who still had clinical evidence of SARS-CoV-2 acute hamster data. There was significant viral load at the time of death to be confirmed. validity. In addition, at 31 days after SARS-CoV-2 or IAV infection, they assessed heart, lung and kidney by histological studies to detect long-lasting organ damage irrespective of transcriptional response. Since long-term COVID can cause neuropsychiatric and neurological symptoms, the authors examined the effects on the nervous system as a result of SARS-CoV-2 infection.

Considering the unique extended duration of the proinflammatory response in the olfactory bulb (OB) to SARS-CoV-2, the researchers analyzed the genes driving this transcriptional program. They also examined whether the olfactory epithelium (OE) had this proinflammatory signature. In SARS-CoV-2-infected hamsters four weeks after infection, the team evaluated the functional consequences of chronic neuronal changes such as long-term OB and OE inflammation. Finally, the researchers used RNA-seq on post-mortem OB and OE tissue to determine whether the results could be extrapolated to features of the human disease.

RESULTS AND CONCLUSIONS

Study results showed that IAV- and SARS-CoV-2-infected hamsters exhibit a host response similar to human biology and resolved within two weeks. Longitudinal data showed that both respiratory RNA viruses multiply in the lungs of the golden hamster, with slight variation in SARS-CoV-2 clearance, as previously reported.

Delayed SARS-CoV-2 clearance overlapped with reduced appetite as SARS-CoV-2-infected hamsters gained weight at a significantly slower rate than IAV-infected or phosphate-buffered saline (PBS)-treated animals. Peak SARS-CoV-2 titers, approximately 108 pfu/g, were observed three days after infection and remained stable for five days before falling.

Although both model systems had different rates of virus replication long after peak viral titers were achieved, none was able to isolate infective virus at day 7. In contrast, influenza nucleoprotein (NP) RNA and SARS-CoV-2 sub-genomic nucleocapsid (SGN) RNA can be detected using quantitative reverse-transcription-based polymerase chain reaction (qRT-PCR).

SARS-CoV-2 outperformed IAV in causing permanent kidney and lung injury and displayed a distinct effect on OE and OB. Despite the absence of infectious SARS-CoV-2 load, OE and OB harbored T cell and myeloid stimulation, proinflammatory cytokine release, and interferon response, all of which were associated with behavioral changes that lasted up to one month after viral clearance.

The researchers noted that tissue extracted from COVID-19 convalescent individuals also confirmed these long-term transcriptional changes. The present findings provide a molecular pathway to COVID-19 symptom persistence and reflect a small animal paradigm for future clinical testing.

To conclude, the study findings suggest that although both SARS-CoV-2 and IAV cause a systemic antiviral response, just prior infection caused a long-term inflammatory pathology that persists after clearing the primary infection. Keeps maintained. Investigators believe this biology may underlie the origin of PASC in both hamsters and humans because prolonged inflammation corresponds to behavioral disorders.

Journal Reference:

  • JJ Frere, RA Serafini, KD Price, et al., SARS-CoV-2 infection in hamsters and humans results in permanent and unique systemic disturbances post-recovery, in Science. translation med. (2022), doi: 10.1126/scitranslmed.abq3059, https://www.science.org/doi/10.1126/scitranslmed.abq3059
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