Many Long COVID-19 Patients Have Higher Levels Of Circulating SARS-CoV-2 Viral RNA Compared To Those With Acute Infection

A new study by researchers from the Division of Pulmonary and Critical Care Medicine at University of Kansas-USA has revealed that many Long COVID-19 patients have higher levels of circulating SARS-CoV-2 Viral RNA compared to individuals with acute COVID-19 infection.

The study findings were published on a preprint server by Lancet. 

https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4186787

The COVID-19 pandemic caused by SARS-CoV-2 continues to have devastating global consequences with more than 579 million infections and over 6.4 million deaths internationally at the time of this writing1. The infection can progress to a severe illness that necessitates hospitalization and intensive care or can be mild and even asymptomatic.

As the pandemic progressed, it quickly became apparent that a plethora of symptoms can persist long after the acute infection, no matter the initial severity. This has become known as Post-acute Sequelae  of COVID-19 or PASC. Studies to date estimate that 30-50% of people who had COVID-19 still experience at least one post-COVID symptom 4 weeks after infection and 10-30% even after 12 weeks of acute infection 2, 3.

While the definition and scope of PASC remains to be determined, it is currently defined as new or persistent symptoms of COVID-19 beyond 4 weeks of acute infection that cannot be explained by other underlying etiologies 4, 5. With the huge toll of acute infections that have and continue to occur worldwide, even if only a small fraction of patients goes on to develop PASC, it will have an enormous impact on society and the healthcare system for years to come.

Therefore, it is imperative to understand the mechanism(s) of acute and post-acute COVID-19 disease pathogenesis, identify those most at risk of developing PASC, and investigate targets for future treatments.

Recent studies suggest that SARS-CoV-2 RNA can disseminate to extra-pulmonary tissues even in individuals with asymptomatic infection or mild COVID-19 disease and that viral RNA can reside in tissues for over 7 months in some individuals6. Multiple findings report SARS-CoV-2 Spike protein mediated lung injury and vascular damage by inducing endothelial barrier dysfunction and inflammation7-9.

We previously reported significant apoptosis of microvascular endothelial cells on exposure to plasma-derived extracellular vesicles (EVs) from hospitalized COVID-19 patients 10. Additionally, EVs released by lung epithelial cells transduced with lentivirus encoding SARS-CoV-2 proteins have been shown to transfer viral RNA to recipient cardiomyocytes, which might contribute to COVID-19-related myocardial inflammation and dysfunction 11.

Furthermore, some of the prolonged symptoms of PASC, such as persistent dyspnea, chest pain, and fatigue, suggest that the endothelial injury and thrombo-inflammation that occur in acute SARS CoV-2 infection may not resolve, thereby contributing to the persistence of symptoms 12.

A recent study reported the presence of microclots in the plasma from COVID-19 patients with PASC symptoms 13. Therefore, in this study we examined if circulation of SARS-CoV-2 RNA or Spike protein is associated with acute disease severity and if its persistence correlated with manifestations of PASC. We report that both viral RNA and/or

Spike protein remain in circulation long after acute infection (more than one-year post-infection in some cases) and this persistent circulation of viral components is associated with PASC. Further, we show the presence of Spike protein, but not viral RNA, in plasma-derived small EVs from individuals with acute or long-COVID-19.