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Persistent Circulation of Soluble/EV-Linked Spike Protein and Viral RNA in Individuals with Post-Acute Sequelae of COVID-19

29 Pages Posted: 10 Aug 2022

See all articles by Vaughn Craddock

Vaughn Craddock

University of Kansas - Division of Pulmonary and Critical Care Medicine

Aatish Mahajan

University of Kansas - Division of Pulmonary and Critical Care Medicine

Balaji Krishnamachary

University of Kansas - Division of Pulmonary and Critical Care Medicine

Leslie Spikes

University of Kansas - Division of Pulmonary and Critical Care Medicine

Prabhakar Chalise

University of Kansas - Department of Biostatistics & Data Science

Navneet Dhillon

University of Kansas - Division of Pulmonary and Critical Care Medicine

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Abstract

SARS-CoV-2, the causative agent of COVID-19 disease has resulted in the death of millions worldwide since the beginning of the pandemic in December 2019. While much progress has been made to understand acute manifestations of SARS-CoV-2 infection, less is known about post-acute sequelae of COVID-19 (PASC). We investigated the levels of circulating SARS-CoV-2 components, Spike protein and viral RNA, in patients hospitalized with acute COVID-19 and in patients with and without PASC. In hospitalized patients with acute COVID-19 (n=116), we observed a positive correlation of Spike protein with D-dimer, length of hospitalization, and peak WHO score while viral RNA correlated with a tissue injury marker, lactate dehydrogenase (LDH). When comparing patients with post-COVID symptoms (n=33) and patients without (n=14), we found that Spike protein and viral RNA were more likely to be present in patients with PASC and in some cases at higher levels compared to acute COVID-19 patients. We also observed that the percent positivity of circulating viral RNA increased in the PASC positive individuals compared to acute COVID-19 group while Spike protein positivity remained the same.  Additionally, we report that part of the circulating Spike protein is linked to extracellular vesicles without any presence of viral RNA in these vesicles. In conclusion, our findings suggest that Spike protein and/or viral RNA fragments persist in the recovered COVID-19 patients with PASC, regardless of their presence or absence during the acute COVID-19 phase. These results may help in understanding the reason(s) for why patients experience PASC symptoms and may offer potential therapeutic targets.

Funding Information: The funds to carry out the study were supported by National Institute of Health (NIH) grants R01 HL129875 awarded to N.K.D.

Declaration of Interests: The authors report no conflict of interest.

Ethics Approval Statement: These studies were approved by the local IRB at the University of Kansas Medical Center and all individuals gave consent.

Keywords: SARS-CoV-2, Extracellular vesicles, Acute COVID-19, Long-COVID

Suggested Citation

Craddock, Vaughn and Mahajan, Aatish and Krishnamachary, Balaji and Spikes, Leslie and Chalise, Prabhakar and Dhillon, Navneet, Persistent Circulation of Soluble/EV-Linked Spike Protein and Viral RNA in Individuals with Post-Acute Sequelae of COVID-19. Available at SSRN: https://ssrn.com/abstract=4186787 or http://dx.doi.org/10.2139/ssrn.4186787

Vaughn Craddock

University of Kansas - Division of Pulmonary and Critical Care Medicine ( email )

Aatish Mahajan

University of Kansas - Division of Pulmonary and Critical Care Medicine ( email )

Balaji Krishnamachary

University of Kansas - Division of Pulmonary and Critical Care Medicine ( email )

Leslie Spikes

University of Kansas - Division of Pulmonary and Critical Care Medicine ( email )

Prabhakar Chalise

University of Kansas - Department of Biostatistics & Data Science ( email )

Navneet Dhillon (Contact Author)

University of Kansas - Division of Pulmonary and Critical Care Medicine ( email )

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