Are circulating SARS-CoV-2 RNA or spike protein levels associated with acute disease severity?

In a recent study posted on medrex sib*Preprint server, researchers hospitalized with acute coronavirus disease 2019 (COVID-19) and patients with and without acute sequelae of COVID-19 (PASC).

Background

There have been considerable research advances on acute symptoms of COVID-19. However, PASC data are missing. To identify individuals most likely to develop PASC and explore targets for the development of potential anti-SARS-CoV-2 drugs, it is imperative to elucidate the mechanisms underlying the pathophysiology of PASC. .

About research

In the current study, researchers sought to determine whether circulating SARS-CoV-2 S or RNA was associated with acute COVID-19 severity and whether persistence of viral components correlated with PASC symptoms. I investigated.

Levels of SARS-CoV-2 S and RNA in plasma obtained from 151 acute COVID-19 (n=116, symptomatic and hospitalized) or PASC patients were analyzed and the diagnosis of COVID-19 was confirmed by polymerase chain was confirmed by the reaction (PCR). test. Based on the World Health Organization (WHO) Disease Severity/Clinical Progression Score, acute COVID-19 patients were classified as: (i) moderate COVID-19 without oxygen (O₂) requirement (n=39), (ii) moderate COVID-19 requiring supplemental oxygen (n=40), and (iii) severe COVID-19 (n=37).

Individuals who experienced one or more COVID-19 symptoms >8 weeks after COVID-19 diagnosis were considered PASC patients. Additionally, 12 patients from the acute COVID biorepository were included in the analysis. Samples from the acute COVID-19 group were obtained on the first day of enrollment and every 3 days until hospital discharge or death.

Samples from the PASC group were collected on the recruitment day, at least 18 weeks after the acute phase of COVID-19. SARS-CoV-2 RNA extracted from the samples was evaluated by reverse transcription droplet digital PCR (RT-ddPCR) test. Plasma-derived small extracellular vesicles (SEV) were isolated and analyzed, and SARS-CoV-2 S and SEV levels were measured by enzyme-linked immunosorbent assay (ELISA).

demographics, comorbidities, body mass index (BMI), COVID-19 symptoms, the time from the most recent SARS-CoV-2 positive report to study recruitment was obtained from the REDCap survey and/or electronic medical records. Surveys were conducted using the WHO His Post-COVID Condition Case Report Form (Post-COVID-19 CRF) at the time of recruitment and every 3 months.

result

A positive correlation with SARS-CoV-2 S was observed in hospitalized patients with acute SARS-CoV-2 infection. D-dimer, duration of hospital stay, WHO peak score, and between SARS-CoV-2 RNA levels and LDH (lactate dehydrogenase, a tissue damage biomarker) levels. A comparison of 33 PASC patients (PASC-positive) with post-COVID-19 symptoms and 14 PASC-negative patients showed the likely presence of SARS-CoV-2 and viral RNA among PASC patients. indicated (in some cases quite high levels). ) compared with patients with acute SARS-COV-2 infection.

SARS-CoV-2 RNA positivity was higher in PASC patients with acute SARS-CoV-2 infection, whereas SARS-CoV-2 S was similar between the two groups. Moreover, some SARS-CoV-2 S proteins bound to EVs that did not contain SARS-CoV-2 RNA in their vesicles. SARS-CoV-2 RNA was found in 33%, 35%, and 37% of patients with moderate COVID-19 without O2, moderate COVID-19 with O2, and severe COVID-19, respectively. Detected in %. group.

The corresponding percentages of the three groups with SARS-CoV-2 S presence were 51%, 68%, and 68%, respectively. Approximately 45%, 37%, and 50% of SARS-CoV-2 S-positive samples in the corresponding groups showed SARS-CoV-2 S in EVs. SARS-CoV-2 RNA levels were significantly correlated with her BMI values ​​in severe her COVID-19 patients.

Overall positivity rates for SARS-CoV-2 RNA and S protein were 35% and 62%, respectively, in symptomatic acute COVID-19 patients. Approximately 34% and 6% of patients in the acute COVID-19 group were positive for SARS-CoV-2 S only and SARS-CoV-2 RNA only. Symptoms of PASC were more likely to develop in women with respiratory comorbidities such as obstructive sleep apnea and asthma.

PASC-negative patients were more likely to have diabetes, renal disease, and coronary artery disease, and were more likely to be hospitalized for acute COVID-19. SARS-CoV-2 RNA was present in 28% of PASC-negative patients (copy number 0.1–2.1 copies/ul) and 59% of PASC-positive patients (copy number 0.1–12.7 copies/ul).

SARS-CoV-2 S was present in 14 PASC-negative and 21 PASC-positive patients, respectively. Among PASC-positive patients, 33% (n=11) samples were positive for SARS-CoV-2 S and viral RNA, 30% (n=10) were positive for SARS-CoV-2 S only, and 18% (n=11) =6) SARS-CoV-2 RNA only. However, no PASC-negative patient was positive for both viral components. In addition, 53% (n = 8) of PASC-positive patients were positive for EV-associated S, with levels similar to those seen in acute COVID-19 patients, whereas EVs in PASC-negative patients were It was SARS-CoV-2. S-negative.

Conclusion

Overall, the results of this study demonstrated sustained circulation of SARS-CoV-2 S and RNA fragments among PASC patients with or without their presence during the acute phase of COVID-19 (a small number of cases >1 year from COVID-19 diagnosis). 19. Findings also showed that SARS-CoV-2 S is present in her SEV in plasma obtained from acute COVID-19 or long his COVID patients, but not in RNA.

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .