Multiple Early Factors Anticipate Post-Acute COVID-19 Sequelae, 2022, Su et al

Highlights

• Longitudinal multiomics associate PASC with autoantibodies, viremia and comorbidities
• Reactivation of latent viruses during initial infection may contribute to PASC
• Subclinical autoantibodies negatively correlate with anti-SARS-CoV-2 antibodies
• Gastrointestinal PASC uniquely present with post-acute expansion of cytotoxic T cells

SUMMARY

Post-acute sequelae of COVID-19 (PASC) represent an emerging global crisis. However, quantifiable risk-factors for PASC and their biological associations are poorly resolved. We executed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data, and patient-reported symptoms.

We resolved four PASC-anticipating risk factors at the time of initial COVID-19 diagnosis: type 2 diabetes, SARS-CoV-2 RNAemia, Epstein-Barr virus viremia, and specific autoantibodies. In patients with gastrointestinal PASC, SARS-CoV-2-specific and CMV-specific CD8+ T cells exhibited unique dynamics during recovery from COVID-19. Analysis of symptom-associated immunological signatures revealed coordinated immunity polarization into four endotypes exhibiting divergent acute severity and PASC.

We find that immunological associations between PASC factors diminish over time leading to distinct convalescent immune states. Detectability of most PASC factors at COVID-19 diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests PASC treatment strategies.

Open access (in PDF): https://www.cell.com/cell/fulltext/S0092-8674(22)00072-1

 

This study didn't only involve people with mild covid infections but many were hospitalized. There is a New York Times article where some experts comment on it, including Avindra Nath: https://www.nytimes.com/2022/01/25/health/long-covid-risk-factors.html

But the thing is that it mentions Epstein-Barr reactivation as one of the risk factors:

That some patients had reactivated Epstein-Barr virus also made sense, Dr. Nath said, because other diseases have reawakened that virus, and its reactivation has been linked to conditions like chronic fatigue syndrome, which some cases of long Covid resemble, and multiple sclerosis. Dr. Deeks said it might be possible to give antivirals or immunotherapy to patients with reactivated Epstein-Barr virus.​

 

I would be more impressed by the work being done on EBV if they hadn't been looking at it for the last 30 years yet getting nowhere. I'd love to be wrong.

 

This paper seems to be the cover issue of the March edition of Cell journal:

 

Merged thread

Study Looks for Long COVID Risk Factors Su et al 2022

https://covid19.nih.gov/news-and-stories/study-looks-risk-factors-long-covid

 

It looks like a significant part of the study was only done on the cohort that was 70% hospitalized and 30% ICU. It's not clear which parts included which cohorts (the EBV part, for instance, was just in the first cohort). The second cohort was only 10% hospitalized and reported significantly fewer LC symptoms.