Long-term perturbation of the peripheral immune system months after SARS-CoV-2 infection, 2022, Ryan et al

Andy

Senior Member (Voting rights)
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly infectious respiratory virus which is responsible for the coronavirus disease 2019 (COVID-19) pandemic. It is increasingly clear that recovered individuals, even those who had mild COVID-19, can suffer from persistent symptoms for many months after infection, a condition referred to as “long COVID”, post-acute sequelae of COVID-19 (PASC), post-acute COVID-19 syndrome, or post COVID-19 condition. However, despite the plethora of research on COVID-19, relatively little is known about the molecular underpinnings of these long-term effects.

Methods
We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection.

Results
Anti-Spike and anti-RBD IgG responses were largely stable up to 24 wpi and correlated with disease severity. Deep immunophenotyping revealed significant differences in multiple innate (NK cells, LD neutrophils, CXCR3+ monocytes) and adaptive immune populations (T helper, T follicular helper, and regulatory T cells) in convalescent individuals compared to healthy controls, which were most strongly evident at 12 and 16 wpi. RNA sequencing revealed significant perturbations to gene expression in COVID-19 convalescents until at least 6 months post-infection. We also uncovered significant differences in the transcriptome at 24 wpi of convalescents who were referred to a long COVID clinic compared to those who were not.

Conclusions
Variation in the rate of recovery from infection at a cellular and transcriptional level may explain the persistence of symptoms associated with long COVID in some individuals.

Open access, https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-021-02228-6
 
South Australian team
Feargal J. Ryan, Christopher M. Hope, Makutiro G. Masavuli, Miriam A. Lynn contribued equally as first authors. Simon C. Barry, Branka Grubor-Bauk and David J. Lynn contributed equally as senior authors.
authors said:
 
From the News from Australia thread - looks a though this work is being built on:

You can help create a world-first test for long Covid!

Recruitment is underway for an Adelaide-based study that could help produce the world’s first diagnostic test for long Covid.

The million-dollar study is co-funded by The Hospital Research Foundation Group (THRFG), The University of Adelaide and the Australian Government through the Medical Research Future Fund (MRFF) and builds on earlier research also supported by THRFG.

Currently, no single test exists to diagnose long Covid, leaving millions of people worldwide struggling for answers.

However, a landmark discovery by South Australian researchers has identified a potential biomarker for long Covid, raising hopes that a future diagnostic test might not be far away.

The multidisciplinary team, led by University of Adelaide Associate Professor Branka Grubor-Bauk and Professor Simon Barry, were among the first in the world to show that Covid-19 can disrupt the immune system long after the initial infection.

“Our study was one of the first in the world to show that the immune system remains dysfunctional even six months after you’ve had Covid-19,” said A/Prof Grubor-Bauk
 
Abstract said:
We have undertaken an integrated analysis of immune responses in blood at a transcriptional, cellular, and serological level at 12, 16, and 24 weeks post-infection (wpi) in 69 patients recovering from mild, moderate, severe, or critical COVID-19 in comparison to healthy uninfected controls. Twenty-one of these patients were referred to a long COVID clinic and > 50% reported ongoing symptoms more than 6 months post-infection.

That's quite a small Covid-19 sample, considering it is covering mild, moderate, severe and critical Covid-19 and long covid/not long covid. And males and females. And the healthy control sample is very small:

Methods said:
Healthy controls (n = 14) in the same ranges of age and sex as the COVID-19 convalescent cohort were also recruited.

I think all that variation means that any generalisation of the results has a lot of uncertainty.
 
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