Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection, 2024, Lu, Peluso et al

[EndME]

Link to published version here

Preprint
Abstract
To understand the roles of acute phase viral dynamics and host immune responses in PASC, we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR. Participants self-collected nasal specimens up to 21 times within the first 28 days after symptom onset; Interviewer-administered clinical questionnaires and blood samples were collected at enrollment and days 9, 14, 21, 28, and month 4 and 8 post-symptom.

Defining PASC as the presence of any symptom new or worse since infection reported at their 4-month visit, we compared viral markers (quantity and duration of viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-a, IFN-a, IFN-g, MCP, IP-10, and Spike IgG) over the acute period. In comparison to those who fully recovered, those who developed PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA, infectious virus, and N-antigen, longer duration of viral shedding, and lower Spike-specific IgG levels within the first 10 days of the acute phase of illness. No significant differences were identified among a panel of host immune markers, though there was a trend toward higher initial levels of certain markers (e.g., MCP-1, IFN-a, and IFN-g) in those who went on to develop PASC. Early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC.

These findings highlight the importance of understanding the early biological markers from acute SARS-CoV-2 infection in the natural history of PASC.

https://www.medrxiv.org/content/10.1101/2023.07.14.23292649v1

This work seems to be a collaboration of the great UCSF team and Monogram Biosciences a subsidiary of LabCorp.

 

[Hutan]

I don't think this was a population sample - for example, people with a history of autoimmune disease were excluded. This was a relatively young sample, median 35.5. years. 51% with a BMI less than 25.

30% with PASC at followup - approx 4 months (31 people with PASC; 73 without). Vaccination didn't make a difference to the incidence of PASC.
The criteria for PASC was loose - just one new or worsened symptom post-infection was enough. The median for the number of symptoms in the PASC group in the 2 to 6 period was only 2. Only 32% of the PASC group reported fatigue.

Among 104 SARS-CoV-2 infected participants with a post-acute follow-up visit, 31 (30%) reported new, worsened or persistent symptoms since the time of SARS-CoV-2 infection,
consistent with PASC. We did not identify a difference between those with and without PASC in terms of vaccination status (31% vs 36%). All participants with PASC had been symptomatic during acute illness with a median of 12 (9 to 14); among those without PASC the median number of symptoms in the acute period was 7 (3 to 12). Those meeting criteria for PASC reported a median of 2 (IQR: 1 to 6) symptoms during the post-acute period 2-6 months after SARS-CoV-2 infection. The most commonly reported PASC symptoms were fatigue (32%), difficulty with concentration/memory (33%), rhinorrhea (29%), cough (29%), and headache (26%).

There was no sex bias (52% female) for the development of PASC (non-PASC was 51% female).
Having a BMI>30 definitely increased the odds of PASC.

Associations of virologic factors with PASC

Compared to those who did not develop PASC, those who developed PASC had higher maximum RNA viral load, infectious viral load, and N-antigen levels (Table 2; Figure 2a). Viral RNA decay rates did not significantly differ by PASC status, but decay rates of N-antigen levels were faster in the first 9 days after symptom onset among those with PASC than those without PASC (Figure 2a).

In the acute stage of the illness, the PASC group had higher viral load and IgG levels were lower.

Inflammatory markers
There isn't much there. Really the only difference is that, at enrolment in the acute stage of the illness, IFN-a, IFN-g and MCP were higher in PASC and IP-10 was lower, but levels had normalised by 2 weeks. IL-6, TNF-a and IL-10 weren't different.

Only 80 people had the blood draw. Of the 28 PASC people, 13 female, 15 male.

I think there needed to be more analysis of reported symptoms, and analysis of the inflammatory markers by symptom, including PEM.

 

[SNT Gatchaman]

Now published as —

Early biological markers of post-acute sequelae of SARS-CoV-2 infection (2024)
Lu, Scott; Peluso, Michael J.; Glidden, David V.; Davidson, Michelle C.; Lugtu, Kara; Pineda-Ramirez, Jesus; Tassetto, Michel; Garcia-Knight, Miguel; Zhang, Amethyst; Goldberg, Sarah A.; Chen, Jessica Y.; Fortes-Cobby, Maya; Park, Sara; Martinez, Ana; So, Matthew; Donovan, Aidan; Viswanathan, Badri; Hoh, Rebecca; Donohue, Kevin; McIlwain, David R.; Gaudiliere, Brice; Anglin, Khamal; Yee, Brandon C.; Chenna, Ahmed; Winslow, John W.; Petropoulos, Christos J.; Deeks, Steven G.; Briggs-Hagen, Melissa; Andino, Raul; Midgley, Claire M.; Martin, Jeffrey N.; Saydah, Sharon; Kelly, J. Daniel

To understand the roles of acute-phase viral dynamics and host immune responses in post-acute sequelae of SARS-CoV-2 infection (PASC), we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR test.

Participants self-collected up to 21 nasal specimens within the first 28 days post-symptom onset; interviewer-administered questionnaires and blood samples were collected at enrollment, days 9, 14, 21, 28, and month 4 and 8 post-symptom onset. Defining PASC as the presence of any COVID-associated symptom at their 4-month visit, we compared viral markers (quantity and duration of nasal viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ , MCP, IP-10, and Spike IgG) over the acute period.

Compared to those who fully recovered, those reporting PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA and N-antigen, burden of RNA and infectious viral shedding, and lower Spike-specific IgG levels within 9 days post-illness onset. No significant differences were identified among a panel of host immune markers.

Our results suggest early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC, highlighting the importance of understanding early biological markers in the natural history of PASC.

Link | PDF (Nature Communications) [Open Access]