Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection

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.

Source: Scott LuMichael J. PelusoDavid V. GliddenMichelle C. DavidsonKara LugtuJesus Pineda-RamirezMichel TassettoMiguel Garcia-KnightAmethyst ZhangSarah A. GoldbergJessica Y. ChenMaya Fortes-CobbySara ParkAna MartinezMatthew SoAidan DonovanBadri ViswanathanRebecca HohKevin DonohueDavid R. McIlwainBrice GaudiliereKhamal AnglinBrandon C. YeeAhmed ChennaJohn W. WinslowChristos PetropoulosSteven G. DeeksMelissa Briggs-HagenRaul AndinoClaire M. MidgleyJeffrey N. MartinSharon SaydahJ. Daniel Kelly. Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection. https://www.medrxiv.org/content/10.1101/2023.07.14.23292649v1.full-text (Full text)

Post-COVID-19 syndrome and humoral response association after one year in vaccinated and unvaccinated patients

Abstract:

Objectives: To describe the impact of vaccination and the role of humoral responses on post-coronavirus disease 2019 (COVID-19) syndrome one year after the onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Methods: A prospective study. Interviews investigated post-COVID-19 syndrome 6 and 12 months after the disease onset of all adult in- and outpatients with COVID-19 attending Udine Hospital (March-May 2020). Vaccination status and two different serological assays to distinguish between response to vaccination (receptor-binding domain -RBD SARS-CoV-2 IgG) and/or natural infection (non-RBD- SARS-CoV-2 IgG) were also assessed.

Results: 479 individuals (52.6% female, mean age 53 years) were interviewed 13.5 months (0.6 SD) after acute infection. Post-COVID-19 syndrome was observed in 47.2% (226/479) of patients after one year. There were no significant differences in the worsening of post-COVID 19 symptoms (22.7% vs 15.8%, p = 0.209) among vaccinated (n=132) and unvaccinated (n=347) patients. The presence of non-RBD SARS-CoV-2 IgG induced by natural infection showed a significant association with post-COVID-19 syndrome (OR 1.35, 95% CI 1.11-1.64, p = 0.003), and median non-RBD SARS-CoV-2 IgG titres were significantly higher in long-haulers than in patients without symptoms 22 (IQR 9.7-37.2) vs 14.1 (IQR 5.4-31.3) kAU/L, p = 0.009) after one year.

In contrast, the presence of RBD SARS-CoV-2 IgG was not associated with the occurrence of post-COVID-19 syndrome (>2500 U/mL vs 0.9-2500 U/mL, OR 1.36, 95% CI 0.62-3.00, p = 0.441) and RBD SARS-CoV-2 IgG titres were similar in long-haulers than in patients without symptoms (50% values > 2500 U/mL vs 55.6% values > 2500 U/mL, p = 0.451)

Conclusions: The SARS-CoV-2 vaccination is not associated with the emergence of post-COVID-19 symptoms over one year after acute infection. The persistence of high serological titres response induced by natural infection but not by vaccination, may play a role in long-COVID-19.

Source: Peghin M, De Martino M, Palese A, Gerussi V, Bontempo G, Graziano E, Visintini E, Elia D, Dellai F, Marrella F, Fabris M, Curcio F, Sartor A, Isola M, Tascini C. Post-COVID-19 syndrome and humoral response association after one year in vaccinated and unvaccinated patients. Clin Microbiol Infect. 2022 Mar 23:S1198-743X(22)00155-0. doi: 10.1016/j.cmi.2022.03.016. Epub ahead of print. PMID: 35339673; PMCID: PMC8940723.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8940723/ (Full text)