In a recent article published in the International Journal of Infectious Diseases, researchers evaluated a cohort of post-COVID-19 conditions (PCC) patients before and after coronavirus disease 2019 (COVID-19) vaccination to find out its potential role in PCC management.

Study: Vaccination after developing long COVID: impact on clinical presentation, viral persistence and immune responses. Image Credit: MuchMania / Shutterstock

Background

The prevalence of PCC or long-COVID in COVID-19-related non-hospitalized and hospitalized cases is high. Given its scale, PCC has emerged as a public health crisis, generating enormous social and economic impact.

Clinically, PCC is heterogeneous, with over 200 symptoms, but its precise underpinnings remain unclear. The World Health Organization (WHO) defines PCC because the persistence of symptoms beyond 12 weeks from diagnosis for at the very least two months. 

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) persistence is a key driver of PCC symptoms in adults and youngsters. As well as, PCC patients even have persistently increased serum levels of proinflammatory cytokines/chemokines, resembling interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in comparison with individuals who contracted COVID-19 but not PCC. 

Several studies have correlated increased inflammatory cytokine/chemokine levels with COVID-19 severity, poor prognosis, and recently with PCC.

Studies have demonstrated that vaccination, received before or after acute SARS-CoV-2 infection, protects against severe COVID-19. Nevertheless, there may be a scarcity of evidence that COVID-19 vaccines confer protective and therapeutic effects on PCC.

Concerning the study

In the current prospective observational study, researchers hypothesized that COVID-19 vaccination influences the evolution of PCC symptoms, systemic immune responses, including chemokine/cytokine levels, and viral persistence in PCC patients. 

So, they set out to judge the variety of PCC symptoms, organ systems affected by PCC, and psychological well-being of PCC patients before and after receiving the COVID-19 vaccine. As well as, they evaluated biomarkers of systemic inflammation, plasma cytokines/chemokine levels, plasma and intracellular SARS-CoV-2 antigens levels, and immunoreactivity to those antigens post-vaccination.

The study cohort comprised 83 individuals infected with SARS-CoV-2 and diagnosed with PCC per the WHO PCC case definition. Of those, 44 had not received a COVID-19 vaccine at baseline (unvaccinated), while 39 had received one to 2 vaccine doses. 

First, the team performed a longitudinal evaluation on 44 unvaccinated participants, including 23 and 16 individuals who had received one or two vaccine doses. Next, they performed a cross-sectional evaluation to match the outcomes for 44 unvaccinated participants vis-a-vis 61 and 39 participants who received one or two vaccine doses, respectively.

Further, the researchers collected their sociodemographic and clinical data using a self-administered questionnaire and a case report form. At each study visit, these participants also accomplished the WHO-5 Well-Being Index, underwent a physical examination for body mass index (BMI) measurement, and provided information regarding their vaccination status and 49 PCC-associated symptoms with their frequencies. Additionally they provided saliva samples for reverse-transcription-polymerase chain response (RT-PCR) testing and blood samples for plasma isolation and cytokine/chemokine measurements.

Moreover, the team quantified soluble SARS-CoV-2 spike (S) and nucleocapsid (NC) proteins (SARS-CoV-2 antigens) and immunoglobulins (Ig)G and IgM levels elicited in response to those antigens.

Results

The present study data supports the hypothesis that COVID-19 vaccination post-PCC reduced the variety of PCC symptoms and improved patient well-being. It also markedly down-regulated systemic markers of inflammation, no matter several vaccine doses received, in each longitudinal and cross-sectional evaluations.

Pre-vaccination, PCC patients had elevated plasma levels of some cytokines, resembling macrophage inflammatory protein-1 alpha (MIP-1α), IL-1β, and IL-12p40, harking back to the innate immune signature of past severe acute COVID-19 episodes. It also reflected probable inflammatory chronicity and altered immune competence in PCC patients. 

Although inflammation impaired the immunocompetence of PCC patients, post-PCC vaccination promoted anti-S IgG responses, which likely lowered persistent viral burden and reduced autoantibody titers.

Despite COVID-19 vaccination post-PCC, some viral products persevered and contributed to sustained inflammation. Peluso et al. found that viral persistence increased the chance of PCC in children, raising the necessity for long-term studies on viral persistence and immune dysregulation in pediatric cohorts. 

PCC participants had some immunoreactivity towards SARS-CoV-2 antigen(s), and vaccination further boosted it. Accordingly, researchers detected NC more steadily than S in PCC patients, no matter vaccination status. SARS-CoV-2 S1 antigen also persevered within the blood of PCC participants, mostly in non-classical monocytes, no matter vaccination. 

Conclusions

Overall, the study highlighted how COVID-19 vaccination could mitigate PCC symptoms by decreasing systemic inflammation, though SARS-CoV-2 antigen(s) not cleared by vaccines persevered and sure perpetuated inflammation through non-classical monocytes.

Journal reference:

• Vaccination after developing long COVID: impact on clinical presentation, viral persistence, and immune responses, Maryam Nayyerabadi, Lyvia Fourcade, Swarali A. Joshi, Prabha Chandrasekaran, Arpita Chakravarti, Chantal Massé, Marie-Lorna Paul, Joanie Houle, Amina M. Boubekeur, Charlotte DuSablon, Valérie Boudreau, Danijela Bovan, Emma Darbinian, Emilia Aïsha Coleman, Sandra Vinci, Jean-Pierre Routy, Pierre-Olivier Hétu, International Journal of Infectious Diseases Published: September 15, 2023, DOI:https://doi.org/10.1016/j.ijid.2023.09.006, https://www.ijidonline.com/article/S1201-9712(23)00720-8/fulltext