Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-, Vis. et al. 2022

[Jaybee00]

https://www.frontiersin.org/articles/10.3389/fmed.2022.1003103/full

Introduction: Long COVID, or post-acute sequelae of SARS-CoV-2 infection (PASC) in ∼30% of all infected individuals. Here, we present a case of PASC in a patient with rheumatoid arthritis characterized by viral persistence in the nasopharynx for 6 months after acute infection. We demonstrate transient disappearance of antigen persistence and decreased antiviral and autoimmune T cell responses after nirmatrelvir/ritonavir and tocilizumab treatment.

Case presentation: A 37-year-old female with a 7-year history of rheumatoid arthritis enrolled in a COVID-19 research study was found to continuously test SARS-CoV-2 antigen positive in the nasopharynx for 6 months after acute infection. She simultaneously presented with new-onset PASC symptoms including chronic occipital headache and periods of intense fatigue 8 weeks after acute infection. The patient was prescribed nirmatrelvir/ritonavir to treat SARS-CoV-2 persistence at 3.5 months post-acute infection and observed a reduction in PASC symptoms 3 weeks after completing antiviral treatment. After resurgence of PASC symptoms, she stopped treatment with tocilizumab for rheumatoid arthritis to attempt complete SARS-CoV-2 viral clearance. The severity of the patient’s PASC symptoms subsequently increased, and she developed new-onset brain fog in addition to previous symptoms, which resolved after resumption of tocilizumab treatment. Assessment of adaptive immune responses demonstrated that nirmatrelvir/ritonavir and tocilizumab treatment decreased antiviral and autoreactive T cell activation. After resuming tocilizumab treatment, the patient’s PASC symptoms were significantly reduced, but nasopharyngeal antigen positivity remained.

Conclusion: These data suggest that nirmatrelvir/ritonavir should be considered in the treatment of PASC in patients who have SARS-CoV-2 antigen persistence, though care must be taken to monitor the patient for symptom resurgence or viral reactivation. In addition, the IL-6 inhibitor tocilizumab may ameliorate PASC symptoms in patients with persistent headache, fatigue, and brain fog.

 

[Hutan]

This case study has the problems that case studies have - n=1 and confounding factors of the RA and vaccinations. Tocilizumab reduces the effectiveness of the immune system, the woman was immunocompromised.

Tocilizumab (Actemra) can lower the ability of your immune system to fight infections....
In COVID-19 patients, ACTEMRA should not be administered if patients have any other concurrent active infection, including localized infection.

Still, the discussion in the case study is interesting. Nirmatrelvir/ritonavir is Paxlovid.

Increased IL-6 has been associated with PASC in multiple studies. Elevated serum IL-6 was found in the majority of PASC patients compared with asymptomatic convalescent controls 8 months post-infection (20). There is speculation that IL-6 dysfunction may underlie persistent neuropsychiatric symptoms of PASC (21), and IL-6-producing B effector cells were elevated relative to IL-10-producing B regulatory cells in severe COVID-19 patients (22). Finally, a large cohort study of PASC patients assessed at 5 months post-infection found increased plasma IL-6 levels in patients with severe or moderate symptoms with cognitive impairment (23). Our own group has shown that Neuro-PASC patients have increased CD8+ T cell production of IL-6 following stimulation with SARS-CoV-2 antigens compared with healthy COVID convalescents (24). Combined with the data in this case report, these studies provide a compelling argument for investigating the efficacy of IL-6 blockade with tocilizumab in treatment of PASC.

Those mentioned papers would be interesting to sift through. The fact that the virus appeared to have been cleared, and then it re-appeared, even though the patient did not seem to have any interim exposure to a new infection suggests that the virus can simmer along at undetectable levels, supporting the idea of a viral/antigen persistence cause of ME/CFS-like syndromes.

In this case, the patient’s autoreactive T cell response to the RA-associated cartilage antigen YKL-40 (26) fluctuated depending on PASC symptom severity and RA disease activity (Figure 1C) as well as tocilizumab treatment (Figure 4). This suggests that tocilizumab may be used for management of rheumatic disease as well as Neuro-PASC symptoms. This case report highlights the need for further research into the contribution of autoimmunity to Neuro-PASC in addition to exploring the use of tocilizumab in Neuro-PASC treatment.

Currently, there are only symptomatic treatments for Neuro-PASC (8). We present the first case of a Neuro-PASC patient whose symptoms and antiviral adaptive immune responses were reduced by a 5-day course of nirmatrelvir-ritonavir. Additionally, we raise the possibility that tocilizumab should be further studied as a therapeutic intervention for Neuro-PASC. PASC impacts millions of people worldwide, and its incidence is only modestly diminished by vaccination (27, 28). Urgent research is needed to study the role of existing treatments to ameliorate the devastating impacts of PASC.

@Jonathan Edwards - one for you.

Personally, I'd like to see a prospective trial of paxlovid at Covid-19 onset as a preventative, and a trial of paxlovid as a treatment for ME/CFS-like PASC.

 

[Jonathan Edwards]

I had a quick look. I cannot see how one can really draw any conclusions without any control data. Goodness knows what caused what here.