Case report: Treatment of long COVID with a SARS-CoV-2 antiviral and IL-6 blockade in a patient with rheumatoid arthritis and SARS-CoV-2 antigen persistence

Abstract

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.

Keywords: autoimmunity; case report; long COVID; nirmatrelvir/ritonavir; tocilizumab.

FIGURE 1

Post-acute sequelae of SARS-CoV-2 infection (PASC) patient exhibits persistent SARS-CoV-2 antigen positivity in nasopharynx. (A) Study visit timeline, including vaccination, infection, and intervention dates. (B) FlowFlex™ SARS-CoV-2 antigen test results over time. Time p.i., weeks post-infection. (C) PASC symptoms vs. rheumatoid arthritis symptoms.

FIGURE 2

IFN-γ T cell responses to SARS-CoV-2 vary over time. (A) IFN-γ production from SARS-CoV-2 Spike- and Nucleocapsid-specific T cells at each visit as determined by ELISPOT. (B) Spike receptor-binding domain (RBD)-specific IgG titers (top) and Nucleocapsid-specific IgG (bottom) at each visit. LoD, limit of detection. All ELISPOT data in panel (A) from duplicate wells. Data representative of 2 individual experiments, *p < 0.05 by Student’s t-test.

FIGURE 3

Virus-specific CD4⁺ and CD8⁺ T cell subset activation correlates with antiviral and tocilizumab treatment. (A) Flow cytometry showing elevated virus-specific CD4⁺ T helper cell (Tfh) cell activation after vaccine booster dose (V3; 2nd row) and stopping tocilizumab treatment (V5; 4th row). (B) Total CD4⁺ T cells (left), CD4⁺ T helper cells (Tfh, middle), and CD4⁺ memory T cells (TEM, right) have enhanced reactivity to SARS-CoV-2 structural (S, N) and non-structural (Orf1ab, Orf7) peptides after vaccine booster (V3) and stopping tocilizumab (V5), but low reactivity after nirmatrelvir/ritonavir treatment (V4) and resuming tocilizumab therapy (V6). (B) Total CD8⁺ T cells (right) and CD8⁺ memory T cell subsets (CD8⁺ TEMRA, TEM; middle, right) show increased activation after vaccine boost (V3) and stopping tocilizumab (V5), but low reactivity after nirmatrelvir/ritonavir treatment (V4) and resuming tocilizumab (V5). Data combined from 3 independent experiments.

FIGURE 4

Autoreactive T cell responses oscillate in coordination with SARS-CoV-2-specific responses after infection. (A) T cell production of IFN-γ after stimulation with rheumatoid arthritis-associated cartilage autoantigen YKL-40 compared with Spike- and Orf1ab-specific activation. (B) Activation of T cell subsets over the course of the study after stimulation with the rheumatoid arthritis-associated antigen YKL-40 or SARS-CoV-2 Orf7 peptides. Stopping tocilizumab resulted in increased virus-specific and autoreactive T cell reactivity, while resuming tocilizumab suppressed autoreactivity in most T cell subsets. Data representative of 2 individual experiments, *p < 0.05, **p < 0.01 by one-way ANOVA with Tukey’s post-test.