Does Nirmatrelvir/Ritonavir Influence the Immune Response against SARS-CoV-2, Independently from Rebound?

• Published in: Microorganisms (Basel) Vol. 11; no. 10; p. 2607
• Main Authors: Panza, Francesca, Fiorino, Fabio, Pastore, Gabiria, Fiaschi, Lia, Tumbarello, Mario, Medaglini, Donata, Ciabattini, Annalisa, Montagnani, Francesca, Fabbiani, Massimiliano
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.10.2023; MDPI
• Subjects: antagonists; Antibodies; antibody formation; Antibody response; Antigen presentation; Antigens; Antiviral agents; Cell activation; chemokine CCL5; Chemokines; Coronaviruses; COVID-19; COVID-19 infection; COVID-19 vaccines; Cytokines; Disease transmission; Dosage and administration; Drug resistance; drugs; etiology; Growth factors; Health aspects; Health services; Immune response; Immune system; Immunoglobulin G; immunological response; Immunology; Immunosuppressive agents; Infections; Interleukin 1 receptor antagonist; Interleukin 9; interleukin-1; Lymphocytes; Lymphocytes T; nirmatrelvir/ritonavir; Patients; Platelet-derived growth factor; Platelet-derived growth factor BB; RANTES; rebound; relapse; Ritonavir; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Signs and symptoms; T-lymphocytes; Vascular endothelial growth factor; Viral diseases; viral load; Italy; St Louis Missouri; United States > US
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms11102607

Recurrence of coronavirus disease 19 (COVID-19) symptoms and SARS-CoV-2 viral load relapse have been reported in people treated with nirmatrelvir/ritonavir (NM/r). However, little is understood about the etiology of this phenomenon. Our aim was to investigate the relation between the host’s immune response and viral rebound. We described three cases of COVID-19 rebound that occurred after treatment with nirmatrelvir/ritonavir (group A). In addition, we compared spike-specific antibody response and plasma cytokine/chemokine patterns of the rebound cases with those of (i) control patients treated with nirmatrelvir/ritonavir who did not show rebound (group B), and (ii) subjects not treated with any anti-SARS-CoV-2 drug (group C). The anti-spike antibodies and plasma cytokines/chemokines were similar in groups A and B. However, we observed a higher anti-BA.2 spike IgG response in patients without antiviral treatment (group C) [geometric mean titer 210,807, 5.1- and 8.2-fold higher compared to group A (p = 0.039) and group B (p = 0.032)]. Moreover, the patients receiving antiviral treatment (groups A-B) showed higher circulating levels of platelet-derived growth factor subunit B (PDGF-BB) and vascular endothelial growth Factors (VEGF) and lower levels of interleukin-9 (IL-9), interleukine-1 receptor antagonist (IL-1 RA), and regulated upon activation normal T cell expressed and presumably secreted chemokine (RANTES) when compared to group C. In conclusion, we observed lower anti-spike IgG levels and different cytokine patterns in nirmatrelvir/ritonavir-treated patients compared to those not treated with anti-SARS-CoV-2 drugs. This suggests that early antiviral treatment, by reducing viral load and antigen presentation, could mitigate the immune response against SARS-CoV-2. The clinical relevance of such observation should be further investigated in larger populations.