Panza Francesca, Fiorino Fabio, Pastore Gabiria, Fiaschi Lia, Tumbarello Mario, Medaglini Donata, Ciabattini Annalisa, Montagnani Francesca, Fabbiani Massimiliano
Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Infectious and Tropical Diseases Unit, Azienda Ospedaliera Universitaria Senese, 53100 Siena, Italy.
Microorganisms. 2023 Oct 22;11(10):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 ( = 0.039) and group B ( = 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.
接受奈玛特韦/利托那韦（NM/r）治疗的患者中，已报告出现新型冠状病毒肺炎（COVID-19）症状复发和严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒载量反弹的情况。然而，对于这一现象的病因了解甚少。我们的目的是研究宿主免疫反应与病毒反弹之间的关系。我们描述了3例在接受奈玛特韦/利托那韦治疗后出现COVID-19反弹的病例（A组）。此外，我们将反弹病例的刺突特异性抗体反应和血浆细胞因子/趋化因子模式与以下两组进行了比较：（i）接受奈玛特韦/利托那韦治疗但未出现反弹的对照患者（B组），以及（ii）未接受任何抗SARS-CoV-2药物治疗的受试者（C组）。A组和B组的抗刺突抗体及血浆细胞因子/趋化因子相似。然而，我们观察到未接受抗病毒治疗的患者（C组）中抗BA.2刺突IgG反应更高[几何平均滴度210,807，与A组（P = 0.039）和B组（P = 0.032）相比分别高5.1倍和8.2倍]。此外，与C组相比，接受抗病毒治疗的患者（A组 - B组）循环中的血小板衍生生长因子亚基B（PDGF - BB）和血管内皮生长因子（VEGF）水平较高，而白细胞介素 - 9（IL - 9）、白细胞介素 - 1受体拮抗剂（IL - 1 RA）和活化正常T细胞表达并可能分泌的趋化因子（RANTES）水平较低。总之，与未接受抗SARS-CoV-2药物治疗的患者相比，我们观察到接受奈玛特韦/利托那韦治疗的患者抗刺突IgG水平较低且细胞因子模式不同。这表明早期抗病毒治疗通过降低病毒载量和抗原呈递，可能减轻针对SARS-CoV-2的免疫反应。这一观察结果的临床相关性应在更大规模人群中进一步研究。
