Real-world experience of arbidol for Omicron variant of SARS-CoV-2.

Background: At a crucial time with the rapid spread of Omicron severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus variant globally, we conducted a study to evaluate the efficacy and safety of arbidol tablets in the treatment of this variant. Methods: From Mar 26 to April 26, 2022, we conducted a prospective, open-labeled, controlled, and investigator-initiated trial involving adult patients with confirmed Omicron variant infection. Patients with asymptomatic or mild clinical status were stratified 1:2 to receive either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 5 days). The primary endpoint was the negative conversion rate within the first week. Results: A total of 367 patients were enrolled in the study; 246 received arbidol tablet treatment, and 121 were in the control group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group [47.2% (116/246) vs. 35.5% (43/121); odds ratio (OR), 1.619; 95% confidence interval (CI): 1.034-2.535; P=0.035]. Compared to those in the SOC group, patients receiving arbidol tablets had a shorter negative conversion time [median 8.3 vs. 10.0 days; hazard ratio (HR), 0.645; 95% CI: 0.516-0.808; P<0.001], and a shorter duration of hospitalization (median 11.4 vs. 13.7 days; HR, 1.214; 95% CI: 0.966-1.526; P<0.001). Moreover, the addition of arbidol tablets led to better recovery of declined blood lymphocytes, CD3+, CD4+, and CD8+ cell counts. The most common adverse event (AE) was transaminase elevation in patients treated with arbidol tablets (3/246, 1.2%). No one withdrew from the study due to AEs or disease progression. Conclusions: As a whole, arbidol may represent an effective and safe treatment in asymptomatic-mild patients suffering from Omicron variant during the pandemic of coronavirus disease 2019 (COVID-19).

Frontline Science: COVID-19 infection induces readily detectable morphologic and inflammation-related phenotypic changes in peripheral blood monocytes.

Excessive monocyte/macrophage activation with the development of a cytokine storm and subsequent acute lung injury, leading to acute respiratory distress syndrome (ARDS), is a feared consequence of infection with COVID-19. The ability to recognize and potentially intervene early in those patients at greatest risk of developing this complication could be of great clinical utility. In this study, we performed flow cytometric analysis of peripheral blood samples from 34 COVID-19 patients in early 2020 in an attempt to identify factors that could help predict the severity of disease and patient outcome. Although we did not detect significant differences in the number of monocytes between patients with COVID-19 and normal healthy individuals, we did identify significant morphologic and functional differences, which are more pronounced in patients requiring prolonged hospitalization and intensive care unit (ICU) admission. Patients with COVID-19 have larger than normal monocytes, easily identified on forward scatter (FSC), side scatter analysis by routine flow cytometry, with the presence of a distinct population of monocytes with high FSC (FSC-high). On more detailed analysis, these CD14+ CD16+ , FSC-high monocytes show features of mixed M1/M2 macrophage polarization with higher expression of CD80+ and CD206+ compared with the residual FSC-low monocytes and secretion of higher levels of IL-6, IL-10, and TNF-α, when compared with the normal controls. In conclusion, the detection and serial monitoring of this subset of inflammatory monocytes using flow cytometry could be of great help in guiding the prognostication and treatment of patients with COVID-19 and merits further evaluation.

Leptin correlates with monocytes activation and severe condition in COVID-19 patients.

Excessive monocyte activation with the development of excessive or uncontrolled release of proinflammatory cytokines often results in host tissue injury and even death in patients with pneumonia caused by the 2019 novel coronavirus. However, the changes of cytokine profiles of coronavirus disease 2019 (COVID-19) patients, as well as the underlying mechanisms that are involved, remain unknown. Using a cytokine array containing 174 inflammation-related cytokines, we found significantly altered cytokine profiles in severe COVID-19 patients compared with those in mild patients or healthy controls, and identified leptin, CXCL-10, IL-6, IL-10, IL-12, and TNF-α as the top differentially expressed cytokines. Notably, leptin showed high consistency with CXCL-10 and TNF-α in predicting disease severity, and correlated with body mass index, decreased lymphocyte counts, and disease progression. Further analysis demonstrated that monocytes in severe patients with higher leptin levels were inclined toward M1 polarization. Mechanistic studies revealed that leptin synergistically up-regulated expression levels of inflammatory cytokines and surface markers with IL-6 in monocytes through STAT3 and NF-κB signaling pathways. Collectively, our results suggest that overweight COVID-19 patients were prone to have higher leptin levels, which further activated monocytes, resulting in amplified or dysregulated immune responses. Taken together, our findings argue that leptin correlates severity of COVID-19 and may indicate a possible mechanism by which overweight patients have a greater tendency to develop severe conditions.

The phenotypic changes of γδ T cells in COVID-19 patients.

A novel pneumonia-associated respiratory syndrome named coronavirus disease-2019 (COVID-19), which was caused by SARS-CoV-2，broke out in Wuhan, China, in the end of 2019. Unfortunately, there is no specific antiviral agent or vaccine available to treat SARS-CoV-2 infections. The information regarding the immunological characteristics in COVID-19 patients remains limited. Here, we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes on γδ T cell population. In comparison with HD, the γδ T cell percentage decreased, while the activation marker CD25 expression increased in response to SARS-CoV-2 infection. Interestingly, the CD4 expression was upregulated in γδ T cells reflecting the occurrence of a specific effector cell population, which may serve as a biomarker for the assessment of SARS-CoV-2 infection.

Naturally activated adaptive immunity in COVID-19 patients.

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2) has rapidly spread worldwide, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics of COVID-19 patients remains limited. Herein, we collected blood samples from 18 healthy donors (HDs) and 38 COVID-19 patients to analyse changes in the adaptive immune cell populations and their phenotypes. We observed that the lymphocyte percentage moderately decreased, CD4 and CD8 T cell percentage among lymphocytes were similar, and B cell percentage was increased in COVID-19 patients in comparison to that in HDs. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 infection increased the percentage of T follicular helper- and germinal centre B-like cells in the blood. The parameters in COVID-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells are activated naturally and are functional during SARS-CoV-2 infection. These data provide evidence that the adaptive immunity in most patients could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.