Low Innate Immunity and Lagged Adaptive Immune Response in the Re-Tested Viral RNA Positivity of a COVID-19 Patient.

Recent studies have highlighted observations regarding re-tested positivity (RP) of SARS-CoV-2 RNA in discharged COVID-19 patients, however, the immune mechanisms underlying SARS-CoV-2 RNA RP in immunocompetent patients remain elusive. Herein, we describe the case of an immunocompetent COVID-19 patient with moderate symptoms who was twice re-tested as positive for SARS-CoV-2 RNA, and the period between first and third viral RNA positivity was 95 days, longer than previously reported (18-25 days). The chest computed tomography findings, plasma anti-SARS-CoV-2 antibody, neutralizing antibodies (NAbs) titer, and whole blood transcriptic characteristics in the viral RNA RP patient and other COVID-19 patients were analyzed. During the SARS-CoV-2 RNA RP period, new lung lesions were observed. The COVID-19 patient with viral RNA RP had delayed seroconversion of anti-spike/receptor-binding domain (RBD) IgA antibody and NAbs and were accompanied with disappearance of the lung lesions. Further experimental data validated that NAbs titer was significantly associated with anti-RBD IgA and IgG, and anti-spike IgG. The RP patient had lower interferon-, T cells- and B cell-related genes expression than non-RP patients with mild-to-moderate symptoms, and displayed lower cytokines and chemokines gene expression than severe patients. Interestingly, the RP patient had low expression of antigen presentation-related genes and low B cell counts which might have contributed to the delayed anti-RBD specific antibody and low CD8+ cell response. Collectively, delayed antigen presentation-related gene expression was found related to delayed adaptive immune response and contributed to the SARS-CoV-2 RNA RP in this described immunocompetent patient.

Lipidomic alteration of plasma in cured COVID-19 patients using ultra high-performance liquid chromatography with high-resolution mass spectrometry.

BACKGROUND: The pandemic of novel coronavirus disease 2019 (COVID-19) has become a serious public health crisis worldwide. The symptoms of COVID-19 vary from mild to severe among different age groups, but the physiological changes related to COVID-19 are barely understood. METHODS: In the present study, a high-resolution mass spectrometry (HRMS)-based lipidomic strategy was used to characterize the endogenous plasma lipids for cured COVID-19 patients with different ages and symptoms. These patients were further divided into two groups: those with severe symptoms or who were elderly and relatively young patients with mild symptoms. In addition, automated lipidomic identification and alignment was conducted by LipidSearch software. Multivariate and univariate analyses were used for differential comparison. RESULTS: Nearly 500 lipid compounds were identified in each cured COVID-19 group through LipidSearch software. At the level of lipid subclasses, patients with severe symptoms or elderly patients displayed dramatic changes in plasma lipidomic alterations, such as increased triglycerides and decreased cholesteryl esters (ChE). Some of these differential lipids might also have essential biological functions. Furthermore, the differential analysis of plasma lipids among groups was performed to provide potential prognostic indicators, and the change in signaling pathways. CONCLUSIONS: Dyslipidemia was observed in cured COVID-19 patients due to the viral infection and medical treatment, and the discharged patients should continue to undergo consolidation therapy. This work provides valuable knowledge about plasma lipid markers and potential therapeutic targets of COVID-19 and essential resources for further research on the pathogenesis of COVID-19.

Preliminary evidence from a multicenter prospective observational study of the safety and efficacy of chloroquine for the treatment of COVID-19.

Effective therapies are urgently needed for the SARS-CoV-2 pandemic. Chloroquine has been proved to have antiviral effect against coronavirus in vitro. In this study, we aimed to assess the efficacy and safety of chloroquine with different doses in COVID-19. In this multicenter prospective observational study, we enrolled patients older than 18 years old with confirmed SARS-CoV-2 infection excluding critical cases from 12 hospitals in Guangdong and Hubei Provinces. Eligible patients received chloroquine phosphate 500 mg, orally, once (half dose) or twice (full dose) daily. Patients treated with non-chloroquine therapy were included as historical controls. The primary endpoint is the time to undetectable viral RNA. Secondary outcomes include the proportion of patients with undetectable viral RNA by day 10 and 14, hospitalization time, duration of fever, and adverse events. A total of 197 patients completed chloroquine treatment, and 176 patients were included as historical controls. The median time to achieve an undetectable viral RNA was shorter in chloroquine than in non-chloroquine (absolute difference in medians -6.0 days; 95% CI -6.0 to -4.0). The duration of fever is shorter in chloroquine (geometric mean ratio 0.6; 95% CI 0.5 to 0.8). No serious adverse events were observed in the chloroquine group. Patients treated with half dose experienced lower rate of adverse events than with full dose. Although randomized trials are needed for further evaluation, this study provides evidence for safety and efficacy of chloroquine in COVID-19 and suggests that chloroquine can be a cost-effective therapy for combating the COVID-19 pandemic.