Clinical application of SARS-CoV-2 antibody detection and monoclonal antibody therapies against COVID-19.

The purpose of this study was to investigate the clinical application of severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) specific antibody detection and anti-SARS-CoV-2 specific monoclonal antibodies (mAbs) in the treatment of coronavirus infectious disease 2019 (COVID-19). The dynamic changes of SARS-CoV-2 specific antibodies during COVID-19 were studied. Immunoglobulin M (IgM) appeared earlier and lasted for a short time, while immunoglobulin G (IgG) appeared later and lasted longer. IgM tests can be used for early diagnosis of COVID-19, and IgG tests can be used for late diagnosis of COVID-19 and identification of asymptomatic infected persons. The combination of antibody testing and nucleic acid testing, which complement each other, can improve the diagnosis rate of COVID-19. Monoclonal anti-SARS-CoV-2 specific antibodies can be used to treat hospitalized severe and critically ill patients and non-hospitalized mild to moderate COVID-19 patients. COVID-19 convalescent plasma, highly concentrated immunoglobulin, and anti-SARS-CoV-2 specific mAbs are examples of anti-SARS-CoV-2 antibody products. Due to the continuous emergence of mutated strains of the novel coronavirus, especially omicron, its immune escape ability and infectivity are enhanced, making the effects of authorized products reduced or invalid. Therefore, the optimal application of anti-SARS-CoV-2 antibody products (especially anti-SARS-CoV-2 specific mAbs) is more effective in the treatment of COVID-19 and more conducive to patient recovery.

Intranasal delivery of a chimpanzee adenovirus vector expressing a pre-fusion spike (BV-AdCoV-1) protects golden Syrian hamsters against SARS-CoV-2 infection.

We evaluated the immunogenicity and protective ability of a chimpanzee replication-deficient adenovirus vectored COVID-19 vaccine (BV-AdCoV-1) expressing a stabilized pre-fusion SARS-CoV-2 spike glycoprotein in golden Syrian hamsters. Intranasal administration of BV-AdCoV-1 elicited strong humoral and cellular immunity in the animals. Furthermore, vaccination prevented weight loss, reduced SARS-CoV-2 infectious virus titers in the lungs as well as lung pathology and provided protection against SARS-CoV-2 live challenge. In addition, there was no vaccine-induced enhanced disease nor immunopathological exacerbation in BV-AdCoV-1-vaccinated animals. Furthermore, the vaccine induced cross-neutralizing antibody responses against the ancestral strain and the B.1.617.2, Omicron(BA.1), Omicron(BA.2.75) and Omicron(BA.4/5) variants of concern. These results demonstrate that BV-AdCoV-1 is potentially a promising candidate vaccine to prevent SARS-CoV-2 infection, and to curtail pandemic spread in humans.

A genetic variant in IL-6 lowering its expression is protective for critical patients with COVID-19.

Critical coronavirus disease 2019 (COVID-19) is associated with high mortality and potential genetic factors have been reported to be involved in the development of critical COVID-19. We performed a genome-wide association study to identify the genetic factors responsible for developing critical COVID-19. 632 critical patients with COVID-19 and 3021 healthy controls from the Chinese population were recruited. First, we identified a genome-wide significant difference of IL-6 rs2069837 (p = 9.73 × 10-15, OR = 0.41) between 437 critical patients with COVID-19 and 2551 normal controls in the discovery cohort. When replicated these findings in a set of 195 patients with critical COVID-19 and 470 healthy controls, we detected significant association of rs2069837 with COVID-19 (p = 8.89 × 10-3, OR = 0.67). This variant surpassed the formal threshold for genome-wide significance (combined p = 4.64 × 10-16, OR = 0.49). Further analysis revealed that there was a significantly stronger expression of IL-6 in the serum from patients with critical COVID-19 than in that from patients with asymptomatic COVID-19. An in vitro assay showed that the A to G allele changes in rs2069837 within IL-6 obviously decreased the luciferase expression activity. When analyzing the effect of this variant on the IL-6 in the serum based on the rs2069837 genotype, we found that the A to G variation in rs2069837 decreased the expression of IL-6, especially in the male. Overall, we identified a genetic variant in IL-6 that protects against critical conditions with COVID-19 though decreasing IL-6 expression in the serum.

Quantitative CT imaging features for COVID-19 evaluation: The ability to differentiate COVID-19 from non- COVID-19 (highly suspected) pneumonia patients during the epidemic period.

OBJECTIVES: COVID-19 and Non-Covid-19 (NC) Pneumonia encountered high CT imaging overlaps during pandemic. The study aims to evaluate the effectiveness of image-based quantitative CT features in discriminating COVID-19 from NC Pneumonia. MATERIALS AND METHODS: 145 patients with highly suspected COVID-19 were retrospectively enrolled from four centers in Sichuan Province during January 23 to March 23, 2020. 88 cases were confirmed as COVID-19, and 57 patients were NC. The dataset was randomly divided by 3:2 into training and testing sets. The quantitative CT radiomics features were extracted and screened sequentially by correlation analysis, Mann-Whitney U test, the least absolute shrinkage and selection operator (LASSO) logistic regression (LR) and backward stepwise LR with minimum AIC methods. The selected features were used to construct the LR model for differentiating COVID-19 from NC. Meanwhile, the differentiation performance of traditional quantitative CT features such as lesion volume ratio, ground glass opacity (GGO) or consolidation volume ratio were also considered and compared with Radiomics-based method. The receiver operating characteristic curve (ROC) analysis were conducted to evaluate the predicting performance. RESULTS: Compared with traditional CT quantitative features, radiomics features performed best with the highest Area Under Curve (AUC), sensitivity, specificity and accuracy in the training (0.994, 0.942, 1.0 and 0.965) and testing sets (0.977, 0.944, 0.870, 0.915) (Delong test, P < 0.001). Among CT volume-ratio based models using lesion or GGO component ratio, the model combining CT lesion score and component ratio performed better than others, with the AUC, sensitivity, specificity and accuracy of 0.84, 0.692, 0.853, 0.756 in the training set and 0.779, 0.667, 0.826, 0.729 in the testing set. The significant difference of the most selected wavelet transformed radiomics features between COVID-19 and NC might well reflect the CT signs. CONCLUSIONS: The differentiation between COVID-19 and NC could be well improved by using radiomics features, compared with traditional CT quantitative values.

Dynamic blood single-cell immune responses in patients with COVID-19.

The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.

Quantitative assessment of SARS-CoV-2 RNAemia and outcome in patients with coronavirus disease 2019.

The disease spectrum of coronavirus disease 2019 (COVID-19) varies from asymptomatic infection to critical illness and death. Identification of prognostic markers is vital for predicting progression and clinical practice. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA, known as RNAemia, has been detected in the blood. However, the potential clinical value of SARS-CoV-2 RNAemia remains unknown. We, therefore, conducted a meta-analysis using a random-effects model to estimate the pooled prevalence of SARS-CoV-2 RNAemia as well as summary strength of RNAemia in association with disease severity and unfavorable clinical outcomes. A total of 21 studies involving 2181 patients were included. SARS-CoV-2 RNAemia in COVID-19 patients varied from 9.4% to 74.1%, with a pooled estimate of 34% (95% confidene interval [CI]: 26%-43%). Overall, SARS-CoV-2 RNAemia was associated with COVID-19 severity with odds ratio (OR) of 5.43 (95% CI: 3.46-8.53). In addition, SARS-CoV-2 RNAemia was a significant risk factor for unfavorable clinical outcomes (OR = 6.54, 95% CI: 3.82-11.21). The summary OR was 4.28 (95% CI: 2.20-8.33) for intensive care unit (ICU) admission, 11.07 (95% CI: 5.60-21.88) for mortality. Furthermore, RNAemia was also a significant risk factor for invasive mechanical ventilation and multiple organ failure. SARS-CoV-2 RNAemia is associated with disease severity, ICU admission, death in COVID-19, and may serve as a clinical predictor. More prospective trials in evaluating the potential of SARS-CoV-2 RNAemia as a prognostic indicator are necessary.

Comparison of different samples for 2019 novel coronavirus detection by nucleic acid amplification tests.

An ongoing outbreak of severe respiratory pneumonia associated with the 2019 novel coronavirus has recently emerged in China. Here we report the epidemiological, clinical, laboratory and radiological characteristics of 19 suspect cases. We compared the positive ratio of 2019-nCoV nucleic acid amplification test results from different samples including oropharyngeal swab, blood, urine and stool with 3 different fluorescent RT-PCR kits. Nine out of the 19 patients had 2019-nCoV infection detected using oropharyngeal swab samples, and the virus nucleic acid was also detected in eight of these nine patients using stool samples. None of positive results was identified in the blood and urine samples. These three different kits got the same result for each sample and the positive ratio of nucleic acid detection for 2019-nCoV was only 47.4% in the suspect patients. Therefore, it is possible that infected patients have been missed by using nucleic acid detection only. It might be better to make a diagnosis combining the computed tomography scans and nucleic acid detection.