Deciphering the dynamic changes in antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. Here we analyze the laboratory findings of 1,850 patients to ...describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)-specific immunoglobulin M (IgM) and G (IgG) levels during SARS-CoV-2 infection and recovery. The generation of S-, RBD-, and N-specific IgG occurs one week later in patients with severe/critical COVID-19 compared to patients with mild/moderate disease, while S- and RBD-specific IgG levels are 1.5-fold higher in severe/critical patients during hospitalization. The RBD-specific IgG levels are 4-fold higher in older patients than in younger patients during hospitalization. In addition, the S- and RBD-specific IgG levels are 2-fold higher in the recovered patients who are SARS-CoV-2 RNA negative than those who are RNA positive. Lower S-, RBD-, and N-specific IgG levels are associated with a lower lymphocyte percentage, higher neutrophil percentage, and a longer duration of viral shedding. Patients with low antibody levels on discharge might thereby have a high chance of being tested positive for SARS-CoV-2 RNA after recovery. Our study provides important information for COVID-19 diagnosis, treatment, and vaccine development.
The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat. The efficacy of several ...repurposed drugs has been evaluated in clinical trials. Among these drugs, a second-generation antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and Ad-ACE2-transduced mice. Tmprss2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cells, however, such antiviral efficacy was lacking in human lung cells and organoids. Accordingly, enzalutamide showed no antiviral activity due to the AR-independent TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 regulatory locus in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19 through reducing TMPRSS2 expression in lung cells.
People more accurately remember faces of their own racial group compared to faces of other racial groups; this phenomenon is called the other-race effect. To date, numerous researchers have devoted ...themselves to exploring the reasons for this other-race effect, and they have posited several theoretical explanations. One integrated explanation is the categorization-individuation model, which addresses two primary ways (categorization and individuation) of racial face processing and emphasizes the emergence of these two ways during the encoding stage. Learning-recognition and racial categorization tasks are two classical tasks used to explore racial face processing. Event-related potentials can facilitate investigation of the encoding differences of own- and other-race faces under these two typical task demands. Unfortunately, to date, results have been mixed. In the current study, we investigated whether categorization and individuation differ for own- and other-race faces during the encoding stage by using racial categorization and learning-recognition tasks. We found that task demands not only influence the encoding of racial faces, but also have a more profound effect in the encoding stage of recognition tasks for other-race faces. More specifically, own-race faces demonstrate deeper structural encoding than other-race faces, with less attentional involvement. Moreover, recognitions tasks might ask for more individual-level encoding, requiring more attentional resources in the early stage that may be maintained until relatively late stages. Our results provide some evidence concerning task selection for future racial face studies and establish a groundwork for a unified interpretation of racial face encoding.
Five new meroterpenoids, clavipols A-B (
-
) with a 12-membered ether ring and clavilactones G-I (
-
) having a 10-membered carbocycle connected to a hydroquinone and an α,β-epoxy/unsaturated ...lactone, were obtained from the fruiting bodies of the basidiomycete
. Their structures were determined by comprehensive analysis of their spectroscopic data, and the absolute configuration of
was established by quantum chemical calculations of electronic circular dichroism (ECD). All the isolated compounds (
-
) were tested for their cytotoxic activity against three human tumor cell lines (Hela, SGC-7901, and SHG-44) in vitro after treatment for 48 h. Compound
exhibited moderate cytotoxic activity against Hela and SGC-7901 tumor cell lines, with IC
values of 23.5 and 14.5 µM, respectively.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes a broad clinical spectrum of coronavirus disease 2019 (COVID-19). The development of COVID-19 may be the result ...of a complex interaction between the microbial, environmental, and host genetic components. To reveal genetic determinants of susceptibility to COVID-19 severity in the Chinese population, we performed a genome-wide association study on 885 severe or critical COVID-19 patients (cases) and 546 mild or moderate patients (controls) from two hospitals, Huoshenshan and Union hospitals at Wuhan city in China. We identified two loci on chromosome 11q23.3 and 11q14.2, which are significantly associated with the COVID-19 severity in the meta-analyses of the two cohorts (index rs1712779: odds ratio OR = 0.49; 95% confidence interval CI, 0.38–0.63 for T allele;
P
= 1.38 × 10
−8
; and index rs10831496: OR = 1.66; 95% CI, 1.38–1.98 for A allele;
P
= 4.04 × 10
−8
, respectively). The results for rs1712779 were validated in other two small COVID-19 cohorts in the Asian populations (
P
= 0.029 and 0.031, respectively). Furthermore, we identified significant eQTL associations for
REXO2
,
C11orf71
,
NNMT
, and
CADM1
at 11q23.3, and
CTSC
at 11q14.2, respectively. In conclusion, our findings highlight two loci at 11q23.3 and 11q14.2 conferring susceptibility to the severity of COVID-19, which might provide novel insights into the pathogenesis and clinical treatment of this disease.
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