COVID-19 Serology Control Panel Using the Dried Tube Specimen Method

We used the dried tube specimen (DTS) procedure to develop the COVID-19 Serology Control Panel (CSCP). The CSCP contains five well-characterized SARS-CoV-2 pooled plasma samples made available for labs around the world to compare test kits, use for external quality assurance, harmonize laboratory testing, and train laboratory workers. Article Summary LineThe dried tube specimen system is a highly effective and resilient way to provide laboratories with well-characterized serology materials. The CSCP can help clinical laboratories inform their choice of diagnostic test to supplement clinical diagnoses of SARS-CoV-2 infection.

Recovery from acute SARS-CoV-2 infection and development of anamnestic immune responses in T cell-depleted rhesus macaques

Severe COVID-19 has been associated with T cell lymphopenia 1,2, but no causal effect of T cell deficiency on disease severity has been established. To investigate the specific role of T cells in recovery from SARS-CoV-2 infections we studied rhesus macaques that were depleted of either CD4+, CD8+ or both T cell subsets prior to infection. Peak virus loads were similar in all groups, but the resolution of virus in the T cell-depleted animals was slightly delayed compared to controls. The T cell-depleted groups developed virus-neutralizing antibody responses and also class-switched to IgG. When re-infected six weeks later, the T cell-depleted animals showed anamnestic immune responses characterized by rapid induction of high-titer virus-neutralizing antibodies, faster control of virus loads and reduced clinical signs. These results indicate that while T cells play a role in the recovery of rhesus macaques from acute SARS-CoV-2 infections, their depletion does not induce severe disease, and T cells do not account for the natural resistance of rhesus macaques to severe COVID-19. Neither primed CD4+ or CD8+ T cells appeared critical for immunoglobulin class switching, the development of immunological memory or protection from a second infection.

Interferon Resistance of Emerging SARS-CoV-2 Variants

The emergence of SARS-CoV-2 variants with enhanced transmissibility, pathogenesis and resistance to vaccines presents urgent challenges for curbing the COVID-19 pandemic. While Spike mutations that enhance virus infectivity or neutralizing antibody evasion may drive the emergence of these novel variants, studies documenting a critical role for interferon responses in the early control of SARS-CoV-2 infection, combined with the presence of viral genes that limit these responses, suggest that interferons may also influence SARS-CoV-2 evolution. Here, we compared the potency of 17 different human interferons against multiple viral lineages sampled during the course of the global outbreak, including ancestral and four major variants of concern. Our data reveal increased interferon resistance in emerging SARS-CoV-2 variants, suggesting that evasion of innate immunity may be a significant, ongoing driving force for SARS-CoV-2 evolution. These findings have implications for the increased lethality of emerging variants and highlight the interferon subtypes that may be most successful in the treatment of early infections. Author SummaryIn less than 2 years since its spillover into humans, SARS-CoV-2 has infected over 220 million people, causing over 4.5 million COVID-19 deaths. High infection rates provided substantial opportunities for the virus to evolve, as variants with enhanced transmissibility, pathogenesis, and resistance to vaccine-elicited neutralizing antibodies have emerged. While much focus has centered on the Spike protein which the virus uses to infect target cells, mutations were also found in other viral proteins that might inhibit innate immune responses. Specifically, viruses encounter a potent innate immune response mediated by the interferons, two of which, IFN2 and IFN{beta}, are being repurposed for COVID-19 treatment. Here, we compared the potency of human interferons against ancestral and emerging variants of SARS-CoV-2. Our data revealed increased interferon resistance in emerging SARS-CoV-2 strains that included the alpha, beta, gamma and delta variants of concern, suggesting a significant, but underappreciated role for innate immunity in driving the next phase of the COVID-19 pandemic.

Effect of apoptosis and proliferation of endometrial cancer HEC-1B cell by siRNA down-regulating expression of Ezrin / 中国综合临床

Objective To observe the changes of cell cycle,apoptosis and proliferation of endometrial cancer cells after the expression and down-regulation of Ezrin in endometrial cancer cells and to explore whether Ezrin may be a candidate gene for targeted therapy.Methods Endometrial cancer cells were from Shanghai Institute of Cell Research,of Chinese Academy of Medical Sciences in February 2017 and divided into blank control group and siEzrin group according to the intervention methods.Western blot and qRT-PCR was used to detect the expression of Ezrin protein and mRNA in endometrial cell lines.Small interfering RNA (siRNA) was used to transfect HEC-1B cell and down-regulate Ezrin.Cell cycle and apoptosis were detected by flow cytometry.MTT assay was used to detect multiplication.Results Western blot showed that Ezrin protein was expressed in Ishikawa (31.742 ± 5.832)、HEC-1A (16.326 ± 3.135)、HEC-1B(17.636±4.426) and KLE(14.862±5.109) and qRT-PCR showed that mRNA was expressed in Ishikawa (2.513±0.725),HEC-1A (1.655±0.692),HEC-1B (3.237±0.411) and KLE (0.962±0.235) cell lines,and expressed highest in HEC-1B cells (F=6.173,P＜0.05;F=7.042,P＜0.05).Flow cytometry assay showed that compared with blank control group less cells stayed in G1 phase and G2 phase,more stayed in S phase (t=3.118,P＜0.05;t=5.435,P＜0.05;t=3.332,P＜0.05).The apoptotic rate of HEC-1B cells increased from (9.84 ± 2.37) ％ to (17.64 ± 5.96) ％ (t =8.963,P ＜ 0.01) after Ezrin was downregulated.MTT assay showed that the proliferation of HEC-1B cells in 72 h and 96 h siEzrin transfection group was lower than that in blank control group (t =3.209,P＜ 0.05;t =3.726,P＜ 0.05).Conclusion Down-regulating of Ezrin may promote more endometrial cancer cells stay in S phase and promote apoptosis,inhibit proliferation,Ezrin may become target candidate gene in target therapy.