Lower respiratory tract samples are reliable for severe acute respiratory syndrome coronavirus 2 nucleic acid diagnosis and animal model study

Severe acute respiratory syndrome coronavirus 2(SARS-Co V-2) and coronavirus disease 2019(COVID-19) continue to impact countries worldwide.At present, inadequate diagnosis and unreliable evaluation systems hinder the implementation and development of effective prevention and treatment strategies. Here, we conducted a horizontal and longitudinal study comparing the detection rates of SARS-Co V-2 nucleic acid in different types of samples collected from COVID-19 patients and SARS-Co V-2-infected monkeys. We also detected anti-SARS-Co V-2 antibodies in the above clinical and animal model samples to identify a reliable approach for the accurate diagnosis of SARS-Co V-2 infection. Results showed that, regardless of clinical symptoms, the highest detection levels of viral nucleic acid were found in sputum and tracheal brush samples, resulting in a high and stable diagnosis rate. Anti-SARS-Co V-2 immunoglobulin M(Ig M) and G(Ig G) antibodies were not detected in6.90% of COVID-19 patients. Furthermore,integration of nucleic acid detection results from the various sample types did not improve the diagnosis rate. Moreover, dynamic changes in SARS-Co V-2 viral load were more obvious in sputum and tracheal brushes than in nasal and throat swabs. Thus,SARS-Co V-2 nucleic acid detection in sputum and tracheal brushes was the least affected by infection route, disease progression, and individual differences. Therefore, SARS-Co V-2 nucleic acid detection using lower respiratory tract samples alone is reliable for COVID-19 diagnosis and study.

SARS-CoV-2 breakthrough infections following inactivated vaccine vaccination induce few neutralizing antibodies against the currently emerging Omicron XBB variants

Dear Editor,COVID-19 inactivated vaccines have been extensively administered inChina.However,the majority of the Chinese population has experiencedbreakthrough infections from SARS-CoV-2 ancestral,Delta or Omicronvariants over the past three years,particularly during the wave of Omicron BA.5 and BA.7 variants at the end of 2022(Zhu et al.,2023).Subsequently,new Omicron variants,such as BQ.1,BQ.1.1,XBB,XBB.1/XBB.1.9,and XBB.1.5/XBB.1.9.1,are emerging in China(Yueetal.,2023;Zhu et al.,2023).Therefore,it is an urgentneed and a publichealth imperative to assess the extent of the immunoprotection established in this population.

Efficacy and Safety of Tenofovir and Lamivudine in Combination with Efavirenz in Patients Co-infected with Human Immunodeficiency Virus and Hepatitis B Virus in China

Background： The prevalence of hepatitis B virus （HBV） infection is high among individuals infected with human immunodeficiency virus （HIV） in China.Both HIV and HBV can be treated with tenofovir disoproxil fumarate （TDF） and lamivudine （3TC）, so we evaluated the safety and efficacy of combination antiretroviral therapy （ART） that included TDF, 3TC, and efavirenz （EFV） among ART-naive individuals who were co-infected with HIV and HBV.Methods： One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen ofTDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.Results： Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels （71%） and/or HIV RNA levels （90%）.Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline （109 ml＆#183;min-1＆#183; 1.73 m-2） to week 12 （104 ml＆#183;min-1＆#183; 1.73 m-2） but was almost back to baseline at week 48 （1 1 1 ml＆#183;min-1＆#183; 1.73 m-2）.Conclusion： This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.Trial Registration： ClinicalTrials.gov, NCT01751555;https：//clinicaltrials.gov/ct2/show/NCT01751555.

Longitudinal transcriptome analyses show robust T cell immunity during recovery from COVID-19

Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell(PBMC)samples from 18 patients with coronavirus disease 2019(COVID-19)during their treatment,convalescence,and rehabilitation.After analyzing the regulatory networks of differentially expressed messenger RNAs(mRNAs),microRNAs(miRNAs)and long non-coding RNAs(lncRNAs)between the different clinical stages,we found that humoral immunity and type I interferon response were significantly downregulated,while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19.The formation of this T cell immune response might be driven by the activation of activating protein-1(AP-1)related signaling pathway and was weakly affected by other clinical features.These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.

Characteristics of replication and pathogenicity of SARS-CoV-2 Alpha and Delta isolates

The continuously arising of SARS-CoV-2 variants has been posting a great threat to public health safety globally,from B.1.17(Alpha), B.1.351(Beta), P.1(Gamma), B.1.617.2(Delta) to B.1.1.529(Omicron). The emerging or reemerging of the SARS-CoV-2 variants of concern is calling for the constant monitoring of their epidemics,pathogenicity and immune escape. In this study, we aimed to characterize replication and pathogenicity of the Alpha and Delta variant strains isolated from patients infected in Laos. The amino acid mutations within the spike fragment of the isolates were determined via sequencing. The more efficient replication of the Alpha and Delta isolates was documented than the prototyped SARS-CoV-2 in Calu-3 and Caco-2 cells, while such features were not observed in Huh-7, Vero E6 and HPA-3 cells. We utilized both animal models of human ACE2(hACE2)transgenic mice and hamsters to evaluate the pathogenesis of the isolates. The Alpha and Delta can replicate well in multiple organs and cause moderate to severe lung pathology in these animals. In conclusion, the spike protein of the isolated Alpha and Delta variant strains was characterized, and the replication and pathogenicity of the strains in the cells and animal models were also evaluated.

Longitudinal transcriptome analyses show robust T cellimmunity during recovery from COVID-19

Understanding the processes of immune regulation in patients infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is crucial for improving treatment.Here,we performed longitudinal whole-transcriptome RNA sequencing on peripheral blood mononuclear cell(PBMC)samples from 18 patients with coronavirus disease 2019(COVID-19)during their treatment,convalescence,and rehabilitation.After analyzing the regulatory networks of differentially expressed messenger RNAs(mRNAs),microRNAs(miRNAs)and long non-coding RNAs(lncRNAs)between the different clinical stages,we found that humoral immunity and type I interferon response were significantly downregulated,while robust T-cell activation and differentiation at the whole transcriptome level constituted the main events that occurred during recovery from COVID-19.The formation of this T cell immune response might be driven by the activation of activating protein-1(AP-1)related signaling pathway and was weakly affected by other clinical features.These findings uncovered the dynamic pattern of immune responses and indicated the key role of T cell immunity in the creation of immune protection against this disease.