Comparing T- and B-cell responses to COVID-19 vaccines across varied immune backgrounds.

The emergence of adapted variants of the SARS-CoV-2 virus has led to a surge in breakthrough infections worldwide. A recent analysis of immune responses in people who received inactivated vaccines has revealed that individuals with no prior infection have limited resistance to Omicron and its sub-lineages, while those with previous infections exhibit a significant amount of neutralizing antibodies and memory B cells. However, specific T-cell responses remain largely unaffected by the mutations, indicating that T-cell-mediated cellular immunity can still provide protection. Moreover, the administration of a third dose of vaccine has resulted in a marked increase in the spectrum and duration of neutralizing antibodies and memory B cells in vivo, which has enhanced resistance to emerging variants such as BA.2.75 and BA.2.12.1. These results highlight the need to consider booster immunization for previously infected individuals and the development of novel vaccination strategies. The rapid spread of adapted variants of the SARS-CoV-2 virus presents a significant challenge to global health. The findings from this study underscore the importance of tailoring vaccination strategies based on individual immune backgrounds and the potential need for booster shots to combat emerging variants. Continued research and development are crucial to discovering new immunization strategies that will effectively protect public health against the evolving virus.

Research progress and applications of nanobody in human infectious diseases.

Infectious diseases, caused by pathogenic microorganisms, are capable of affecting crises. In addition to persistent infectious diseases such as malaria and dengue fever, the vicious outbreaks of infectious diseases such as Neocon, Ebola and SARS-CoV-2 in recent years have prompted the search for more efficient and convenient means for better diagnosis and treatment. Antibodies have attracted a lot of attention due to their good structural characteristics and applications. Nanobodies are the smallest functional single-domain antibodies known to be able to bind stably to antigens, with the advantages of high stability, high hydrophilicity, and easy expression and modification. They can directly target antigen epitopes or be constructed as multivalent nanobodies or nanobody fusion proteins to exert therapeutic effects. This paper focuses on the construction methods and potential functions of nanobodies, outlines the progress of their research, and highlights their various applications in human infectious diseases.

Follow-Up Study of the Cardiopulmonary and Psychological Outcomes of COVID-19 Survivors Six Months After Discharge in Sichuan, China.

PURPOSE: Some studies have shown that patients with coronavirus disease 2019 (COVID-19) still have sequelae after discharge. However, little is known about the long-term physical and psychological sequelae of patients, especially factors that influenced the prognosis. PATIENTS AND METHODS: Patients with COVID-19 were followed up for 6 months. The psychological status of patients was evaluated by DASS-21 questionnaire, while physical functions were determined using medical history, laboratory examination, thoracic computed tomography (CT), and echocardiography. RESULTS: Fifty patients infected with COVID-19 were enrolled, and 11 (22%) patients still showed symptoms related to COVID-19. The mean contents (cells/ul) of CD3+ cells, CD4+ and CD8+ T, B lymphocytes and NK cells of the survivors elevated significantly after 6-month discharge (P < 0.001). The frequency of ground-glass opacities and consolidations decreased from 90% to 42% (P < 0.001), and 54% to 20%, (P = 0.001), respectively, while the changes of reticulation and bronchiectasis were insignificant (P > 0.05). The frequency of left ventricular diastolic dysfunction decreased from 40% to 15% (P = 0.002). Depression was observed in 5 (12.5%) participants, stress in 3 (7.5%), anxiety in 6 (15%), and among them 1 (2.5%) showed extremely severe anxiety. Covariation analysis elucidated age might be a risk factor (OR: 1.09, 95% CI: 1.01-1.18, P = 0.038), while NK cell was a good prognostic factor for pulmonary recovery. The comorbidities were significantly positive correlated with persist pulmonary damage (r = 0.33, P = 0.020). Compared with patients with antiviral therapy, patients without antiviral therapy had higher anxiety score (3 vs 0, P = 0.033). CONCLUSION: After 6-month discharge, the persisting cardiopulmonary damage was observed in recovery patients, and psychological implications should not be ignored. Age, comorbidities, NK cell and antiviral therapy might be associated with the prognosis of COVID-19.

Detection of SARS-CoV-2 and Its Mutated Variants via CRISPR-Cas13-Based Transcription Amplification.

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global health emergency, and its gene mutation and evolution further posed uncertainty of epidemic risk. Herein, we reported a light-up CRISPR-Cas13 transcription amplification method, which enables the detection of SARS-CoV-2 and its mutated variants. Sequence specificity was ensured by both the ligation process and Cas13a/crRNA recognition, allowing us to identify viral RNA mutation. Light-up RNA aptamer allows sensitive output of amplification signals via target-activated ribonuclease activity of CRISPR-Cas13a. The RNA virus assay has been designed to detect coronavirus, SARS-CoV-2, Middle East respiratory syndrome (MERS), and SARS, as well as the influenza viruses such as, H1N1, H7N9, and H9N2. It was accommodated to sense as low as 82 copies of SARS-CoV-2. Particularly, it allowed us to strictly discriminate key mutation of the SARS-CoV-2 variant, D614G, which may induce higher epidemic and pathogenetic risk. The proposed RNA virus assays are promising for point-of-care monitoring of SARS-CoV-2 and its risking variants.

Comparison of Seven Commercial Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Detection Reagents with Pseudovirus as Quality Control Material.

The ongoing pandemic of coronavirus disease 2019 threatens the whole world, which catalyzes a variety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test (NAT) kits. To monitor test quality and evaluate NAT kits, quality control materials that best simulate real clinical samples are needed. In this study, the performance of SARS-CoV-2 cell culture supernatant, PCDH-based pseudovirus, and MS2-based pseudovirus as quality control materials was compared. PCDH-based pseudovirus was found to be more similar in characteristics to SARS-CoV-2 particle, and more suitable for evaluating SARS-CoV-2 NAT kits than MS2-based pseudovirus. Proper detection using sensitive and precise NAT kits is essential to guarantee diagnosis. Thus, limit of detection, precision, anti-inference ability, and cross-reactivity of NAT kits from PerkinElmer, Beijing Wantai Biological Pharmacy Enterprise Co, Ltd, Shanghai Kehua Bio-Engineering Co, Ltd, Sansure Biotech Inc., Da An Gene Co, Ltd, Shanghai BioGerm Medical Biotechnology Co, Ltd, and Applied Biological Technologies Co, Ltd, were compared using PCDH-based pseudovirus. For the seven kits evaluated, N gene was more sensitive than ORF1ab gene in most kits, whereas E gene was most sensitive among the three genes in Shanghai Kehua Bio-Engineering Co, Ltd, and Applied Biological Technologies Co, Ltd. PerkinElmer got the lowest limit of detection for N gene at 11.61 copies/mL, and the value was 34.66 copies/mL for ORF1ab gene. All of the kits showed good precision, with CV values less than 5%, as well as acceptable anti-interference ability of 2 mg/L human genomic DNA. No cross-reactivity was observed with other respiratory viruses.

Risk factors for predicting mortality of COVID-19 patients: A systematic review and meta-analysis.

BACKGROUND: Early and accurate prognosis prediction of the patients was urgently warranted due to the widespread popularity of COVID-19. We performed a meta-analysis aimed at comprehensively summarizing the clinical characteristics and laboratory abnormalities correlated with increased risk of mortality in COVID-19 patients. METHODS: PubMed, Scopus, Web of Science, and Embase were systematically searched for studies considering the relationship between COVID-19 and mortality up to 4 June 2020. Data were extracted including clinical characteristics and laboratory examination. RESULTS: Thirty-one studies involving 9407 COVID-19 patients were included. Dyspnea (OR = 4.52, 95%CI [3.15, 6.48], P < 0.001), chest tightness (OR = 2.50, 95%CI [1.78, 3.52], P<0.001), hemoptysis (OR = 2.00, 95%CI [1.02, 3.93], P = 0.045), expectoration (OR = 1.52, 95%CI [1.17, 1.97], P = 0.002) and fatigue (OR = 1.27, 95%CI [1.09, 1.48], P = 0.003) were significantly related to increased risk of mortality in COVID-19 patients. Furthermore, increased pretreatment absolute leukocyte count (OR = 11.11, 95%CI [6.85,18.03], P<0.001) and decreased pretreatment absolute lymphocyte count (OR = 9.83, 95%CI [6.72, 14.38], P<0.001) were also associated with increased mortality of COVID-19. We also compared the mean value of them between survivors and non-survivors, and found that non-survivors showed significantly raise in pretreatment absolute leukocyte count (WMD: 3.27×109/L, 95%CI [2.34, 4.21], P<0.001) and reduction in pretreatment absolute lymphocyte count (WMD = -0.39×109/L, 95%CI [-0.46, -0.33], P<0.001) compared with survivors. The results of pretreatment lactate dehydrogenase (LDH), procalcitonin (PCT), D-Dimer and ferritin showed the similar trend with pretreatment absolute leukocyte count. CONCLUSIONS: Among the common symptoms of COVID-19 infections, fatigue, expectoration, hemoptysis, dyspnea and chest tightness were independent predictors of death. As for laboratory examinations, significantly increased pretreatment absolute leukocytosis count, LDH, PCT, D-Dimer and ferritin, and decreased pretreatment absolute lymphocyte count were found in non-survivors, which also have an unbeneficial impact on mortality among COVID-19 patients. Motoring these indicators during the hospitalization plays a very important role in predicting the prognosis of patients.

COVID-19: Progress in diagnostics, therapy and vaccination.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently become a pandemic. As the sudden emergence and rapid spread of SARS-CoV-2 is endangering global health and the economy, the development of strategies to contain the virus's spread are urgently needed. At present, various diagnostic kits to test for SARS-CoV-2 are available for use to initiate appropriate treatment faster and to limit further spread of the virus. Several drugs have demonstrated in vitro activity against SARS-CoV-2 or potential clinical benefits. In addition, institutions and companies worldwide are working tirelessly to develop treatments and vaccines against COVID-19. However, no drug or vaccine has yet been specifically approved for COVID-19. Given the urgency of the outbreak, we focus here on recent advances in the diagnostics, treatment, and vaccine development for SARS-CoV-2 infection, helping to guide strategies to address the current COVID-19 pandemic.