Association between clinical symptoms during the COVID-19 infection and SARS-CoV-2 immunoglobulin G titers in COVID-19 convalescent whole-blood donors in China.

BACKGROUND: Limited studies have explored the association between clinical symptoms and titers of SARS-CoV-2 antibodies. STUDY DESIGN AND METHODS: In this cross-sectional study, whole-blood donors who had experienced a confirmed or suspected COVID-19 infection completed questionnaires at the time of blood donation. Plasma SARS-CoV-2 immunoglobulin G (IgG) titers were measured using an enzyme-linked immunosorbent assay. Logistic regression models were used to calculate odds ratios (ORs) for high-titer COVID-19 convalescent plasma (CCP) for each variable. RESULTS: Among the total 386 donors, 120 (31%) donors with IgG titers ≥1:160 were classified as high-titer donors. The multivariable ORs (95% confidence intervals [CIs]) for high titers were 2.33 (1.45-3.75), 2.11 (1.29-3.43), 1.10 (1.01-1.21), 1.19 (1.00-1.43), and 1.97 (1.05-3.71) for sore throat, cough, symptom count, fever duration, and low fever (compared with non-fever), respectively. No significant association was observed between other symptoms and medical visits and the odds of high-titer CCP. The association between high-titer CCP and fever duration was restricted to confirmed COVID-19-infected donors, while associations with sore throat and cough remained significant in suspected infected donors. In addition, medical visit was positively associated with high-titer CCP in suspected donors, but not in confirmed donors. In bootstrapped logistic regression models, the associations remained significant and reproducible for medical visit in suspected donors and for sore throat and cough in both suspected donors and total donors. DISCUSSION: Experiencing a sore throat and cough were associated with high-titer CCP in overall donors. We also identified sore throat, cough, and medical visits as potential predictors of high-titer CCP for suspected donors during the pandemic.

Development and evaluation of a Novel RT-PCR system for reliable and rapid SARS-CoV-2 screening of blood donations.

BACKGROUND: The ongoing outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused great global concerns. In contrast to SARS, some SARS-CoV-2-infected people can be asymptomatic or have only mild nonspecific symptoms. Furthermore, there is evidence that SARS-CoV-2 may be infectious during an asymptomatic incubation period. With the discovery that SARS-CoV-2 can be detected in plasma or serum, blood safety is worthy of consideration. STUDY DESIGN AND METHODS: We developed a nucleic acid test (NAT) screening system for SARS-CoV-2 targeting nucleocapsid protein (N) and open reading frame 1ab (ORF 1ab) gene that could screen 5076 samples every 24 hours. The 2019 novel coronavirus RNA standard was used to evaluate linearity of standard curves. Diagnostic sensitivity and reproducibility were evaluated using artificial SARS-CoV-2. Specificity was evaluated with 61 other respiratory pathogens. Diagnostic performance was evaluated by testing two sputum and nine oropharyngeal swab specimens. The reverse transcription polymerase chain reaction (RT-PCR) assay was used to screen SARS-CoV-2 RNA in blood donor specimens collected during the outbreak of SARS-CoV-2 in Chengdu. RESULTS: Limits of detection of the SARS-CoV-2 RT-PCR assay for N and ORF 1ab gene were 12.5 and 27.58 copies/mL, respectively. Intra-assay and interassay for the SARS-CoV-2 RT-PCR assay based on cycle threshold were acceptably low. No cross-reactivity was observed with other respiratory virus and bacterial isolates. The overall agreement value between the SARS-CoV-2 RT-PCR assay and clinical diagnostic results was 100%. A total of 16 287 blood specimens collected from blood donors during SARS-CoV-2 surveillance were tested negative. CONCLUSIONS: A high-throughput NAT screening system was developed for SARS-CoV-2 screening of blood donations during the outbreak of SARS-CoV-2.

Factors associated with the SARS-CoV-2 immunoglobulin-G titer levels in convalescent whole-blood donors: a Chinese cross-sectional study.

Blood transfusions from convalescent Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infected patients could be used to treat patients with severe infections or immunocompromised patients. However, it is necessary to select the optimal donors to maximize the utilization of resources. In this study, we investigated the associations among body mass index (BMI), tobacco smoking, exercise frequency and duration, and alcohol consumption with the SARS-CoV-2 immunoglobulin-G (IgG) antibody titer levels with in the Chinese convalescent blood donor population. Here we show that BMI, smoking habits, and exercise frequency appear to be predictive factors for IgG levels in convalescent male blood donors. However, these variables were not observed as predictive of IgG levels in female convalescent blood donors. The findings could be used to optimize the screening for potential blood donors to treat immunocompromised or severely ill COVID-19 patients.

Predictors of high SARS-CoV-2 immunoglobulin G titers in COVID-19 convalescent whole-blood donors: a cross-sectional study in China.

Background: Demographic information has been shown to help predict high antibody titers of COVID-19 convalescent plasma (CCP) in CCP donors. However, there is no research on the Chinese population and little evidence on whole-blood donors. Therefore, we aimed to investigate these associations among Chinese blood donors after SARS-CoV-2 infection. Methods: In this cross-sectional study, 5,064 qualified blood donors with confirmed or suspected SARS-CoV-2 infection completed a self-reported questionnaire and underwent tests of SARS-CoV-2 Immunoglobulin G (IgG) antibody and ABO blood type. Logistic regression models were used to calculate odds ratios (ORs) for high SARS-CoV-2 IgG titers according to each factor. Results: Totally, 1,799 participants (with SARS-CoV-2 IgG titers≥1:160) had high-titer CCPs. Multivariable analysis showed that a 10-year increment in age and earlier donation were associated with higher odds of high-titer CCP, while medical personnel was associated with lower odds. The ORs (95% CIs) of high-titer CCP were 1.17 (1.10-1.23, p< 0.001) and 1.41 (1.25-1.58, p< 0.001) for each 10-year increment in age and earlier donation, respectively. The OR of high-titer CCP was 0.75 (0.60-0.95, p = 0.02) for medical personnel. Female early donors were associated with increased odds of high-titer CCP, but this association was insignificant for later donors. Donating after 8 weeks from the onset was associated with decreased odds of having high-titer CCP compared to donating within 8 weeks from the onset, and the HR was 0.38 (95% CI: 0.22-0.64, p <0.001). There was no significant association between ABO blood type or race and the odds of high-titer CCP. Discussion: Older age, earlier donation, female early donors, and non-medical-related occupations are promising predictors of high-titer CCP in Chinese blood donors. Our findings highlight the importance of CCP screening at the early stage of the pandemic.

Corrigendum: Predictors of high SARS-CoV-2 immunoglobulin G titers in COVID-19 convalescent whole-blood donors: a cross-sectional study in China.

[This corrects the article DOI: 10.3389/fimmu.2023.1191479.].

Metabolomic profiling identifies biomarkers and metabolic impacts of surgery for colorectal cancer.

Background: Colorectal cancer (CRC) is one of the most common malignant tumors with recurrence and metastasis after surgical resection. This study aimed to identify the physiological changes after surgery and explore metabolites and metabolic pathways with potential prognostic value for CRC. Methods: An ultra-high-performance liquid chromatography Q-exactive mass spectrometry was used to profile serum metabolites from 67 CRC patients and 50 healthy volunteers. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis were used to distinguish the internal characteristics of data in different groups. Multivariate statistics were compiled to screen the significant metabolites and metabolic pathways. Result: A total of 180 metabolites were detected. Under the conditions of variable importance in projection >1 and p-value <0.05, 46 differentially expressed metabolites were screened for further pathway enrichment analysis. Based on the Kyoto Encyclopedia of Genes and Genomes database and Small Molecule Pathway Database, three metabolic pathways-arginine and proline metabolism, ascorbate and aldarate metabolism, and phenylalanine metabolism-were significantly altered after surgical resection and identified as associated with the removal of CRC. Notably, gamma-linolenic acid was upregulated in the CRC preoperative patients compared with those in healthy volunteers but returned to healthy levels after surgery. Conclusion: Through serum-based metabolomics, our study demonstrated the differential metabolic characteristics in CRC patients after surgery compared with those before surgery. Our results suggested that metabonomic analysis may be a powerful method for exploring physiological alterations in CRC patients after surgery as well as a useful tool for identifying candidate biomarkers and monitoring disease recurrence.

Prevalence of and risk factors for hepatitis C virus infection among blood donors in Chengdu, China.

The objectives of the study were to estimate the prevalence of anti-hepatitis C virus (HCV) positivity among blood donors from Chengdu, China, and to determine risk factors associated with infection. In this study, data were collected from volunteer blood donors between July 2006 and June 2007. Anti-HCV test was performed in 119,518 donors. To identify risk factors associated with HCV infections a case-control study was conducted in 305 unique HCV-seropositive blood donors and 610 seronegative donors matched for age and sex. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression. The population attributable risk (PAR) to risk factor was estimated according to the Bruzzi's formula. The prevalence of anti-HCV positivity was 0.53% (95% CI: 0.489-0.572%). The final multivariate model included the following independent HCV risk factors: razor sharing (OR=29.16; 95% CI: 12.89-66.00), blood transfusion (OR=20.84; 95% CI: 3.76-115.45), acupuncture (OR=8.01; 95% CI: 3.16-20.30), a history of hospitalization, injections >10 years earlier, a family history of hepatitis B, dental treatment, and ear piercing. The PAR of risk factors are 68.4%, 6.3%, 14.1%, 23.1%, 29.5%, 29.3%, 38.9%, and 27.8%, respectively, and the total PAR is 98.3%. Infection with HCV among blood donors in Chengdu is associated with iatrogenic risk factors and beauty treatment-related risk. Razor sharing is an important risk factor for HCV infection. These results indicate that infection control measures in healthcare settings may reduce the burden of HCV infection and there is a need for development of effective educational programs to improve HCV knowledge among beauty culture professionals, barber cosmetologists, and the general public to avoid risk behaviors.

Metabolomic Profiling Identified Serum Metabolite Biomarkers and Related Metabolic Pathways of Colorectal Cancer.

BACKGROUND: The screening and early detection of colorectal cancer (CRC) still remain a challenge due to the lack of reliable and effective serum biomarkers. Thus, this study is aimed at identifying serum biomarkers of CRC that could be used to distinguish CRC from healthy controls. METHODS: A prospective 1 : 2 individual matching case-control study was performed which included 50 healthy control subjects and 98 CRC patients. Untargeted metabolomic profiling was conducted with liquid chromatography tandem mass spectrometry (LC-MS/MS) to identify CRC-related metabolites and metabolic pathways. RESULTS: In total, 178 metabolites were detected, and an orthogonal partial least-squares-discriminant analysis (OPLS-DA) model was useful to distinguish CRC patients from healthy controls. Nine metabolites showed significantly differential serum levels in CRC patients under the conditions of variable importance in projection (VIP) > 1, p < 0.05 using Student's t-test, and fold change (FC) ≥ 1.2 or ≤0.5. The above nine metabolites were 3-hydroxybutyric acid, hexadecanedioic acid, succinic acid semialdehyde, 4-dodecylbenzenesulfonic acid, prostaglandin B2, 2-pyrocatechuic acid, xanthoxylin, 12-hydroxydodecanoic acid, and formylanthranilic acid. Four potential biomarkers were identified to diagnose CRC through ROC curves: hexadecanedioic acid, 4-dodecylbenzenesulfonic acid, 2-pyrocatechuic acid, and formylanthranilic acid. All AUC values of these four serum biomarkers were above 0.70. In addition, the exploratory analysis of metabolic pathways revealed the activated states for the vitamin B metabolic pathway and the alanine, aspartate, and glutamate metabolic pathways associated with CRC. CONCLUSION: The 4 identified potential metabolic biomarkers could discriminate CRC patients from healthy controls, and the 2 metabolic pathways may be activated in the CRC tissues.

Prevalence of human T-cell lymphotropic virus type-1 infection among blood donors in mainland China: a systematic review and meta-analysis of the last 20 years.

Background: The southeastern coastal area of China has a high prevalence of HTLV-1 infection among blood donors. However, the estimation of HTLV-1 prevalence on a national and regional level is little known. The aim of this study is to understand and explore the estimation of HTLV-1 infection prevalence among blood donors on a national and regional level in mainland China by using a systematic review and meta-analysis. Study design and methods: All relevant publications of the past two decades (1998-2017), which were reported in both English and Chinese languages, were adopted and systematically assessed. The estimation of prevalence and its 95% confidence interval (CI) at the level of provinces/municipalities and overall were estimated using meta-analysis method. Results: From the 327 studies searched, 60 met the inclusion criteria. These were from 18 provinces and four municipalities and included 1,420,079 blood donors. The overall estimation of the HTLV-1 prevalence in blood donors was 0.169‰, and its 95% CI was 0.121‰-0.240‰. Conclusion: A disproportionate distribution of HTLV-1 infection among blood donors in different provinces/municipalities regarding its prevalence has been reported. This study recommends developing appropriate HTLV-1 screening strategies of blood donors in various regions of China considering regional prevalence, and cost-effectiveness.

Contribution of sex­based immunological differences to the enhanced immune response in female mice following vaccination with hepatitis B vaccine.

Hepatitis B virus (HBV) vaccination is regarded as the most economical and effective method for the prevention and control of HBV infection, a major global health problem. Previous studies have suggested that there may be sex­specific differences regarding the immune response to the HBV vaccine in humans; however, the mechanisms associated with these sex­specific differences are yet to be elucidated. In the present study, sex­based immunological differences in mice following HBV vaccination were investigated to determine the mechanisms underlying sexual dimorphism, with the aim of identifying potential targets for clinical intervention. Balb/c mice (n=6) were vaccinated intramuscularly on 3 different days (days 0, 14 and 28) with the HBV vaccine. Sera were analyzed via ELISA for the presence of HBV surface antigen (HBsAg)­specific immunoglobulin G (IgG), and of different IgG subtypes, 3 weeks following the third injection. Enzyme­linked immunosorbent spot assays were conducted to determine interleukin­4/interferon­Î³ secretion. Immunological memory stimulated by the vaccine was detected via flow cytometry analysis and ELISA 1 week following the booster immunization. The seroconversion of the treated female group was higher compared with the male group at one week following the second vaccination. Female mice exhibited significantly increased HBsAg antibody titers compared with males at 1­5 weeks following the third vaccination. Sera obtained from vaccinated female mice exhibited markedly increased titers of IgG1 and IgG2b compared with those from male mice. Furthermore, female mice exhibited elevated cytotoxic T lymphocyte responses and immune memory. Collectively, the results of the present study indicated that sex­based immunological differences affected the dynamics and characteristics of the immune response in mice immunized with the HBV vaccine.