Protective effectiveness of previous infection against subsequent SARS-Cov-2 infection: systematic review and meta-analysis.

Background: The protective effectiveness provided by naturally acquired immunity against SARS-CoV-2 reinfection remain controversial. Objective: To systematically evaluate the protective effect of natural immunity against subsequent SARS-CoV-2 infection with different variants. Methods: We searched for related studies published in seven databases before March 5, 2023. Eligible studies included in the analysis reported the risk of subsequent infection for groups with or without a prior SARS-CoV-2 infection. The primary outcome was the overall pooled incidence rate ratio (IRR) of SARS-CoV-2 reinfection/infection between the two groups. We also focused on the protective effectiveness of natural immunity against reinfection/infection with different SARS-CoV-2 variants. We used a random-effects model to pool the data, and obtained the bias-adjusted results using the trim-and-fill method. Meta-regression and subgroup analyses were conducted to explore the sources of heterogeneity. Sensitivity analysis was performed by excluding included studies one by one to evaluate the stability of the results. Results: We identified 40 eligible articles including more than 20 million individuals without the history of SARS-CoV-2 vaccination. The bias-adjusted efficacy of naturally acquired antibodies against reinfection was estimated at 65% (pooled IRR = 0.35, 95% CI = 0.26-0.47), with higher efficacy against symptomatic COVID-19 cases (pooled IRR = 0.15, 95% CI = 0.08-0.26) than asymptomatic infection (pooled IRR = 0.40, 95% CI = 0.29-0.54). Meta-regression revealed that SARS-CoV-2 variant was a statistically significant effect modifier, which explaining 46.40% of the variation in IRRs. For different SARS-CoV-2 variant, the pooled IRRs for the Alpha (pooled IRR = 0.11, 95% CI = 0.06-0.19), Delta (pooled IRR = 0.19, 95% CI = 0.15-0.24) and Omicron (pooled IRR = 0.61, 95% CI = 0.42-0.87) variant were higher and higher. In other subgroup analyses, the pooled IRRs of SARS-CoV-2 infection were statistically various in different countries, publication year and the inclusion end time of population, with a significant difference (p = 0.02, p < 0.010 and p < 0.010), respectively. The risk of subsequent infection in the seropositive population appeared to increase slowly over time. Despite the heterogeneity in included studies, sensitivity analyses showed stable results. Conclusion: Previous SARS-CoV-2 infection provides protection against pre-omicron reinfection, but less against omicron. Ongoing viral mutation requires attention and prevention strategies, such as vaccine catch-up, in conjunction with multiple factors.

Enhanced Transmissibility and Decreased Virulence of HIV-1 CRF07_BC May Explain Its Rapid Expansion in China.

HIV-1 CRF07_BC is one of the most common circulating recombinant forms (CRFs) in China and is becoming increasingly prevalent especially in HIV-infected men who have sex with men (MSM). The reason why this strain expanded so quickly in China remains to be defined. We previously observed that individuals infected with HIV-1 CRF07_BC showed slower disease progression than those infected with HIV-1 subtype B or CRF01_AE. CRF07_BC viruses carry two unique mutations in the p6Gag protein: insertion of PTAPPE sequences downstream of the original Tsg101 binding domain, and deletion of a seven-amino-acid sequence (30PIDKELY36) that partially overlaps with the Alix binding domain. In this study, we confirmed the enhanced transmission capability of CRF07_BC over HIV-1 subtype B or CRF01_AE by constructing HIV-1 transmission networks to quantitatively evaluate the growth rate of transmission clusters of different HIV-1 genotypes. We further determined lower virus infectivity and slower replication of CRF07_BC with aforementioned PTAPPE insertion (insPTAP) and/or PIDKELY deletion (Δ7) in the p6Gag protein, which in turn may increase the pool of people infected with CRF07_BC and the risk of HIV-1 transmission. These new features of CRF07_BC may explain its quick spread and will help adjust prevention strategy of HIV-1 epidemic. IMPORTANCE HIV-1 CRF07_BC is one of the most common circulating recombinant forms (CRFs) in China. The question is why and how CRF07_BC expanded so rapidly remains unknown. To address the question, we explored the transmission capability of CRF07_BC by constructing HIV-1 transmission networks to quantitatively evaluate the growth rate of transmission clusters of different HIV-1 genotypes. We further characterized the role of two unique mutations in CRF07_BC, PTAPPE insertion (insPTAP) and/or PIDKELY deletion (Δ7) in the p6Gag in virus replication. Our results help define the molecular mechanism regarding the association between the unique mutations and the slower disease progression of CRF07_BC as well as the quick spread of CRF07_BC in China.

Syphilis Testing as a Proxy Marker for a Subgroup of Men Who Have Sex With Men With a Central Role in HIV-1 Transmission in Guangzhou, China.

Objectives: The objectives of this study were to distinguish the role of men who have sex with men (MSM) with or without syphilis testing in HIV-1 transmission and to provide molecular evidence of syphilis testing as a proxy marker for identifying the subgroup of MSM. Methods: HIV-1 transmission clusters were constructed by HIV-TRACE and Cluster Picker using HIV-1 pol sequences from 729 newly diagnosed HIV-infected MSM from 2008 to 2012 in Guangzhou, China. The role of MSM in HIV-1 transmission networks was determined by a node influence measurement and centrality analysis. The association between syphilis testing and factors related to HIV-1 transmission and antiretroviral treatment (ART) were analyzed by the Cox regression model. Results: Among HIV-infected MSM, 56.7% did not test for syphilis at the time of HIV-1 diagnosis. MSM without syphilis testing was a specific subgroup of MSM with a larger closeness centrality and clustering coefficient than the recipients of syphilis testing (P < 0.001), indicating their central position in the HIV-1 transmission networks. The median degree and radiality within HIV-1 transmission networks as well as the median K-shell scores were also greater for MSM without syphilis testing (P < 0.001), suggesting their relatively greater contribution in transmitting HIV-1 than the receipts of syphilis testing. MSM with syphilis testing usually did not disclose their occupation or were more likely to be unemployed or to take non-skilled jobs, to have a history of sexually transmitted infections (STIs), and to be AIDS patients when diagnosed with HIV-1 infection (P < 0.05). Multivariable Cox regression analysis indicated that syphilis testing per se did not promote the engagement of ART (P = 0.233) or affect the speed of CD4+ T cell count recovery after treatment (P = 0.256). Conclusions: Our study identifies syphilis testing as a proxy marker of a specific subgroup of HIV-infected MSM who refuse syphilis testing during HIV-1 diagnosis with an important role in HIV-1 transmission. Specific prevention and intervention targeting MSM without syphilis testing during HIV-1 care are urgently needed.

Acquisition and transmission of HIV-1 among migrants and Chinese in Guangzhou, China from 2008 to 2012: Phylogenetic analysis of surveillance data.

BACKGROUND: Post-migration infection and domestic transmission of HIV-1 between immigrants and local population are critical for the HIV epidemic, but have not been addressed thus far in China. METHODS: Transmission clusters were analyzed with two cluster reconstruction methods, HIV-TRACE and Cluster Picker, using 1695 HIV-1 pol sequences obtained from 139 HIV-infected foreigners and 1556 Chinese natives in Guangzhou, China from 2008 to 2012. The geographic origin of the HIV-1 sequences was further determined by PastML while the factors associated with recent HIV-1 transmission were documented by logistic regression analysis. RESULTS: HIV-1 genotypes that are prevalent in African and East Asian countries were identified in HIV-infected Chinese subjects and vice versa. In addition, more NRTI drug resistance mutations were found in HIV-infected foreigners than in native Chinese (p < 0.001). HIV-1 transmission between HIV-infected foreigners and native Chinese individuals was documented in 12.95% (18/139) of the HIV-infected foreigners. Furthermore, Asian (odds ratio [OR] = 3.45), male (OR = 16.88) and those with known HIV-1 infection routes (OR = 3.23) were more likely associated with recent HIV-1 transmission in China. The Chinese natives linked to recent HIV-1 transmission were more likely to be infected through men who have sex with men (OR = 3.05) or people who inject drugs (OR = 3.05), rather than by heterosexual transmission. CONCLUSION: Our study demonstrates the impact of recent HIV-1 transmission between HIV-infected foreigners and Chinese natives on the HIV-1 epidemic in Guangzhou, China. Moreover, the results highlight the importance of phylogenetic analysis of HIV-1 surveillance data and the need for specific prevention strategies that target the immigrant population.

A luciferase immunosorbent assay for quantitative detection of IgG antibodies against SARS-CoV-2 nucleoprotein.

In this study, we developed and evaluated a luciferase immunosorbent assay (LISA) for quantitative detection of IgG antibody against SARS-CoV-2 nucleoprotein (NP). Anti-SARS-CoV-2 NP antibody in serum or plasma samples was captured by protein G-coated microtiter plate and detected using the crude cell lysates expressing Nanoluc luciferase (Nluc) enzyme fused with SARS-CoV-2 NP. After the addition of furimazine substrate, the levels of anti-SARS-CoV-2 NP IgG antibody were quantitatively measured as luciferase light units. As expected, SARS-CoV-2 NP showed cross-reactivity with the monoclonal antibodies against SARS-CoV NP, but not MERS-CoV NP-specific monoclonal antibodies or the monoclonal antibodies against SARS-CoV Spike protein. LISA for detecting murine monoclonal antibody against SARS-CoV NP showed a low limit of detection of 0.4 pg/µl and linear detection range from 0.4 pg/µl to 75 pg/µl. Furthermore, LISA had a sensitivity of 71 % when testing COVID-19 patients at the second week post onset and a specificity of 100 % when testing healthy blood donors.

A benchmark dose analysis for urinary cadmium and type 2 diabetes mellitus.

Cadmium (Cd) is a heavy metal referred to as one of the environmental endocrine disruptors. The dose-dependent association between Cd and type 2 diabetes mellitus (T2DM) has been elucidated, but the corresponding threshold has not been established. To evaluate the urinary Cd levels associated with T2DM, we perform a benchmark dose (BMD) analysis based on data from the 1999-2006 National Health and Nutrition Examination Survey (NHANES). Weighted datasets were generated by the inverse probability of treatment weighting analysis to develop the robustness of our analysis. We inferred a strong positive association between urinary Cd and T2DM in unweighted and weighted populations. BMD and its low limit (BMDL) estimates for 5% benchmark responses (BMR) was 0.297 (0.198) and 0.190 (0.178) µg/g creatinine for each population, respectively. The sensitivity analysis by race, followed by weight of sum method showed similar estimates of urinary Cd level for the risk of developing T2DM, which are rather low and far less than those for the renal or bone disease development risk. This indicates that T2DM can be a sensitive outcome of Cd exposure and therefore should be taken into account in the development of standard regulatory limits for safe exposure to Cd.

Molecular and serological characterization of SARS-CoV-2 infection among COVID-19 patients.

BACKGROUND: SARS-CoV-2 is a novel coronavirus and the cause of COVID-19. More than 80% of COVID-19 patients exhibit mild or moderate symptoms. In this study, we investigated the dynamics of viral load and antibodies against SARS-CoV-2 in a longitudinal cohort of COVID-19 patients with severe and mild/moderate diseases. METHODS: Demographic and clinical information were obtained. Serial samples of blood, nasal and pharyngeal and anal swabs were collected at different time points post-onset. SARS-CoV-2 RNA and anti-SARS-CoV-2 antibodies were measured by qRT-PCR and immunoassays, respectively. RESULTS: Respiratory SARS-CoV-2 RNA was detectable in 58.0% (58/100) COVID-19 patients upon admission and lasted for a median of 13 days post-onset. In addition, 5.9% (1/17) and 20.2% (19/94) of the blood and anal swab specimens were positive for SARS-CoV-2 RNA, respectively. Anal viral RNA was more frequently detected in the patients who were positive for viral RNA in the respiratory samples upon admission. Specific anti-SARS-CoV-2 antibody developed within two weeks after onset, reached peak approximately 17 days post-onset and then maintained at relatively high level up to 50 days we analyzed in most patients. However, the levels of antibodies were variable among the patients. High titers of antibodies appeared to be associated with the severity of the disease. Furthermore, viral proteins from different sources showed significant difference of serological sensitivity especially during the first week post-onset. CONCLUSIONS: Our results indicate rapid clearance or self-elimination of viral RNA in about half of the COVID-19 patients upon admission. Viral RNA shedding of SARS-CoV-2 occurred in multiple tissues including the respiratory system, blood, and intestine. Variable levels of specific anti-SARS-CoV-2 antibody may be associated with disease severity. These findings have shed light on viral kinetics and antibody response in COVID-19 patients and provide scientific evidence for infection control and patient management.

The Central Role of Nondisclosed Men Who Have Sex With Men in Human Immunodeficiency Virus-1 Transmission Networks in Guangzhou, China.

BACKGROUND: Men who have sex with men (MSM) are vulnerable risk group for human immunodeficiency virus (HIV)-1 infection. However, some MSM do not disclose their same-sex behavior and could impact the transmission and prevention of HIV-1 infection. Here, we evaluated the role of nondisclosed MSM in HIV-1 transmission in Guangzhou, China. METHODS: The HIV-1 pol sequences were obtained from HIV-infected subjects from 2008 to 2015. A transmission network was constructed using HIV TRAnsmission Cluster Engine (HIV-TRACE) at a pairwise genetic distance of 0.5%. The position of nondisclosed MSM in the network was determined by centrality analysis. RESULTS: Nondisclosed MSM were inferred in 9.92% (61 of 615) of slightly older, self-reported non-MSM (P = .006). They were more likely to be married (P = .002) and less educated (P < .001) than the MSM with whom they clustered. Closeness centrality was bigger for nondisclosed MSM than for MSM (P < .001), indicating the central position of nondisclosed MSM in the networks. The average shortest path length was smaller for nondisclosed MSM than for MSM (P < .001), whereas radiality was bigger for nondisclosed MSM than for MSM, suggesting a relatively greater contribution of nondisclosed MSM in transmitting HIV-1 than MSM. Assortativity analysis indicated that nondisclosed MSM were more likely to link each other with coefficient of 0.025. CONCLUSIONS: Nondisclosed MSM are a specific group, and they play an important role in HIV-1 transmission. They could be bisexual and might increase the risk of HIV-1 infection to their sex partners. Therefore, specific prevention and intervention targeting nondisclosed MSM are urgently needed.

Impact of temperature on the dynamics of the COVID-19 outbreak in China.

A COVID-19 outbreak emerged in Wuhan, China at the end of 2019 and developed into a global pandemic during March 2020. The effects of temperature on the dynamics of the COVID-19 epidemic in China are unknown. Data on COVID-19 daily confirmed cases and daily mean temperatures were collected from 31 provincial-level regions in mainland China between Jan. 20 and Feb. 29, 2020. Locally weighted regression and smoothing scatterplot (LOESS), distributed lag nonlinear models (DLNMs), and random-effects meta-analysis were used to examine the relationship between daily confirmed cases rate of COVID-19 and temperature conditions. The daily number of new cases peaked on Feb. 12, and then decreased. The daily confirmed cases rate of COVID-19 had a biphasic relationship with temperature (with a peak at 10 °C), and the daily incidence of COVID-19 decreased at values below and above these values. The overall epidemic intensity of COVID-19 reduced slightly following days with higher temperatures with a relative risk (RR) was 0.96 (95% CI: 0.93, 0.99). A random-effect meta-analysis including 28 provinces in mainland China, we confirmed the statistically significant association between temperature and RR during the study period (Coefficient = -0.0100, 95% CI: -0.0125, -0.0074). The DLNMs in Hubei Province (outside of Wuhan) and Wuhan showed similar patterns of temperature. Additionally, a modified susceptible-exposed-infectious-recovered (M-SEIR) model, with adjustment for climatic factors, was used to provide a complete characterization of the impact of climate on the dynamics of the COVID-19 epidemic.

Comparison of various anthropometric indices in predicting abdominal obesity in Chinese children: a cross-sectional study.

BACKGROUND: Former evidence regarding reference values of abdominal fat percentage (AFP) and optimal anthropometric indicators in predicting abdominal obesity measured by dual-energy X-ray absorptiometry (DXA) scan in Chinese children were scarce. METHODS: A total of 452 Chinese children aged 6-9 years were included in this cross-sectional study. Abdominal fat and lean mass were measured by a DXA scan, and AFP were calculated. Anthropometric indicators including body mass index (BMI), chest circumference (CC), waist circumference (WC) and hip circumference (HC) were measured, waist-to-hip ratio (WHR), waist-to-height ratio (WHtR) was also calculated. RESULTS: By defining abdominal obesity as those with an AFP ≥ 85th percentile, the cutoffs values are 24.80, 30.29, 31.58, 31.86% in boys, and 25.02, 30.32, 31.66, 31.79% in girls, for children aged 6, 7, 8, and 9 years old, respectively. All anthropometric indicators were independently and positively associated with AFP (P all < 0.01). In girls, BMI was found to be the optimal predictors of childhood abdominal obesity. The values of area under curves (AUCs) were significantly higher (P all < 0.05) than other anthropometric indicators, except for WHtR (AUCs value: 0.886). However, in boys, WHtR instead of BMI, provided the largest AUCs value (0.922) in predicting abdominal obesity, followed by BMI ((AUCs value: 0.913). CONCLUSION: This study provides reference values of AFP measured by DXA in Chinese children aged 6-9 years. BMI and WHtR tend to be the optimal anthropometric indicators in predicting abdominal obesity in Chinese girls and boys, respectively.

Characterization of HIV-1 genotype specific antigens for the detection of recent and long-term HIV-1 infection in China.

To characterize HIV-1 gp41 as an antigen for developing HIV-1 incidence assay and to investigate the impact of HIV-1 genetic diversity on the assay performance, a number of truncated peptides were synthesized to identify the immunodominant epitopes (IDEs) of HIV-1 gp41 protein. Subsequently, the mixed peptides (MP3) or the recombinant protein (MP4) containing HIV-1 gp41 IDEs of the major HIV-1 genotype CRF01_AE, CRF07_BC/ CRF08_BC and subtype B in China were used to verify the sensitivity and specificity of HIV-1 recency testing. We identified the QKFLG and GKIIC motifs located in the loop region of HIV-1 gp41 as the two major IDEs. The surrounding amino acids EAQQHLLQLT and WNSSWSN could block the binding of gp41 peptide and anti-HIV antibody with low avidity, making the gp41 peptide p57 suitable for distinguishing recent and long-term HIV-1 infections. Furthermore, MP3 or MP4-based immunoassay could significantly improve the assay sensitivity and showed 93.33% (140/150) vs. 94.59% (35/37) and 94.08% (143/152) vs. 94.59% (35/37) concordance with commercially available LAg-Avidity EIA test among the cross-sectional and longitudinal samples, respectively. The estimated mean duration of recent infection (MDRI) was 130 days (95% CI: 83-167) and 166 days (95% CI: 123-202) for MP3 and MP4 assays, respectively. Our preliminary results indicate that the HIV-1 gp41 peptide-based immunoassay specifically targeting the major HIV-1 genotype CRF01_AE, CRF07_BC/CRF08_BC and subtype B could serve as a simple incidence assay for differentiating recent and long-term HIV-1 infections in China.