Epidemiological characteristics, clinical manifestations, and mental health status of human mpox cases: A multicenter cross-sectional study in China.

Human mpox is occurring worldwide, however, evidence from the Asian Pacific Region is limited. In this multicenter cross-sectional study, information of confirmed mpox cases diagnosed between June 1 and July 31, 2023 in China. Information included demographic and epidemiological characteristics, and clinical manifestations, laboratory results, and mental health status of mpox cases. A total of 115 confirmed mpox cases were enrolled. All cases were men. A total of 102 (90.3%) identified as homosexual. The median age was 31.0 years (interquartile range 27.0-36.5). A total of 65 (56.5%) were HIV-positive, of whom 92.3% were receiving antiretroviral therapy (ART). A total of 19/39 (40.4%) had a CD4 cell count <500 cells/µL. Systemic features such as fever (73.0%), lymphadenopathies (49.6%), and myalgia (28.7%) were commonly observed. Skin lesions were present in all participants: 49.6% in the genital area and 27.0% in the perianal area. Vesicular rash (78.3%) and papular rash (44.3%) were the most common lesion morphologies. People living with HIV were more likely to have anxiety than those living without HIV. The majority of mpox cases had primary genital lesions and sexual activities before diagnosis, which supports the likelihood of sexual contact transmission. Guidelines on hospitalization and isolation protocols for mpox patients necessitate further confirmation.

High Genetic Diversity of HIV-1 and Active Transmission Clusters among Male-to-Male Sexual Contacts (MMSCs) in Zhuhai, China.

Monitoring genetic diversity and recent HIV infections (RHIs) is critical for understanding HIV epidemiology. Here, we report HIV-1 genetic diversity and RHIs in blood samples from 190 HIV-positive MMSCs in Zhuhai, China. MMSCs with newly reported HIV were enrolled from January 2020 to June 2022. A nested PCR was performed to amplify the HIV polymerase gene fragments at HXB2 positions 2604-3606. We constructed genetic transmission network at both 0.5% and 1.5% distance thresholds using the Tamura-Nei93 model. RHIs were identified using a recent infection testing algorithm (RITA) combining limiting antigen avidity enzyme immunoassay (LAg-EIA) assay with clinical data. The results revealed that 19.5% (37/190) were RHIs and 48.4% (92/190) were CRF07_BC. Two clusters were identified at a 0.5% distance threshold. Among them, one was infected with CRF07_BC for the long term, and the other was infected with CRF55_01B recently. We identified a total of 15 clusters at a 1.5% distance threshold. Among them, nine were infected with CRF07_BC subtype, and RHIs were found in 38.8% (19/49) distributed in eight genetic clusters. We identified a large active transmission cluster (n = 10) infected with a genetic variant, CRF79_0107. The multivariable logistic regression model showed that clusters were more likely to be RHIs (adjusted OR: 3.64, 95% CI: 1.51~9.01). The RHI algorithm can help to identify recent or ongoing transmission clusters where the prevention tools are mostly needed. Prompt public health measures are needed to contain the further spread of active transmission clusters.

Wogonin inhibits latent HIV-1 reactivation by downregulating histone crotonylation.

BACKGROUND: Wogonin, a flavone isolated from Scutellaria baicalensis Georgi, is a commonly used phytochemical with anti-inflammatory and antitumor properties. However, the antiviral activity of wogonin against human immunodeficiency virus type 1 (HIV-1) has not been reported. PURPOSE: The current study aimed to explore whether wogonin can suppress latent HIV-1 reactivation and the mechanism of wogonin in inhibiting proviral HIV-1 transcription. METHODS: We assessed the effects of wogonin on HIV-1 reactivation using flow cytometry, cytotoxicity assay, quantitative PCR (qPCR), viral quality assurance (VQA), and western blot analysis. RESULTS: Wogonin, a flavone isolated from S. baicalensis, significantly inhibited the reactivation of latent HIV-1 in cellular models and in primary CD4+ T cells from antiretroviral therapy (ART)-suppressed individuals ex vivo. Wogonin exhibited low cytotoxicity and long-lasting inhibition of HIV-1 transcription. Triptolide is a latency-promoting agent (LPA) that inhibits HIV-1 transcription and replication; wogonin had a stronger ability to inhibit HIV-1 latent reactivation than triptolide. Mechanistically, wogonin inhibited the reactivation of latent HIV-1 by inhibiting the expression of p300, a histone acetyltransferase, and decreasing the crotonylation of histone H3/H4 in the HIV-1 promoter region. CONCLUSION: Our study found that wogonin is a novel LPA that can inhibit HIV-1 transcription by HIV-1 epigenetic silencing, which could bear promising significance for future applications of HIV-1 functional cure.

Development and clinical application of a rapid and visual loop-mediated isothermal amplification test for tetM gene in Clostridioides difficile strains cultured from feces.

OBJECTIVES: In this study, we aimed to develop a rapid and visual loop-mediated isothermal amplification (LAMP) assay targeting the tetM gene in Clostridioides difficile strains cultured from feces. METHODS: Primers were designed to recognize the tetM gene in C. difficile by LAMP, using turbidity and visual detection. The sensitivity and specificity of LAMP primers were determined. In addition, we conducted both LAMP and polymerase chain reaction (PCR) for the tcdA, tcdB, cdtA, cdtB, ermB, and tetM genes in 300 toxigenic C. difficile strains cultured from feces. RESULTS: The target DNA was amplified and visualized within 60 minutes at a temperature of 62°C. A total of 26 bacterial strains were found negative for tetM, which manifested high specificity of the primers. The detection limit of LAMP was 36.1 pg/µl, which was 100-fold more sensitive than PCR. The positive rate of tetM in toxigenic C. difficile strains cultured from feces was 93.3% by both LAMP and PCR. The proportion of toxin types in those C. difficile strains was 95.7% for A+B+CDT-, 4% for A-B+CDT-, and 0.3% for A+B+CDT+, respectively. CONCLUSION: This is the first study examining the tetM gene by LAMP in C. difficile strains cultured from feces. Its high specificity, sensitivity, and visual detection make the new assay a powerful diagnostic tool for rapid testing.

Depression, anxiety and post-traumatic growth among COVID-19 survivors six-month after discharge.

Background: Pre-hospitalisation, hospitalisation and post-hospitalisation factors may significantly affect depression, anxiety and post-traumatic growth (PTG) among COVID-19 survivors. Objective: Our study investigated depression, anxiety and PTG and their correlates among COVID-19 survivors. Method: A cross-sectional telephone survey recruited 199 COVID-19 patients (Mean age = 42.7; 53.3% females) at six-month follow-up after hospital discharge in five Chinese cities (i.e. Wuhan, Shenzhen, Zhuhai, Dongguan and Nanning). Their demographic information, clinical records and experiences during (e.g. severity of covid-19 symptoms, treatment and exposure to other patients' suffering) and after hospitalisation (e.g. perceived impact of covid-19, somatic symptoms after hospitalisation), and psychosocial factors (e.g. perceived discrimination, self-stigma, affiliate stigma, resilience and social support) were investigated. Depressive and anxiety symptoms were measured by the Patient Health Questionnaire (PHQ-9) and the Generalised anxiety disorder (GAD-7) scale, respectively. PTG was examined by the Post-traumatic Growth Inventory (PTGI) instrument. Results: The proportion of depressive symptoms <5, ≥5 and <10, ≥10 were 76.9%, 12.0% and 11.1%, respectively. The proportion of anxiety symptoms <5, ≥5 and <10, ≥10 were 77.4%, 15.1% and 7.5%, respectively. Multivariate logistic regression showed that receiving mental health care services during hospitalisation, somatic symptoms after discharge, perceived affiliate stigma and perceived impact of being infected with COVID-19 were significantly and positively associated with probable depression. Significant correlates of probable anxiety also included permanent residents of the city, somatic symptoms after discharge, perceived impact of being infected with COVID-19 and self-stigma. Social support, self-stigma and receiving mental health care services during hospitalisation were positively associated with PTG.Conclusions: The results suggest that post-hospitalisation and psychosocial factors had relatively stronger associations with depression, anxiety and PTG than pre-hospitalisation and hospitalisation factors. Promoting social support and social inclusion may be useful strategies to improve the mental health of COVID-19 survivors. HIGHLIGHTS: • Post-hospitalisation and psychosocial factors had relatively stronger associations with depression, anxiety and PTG than pre-hospitalisation and hospitalisation factors, promoting social support and social inclusion may be useful strategies to improve mental health of COVID-19 survivors.

Antecedentes: Los factores pre-hospitalización, durante la hospitalización y post-hospitalización pueden afectar significativamente la depresión, la ansiedad y el crecimiento postraumático (CPT) en los sobrevivientes de COVID-19.Objetivo: Nuestro estudio investigó la depresión, la ansiedad y el CPT y sus correlatos en sobrevivientes de COVID-19.Método: Una encuesta telefónica transversal reclutó a 199 pacientes con COVID-19 (edad promedio = 42,7; 53,3% mujeres) a los seis meses de seguimiento después del alta hospitalaria en cinco ciudades chinas (Wuhan, Shenzhen, Zhuhai, Dongguan y Nanning). Su información demográfica, registros clínicos y experiencias durante la hospitalización (e.g. gravedad de los síntomas de COVID-19, tratamiento, exposición al sufrimiento de otros pacientes) y después de la hospitalización (e.g. impacto percibido de COVID-19, síntomas somáticos después de la hospitalización) y factores psicosociales (e.g. discriminación percibida, autoestigma, estigma de afiliación, resiliencia, apoyo social) fueron investigados. Los síntomas depresivos y de ansiedad se midieron mediante el Cuestionario de Salud del Paciente (PHQ-9 en su sigla en inglés) y la escala de trastorno de ansiedad generalizada (GAD-7 en su sigla en inglés) respectivamente, el CPT se examinó mediante el instrumento Inventario de Crecimiento Postraumático (PTGI en su sigla en inglés).Resultados: La proporción de síntomas depresivos <5, ≥5 y <10, y ≥10 fue 76,9%, 12,0% y 11,1% respectivamente. La proporción de síntomas de ansiedad <5, ≥5 y <10, y ≥10 fue del 77,4%, 15,1% y 7,5% respectivamente. La regresión logística multivariante mostró que recibir servicios de atención de salud mental durante la hospitalización, los síntomas somáticos después del alta, el estigma de afiliación percibido y el impacto percibido de estar infectado con COVID-19 se asociaron significativa y positivamente con una probable depresión. Los correlatos significativos de ansiedad probable también incluyeron ser residente permanente de la ciudad, síntomas somáticos después del alta, impacto percibido de estar infectado con COVID-19 y autoestigma. El apoyo social, el autoestigma y recibir servicios de salud mental durante la hospitalización se asociaron positivamente con el CPT.Conclusiones: Los resultados sugieren que los factores psicosociales y posteriores a la hospitalización tuvieron asociaciones relativamente más fuertes con la depresión, la ansiedad y el CPT que los factores previos a la hospitalización y hospitalización. Promover el apoyo social y la inclusión social pueden ser estrategias útiles para mejorar la salud mental de los sobrevivientes de COVID-19.

Incidence Trends of Five Common Sexually Transmitted Infections Excluding HIV From 1990 to 2019 at the Global, Regional, and National Levels: Results From the Global Burden of Disease Study 2019.

Objective: Sexually transmitted infections (STIs) are common worldwide and pose a challenge to public health. We conducted this study to assess the annual incidence of five common STIs, including syphilis, chlamydia, gonorrhea, trichomoniasis, and genital herpes at the global, regional, and national levels. Materials and Methods: We obtained detailed data on STIs excluding HIV from 1990 to 2019 from the Global Burden of Disease (GBD) 2019 database. Estimated annual percentage change (EAPC) was calculated to quantify trends in age-standardized incidence rates (ASR) of STIs, stratified by gender, sociodemographic index (SDI) region, and pathogenic microorganism. Results: Globally, incident cases of STIs increased by 58.15% from 486.77 million in 1990 to 769.85 million in 2019, but the annual change in ASR was only -0.04% (95% CI -0.09 to 0.01) per year. EAPC was 0.16 (0.06 to 0.26) for syphilis, 0.09 (0.05 to 0.13) for genital herpes, 0.06 (0.03 to 0.09) for trichomoniasis, -0.21 (-0.36 to -0.06) for chlamydia, and -0.14 (-0.19 to -0.08) for gonorrhea. High SDI regions reported significant increases in ASR of syphilis and chlamydia. Conclusions: The burden of disease from STIs remains large, though control of STIs has contributed to the decreasing incidence in most regions, especially in the low-SDI regions. Globally, over the past 20 years, the ASR has remained stable for trichomoniasis and genital herpes decreased for chlamydia and gonorrhea, and increased for syphilis.

Hospitalization, interpersonal and personal factors of social anxiety among COVID-19 survivors at the six-month follow-up after hospital treatment: the minority stress model.

Background: As a highly infectious disease with human-to-human transmission characteristics, COVID-19 has caused panic in the general public. Those who have recovered from COVID-19 may experience discrimination and internalized stigma. They may be more likely to worry about social interaction and develop social anxiety. Objectives: This study investigated the associations among hospitalization factors, social/interpersonal factors, personal factors, and social anxiety to reveal the mechanism of social anxiety in COVID-19 survivors. Methods: A cross-sectional, multicenter telephone survey was conducted from July to September 2020 in five Chinese cities (i.e. Wuhan, Nanning, Shenzhen, Zhuhai, and Dongguan); adult COVID-19 survivors were recruited 6 months after they were discharged from the hospital. Linear regressions and path analysis based on the minority stress model were conducted to test the relationships among hospitalization, social/interpersonal factors, personal factors, and social anxiety. Results: The response rate was 74.5% (N = 199, 55.3% females). Linear regression analyses showed that various hospitalization, social/interpersonal, and personal factors were statistically significantly associated with social anxiety. Path analysis showed that the proposed model fit the data well (χ2(df) = 3.196(3), p = .362, CFI = .999, NNFI = .996, RMSEA = .018). Internalized stigma fully mediated the association between perceived discrimination/social support and social anxiety, while it partially mediated the association between perceived affiliate stigma and social anxiety. Conclusions: The results suggest that social/interpersonal and personal factors have a stronger association with social anxiety than hospitalization factors and highlight the importance of internalized stigma in understanding the mechanisms of these relationships. Clinical psychologists can refer to these modifiable psychosocial factors to develop efficient interventions for mental health promotion.

Antecedentes: Como una enfermedad altamente infecciosa con características de transmisión de persona a persona, el COVID-19 ha causado pánico en el público en general. Aquellos que se han recuperado del COVID-19 pueden experimentar discriminación y estigma internalizado. Es más probable que se preocupen por la interacción social y desarrollen ansiedad social.Objetivos: Este estudio investigó las asociaciones entre factores de hospitalización, factores sociales /interpersonales, factores personales y ansiedad social para revelar el mecanismo de ansiedad social en sobrevivientes de COVID-19.Métodos: Se realizó una encuesta telefónica transversal multicentro de julio a septiembre de 2020 en cinco ciudades chinas (es decir, Wuhan, Nanning, Shenzhen, Zhuhai y Dongguan). Se reclutaron sobrevivientes adultos de COVID-19 seis meses después de ser dados de alta del hospital. Se realizaron regresiones lineales y análisis de ruta basados en el modelo de estrés de minoría para probar las relaciones entre la hospitalización, los factores sociales/interpersonales, los factores personales y la ansiedad social.Resultados: La tasa de respuesta fue del 74,5% (N = 199, 55,3% mujeres). Los análisis de regresión lineal mostraron que varios factores de hospitalización, sociales/interpersonales y personales se asociaron de manera estadísticamente significativa con la ansiedad social. El análisis de ruta mostró que el modelo propuesto se ajustaba bien a los datos (χ2 (df) = 3.196 (3), p = .362, CFI = .999, NNFI = .996, RMSEA = .018). El estigma internalizado medió completamente la asociación entre discriminación/apoyo social percibido y ansiedad social, mientras que medió parcialmente la asociación entre el estigma percibido de afiliados y ansiedad social.Conclusiones: Los resultados sugieren que los factores sociales/interpersonales y personales tienen una asociación más fuerte con la ansiedad social que los factores de hospitalización y resaltan la importancia del estigma internalizado en la comprensión de los mecanismos de estas relaciones. Los psicólogos clínicos pueden referirse a estos factores psicosociales modificables para desarrollar intervenciones eficientes para la promoción de la salud mental.

Dolutegravir plus lamivudine versus efavirenz plus tenofovir disoproxil fumarate and lamivudine in antiretroviral-naive adults with HIV-1 infection.

BACKGROUND: Concerns regarding potential toxicity and drug-drug interactions during long-term treatment with three-drug active antiretroviral therapy (ART) regimens have been attracting increasing attention. We aimed to evaluate the efficacy and safety of dolutegravir (DTG) plus lamivudine (3TC) in ART-naive adults in China. METHODS: This prospective observational cohort study enrolled HIV-naive inpatients treated with DTG + 3TC (2DR arm) or efavirenz (EFV) plus tenofovir disoproxil fumarate (TDF) and 3TC (3DR arm). There were no limits on baseline viral load. Inflammatory biomarkers were also investigated in the 2DR arm. RESULTS: Between September 2019 and January 2020, 27 patients treated with DTG + 3TC and 28 patients treated with EFV + TDF + 3TC were enrolled in the study. At week 12, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 81.5% (22/27) compared with 53.6% (15/28) in the 3DR arm (p < 0.01). At week 24, the proportion of patients with viral loads < 50 copies/mL in the 2DR arm was 100% (26/26) compared with 83.3% (20/24) in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 12 were 125.46 cells/µL in the 2DR arm and 41.20 cells/µL in the 3DR arm (p < 0.05). Mean changes in CD4 cell counts from baseline at week 24 were 209.68 cells/µL in the 2DR arm and 73.28 cells/µL in the 3DR arm (p < 0.05). CONCLUSIONS: DTG + 3TC achieved virologic suppression more rapidly than EFV + TDF + 3TC after 12 and 24 weeks. DTG + 3TC could represent an optimal regimen for advanced patients. Clinical Trial Registration ChiCTR1900027640 (22/November/2019).

Associations between COVID-19 related stigma and sleep quality among COVID-19 survivors six months after hospital discharge.

BACKGROUND: Many COVID-19 survivors reported stigmatization after recovery. This study investigated the association between stigma (discrimination experiences, self-stigma and perceived affiliate stigma) and sleep quality among COVID-19 survivors six months after hospital discharge. METHODS: Participants were recovered adult COVID-19 survivors discharged between February 1 and April 30, 2020. Medical staff of five participating hospitals approached all discharged COVID-19 period during this period. A total of 199 participants completed the telephone interview during July to September, 2020. Structural equation modeling was performed to test the hypothesize that resilience and social support would mediate the associations between stigma and sleep quality. RESULTS: The results showed that 10.1% of the participants reported terrible/poor sleep quality, 26.1% reported worse sleep quality in the past week when comparing their current status versus the time before COVID-19. After adjusting for significant background characteristics, participants who had higher number of discrimination experience, perceived stronger self-stigma and stronger perceived affiliate stigma reported poorer sleep quality. Resilience and social support were positively and significantly associated with sleep quality. The indirect effect of self-stigma on sleep quality through social support and resilience was significant and negative. Perceived affiliate stigma also had a significant and negative indirect effect on sleep quality through social support and resilience. CONCLUSIONS: Various types of stigma after recovery were associated with poor sleep quality among COVID-19 survivors, while social support and resilience were protective factors. Resilience and social support mediated the associations between self-stigma/perceived affiliate stigma and sleep quality.

Pre-hospital, in-hospital and post-hospital factors associated with sleep quality among COVID-19 survivors 6 months after hospital discharge: cross-sectional survey in five cities in China.

Background: Understanding factors associated with post-discharge sleep quality among COVID-19 survivors is important for intervention development. Aims: This study investigated sleep quality and its correlates among COVID-19 patients 6 months after their most recent hospital discharge. Method: Healthcare providers at hospitals located in five different Chinese cities contacted adult COVID-19 patients discharged between 1 February and 30 March 2020. A total of 199 eligible patients provided verbal informed consent and completed the interview. Using score on the single-item Sleep Quality Scale as the dependent variable, multiple linear regression models were fitted. Results: Among all participants, 10.1% reported terrible or poor sleep quality, and 26.6% reported fair sleep quality, 26.1% reported worse sleep quality when comparing their current status with the time before COVID-19, and 33.7% were bothered by a sleeping disorder in the past 2 weeks. After adjusting for significant background characteristics, factors associated with sleep quality included witnessing the suffering (adjusted B = -1.15, 95% CI = -1.70, -0.33) or death (adjusted B = -1.55, 95% CI = -2.62, -0.49) of other COVID-19 patients during hospital stay, depressive symptoms (adjusted B = -0.26, 95% CI = -0.31, -0.20), anxiety symptoms (adjusted B = -0.25, 95% CI = -0.33, -0.17), post-traumatic stress disorders (adjusted B = -0.16, 95% CI = -0.22, -0.10) and social support (adjusted B = 0.07, 95% CI = 0.04, 0.10). Conclusions: COVID-19 survivors reported poor sleep quality. Interventions and support services to improve sleep quality should be provided to COVID-19 survivors during their hospital stay and after hospital discharge.

MAT2A-Mediated S-Adenosylmethionine Level in CD4+ T Cells Regulates HIV-1 Latent Infection.

Antiretroviral drugs effectively halt HIV-1 replication and disease progression, however, due to the presence of a stable viral latent reservoir, the infection cannot be cured by antiretroviral drugs alone. Elucidating the molecular mechanisms underlying HIV-1 latent infection remains a critical hurdle that precludes the development of novel therapeutic strategies aiming for a potential functional cure. Cellular metabolism has been reported to affect HIV-1 replication in CD4+ T cells, but it remains largely unclear whether it is involved in the regulation of HIV-1 latency. Here, we performed a sub-pooled CRISPR library knockout screen targeting 1773 metabolic-related genes in a cell model of HIV-1 latent infection and found that Methionine Adenosyltransferase 2A (MAT2A) contributes to HIV-1 latency. MAT2A knockout enhanced the reactivation of latent HIV-1 while MAT2A overexpression did the opposite. Mechanistically, MAT2A modulates HIV-1 latency through S-Adenosylmethionine (SAM)-mediated one-carbon flux. MAT2A knockout resulted in a significant downregulation of DNA and histone methylation at the HIV-1 5'-LTR. Importantly, we found that the plasma level of SAM is positively correlated with HIV-1 DNA in PBMCs from ART-treated infected individuals, suggesting SAM could serve as a potential biomarker for the latent viral reservoir. Overall, this study reveals an important role of MAT2A-mediated one-carbon metabolism in regulating HIV-1 latency and provides a promising target for the development of new strategies for a functional cure of HIV-1.

Antibody Responses and the Effects of Clinical Drugs in COVID-19 Patients.

The coronavirus disease 2019 (COVID-19) emerged around December 2019 and have become a global epidemic disease currently. Specific antibodies against SAS-COV-2 could be detected in COVID-19 patients' serum or plasma, but the clinical values of these antibodies as well as the effects of clinical drugs on humoral responses have not been fully demonstrated. In this study, 112 plasma samples were collected from 36 patients diagnosed with laboratory-confirmed COVID-19 in the Fifth Affiliated Hospital of Sun Yat-sen University. The IgG and IgM antibodies against receptor binding domain (RBD) and spike protein subunit 1 (S1) of SAS-COV-2 were detected by ELISA. We found that COVID-19 patients generated specific antibodies against SARS-CoV-2 after infection, and the levels of anti-RBD IgG within 2 to 3 weeks from onset were negatively associated with the time of positive-to-negative conversion of SARS-CoV-2 nucleic acid. Patients with severe symptoms had higher levels of anti-RBD IgG in 2 to 3 weeks from onset. The use of chloroquine did not significantly influence the patients' antibody titer but reduced C-reaction protein (CRP) level. Using anti-viral drugs (lopinavir/ritonavir or arbidol) reduced antibody titer and peripheral lymphocyte count. While glucocorticoid therapy developed lower levels of peripheral lymphocyte count and higher levels of CRP, lactate dehydrogenase (LDH), α-Hydroxybutyrate dehydrogenase(α-HBDH), total bilirubin (TBIL), direct bilirubin (DBIL). From these results, we suggested that the anti-RBD IgG may provide an early protection of host humoral responses against SAS-COV-2 infection within 2 to 3 weeks from onset, and clinical treatment with different drugs displayed distinct roles in humoral and inflammatory responses.

A SARS-CoV-2 antibody curbs viral nucleocapsid protein-induced complement hyperactivation.

Although human antibodies elicited by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-reactive antibodies. Herein, we isolate and profile a panel of 32 N protein-specific monoclonal antibodies (mAbs) from a quick recovery coronavirus disease-19 (COVID-19) convalescent patient who has dominant antibody responses to the SARS-CoV-2 N protein rather than to the SARS-CoV-2 spike (S) protein. The complex structure of the N protein RNA binding domain with the highest binding affinity mAb (nCoV396) reveals changes in the epitopes and antigen's allosteric regulation. Functionally, a virus-free complement hyperactivation analysis demonstrates that nCoV396 specifically compromises the N protein-induced complement hyperactivation, which is a risk factor for the morbidity and mortality of COVID-19 patients, thus laying the foundation for the identification of functional anti-N protein mAbs.

Mycobacterium PPE31 Contributes to Host Cell Death.

Genome scale mutagenesis identifies many genes required for mycobacterial infectivity and survival, but their contributions and mechanisms of action within the host are poorly understood. Using CRISPR interference, we created a knockdown of ppe31Mm gene in Mycobacterium marinum (M. marinum), which reduced the resistance to acid medium. To further explore the function of PPE31, the ppe31 mutant strain was generated in M. marinum and Mycobacterium tuberculosis (M. tuberculosis), respectively. Macrophages infected with the ppe31Mm mutant strain caused a reduced inflammatory mediator expressions. In addition, macrophages infected with M. marinum Δppe31Mm had decreased host cell death dependent on JNK signaling. Consistent with these results, deletion of ppe31Mtb from M. tuberculosis increased the sensitivity to acid medium and reduced cell death in macrophages. Furthermore, we demonstrate that both ppe31 mutants from M. marinum and M. tuberculosis resulted in reduced survival in macrophages, and the survivability of M. marinum was deceased in zebrafish due to loss of ppe31Mm . Our findings confirm that PPE31 as a virulence associated factor that modulates innate immune responses to mycobacterial infection.

Infection with a newly designed dual fluorescent reporter HIV-1 effectively identifies latently infected CD4+ T cells.

The major barrier to curing HIV-1 infection is a small pool of latently infected cells that harbor replication-competent viruses, which are widely considered the origin of viral rebound when antiretroviral therapy (ART) is interrupted. The difficulty in distinguishing latently infected cells from the vast majority of uninfected cells has represented a significant bottleneck precluding comprehensive understandings of HIV-1 latency. Here we reported and validated a newly designed dual fluorescent reporter virus, DFV-B, infection with which primary CD4+ T cells can directly label latently infected cells and generate a latency model that was highly physiological relevant. Applying DFV-B infection in Jurkat T cells, we generated a stable cell line model of HIV-1 latency with diverse viral integration sites. High-throughput compound screening with this model identified ACY-1215 as a potent latency reversing agent, which could be verified in other cell models and in primary CD4+ T cells from ART-suppressed individuals ex vivo. In summary, we have generated a meaningful and feasible model to directly study latently infected cells, which could open up new avenues to explore the critical events of HIV-1 latency and become a valuable tool for the research of AIDS functional cure.

Post-traumatic Stress Disorder Symptoms in COVID-19 Survivors 6 Months After Hospital Discharge: An Application of the Conservation of Resource Theory.

COVID-19 survivors who had acute respiratory symptoms might experience prolonged post-traumatic stress disorder (PTSD) due to further rehabilitation, somatic symptoms and related distress. The conservation of resource (COR) theory is a well-developed theory to understand how people develop PTSD symptoms in traumatic events. The current study aimed to examine the potential factors of PTSD symptoms and interrelationships among this factors among COVID-19 survivors based on the COR theory. This cross-sectional telephone survey enrolled 199 COVID-19 patients (Mean age = 42.7; 53.3% females) 6 months after their hospital discharge in five Chinese cities (i.e., Wuhan, Shenzhen, Zhuhai, Dongguan, and Nanning). The results showed that 7% of participants were classified as having probable PTSD. The significant potential factors relating to PTSD symptoms included socio-demographic status, hospitalization experiences, post-hospitalization experiences, and psychological status. Besides, the proposed statistical mediation model based on the COR framework showed good model fit, χ2(df) = 17.286 (5), p = 0.004, CFI = 0.962, NNFI = 0.951, RMSEA = 0.077. Perceived resource loss/gain fully mediated the association between exposure to other patients' suffering during hospitalization and PTSD symptoms, and partially mediated the relationships from somatic symptoms/perceived impact of being infected with COVID-19 after discharge to PTSD symptoms. On the other hand, resilience was a full mediator in the relationship from ICU experience to PTSD symptoms and a partial mediator in the relationship from perceived impact to PTSD symptoms. The results provide preliminary support on applying the COR theory to understand the factors of PTSD symptoms among COVID-19 survivors. Interventions to reduce PTSD symptoms in this population can be developed based on the modifiable psychosocial mediators.

Crystal Structures of Bat and Human Coronavirus ORF8 Protein Ig-Like Domain Provide Insights Into the Diversity of Immune Responses.

ORF8 is a viral immunoglobulin-like (Ig-like) domain protein encoded by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA genome. It tends to evolve rapidly and interfere with immune responses. However, the structural characteristics of various coronavirus ORF8 proteins and their subsequent effects on biological functions remain unclear. Herein, we determined the crystal structures of SARS-CoV-2 ORF8 (S84) (one of the epidemic isoforms) and the bat coronavirus RaTG13 ORF8 variant at 1.62 Å and 1.76 Å resolution, respectively. Comparison of these ORF8 proteins demonstrates that the 62-77 residues in Ig-like domain of coronavirus ORF8 adopt different conformations. Combined with mutagenesis assays, the residue Cys20 of ORF8 is responsible for forming the covalent disulfide-linked dimer in crystal packing and in vitro biochemical conditions. Furthermore, immune cell-binding assays indicate that various ORF8 (SARS-CoV-2 ORF8 (L84), ORF8 (S84), and RaTG13 ORF8) proteins have different interaction capabilities with human CD14+ monocytes in human peripheral blood. These results provide new insights into the specific characteristics of various coronavirus ORF8 and suggest that ORF8 variants may influence disease-related immune responses.

Risk factors for the COVID-19 severity and its correlation with viral shedding: A retrospective cohort study.

Coronavirus disease 2019 (COVID-19) have become a pandemic in the world. This study is aim to explore risk factors for COVID-19 severity in the early stage and the correlation between the viral shedding and COVID-19 severity. We included inpatient with laboratory confirmed COVID-19 who had been discharged by 9 March 2020. The medical record data and dynamic change of biochemical indicators in-hospital were compared between common and severe patients. Eighty patients were included in this study. Multivariable regression demonstrated increasing odds of severity associated with the duration of fever (odds ratio [OR], 1.42; 95% confidence interval [CI], 1.10-1.82, per day increase; P = .007), C-reactive protein (CRP) (OR, 1.26; 95% CI, 1.04-1.52; P = .02), and PO2 < 80 mm Hg (28.07, 95% CI, 1.50-524.12; P = .026) on admission. We found severe acute respiratory syndrome coronavirus 2 viral RNA could be long-term presence in respiratory tract and fecal sample, up to 43 and 46 days, respectively. However, the duration of viral shedding have no correlation with the COVID-19 severity. The duration of fever, elevated CRP and PO2 < 80 mm Hg on admission were associated with the COVID-19 severity in the early stage and there is no correlation between the viral shedding and COVID-19 severity.

The impact of new modes of electronic communication in the treatment of severe acute respiratory syndrome coronavirus 2 infection.

BACKGROUND: More than 26,760,000 cases of SARS-CoV-2 infection have been reported globally to date. This study aimed to analyze the impact of new electronic communication tools in the diagnosis and treatment of patients with SARS-CoV-2 infection. METHODS: From January 20 to February 26, 2020, adult patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who were treated in The Fifth Affiliated Hospital, Sun Yat-sen University, in Zhuhai, China, were recruited. Forty-seven eligible patients were enrolled and randomly classified into either the test group or the control group. All of the patients received the standard therapeutic regimen and routine ward rounds. The test group was subdivided into three subgroups: the first subgroup (5-minute group) was given an extra 5-minute ward round by WeChat voice call once daily for basic disease communication; the second subgroup (10-minute group) received an extra 10-minute ward round by WeChat voice call once daily for further detail; and the third subgroup (20-minute group) was given an extra 10-minute ward round via WeChat voice call once daily, as well as an extra 10 minutes every 3 days. The primary outcome was the duration of positive-to-negative conversion of SARS-CoV-2 nucleic acid diagnosed by the NAT (nucleic acid testing). RESULTS: In the test groups, the median time from diagnosis to the endpoint was 7.0 days [interquartile range (IQR), 3.8-10.8], compared with 10.0 days (IQR, 6.5-14.5) in the control group. It showed significant reduced the duration time of virus from positive to negative by the NAT (nucleic acid testing), (P=0.032) especially between the 10-minute subgroup (3.0 days; IQR, 3.0-7.5) and the control group (P=0.0065). CONCLUSIONS: The use of new modes of electronic communication can benefit patients during the COVID-19 pandemic and could be extremely valuable in addressing the shortage of medical protective equipment and reducing occupational risk of exposure to infection.