Impaired Humoral Immunity Identified in Inactivated SARS-CoV-2 Vaccine Recipients without Anti-Spike RBD Antibodies.

Inactivated SARS-CoV-2 vaccines have been deployed in a significant portion of the world population, who have widely varied responses to vaccination. Understanding this differential response would help the development of new vaccines for non-responders. Here, we conducted surveillance of anti-Spike receptor-binding domain (RBD) antibody levels in a large cohort of 534 healthy Chinese subjects vaccinated with two doses of inactivated SARS-CoV-2 vaccines. We show that the positive rate of antibodies among vaccinated subjects rapidly wanes as the interval between antibody testing and vaccination increases (14 to 119 days: 81.03%, 363 of 448 subjects; 120 to 149 days: 46.43%, 13 of 28 subjects; more than 150 days: 20%, 1 of 5 subjects). However, the antibodies were maintained at high levels in 16 convalescent COVID-19 patients at more than 150 days after recovery. We also found that increased age and body mass index are associated with decreased antibody levels. Vaccinated subjects who fail to produce antibodies display impaired B-cell activating humoral immunity, which was confirmed in COVID-19 patients without antibodies detected at 4 to 18 days after diagnosis. IMPORTANCE Our study illustrates the immune responses engaged by encountering antigen, highlighting the critical roles of B-cell activating humoral immunity in the body's antibody production.

The impact of COVID-19 non-pharmaceutical interventions on HIV care continuum in China: An interrupted time series analysis.

Background: China implemented strict non-pharmaceutical interventions to contain COVID-19 at the early stage. We aimed to evaluate the impact of COVID-19 on HIV care continuum in China. Methods: Aggregated data on HIV care continuum between 1 January 2017 and 31 December 2020 were collected from centers for disease control and prevention at different levels and major infectious disease hospitals in various regions in China. We used interrupted time series analysis to characterize temporal trend in weekly numbers of HIV post-exposure prophylaxis (PEP) prescriptions, HIV tests, HIV diagnoses, median time intervals between HIV diagnosis and antiretroviral therapy (ART) initiation (time intervals, days), ART initiations, mean CD4+ T cell counts at ART initiation (CD4 counts, cells/µL), ART collections, and missed visits for ART collection, before and after the implementation of massive NPIs (23 January to 7 April 2020). We used Poisson segmented regression models to estimate the immediate and long-term impact of NPIs on these outcomes. Findings: A total of 16,780 PEP prescriptions, 1,101,686 HIV tests, 69,659 HIV diagnoses, 63,409 time intervals and ART initiations, 61,518 CD4 counts, 1,528,802 ART collections, and 6656 missed visits were recorded during the study period. The majority of outcomes occurred in males (55·3-87·4%), 21-50 year olds (51·7-90·5%), Southwestern China (38·2-82·0%) and heterosexual transmission (47·9-66·1%). NPIs was associated with 71·5% decrease in PEP prescriptions (IRR 0·285; 95% CI 0·192-0·423), 36·1% decrease in HIV tests (0·639, 0·497-0·822), 32·0% decrease in HIV diagnoses (0·680, 0·511-0·904), 59·3% increase in time intervals (1·593, 1·270-1·997) and 17·4% decrease in CD4 counts (0·826, 0·746-0·915) in the first week during NPIs. There was no marked change in the number of ART initiations, ART collections and missed visits during the NPIs. By the end of 2020, the number of HIV tests, HIV diagnoses, time intervals, ART initiations, and CD4 counts reached expected levels, but the number of PEP prescriptions (0·523, 0·394-0·696), ART collections (0·720, 0·595-0·872), and missed visits (0·137, 0·086-0·220) were still below expected levels. With the ease of restrictions, PEP prescriptions (slope change 1·024/week, 1·012-1·037), HIV tests (1·016/week, 1·008-1·026), and CD4 counts (1·005/week, 1·001-1·009) showed a significant increasing trend. Interpretation: HIV care continuum in China was affected by the COVID-19 NPIs at various levels. Preparedness and efforts to maintain the HIV care continuum during public health emergencies should leverage collaborations between stakeholders. Funding: Natural Science Foundation of China.

It is time to improve the acceptance of COVID-19 vaccines among people with chronic diseases: A systematic review and meta-analysis.

This study aims to investigated COVID-19 vaccine acceptance among people with chronic diseases and the factors correlating with their vaccination hesitancy. The articles were searched in PubMed, Ovid, EMBASE, and web of science databases between December 2019 and October 2022. Cross-sectional studies, including the acceptance of the COVID-19 vaccine by patients with chronic diseases (≥18 years old), were included in this study. The outcomes included the proportion and 95% confidence interval (95% CI) of chronic disease patients willing to be vaccinated and the odds ratio (OR) and 95% CI of correlating factors. The source of heterogeneity was analyzed through meta-regression and subgroup analysis. We included 31 studies involving 57 875 patients with chronic disease. The overall COVID-19 vaccine acceptance among patients with chronic disease was 0.65 (95% CI, 0.59-0.72). The acceptance among the elderly patients was 0.53 (95% CI, 0.26-0.80). South America had the highest COVID-19 vaccine acceptance rate and Asia the lowest, while on a country level, the United Kingdom had the highest acceptance rate among patients with chronic diseases. People with rheumatic immune diseases had the lowest rate of COVID-19 vaccine acceptance. Concerns about vaccine safety had a statistically different effect on acceptance. Overall, the health systems ought to focus on educating specific groups of individuals on the benefits of COVID-19 vaccination and addressing safety concerns.

Correction: Reasons for COVID-19 Vaccine Hesitancy Among Chinese People Living With HIV/AIDS: Structural Equation Modeling Analysis.

[This corrects the article DOI: 10.2196/33995.].

Reasons for COVID-19 Vaccine Hesitancy Among Chinese People Living With HIV/AIDS: Structural Equation Modeling Analysis.

BACKGROUND: Many countries and organizations recommended people living with HIV/AIDS (PLWHA) receive the COVID-19 vaccine. However, vaccine hesitancy still exists and becomes a barrier for promoting COVID-19 vaccination among PLWHA. OBJECTIVE: This study aims to investigate factors that contributed to COVID-19 vaccine hesitancy among PLWHA. METHODS: The study used a multicenter cross-sectional design and an online survey mode. We recruited PLWHA aged 18-65 years from 5 metropolitan cities in China between January 2021 and February 2021. Participants completed an online survey through Golden Data, a widely used encrypted web-based survey platform. Multiple linear regression models were used to assess the background characteristics in relation to COVID-19 vaccine hesitancy, and structural equation modeling was performed to assess the relationships among perceived benefits, perceived risks, self-efficacy, subjective norms, and COVID-19 vaccine hesitancy. RESULTS: Among 1735 participants, 41.61% (722/1735) reported COVID-19 vaccine hesitancy. Older age, no other vaccinations in the past 3 years, and having chronic disease history were positively associated with COVID-19 vaccine hesitancy. Structural equation modeling revealed a direct relationship of perceived benefits, perceived risks, and subjective norms with self-efficacy and vaccine hesitancy and an indirect relationship of perceived benefits, perceived risks, and subjective norms with vaccine hesitancy. Moreover, self-efficacy toward COVID-19 vaccination was low. PLWHA had concerns of HIV disclosure during COVID-19 vaccination. Family member support could have an impact on COVID-19 vaccination decision-making. CONCLUSIONS: COVID-19 vaccine hesitancy was high among PLWHA in China. To reduce COVID-19 vaccine hesitancy, programs and strategies should be adopted to eliminate the concerns for COVID-19 vaccination, disseminate accurate information on the safety and efficacy of the COVID-19 vaccine, encourage family member support for COVID-19 vaccination, and improve PLWHA's trust of medical professionals.

Medication Non-adherence and Condomless Anal Intercourse Increased Substantially During the COVID-19 Pandemic Among MSM PrEP Users: A Retrospective Cohort Study in Four Chinese Metropolises.

Background: The coronavirus disease (COVID-19) pandemic has impacted HIV prevention strategies globally. However, changes in pre-exposure prophylaxis (PrEP) adherence and HIV-related behaviors, and their associations with medication adherence among men who have sex with men (MSM) PrEP users remain unclear since the onset of the COVID-19 pandemic. Methods: A Retrospective Cohort Study of HIV-negative MSM PrEP users was conducted in four Chinese metropolises from December 2018 to March 2020, assessing the changes in PrEP adherence and HIV-related behaviors before and during the COVID-19. The primary outcome was poor PrEP adherence determined from self-reported missing at least one PrEP dose in the previous month. We used multivariable logistic regression to determine factors correlated with poor adherence during COVID-19. Results: We enrolled 791 eligible participants (418 [52.8%] in daily PrEP and 373 [47.2%] in event-driven PrEP). Compared with the data conducted before the COVID-19, the proportion of PrEP users decreased from 97.9 to 64.3%, and the proportion of poor PrEP adherence increased from 23.6 to 50.1% during the COVID-19 [odds ratio (OR) 3.24, 95% confidence interval (CI) 2.62-4.02]. While the percentage of condomless anal intercourse (CAI) with regular partners (11.8 vs. 25.7%) and with casual partners (4.4 vs. 9.0%) both significantly increased. The proportion of those who were tested for HIV decreased from 50.1 to 25.9%. Factors correlated with poor PrEP adherence during the COVID-19 included not being tested for HIV (adjusted odds ratio [aOR] = 1.38 [95% CI: 1.00, 1.91]), using condoms consistently with regular partners (vs. never, aOR = 2.19 [95% CI: 1.16, 4.13]), and being married or cohabitating with a woman (vs. not married, aOR = 3.08 [95% CI: 1.60, 5.95]). Conclusions: Increased poor PrEP adherence and CAI along with the decrease in HIV testing can lead to an increase in HIV acquisition and drug resistance to PrEP. Targeted interventions are needed to improve PrEP adherence and HIV prevention strategies.

SSA-Net: Spatial self-attention network for COVID-19 pneumonia infection segmentation with semi-supervised few-shot learning.

Coronavirus disease (COVID-19) broke out at the end of 2019, and has resulted in an ongoing global pandemic. Segmentation of pneumonia infections from chest computed tomography (CT) scans of COVID-19 patients is significant for accurate diagnosis and quantitative analysis. Deep learning-based methods can be developed for automatic segmentation and offer a great potential to strengthen timely quarantine and medical treatment. Unfortunately, due to the urgent nature of the COVID-19 pandemic, a systematic collection of CT data sets for deep neural network training is quite difficult, especially high-quality annotations of multi-category infections are limited. In addition, it is still a challenge to segment the infected areas from CT slices because of the irregular shapes and fuzzy boundaries. To solve these issues, we propose a novel COVID-19 pneumonia lesion segmentation network, called Spatial Self-Attention network (SSA-Net), to identify infected regions from chest CT images automatically. In our SSA-Net, a self-attention mechanism is utilized to expand the receptive field and enhance the representation learning by distilling useful contextual information from deeper layers without extra training time, and spatial convolution is introduced to strengthen the network and accelerate the training convergence. Furthermore, to alleviate the insufficiency of labeled multi-class data and the long-tailed distribution of training data, we present a semi-supervised few-shot iterative segmentation framework based on re-weighting the loss and selecting prediction values with high confidence, which can accurately classify different kinds of infections with a small number of labeled image data. Experimental results show that SSA-Net outperforms state-of-the-art medical image segmentation networks and provides clinically interpretable saliency maps, which are useful for COVID-19 diagnosis and patient triage. Meanwhile, our semi-supervised iterative segmentation model can improve the learning ability in small and unbalanced training set and can achieve higher performance.

Utilization of a Mobile Multifunctional Workstation for Coronavirus Nasopharyngeal/Oropharyngeal Specimen Collection.

Objectives: This study aimed to explore the utilization of a mobile multifunctional workstation for COVID-19 sample collection. Methods: Twenty-four nurses and 150 individuals who took nucleic acid tests using mobile multifunctional workstations in Beijing Youan Hospital, Capital Medical University, from September to November 2020, were enrolled in the study as the observation group. As the control group, we included 36 nurses and 150 individuals who did not use the workstations from June to September 2020. We compared the two groups on (1) comfort of working environment, self-perceived security, the convenience of information system, operational process flexibility, pharyngeal acquisition visibility, and effectiveness of communication among nurses; and (2) self-perceived safety, waiting time, and overall satisfaction among individuals who took nucleic acid tests. Results: The satisfaction score of nurses in the observation group of nurses were significantly higher than those of the control group (OR = 17.297 95% CI:4.294, 69.673), as well as the convenience of the information system (OR = 6.250 95% CI: 1.775, 22.008), and communication effectiveness (OR = 5.588 95% CI: 1.590, 19.646). Among individuals who took nucleic acid tests, the overall satisfaction (P < 0.05) and self-perceived security (P < 0.05) had statistical differences between the observation group and the control group. Conclusions: The mobile multifunctional workstation for specimen collection could improve the comfort of the working environment, the convenience of information systems, and the effectiveness of communication among nurses.It can improve satisfaction and self-perceived security among people who took nucleic acid tests.

Comparing Immune Responses to Inactivated Vaccines against SARS-CoV-2 between People Living with HIV and HIV-Negative Individuals: A Cross-Sectional Study in China.

This study compared the immunogenicity of inactivated SARS-CoV-2 vaccines between people living with HIV (PLWH) and HIV-negative individuals. We recruited 120 PLWH and 53 HIV-negative individuals aged 18-59 years who had received an inactivated SARS-CoV-2 vaccine in two Chinese cities between April and June 2021. Blood samples were tested for immunogenicity of the inactivated SARS-CoV-2 vaccines. The prevalence and severity of adverse events associated with SARS-CoV-2 vaccines were similar between PLWH and HIV-negative individuals. The seropositivity of neutralizing activity against authentic SARS-CoV-2, of the total amount of antibody (total antibody) and of S-IgG were 71.3%, 81.9%, and 92.6%, respectively, among fully vaccinated PLWH. Among all participants, PLWH had lower neutralizing activity, total antibody, S-IgG, and T-cell-specific immune response levels, compared to HIV-negative individuals, after controlling for types of vaccine, time interval between first and second dose, time after receiving the second dose, and sociodemographic factors. PLWH with a longer interval since HIV diagnosis, who received their second dose 15-28 days prior to study commencement, and who had an interval of ≥21 days between first and second dose had higher neutralizing activity levels. The immunogenicity of the inactivated SARS-CoV-2 vaccines was lower among PLWH as compared to HIV-negative individuals. Vaccination guideline specific for PLWH should be developed.

The Roles of Tissue-Resident Memory T Cells in Lung Diseases.

The unique environment of the lungs is protected by complex immune interactions. Human lung tissue-resident memory T cells (TRM) have been shown to position at the pathogen entry points and play an essential role in fighting against viral and bacterial pathogens at the frontline through direct mechanisms and also by orchestrating the adaptive immune system through crosstalk. Recent evidence suggests that TRM cells also play a vital part in slowing down carcinogenesis and preventing the spread of solid tumors. Less beneficially, lung TRM cells can promote pathologic inflammation, causing chronic airway inflammatory changes such as asthma and fibrosis. TRM cells from infiltrating recipient T cells may also mediate allograft immunopathology, hence lung damage in patients after lung transplantations. Several therapeutic strategies targeting TRM cells have been developed. This review will summarize recent advances in understanding the establishment and maintenance of TRM cells in the lung, describe their roles in different lung diseases, and discuss how the TRM cells may guide future immunotherapies targeting infectious diseases, cancers and pathologic immune responses.

Willingness to Receive COVID-19 Vaccination Among People Living With HIV and AIDS in China: Nationwide Cross-sectional Online Survey.

BACKGROUND: HIV infection is a significant independent risk factor for both severe COVID-19 presentation at hospital admission and in-hospital mortality. Available information has suggested that people living with HIV and AIDS (PLWHA) could benefit from COVID-19 vaccination. However, there is a dearth of evidence on willingness to receive COVID-19 vaccination among PLWHA. OBJECTIVE: The aim of this study was to investigate willingness to receive COVID-19 vaccination among a national sample of PLWHA in China. METHODS: This cross-sectional online survey investigated factors associated with willingness to receive COVID-19 vaccination among PLWHA aged 18 to 65 years living in eight conveniently selected Chinese metropolitan cities between January and February 2021. Eight community-based organizations (CBOs) providing services to PLWHA facilitated the recruitment. Eligible PLWHA completed an online survey developed using a widely used encrypted web-based survey platform in China. We fitted a single logistic regression model to obtain adjusted odds ratios (aORs), which involved one of the independent variables of interest and all significant background variables. Path analysis was also used in the data analysis. RESULTS: Out of 10,845 PLWHA approached by the CBOs, 2740 completed the survey, and 170 had received at least one dose of the COVID-19 vaccine. This analysis was performed among 2570 participants who had never received COVID-19 vaccination. Over half of the participants reported willingness to receive COVID-19 vaccination (1470/2570, 57.2%). Perceptions related to COVID-19 vaccination were significantly associated with willingness to receive COVID-19 vaccination, including positive attitudes (aOR 1.11, 95% CI 1.09-1.12; P<.001), negative attitudes (aOR 0.96, 95% CI 0.94-0.97; P<.001), perceived support from significant others (perceived subjective norm; aOR 1.53, 95% CI 1.46-1.61; P<.001), and perceived behavioral control (aOR 1.13, 95% CI 1.11-1.14; P<.001). At the interpersonal level, receiving advice supportive of COVID-19 vaccination from doctors (aOR 1.99, 95% CI 1.65-2.40; P<.001), CBO staff (aOR 1.89, 95% CI 1.51-2.36; P<.001), friends and/or family members (aOR 3.22, 95% CI 1.93-5.35; P<.001), and PLWHA peers (aOR 2.38, 95% CI 1.85-3.08; P<.001) was associated with higher willingness to receive COVID-19 vaccination. The overall opinion supporting COVID-19 vaccination for PLWHA on the internet or social media was also positively associated with willingness to receive COVID-19 vaccination (aOR 1.59, 95% CI 1.31-1.94; P<.001). Path analysis indicated that interpersonal-level variables were indirectly associated with willingness to receive COVID-19 vaccination through perceptions (ß=.43, 95% CI .37-.51; P<.001). CONCLUSIONS: As compared to PLWHA in other countries and the general population in most parts of the world, PLWHA in China reported a relatively low willingness to receive COVID-19 vaccination. The internet and social media as well as interpersonal communications may be major sources of influence on PLWHA's perceptions and willingness to receive COVID-19 vaccination.

Clinical features and survival analysis of 97 coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: We aim to investigate the clinical characteristics and survival rate of coronavirus disease 2019 (COVID-19) patients. METHODS: Ninety-seven COVID-19 patients were enrolled. The laboratory results, lung imaging and medical treatment were compared. Patients were followed up after 1 year, and the Kaplan-Meier test was used for survival analysis. RESULTS: Compared with the non-severe group, the age of the severe group was older, and the proportion of concomitant diseases were higher. As fever was the primary clinical manifestation, dyspnea and anorexia were more common in severe patients. Lung imaging manifestations and laboratory indicators were worse in the severe group. Accordingly, the treatment of glucocorticoid, antibiotics, and advanced life support were in high proportion. Of the 97 patients with COVID-19, 4 severe patients died within one month during the 1-year follow-up, with the median survival time of 47.0 weeks (95% CI: 45.1-48.9). CONCLUSIONS: Severe cases of COVID-19 are characterized by advanced age, more concomitant diseases and complications, which lead to a decreased short-term survival rate. However, there were no deaths after one month, which implied a good prognosis if the risk period were passed smoothly.

Preliminary Exploration of the Cause of Liver Disorders During Early Stages in COVID-19 Patients.

Background: Abnormal liver function is a common indication of coronavirus disease 2019 (COVID-19) patients. Two proposed mechanisms are liver injury mediated by angiotensin-converting enzyme 2 (ACE2) and the involvement of the systemic immune response. We investigated the role played by these to determine the cause of liver abnormality in the early stages of COVID-19. Methods: A cross-sectional study was conducted among confirmed cases of COVID-19 at Beijing Youan Hospital from January 21, 2020, to February 24, 2020. We compared clinical characteristics, viremia status, and cytokine profile on admission between patients with and without liver disorder. Results: Of the 44 COVID-19 patients analyzed, there were no differences in the clinical symptoms and signs, disease severity, or computed tomography (CT) image features between the two groups. Lymphopenia was more common in the liver disorder group. Further, C-reactive protein levels were much higher in the hepatic disorder group, with significantly higher concentrations of IL-6, IL-10, and M-CSF. Viremia was detected in only 7% of patients. Conclusions: Due to the infrequency of viremia, ACE2-mediated viral hepatitis does not seem to account for the commonly observed liver disorders in COVID-19 patients. By contrast, a dysregulated immune response may be a crucial pathogenic factor for liver disorder in the early stages of COVID-19.

Histopathological features of multiorgan percutaneous tissue core biopsy in patients with COVID-19.

AIMS: The global outbreak of COVID-19 has resulted in an increased mortality. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can affect multiple organs is still unclear. In this study, postmortem percutaneous biopsies of multiple organs from deceased patients were performed to understand the histopathological changes caused by COVID-19. METHODS: Biopsy specimens of pulmonary, cardiac, hepatic and lymphoid tissues were obtained from three patients, who died due to COVID-19 pneumonia. H&E stain, Masson trichrome stain, immunohistochemistry stain and in-situ hybridisation were used. RESULTS: Pulmonary damages caused by SARS-CoV-2 infection was diffuse alveolar damage (DAD). In the early phase, the histological findings were mainly those of exudative features of DAD. The later phase was characterised by organisation of DAD combined with bacterial pneumonia. No serious damage was found in the bronchiolar epithelium and submucosal glands. The hepatic tissue revealed features of ischaemic necrosis, but findings suggestive of mild lobular hepatitis were also observed. The lymphoid tissue revealed features of non-specific acute lymphadenitis. The cardiac tissue revealed changes of underlying disease. SARS-CoV-2 RNAs were not detected in hepatocytes, cholangiocytes and lymphocytes of lymph nodes. CONCLUSIONS: COVID-19 predominantly involves the pulmonary tissue, causes DAD and aggravates the cardiovascular disease. However, other extrapulmonary tissues did not reveal any virus-specific findings, but were affected by multiple factors. The findings in this report caution the pathologists that they should not mistakenly attribute all the histological features to CoV infection. Moreover, the clinicians should pay attention to the potentially injurious and correctable causes.

Dynamic changes in clinical and CT characteristics of COVID-19 cases with different exposure histories: a retrospective study.

BACKGROUND: To assess the dynamic changes in clinical and CT characteristics of COVID-19 patients with different epidemiology histories. METHODS: Fifty-three discharged COVID-19 patients were enrolled at Beijing YouAn Hospital, Capital Medical University, between January 21 and March 10, 2020. Spearman correlation analysis was performed between CT scores and laboratory indicators. Patients were divided into the Wuhan group (lived in or with travel to Wuhan, numbering 30 cases) and non-Wuhan group (close contacts or unknown exposure, totaling 23 cases). The CT and laboratory findings were compared between and within groups during the clinical process. RESULTS: Fever (88.7%), cough (64.2%), fatigue (34%), and abnormal laboratory indicators, including lymphopenia, reduced albumin, albumin/globulin (A/G), and elevated C-reactive protein (CRP), were mainly observed. Subpleural ground-glass opacities (86.8%) were usually detected at admission. The CT scores were highly correlated with lymphocytes, CRP, albumin, and A/G at initial and follow-ups (all p < 0.05). Four days after admission, most patients (66.7% Wuhan, 47.8% non-Wuhan) showed progression, and the CT scores of Wuhan significantly increased (p = 0.015). Eight days after admission, the vast majority of patients (69.2% Wuhan, 100% non-Wuhan, p = 0.006) presented improvement, and the CT scores of non-Wuhan were significantly lower than Wuhan (p = 0.006). Pneumonia was completely absorbed in most patients 2-4 weeks after discharge. CONCLUSIONS: CT plays a crucial role in the early diagnosis and monitoring of changes in COVID-19. Lymphocytes, CRP, albumin, and A/G are expected to predict disease severity and prognosis. Viral pathogenicity in non-endemic areas may be weaker than core-infected areas. In most patients, lung lesions can disappear around 4 weeks after discharge.