COVID-19 Vaccine Acceptance, Attitude and Perception among Slum and Underserved Communities: A Systematic Review and Meta-Analysis.

This systematic review summarises the literature on Coronavirus Disease 2019 (COVID-19) vaccination, including acceptance, uptake, hesitancy, attitude and perceptions among slum and underserved communities. Relevant studies were searched from PubMed, Scopus, Web of Science and Google Scholar, following a pre-registered protocol in PROSPERO (CRD42022355101) and PRISMA guidelines. We extracted data, used random-effects models to combine the vaccine acceptance, hesitancy and uptake rates categorically, and performed meta-regression by R software (version 4.2.1). Twenty-four studies with 30,323 participants met the inclusion criteria. The overall prevalence was 58% (95% CI: 49-67%) for vaccine acceptance, 23% (95% CI: 13-39%) for uptake and 29% (95% CI: 18-43%) for hesitancy. Acceptance and uptake were positively associated with various sociodemographic factors, including older age, higher education level, male gender, ethnicity/race (e.g., Whites vs African Americans), more knowledge and a higher level of awareness of vaccines, but some studies reported inconsistent results. Safety and efficacy concerns, low-risk perception, long distance to vaccination centres and unfavourable vaccination schedules were prominent reasons for hesitancy. Moreover, varying levels of attitudes and perceptions regarding COVID-19 vaccination were reported with existing misconceptions and negative beliefs, and these were strong predictors of vaccination. Infodemic management and continuous vaccine education are needed to address existing misconceptions and negative beliefs, and this should target young, less-educated women and ethnic minorities. Considering mobile vaccination units to vaccinate people at home or workplaces would be a useful strategy in addressing access barriers and increasing vaccine uptake.

Health Behaviours among Travellers Regarding Risk Compensation Following COVID-19 Vaccination in Taizhou, China.

Background: During the COVID-19 pandemic, public transport was restricted in many countries because of the transmission risk. According to the risk compensation theory, travellers post-COVID-19 vaccination may encounter higher risks; however, no real-world studies provide such evidence. Therefore, we conducted a survey to assess whether risk compensation would occur among travellers' health-related behaviours after COVID-19 vaccination, potentially aggravating the transmission of the virus. Materials and Methods: A self-administered online survey was designed and distributed over WeChat to identify the difference in health behaviours before and after COVID-19 vaccination among travellers at a train station in Taizhou, China, from 13 February to 26 April 2022. Results: A total of 602 individuals completed the questionnaire. The results revealed no statistical difference between the health behaviours reported by the vaccinated and unvaccinated groups. Participants who received the first dose of the vaccine earlier showed no statistical difference in harmful health behaviours (hand washing frequency decreased by 4.1% (P=0.145) and the duration of public transport travel increased by 3.4% (P=0.437)), but showed better protective health behaviours (mask-wearing duration increased by 24.7% (P=0.014)). Compared to those vaccinated less than three times, participants vaccinated against COVID-19 three times showed no statistical differences in harmful health behaviours mask-wearing duration decreased by 7.0% (P=0.927), their hand washing frequency decreased by 4.8% (P=0.905), and the duration of public transport travel increased by 2.5% (P=0.287). After vaccination, when compared to themselves before vaccination, participants exhibited better health behaviours (increased hand washing frequency and mask-wearing duration, and decreased duration of public transport travel) to some extent. Conclusion: In conclusion, this study found no evidence of risk compensation among travellers. After being vaccinated, health behaviours partly improved among travellers.

[Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial].

OBJECTIVE: To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability. METHODS: Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups. RESULTS: After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05). CONCLUSION: Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Differential COVID-19 Vaccination Uptake and Associated Factors among the Slum and Estate Communities in Uganda: A Cross-Sectional Population-Based Survey.

Vaccination against COVID-19 remains one of the ultimate solutions to the ongoing pandemic. This study examined and compared the completion of primary COVID-19 vaccination series and associated factors in the slum and estate communities of Uganda. This was a cross-sectional survey conducted among 1025 slum and estate residents. Logistic regression models were fitted. Of the 1025 participants, 511 were slum residents and 514 were estate residents. Completion of COVID-19 vaccination was 43.8% in the slum community and 39.9% in the estate community (p = 0.03). Having more knowledge about COVID-19 was positively associated with completing COVID-19 vaccination in both communities. Perceived benefits and cues to action also had a positive association, but only among the slum residents. However, perceiving people infected with COVID-19 as having a high death rate, perceived barriers such as serious side effects and long distances, and depressive symptoms had negative associations with vaccine uptake among the slum community, but not in the estate community. Addressing barriers to vaccination, strengthening and utilizing the various cues to action, engagement of religious and cultural leaders, and continued community education and sensitization tailored to the needs of each community are potentially vital strategies in raising vaccination rates. Consideration of socioeconomic impact-alleviation strategies, especially among the urban poor, would also be beneficial.

Hesitancy to Receive the Second COVID-19 Vaccine Booster Dose among Older Adults in Hong Kong: A Random Telephone Survey.

A second COVID-19 vaccine booster dose is effective and safe for older adults. This study investigated hesitancy to take up a second COVID-19 vaccine booster dose and its determinants among older adults in Hong Kong. Participants were Chinese-speaking community-dwelling adults aged 65 years or above. Telephone numbers were randomly selected from up-to-date telephone directories. A total of 370 participants completed the telephone survey. Logistic regression models were fitted for data analysis. Among the participants, half (52.4%) were hesitant to receive the second COVID-19 vaccine booster dose. After adjustment for significant background characteristics, perceived benefits (AOR: 0.50, 95%CI: 0.42, 0.60), cues to action (AOR: 0.39, 95%CI: 0.30, 0.52), and perceived self-efficacy (AOR: 0.37, 95%CI: 0.21, 0.66) of receiving the second booster dose were associated with lower vaccine hesitancy. Perceived barriers (AOR: 1.23, 95%CI: 1.12, 1.34) and vaccine fatigue (tired of receiving repeated COVID-19 vaccination) (AOR: 1.90, 95%CI: 1.52, 2.38) were associated with higher vaccine hesitancy. Level of hesitancy to receive the second booster dose was high among older adults in Hong Kong. Health authorities should address vaccine fatigue and modify perceptions related to the second booster dose.

The ORF7a protein of SARS-CoV-2 initiates autophagy and limits autophagosome-lysosome fusion via degradation of SNAP29 to promote virus replication.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is closely related to various cellular aspects associated with autophagy. However, how SARS-CoV-2 mediates the subversion of the macroautophagy/autophagy pathway remains largely unclear. In this study, we demonstrate that overexpression of the SARS-CoV-2 ORF7a protein activates LC3-II and leads to the accumulation of autophagosomes in multiple cell lines, while knockdown of the viral ORF7a gene via shRNAs targeting ORF7a sgRNA during SARS-CoV-2 infection decreased autophagy levels. Mechanistically, the ORF7a protein initiates autophagy via the AKT-MTOR-ULK1-mediated pathway, but ORF7a limits the progression of autophagic flux by activating CASP3 (caspase 3) to cleave the SNAP29 protein at aspartic acid residue 30 (D30), ultimately impairing complete autophagy. Importantly, SARS-CoV-2 infection-induced accumulated autophagosomes promote progeny virus production, whereby ORF7a downregulates SNAP29, ultimately resulting in failure of autophagosome fusion with lysosomes to promote viral replication. Taken together, our study reveals a mechanism by which SARS-CoV-2 utilizes the autophagic machinery to facilitate its own propagation via ORF7a.

Changes in COVID-19 Vaccine Acceptability among Parents with Children Aged 6-35 Months in China-Repeated Cross-Sectional Surveys in 2020 and 2021.

China is considering to offer COVID-19 vaccination for children aged 6−35 months. This study investigated the changes in COVID-19 vaccine acceptability and associated factors among parents with children aged 6−35 months in 2020 and 2021. Two rounds of cross-sectional online surveys were conducted among adult factory workers in Shenzhen, China. A subset of 208 (first round) and 229 (second round) parents with at least one child aged 6−35 months was included in the study. Parental acceptability of COVID-19 vaccination increased significantly from 66.8% in the first round to 79.5% in the second round (p = 0.01). Positive attitudes, perceived subjective norm, and perceived behavioral control were associated with higher parental acceptability in both rounds of surveys (p values ranged from <0.001 to 0.003). A negative association of negative attitudes with parental acceptability was observed in the second round (p = 0.02). No significant associations of exposure to information related to COVID-19 vaccination on social media with parental acceptability was found in either round of survey. Expanding the existing COVID-19 vaccination programs to cover children aged 6−35 months is necessary in China. Future programs should focus on modifying perceptions among parents to promote COVID-19 vaccination for children in this age group.

CD147 contributes to SARS-CoV-2-induced pulmonary fibrosis.

COVID-19 patients can develop clinical and histopathological features associated with fibrosis, but the pathogenesis of fibrosis remains poorly understood. CD147 has been identified as a universal receptor for SARS-CoV-2 and its variants, which could initiate COVID-19-related cytokine storm. Here, we systemically analyzed lung pathogenesis in SARS-CoV-2- and its delta variant-infected humanized CD147 transgenic mice. Histopathology and Transmission Electron Microscopy revealed inflammation, fibroblast expansion and pronounced fibrotic remodeling in SARS-CoV-2-infected lungs. Consistently, RNA-sequencing identified a set of fibrosis signature genes. Furthermore, we identified CD147 as a crucial regulator for fibroblast activation induced by SARS-CoV-2. We found conditional knockout of CD147 in fibroblast suppressed activation of fibroblasts, decreasing susceptibility to bleomycin-induced pulmonary fibrosis. Meplazumab, a CD147 antibody, was able to inhibit the accumulation of activated fibroblasts and the production of ECM proteins, thus alleviating the progression of pulmonary fibrosis caused by SARS-CoV-2. In conclusion, we demonstrated that CD147 contributed to SARS-CoV-2-triggered progressive pulmonary fibrosis and identified CD147 as a potential therapeutic target for treating patients with post-COVID-19 pulmonary fibrosis.

Association between health behaviours and the COVID-19 vaccination: risk compensation among healthcare workers in Taizhou, China.

This study is conducted to explore the association between health behaviors and the COVID-19 vaccination based on the risk compensation concept among health-care workers in Taizhou, China. We conducted a self-administered online survey to estimate the health behaviors among the staff in a tertiary hospital in Taizhou, China, from May 18 to 21 May 2021. A total of 592 out of 660 subjects (89.7%) responded to the questionnaire after receiving an e-poster on WeChat. Subjects who had been inoculated with the COVID-19 vaccine were asked to mention the differences in their health behaviors before and after the vaccination. The results showed that there were no statistical differences in health behaviors between vaccinated and unvaccinated groups, except in terms of the type of gloves they used (62.8% in the vaccinated group and 49.2% in the unvaccinated group, p = .048). Subjects who received earlier COVID-19 vaccinations exhibited better health behaviors (22.40% increased for duration of wearing masks (P = .007), 25.40% increased for times of washing hands (P = .01), and 20.90% increased for times of wearing gloves (P = .01)). Subjects also revealed better health behaviors (washing hands, wearing gloves, and wearing masks) after vaccination compared to that before. In conclusion, concept of risk compensation was not applied in our findings. The health behaviors did not reduce after the COVID-19 vaccination, which even may improve health behaviors among health-care workers in the hospital setting.

The Effects of Pulsed Electric Field On The Interaction Between SARS-Cov-2 And Human ACE2: Y505 Is A Key Target (preprint)

A novel coronavirus has rapidly spread to almost every country in the world, causing over 233 million confirmed cases of coronavirus disease 2019 (COVID-19) and over 209,761,242 deaths by late September 2021. Binding the receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2), is a key step in virus infection. In this study, we applied a pulsed electric field to the RBD/ACE2 complex based on molecular dynamics simulation and demonstrated that the electric field affects the structure and binding affinity of the complex. Additionally, residue Y505 is the crucial medium for the effects of electric field on the complex. Overall, these results may help apply an external electric field to virus suppression.

CD147 antibody specifically and effectively inhibits infection and cytokine storm of SARS-CoV-2 and its variants delta, alpha, beta, and gamma.

SARS-CoV-2 mutations contribute to increased viral transmissibility and immune escape, compromising the effectiveness of existing vaccines and neutralizing antibodies. An in-depth investigation on COVID-19 pathogenesis is urgently needed to develop a strategy against SARS-CoV-2 variants. Here, we identified CD147 as a universal receptor for SARS-CoV-2 and its variants. Meanwhile, Meplazeumab, a humanized anti-CD147 antibody, could block cellular entry of SARS-CoV-2 and its variants-alpha, beta, gamma, and delta, with inhibition rates of 68.7, 75.7, 52.1, 52.1, and 62.3% at 60 µg/ml, respectively. Furthermore, humanized CD147 transgenic mice were susceptible to SARS-CoV-2 and its two variants, alpha and beta. When infected, these mice developed exudative alveolar pneumonia, featured by immune responses involving alveoli-infiltrated macrophages, neutrophils, and lymphocytes and activation of IL-17 signaling pathway. Mechanistically, we proposed that severe COVID-19-related cytokine storm is induced by a "spike protein-CD147-CyPA signaling axis": Infection of SARS-CoV-2 through CD147 initiated the JAK-STAT pathway, which further induced expression of cyclophilin A (CyPA); CyPA reciprocally bound to CD147 and triggered MAPK pathway. Consequently, the MAPK pathway regulated the expression of cytokines and chemokines, which promoted the development of cytokine storm. Importantly, Meplazumab could effectively inhibit viral entry and inflammation caused by SARS-CoV-2 and its variants. Therefore, our findings provided a new perspective for severe COVID-19-related pathogenesis. Furthermore, the validated universal receptor for SARS-CoV-2 and its variants can be targeted for COVID-19 treatment.

Proteomic Analysis Identifies Prolonged Disturbances in Pathways Related to Cholesterol Metabolism and Myocardium Function in the COVID-19 Recovery Stage.

The COVID-19 pandemic has become a worldwide health crisis. So far, most studies have focused on the epidemiology and pathogenesis of this infectious disease. Little attention has been given to the disease sequelae in patients recovering from COVID-19, and nothing is known about the mechanisms underlying these sequelae. Herein, we profiled the serum proteome of a cohort of COVID-19 patients in the disease onset and recovery stages. Based on the close integration of our proteomic analysis with clinical data, we propose that COVID-19 is associated with prolonged disorders in cholesterol metabolism and myocardium, even in the recovery stage. We identify potential biomarkers for these disorders. Moreover, severely affected patients presented more serious disturbances in these pathways. Our findings potentially support clinical decision-making to improve the prognosis and treatment of patients.

Safety and efficacy of meplazumab in healthy volunteers and COVID-19 patients: a randomized phase 1 and an exploratory phase 2 trial.

Recent evidence suggests that CD147 serves as a novel receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Blocking CD147 via anti-CD147 antibody could suppress the in vitro SARS-CoV-2 replication. Meplazumab is a humanized anti-CD147 IgG2 monoclonal antibody, which may effectively prevent SARS-CoV-2 infection in coronavirus disease 2019 (COVID-19) patients. Here, we conducted a randomized, double-blinded, placebo-controlled phase 1 trial to evaluate the safety, tolerability, and pharmacokinetics of meplazumab in healthy subjects, and an open-labeled, concurrent controlled add-on exploratory phase 2 study to determine the efficacy in COVID-19 patients. In phase 1 study, 59 subjects were enrolled and assigned to eight cohorts, and no serious treatment-emergent adverse event (TEAE) or TEAE grade ≥3 was observed. The serum and peripheral blood Cmax and area under the curve showed non-linear pharmacokinetic characteristics. No obvious relation between the incidence or titer of positive anti-drug antibody and dosage was observed in each cohort. The biodistribution study indicated that meplazumab reached lung tissue and maintained >14 days stable with the lung tissue/cardiac blood-pool ratio ranging from 0.41 to 0.32. In the exploratory phase 2 study, 17 COVID-19 patients were enrolled, and 11 hospitalized patients were involved as concurrent control. The meplazumab treatment significantly improved the discharged (P = 0.005) and case severity (P = 0.021), and reduced the time to virus negative (P = 0.045) in comparison to the control group. These results show a sound safety and tolerance of meplazumab in healthy volunteers and suggest that meplazumab could accelerate the recovery of patients from COVID-19 pneumonia with a favorable safety profile.

Reverse Transcription Recombinase-Aided Amplification Assay With Lateral Flow Dipstick Assay for Rapid Detection of 2019 Novel Coronavirus.

Background: The emerging Coronavirus Disease-2019 (COVID-19) has challenged the public health globally. With the increasing requirement of detection for SARS-CoV-2 outside of the laboratory setting, a rapid and precise Point of Care Test (POCT) is urgently needed. Methods: Targeting the nucleocapsid (N) gene of SARS-CoV-2, specific primers, and probes for reverse transcription recombinase-aided amplification coupled with lateral flow dipstick (RT-RAA/LFD) platform were designed. For specificity evaluation, it was tested with human coronaviruses, human influenza A virus, influenza B viruses, respiratory syncytial virus, and hepatitis B virus, respectively. For sensitivity assay, it was estimated by templates of recombinant plasmid and pseudovirus of SARS-CoV-2 RNA. For clinical assessment, 100 clinical samples (13 positive and 87 negatives for SARS-CoV-2) were tested via quantitative reverse transcription PCR (RT-qPCR) and RT-RAA/LFD, respectively. Results: The limit of detection was 1 copies/µl in RT-RAA/LFD assay, which could be conducted within 30 min at 39°C, without any cross-reaction with other human coronaviruses and clinical respiratory pathogens. Compared with RT-qPCR, the established POCT assay offered 100% specificity and 100% sensitivity in the detection of clinical samples. Conclusion: This work provides a convenient POCT tool for rapid screening, diagnosis, and monitoring of suspected patients in SARS-CoV-2 endemic areas.

A general onepot-method for nucleic acid detection with CRISPR-Cas12a (preprint)

CRISPR/Cas12a system has been shown promising for nucleic acid diagnostics due to its rapid, portable and accurate features. In combination with isothermal amplification technology, single-copy sensitivity can be achieved. However, cleavage of the amplicons and primers by the cis- and trans-activity of Cas12a hinders the attempts to integrate the amplification and detection steps into a single reaction. Through phosphorothioate modification of primer and design of crRNA that allow for the cutting site locating at the modified site of the primer, we realized onepot detection of SARS-CoV-2 with single-copy sensitivity. We also identified the activated Cas12a has a much higher affinity to C nucleotide-rich reporter than others. By applying such reporters, we significantly reduced the reaction time required for the lateral-flow readout. Furthermore, to improve the specificity of the strip-based assay, we created a novel reporter and, when combined with a customized strip, the unspecific signal could be completely eliminated. This established system termed Targeting DNA by Cas12a-based Eye Sight Testing in Onepot Reaction (TESTOR) was validated using clinical cervical samples for human papillomaviruses (HPVs) detection. Our system represents a general approach to integrating the nucleic acid amplification and detection into a onepot reaction in CRISPR-Cas systems, highlighting its potential as a rapid, portable and accurate detection platform of nucleic acids.