Efficacy of SARS-CoV-2 vaccines and the dose-response relationship with three major antibodies: a systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: The efficacy of SARS-CoV-2 vaccines in preventing severe COVID-19 illness and death is uncertain due to the rarity of data in individual trials. How well the antibody concentrations can predict the efficacy is also uncertain. We aimed to assess the efficacy of these vaccines in preventing SARS-CoV-2 infections of different severities and the dose-response relationship between the antibody concentrations and efficacy. METHODS: We did a systematic review and meta-analysis of randomised controlled trials (RCTs). We searched PubMed, Embase, Scopus, Web of Science, Cochrane Library, WHO, bioRxiv, and medRxiv for papers published between Jan 1, 2020 and Sep 12, 2022. RCTs on the efficacy of SARS-CoV-2 vaccines were eligible. Risk of bias was assessed using the Cochrane tool. A frequentist, random-effects model was used to combine efficacy for common outcomes (ie, symptomatic and asymptomatic infections) and a Bayesian random-effects model was used for rare outcomes (ie, hospital admission, severe infection, and death). Potential sources of heterogeneity were investigated. The dose-response relationships of neutralising, spike-specific IgG and receptor binding domain-specific IgG antibody titres with efficacy in preventing SARS-CoV-2 symptomatic and severe infections were examined by meta-regression. This systematic review is registered with PROSPERO, CRD42021287238. FINDINGS: 28 RCTs (n=286 915 in vaccination groups and n=233 236 in placebo groups; median follow-up 1-6 months after last vaccination) across 32 publications were included in this review. The combined efficacy of full vaccination was 44·5% (95% CI 27·8-57·4) for preventing asymptomatic infections, 76·5% (69·8-81·7) for preventing symptomatic infections, 95·4% (95% credible interval 88·0-98·7) for preventing hospitalisation, 90·8% (85·5-95·1) for preventing severe infection, and 85·8% (68·7-94·6) for preventing death. There was heterogeneity in the efficacy of SARS-CoV-2 vaccines against asymptomatic and symptomatic infections but insufficient evidence to suggest whether the efficacy could differ according to the type of vaccine, age of the vaccinated individual, and between-dose interval (p>0·05 for all). Vaccine efficacy against symptomatic infection waned over time after full vaccination, with an average decrease of 13·6% (95% CI 5·5-22·3; p=0·0007) per month but can be enhanced by a booster. We found a significant non-linear relationship between each type of antibody and efficacy against symptomatic and severe infections (p<0·0001 for all), but there remained considerable heterogeneity in the efficacy, which cannot be explained by antibody concentrations. The risk of bias was low in most studies. INTERPRETATION: The efficacy of SARS-CoV-2 vaccines is higher for preventing severe infection and death than for preventing milder infection. Vaccine efficacy wanes over time but can be enhanced by a booster. Higher antibody titres are associated with higher estimates of efficacy but precise predictions are difficult due to large unexplained heterogeneity. These findings provide an important knowledge base for interpretation and application of future studies on these issues. FUNDING: Shenzhen Science and Technology Programs.

Scavenger receptor A in immunity and autoimmune diseases: Compelling evidence for targeted therapy.

INTRODUCTION: Scavenger receptor A (SR-A) is reported to be involved in innate and adaptive immunity and in recent years, the soluble form of SR-A has also been identified. Intriguingly, SR-A displays double-edged sword features in different diseases. Moreover, targeted therapy on SR-A, including genetic modulation, small molecule inhibitor, inhibitory peptides, fucoidan, and blocking antibodies, provides potential strategies for treatment. Currently, therapeutics targeting SR-A are in preclinical studies and clinical trials, revealing great perspectives in future immunotherapy. AREAS COVERED: Through searching PubMed (January 1979-March 2022) and clinicaltrials.gov, we review most of the research and clinical trials involving SR-A. This review briefly summarizes recent study advances on SR-A, with particular concern on its role in immunity and autoimmune diseases. EXPERT OPINION: Given the emerging evidence of SR-A in immunity, its targeted therapy has been studied in various diseases, especially autoimmune diseases. However, many challenges still remain to be overcome, such as the double-sworded effects and the specific isoform targeting. For further clinical success of SR-A targeted therapy, the crystal structure illustration and the dual function discrimination of SR-A should be further investigated. Nevertheless, although challenging, targeting SR-A would be a potential effective strategy in the treatment of autoimmune diseases and other immune-related diseases.

Low-dose IL-2 reduces IL-21+ T cells and induces a long-lived anti-inflammatory gene expression signature inversely modulated in COVID-19 patients (preprint)

Despite early clinical successes, the mechanisms of action of low-dose interleukin-2 (LD-IL-2) immunotherapy remain only partly understood. Here, we examined the effects of interval administration of low-dose recombinant IL-2 (iLD-IL-2) using high-resolution, single-cell multiomics and flow cytometry. We confirmed that iLD-IL-2 selectively expands thymic-derived FOXP3 + HELIOS + Tregs and CD56 br NK cells, and showed that treatment reduced the frequency of IL-21-producing CD4 + T cells and of two subsets of innate-like CD8 + T cells, mucosal-associated invariant T cells and V γ9 V δ2 T cells. The cellular changes induced by LD-IL-2 were associated with an anti-inflammatory gene expression signature, which remains detectable in all T and NK cell subsets analysed one month after treatment. The anti-inflammatory nature of this gene expression signature was supported by the observation that the same genes were also modulated in COVID-19 patients, but in the opposite direction. These findings warrant continued investigations of the potential clinical benefits of iLD-IL-2 in immunotherapy and further understanding of the development of long-term sequelae in convalescent COVID-19 patients.

Exploring the nursing regulation against COVID-19 in hematology department (preprint)

To find out the comprehensive nursing regulation against COVID-19 epidemic in hematology department. Normalized regulation preventing epidemic was set up by improving management of accompany nursing and optimizing the process of admitting to hospital, which include special nursing measures preventing hematology patients with fever during the epidemic; dual quarantine methods for patients with low leukocyte; blood catheter nursing; improving nursing for patients with anemia or low blood platelet. All staff in our department were not infected by COVID-19, and no patients were confirmed, quality of nursing were excellent,100% satisfaction were got both in the staff and patients, the process of admitting and routine work in department were normally running. Awareness of risk is essentially for nurse who practice frontline nursing in hematology ward especially facing the outbreak of epidemic, we should immediately take action against the pandemic to reduce the infection and alleviate the loss.

Paper-Based Point-of-Care Testing of SARS-CoV-2.

The COVID-19 pandemic has resulted in significant global social and economic disruption. The highly transmissive nature of the disease makes rapid and reliable detection critically important. Point-of-care (POC) tests involve performing diagnostic tests outside of a laboratory that produce a rapid and reliable result. It therefore allows the diagnostics of diseases at or near the patient site. Paper-based POC tests have been gaining interest in recent years as they allow rapid, low-cost detection without the need for external instruments. In this review, we focus on the development of paper-based POC devices for the detection of SARS-CoV-2. The review first introduces the principles of detection methods that are available to paper-based devices. It then summarizes the state-of-the-art paper devices and their analytical performances. The advantages and drawbacks among methods are also discussed. Finally, limitations of the existing devices are discussed, and prospects are given with the hope to identify research opportunities and directions in the field. We hope this review will be helpful for researchers to develop a clinically useful and economically efficient paper-based platform that can be used for rapid, accurate on-site diagnosis to aid in identifying acute infections and eventually contain the COVID-19 pandemic.

Chemical profiling of Huashi Baidu prescription, an effective anti-COVID-19 TCM formula, by UPLC-Q-TOF/MS.

Huashi Baidu prescription (HSBDF), recommended in the Guideline for the Diagnosis and Treatment of Novel Coronavirus (2019-nCoV) Pneumonia (On Trials, the Seventh Edition), was clinically used to treat severe corona virus disease 2019 (COVID-19) with cough, blood-stained sputum, inhibited defecation, red tongue etc. symptoms. This study was aimed to elucidate and profile the knowledge on its chemical constituents and the potential anti-inflammatory effect in vitro. In the study, the chemical constituents in extract of HSBDF were characterized by UPLC-Q-TOF/MS in both negative and positive modes, and the pro-inflammatory cytokines were measured by enzyme-linked immunosorbent assays (ELISA) to determine the effects of HSBDF in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results showed that a total of 217 chemical constituents were tentativedly characterized in HSBDF. Moreover, HSBDF could alleviate the expression levels of IL-6 and TNF-α in the cell models, indicating that the antiviral effects of HSBDF might be associated with regulation of the inflammatory cytokines production in RAW264.7 cells. We hope that the results could be served as the basic data for further study of HSBDF on anti-COVID-19 effect.

Analyzing Public Opinion and Misinformation in a COVID-19 Telegram Group Chat.

We analyze a Singapore-based COVID-19 Telegram group with more than 10000 participants. First, we study the group's opinion over time, focusing on five dimensions: participation, sentiment, negative emotions, topics, and message types. We find that participation peaked when the Ministry of Health raised the disease alert level, but this engagement was not sustained. Second, we investigate the prevalence of, and reactions to, authority-identified misinformation in the group. We find that authority-identified misinformation is rare, and that participants affirm, deny, and question misinformation. Third, we explore searching for user skepticism as one strategy for identifying misinformation, finding misinformation not previously identified by authorities.

Medication adherence among patients with chronic obstructive pulmonary disease treated in a primary general hospital during the COVID-19 pandemic.

BACKGROUND: The objective of this study was to investigate medication adherence and the associated influencing factors in patients with chronic obstructive pulmonary disease (COPD) who were treated in a primary general hospital in Shanghai China during the 2019 novel coronavirus (COVID-19) pandemic. METHODS: From March to April 2020, all of the COPD patients treated in our department in the last 7 years were interviewed by telephone. The basic patient data and each questionnaire item were collected, and influencing factors were analyzed by the Chi-square test, U test, and univariate and multivariate logistic regression analyses. RESULTS: A total of 191 patients with COPD were queried, and 84 (44.0%) valid questionnaires were obtained. Among them, individuals with group B symptoms were most represented (45.2%); 53.6% had Medical Research Council (MRC) dyspnea levels of 2 or above. Chronic obstructive pulmonary disease assessment test (CAT) had an average of 9 [3, 13], and 52.4% of patients used two-drug combination therapy. Medication adherence was both good in ordinary times and over the past 2 months of the pandemic, and 88.8% of patients had no acute exacerbation during the pandemic. The CAT scores of male patients <70 years old, and patients with general outpatient follow-up and regular gargling were reduced (P<0.05). Drug combination and doctor's supervision were favorable factors affecting medication adherence during the 2 months of the pandemic, while possible depression was an unfavorable factor (P<0.05). CONCLUSIONS: During the pandemic, medication adherence in patients with COPD was similar to that in regular times, and was significantly related to drug combination, doctor's supervision, and accompanying mood disorders. An effective way to improve patient adherence and disease control could be strengthening follow-up education and diagnosing and treating depression and other complications.

Is this pofma? Analysing public opinion and misinformation in a COVID-19 Telegram group chat (preprint)

We analyse a Singapore-based COVID-19 Telegram group with more than 10,000 participants. First, we study the group's opinion over time, focusing on four dimensions: participation, sentiment, topics, and psychological features. We find that engagement peaked when the Ministry of Health raised the disease alert level, but this engagement was not sustained. Second, we search for government-identified misinformation in the group. We find that government-identified misinformation is rare, and that messages discussing these pieces of misinformation express skepticism.

Analysis and consideration of registration information of global coronavirus disease 2019 clinical study

Objective: To analyze the registration characteristics of registered clinical research, and find the potential scientific and feasibility problems of clinical research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), providing reference for the good management of follow-up research registration. Methods: The key words of coronavirus disease 2019 (COVID-19) were identified and retrieved from Chinese Clinical Trial Registry and ClinicalTrials website. The registration characteristics of ethical status, number of recruits, total time, number of groups, intervention, study endpoint type, withdrawal, randomized controlled trial (RCT), stage, registration type, provinces distribution and patients' condition were summarized. IBM SPSS 22.0 software was used to analyze the above characteristics. Results: A total of 400 registered clinical studies were collected. Among them, 59 studies were not ethically approved, 15 studies were withdrawn, and stages of 303 studies were unclear. The differences of the three registration characteristics on the two official websites were statistically significant (all P<0.05). Fourteen studies recruited more than 1 000 people, the total time of 189 studies exceeded 6 months, and the number of groups in 22 studies exceeded 4 groups. There was no significant difference in the three registration characteristics on the two official websites. Only 15 studies were industry-sponsored trial. Most registered clinical studies were distributed in Hubei Province. Conclusion: The awareness of Chinese investigator initiating trial registration has increased. However, by collating and analyzing the registration information, it is found that the study design is not rigorous, so it is necessary to strengthen the registration quality management and study design methodological demonstration.