Efficacy and effectiveness of COVID-19 vaccines: progress and prospect

To prevent and control COVID-19, COVID-19 vaccines are being developed, tested, and approved at an unprecedented rate. As of September 24, 2021, 22 types of COVID-19 vaccines have been approved for conditional marketing or emergency use by at least one country worldwide. Vaccine efficacy/effectiveness is a crucial concern for vaccination. This article provides an overview of efficacy of phase III clinical trials, vaccination, effectiveness of real-world studies as well as challenges of COVID-19 vaccine.

Characteristics of post-Wuhan COVID-19 outbreaks in mainland China

Objective: To review the characteristic of Coronavirus disease 2019 (COVID-19) outbreaks in mainland China, particularly post-Wuhan outbreaks, and to help design effective responses in the foreseeable future. Method: The data regarding COVID-19 outbreaks between December 2019 and March 16, 2022 were obtained from China's publicly available databases. The data were analyzed using descriptive statistics. Five outbreak stages were defined according to distinct epidemiological characteristics across different time periods over the past two years. Result: Since the 2020 Wuhan outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) local infections were confirmed in 37 995 cases as of March 16, 2022. We identified 285 isolated outbreaks in unrelated people that occurred in four additional distinct stages, over 57% of which had been imported, such as imported infected travelers and fomite transmission. The basic reproduction number (R0) of original SARS-CoV-2 was about 2.79, while the Delta variant was about 5.08 and Omicron was 7.0 or greater, resulting in the disease being more contagious during the fourth (Delta) and fifth (Omicron) stages than previous stages. Conclusion: China has experienced various COVID-19 outbreaks of different levels since the start of the pandemic in Wuhan, and local transmission is mainly caused by imported sources. If the "dynamic COVID-zero" policy is not appropriately followed, it will be difficult to contain the spread in China from overseas and to cope with the Omicron variant.

Characteristics of post-Wuhan COVID-19 outbreaks in mainland China

Objective: To review the characteristic of Coronavirus disease 2019 (COVID-19) outbreaks in mainland China, particularly post-Wuhan outbreaks, and to help design effective responses in the foreseeable future. Method: The data regarding COVID-19 outbreaks between December 2019 and March 16, 2022 were obtained from China’s publicly available databases. The data were analyzed using descriptive statistics. Five outbreak stages were defined according to distinct epidemiological characteristics across different time periods over the past two years. Result: Since the 2020 Wuhan outbreak, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) local infections were confirmed in 37 995 cases as of March 16, 2022. We identified 285 isolated outbreaks in unrelated people that occurred in four additional distinct stages, over 57% of which had been imported, such as imported infected travelers and fomite transmission. The basic reproduction number (R0) of original SARS-CoV-2 was about 2.79, while the Delta variant was about 5.08 and Omicron was 7.0 or greater, resulting in the disease being more contagious during the fourth (Delta) and fifth (Omicron) stages than previous stages. Conclusion: China has experienced various COVID-19 outbreaks of different levels since the start of the pandemic in Wuhan, and local transmission is mainly caused by imported sources. If the “dynamic COVID-zero” policy is not appropriately followed, it will be difficult to contain the spread in China from overseas and to cope with the Omicron variant.

Efficacy and effectiveness of COVID-19 vaccines: Progress and prospect

To prevent and control COVID-19, COVID-19 vaccines are being developed, tested, and approved at an unprecedented rate. As of September 24, 2021, 22 types of COVID-19 vaccines have been approved for conditional marketing or emergency use by at least one country worldwide. Vaccine efficacy/effectiveness is a crucial concern for vaccination. This article provides an overview of efficacy of phase III clinical trials, vaccination, effectiveness of real-world studies as well as challenges of COVID-19 vaccine.

Meta-analysis of 16S rRNA microbial data identified alterations of the gut microbiota in COVID-19 patients during the acute and recovery phases.

BACKGROUND: Dozens of studies have demonstrated gut dysbiosis in COVID-19 patients during the acute and recovery phases. However, a consensus on the specific COVID-19 associated bacteria is missing. In this study, we performed a meta-analysis to explore whether robust and reproducible alterations in the gut microbiota of COVID-19 patients exist across different populations. METHODS: A systematic review was conducted for studies published prior to May 2022 in electronic databases. After review, we included 16 studies that comparing the gut microbiota in COVID-19 patients to those of controls. The 16S rRNA sequence data of these studies were then re-analyzed using a standardized workflow and synthesized by meta-analysis. RESULTS: We found that gut bacterial diversity of COVID-19 patients in both the acute and recovery phases was consistently lower than non-COVID-19 individuals. Microbial differential abundance analysis showed depletion of anti-inflammatory butyrate-producing bacteria and enrichment of taxa with pro-inflammatory properties in COVID-19 patients during the acute phase compared to non-COVID-19 individuals. Analysis of microbial communities showed that the gut microbiota of COVID-19 recovered patients were still in unhealthy ecostates. CONCLUSIONS: Our results provided a comprehensive synthesis to better understand gut microbial perturbations associated with COVID-19 and identified underlying biomarkers for microbiome-based diagnostics and therapeutics.

Investigation on the effectiveness of ventilation dilution on mitigating COVID-19 patients' secondary airway damage due to exposure to disinfectants.

Chlorine-containing disinfectants are widely used in hospitals to prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection. Meanwhile, ventilation is a simple but effective means to maintain clean air. It is essential to explore the exposure level and health effects of coronavirus disease 2019 patients' inhalation exposure to by-products of chloride-containing disinfectants under frequent surface disinfection and understand the role of ventilation in mitigating subsequent airway damage. We determined ventilation dilution performance and indoor air quality of two intensive care unit wards of the largest temporary hospital constructed in China, Leishenshan Hospital. The chloride inhalation exposure levels, and health risks indicated by interleukin-6 and D-dimer test results of 32 patients were analysed. The mean ± standard deviation values of the outdoor air change rate in the two intensive care unit wards were 8.8 ± 1.5 h-1 (Intensive care unit 1) and 4.1 ± 1.4 h-1 (Intensive care unit 2). The median carbon dioxide and fine particulate matter concentrations were 480 ppm and 19 µg/m3 for intensive care unit 1, and 567 ppm and 21 µg/m3 for intensive care unit 2, all of which were around the average levels of those in permanent hospitals (579 ppm and 21 µg/m3). Of these patients, the median (lower quartile, upper quartile) chloride exposure time and calculated dose were 26.66 (2.89, 57.21) h and 0.357 (0.008, 1.317) mg, respectively. A statistically significant positive correlation was observed between interleukin-6 and D-dimer concentrations. To conclude, ventilation helped maintain ward air cleanliness and health risks were not observed.

Coronavirus Antibody Responses before COVID-19 Pandemic, Africa and Thailand.

Prior immune responses to coronaviruses might affect human SARS-CoV-2 response. We screened 2,565 serum and plasma samples collected from 2013 through early 2020, before the COVID-19 pandemic began, from 2,250 persons in 4 countries in Africa (Kenya, Nigeria, Tanzania, and Uganda) and in Thailand, including persons living with HIV-1. We detected IgG responses to SARS-CoV-2 spike (S) subunit 2 protein in 1.8% of participants. Profiling against 23 coronavirus antigens revealed that responses to S, subunit 2, or subunit 1 proteins were significantly more frequent than responses to the receptor-binding domain, S-Trimer, or nucleocapsid proteins (p<0.0001). We observed similar responses in persons with or without HIV-1. Among all coronavirus antigens tested, SARS-CoV-2, SARS-CoV-1, and Middle East respiratory syndrome coronavirus antibody responses were much higher in participants from Africa than in participants from Thailand (p<0.01). We noted less pronounced differences for endemic coronaviruses. Serosurveys could affect vaccine and monoclonal antibody distribution across global populations.

Association between diagnostic delay and prognosis of pulmonary tuberculosis in Shandong, China: a retrospective study.

BACKGROUND: Tuberculosis (TB) is one of the main infectious diseases that seriously threatens global health, while diagnostic delay (DD) and treatment dramatically threaten TB control. METHODS: Between 2005 and 2017 in Shandong, China, we enrolled pulmonary tuberculosis (PTB) patients with DD. DD trends were evaluated by Joinpoint regression, and associations between PTB patient characteristics and DD were estimated by univariate and multivariate logistic regression. The influence of DD duration on prognosis and sputum smear results were assessed by Spearman correlation coefficients. RESULTS: We identified 208,822 PTB cases with a median DD of 33 days (interquartile range (IQR) 18-63). The trend of PTB with DD declined significantly between 2009 and 2017 (annual percent change (APC): - 4.0%, P = 0.047, 2009-2013; APC: - 6.6%, P = 0.001, 2013-2017). Patients aged > 45 years old (adjusted odds ratio (aOR): 1.223, 95% confidence interval (CI) 1.189-1.257, 46-65 years; aOR: 1.306, 95% CI 1.267-1.346, > 65 years), farmers (aOR: 1.520, 95% CI 1.447-1.596), and those with a previous treatment history (aOR: 1.759, 95% CI 1.699-1.821) were prone to developing long DD (> 30 days, P < 0.05). An unfavorable outcome was negatively associated with a short DD (OR: 0.876, 95% CI 0.843-0.910, P < 0.001). Sputum smear positive rate and unfavorable outcomes were positively correlated with DD duration (Spearman correlation coefficients (rs) = 1, P < 0.001). CONCLUSIONS: The DD situation remains serious; more efficient and comprehensive strategies are urgently required to minimize DD, especially for high-risk patients.

Stigmatizing Attitudes Toward COVID-19 Among Patients, Their Relatives and Healthy Residents in Zhangjiajie.

Introduction: In July 2021, Zhangjiajie City became the new epicenter of the COVID-19 outbreak. Aside from the physical manifestations of COVID-19, patients are also victims of severe social stigmatization. Stigma affects not only COVID-19 patients or survivors, but also individuals associated with them. This study aims to describe and assess the COVID-19-related stigma between patients, their relatives, and healthy local residents. Methods: The study included 43 COVID-19 patients, 68 relatives, and 75 healthy residents from Zhangjiajie. Demographic data was collected, including gender, age, marital status, and educational level. Stigma attitudes toward COVID-19 were measured using the Stigma Scale and Social Distance Scale. Frequencies and percentages were described for each item of the scales, and differences among the three groups were examined using the chi-square test. Results: With regards to personal and perceived stigma, most participants agreed that patients with COVID-19 "could snap out of the problem" and that "they were dangerous." For social distance, over 30% of participants from the three groups agreed with the item "unwillingness to marry into the family of someone with COVID-19." In all groups, there were significant statistical differences in the belief that "the problem is not a real medical illness" and the desire to "spend the evening socializing." Conclusion: Although the outbreak was well-contained in Zhangjiajie, stigmatizing attitudes toward COVID-19 and desire for social distance to such patients were common among patients, their relatives and healthy local residents. Our study's results suggest that public education, anti-stigma interventions, and policies are necessary for people living in Zhangjiajie in order to effectively curtail the spread of COVID-19 and provide a useful strategy for a tourist city like Zhangjiajie to recover sooner from economic decline.

SARS-CoV-2 ferritin nanoparticle vaccines elicit broad SARS coronavirus immunogenicity.

The need for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) next-generation vaccines has been highlighted by the rise of variants of concern (VoCs) and the long-term threat of emerging coronaviruses. Here, we design and characterize four categories of engineered nanoparticle immunogens that recapitulate the structural and antigenic properties of the prefusion SARS-CoV-2 spike (S), S1, and receptor-binding domain (RBD). These immunogens induce robust S binding, ACE2 inhibition, and authentic and pseudovirus neutralizing antibodies against SARS-CoV-2. A spike-ferritin nanoparticle (SpFN) vaccine elicits neutralizing titers (ID50 > 10,000) following a single immunization, whereas RBD-ferritin nanoparticle (RFN) immunogens elicit similar responses after two immunizations and also show durable and potent neutralization against circulating VoCs. Passive transfer of immunoglobulin G (IgG) purified from SpFN- or RFN-immunized mice protects K18-hACE2 transgenic mice from a lethal SARS-CoV-2 challenge. Furthermore, S-domain nanoparticle immunization elicits ACE2-blocking activity and ID50 neutralizing antibody titers >2,000 against SARS-CoV-1, highlighting the broad response elicited by these immunogens.

The characteristics of and responses to the two COVID-19 outbreak waves in Hebei Province of China, January 2020 to February 2021.

Hebei Province was affected by two coronavirus disease 2019 (COVID-19) outbreak waves during the period 22 January 2020 through 27 February 2020 (wave 1) and 2 January 2021 through 14 February 2021 (wave 2). To evaluate and compare the epidemiological characteristics, containment delay, cluster events and social activity, as well as non-pharmaceutical interventions of the two COVID-19 outbreak waves, we examined real-time update information on all COVID-19-confirmed cases from a publicly available database. Wave 1 was closely linked with the COVID-19 pandemic in Wuhan, whereas wave 2 was triggered, to a certain extent, by the increasing social activities such as weddings, multi-household gatherings and church events during the slack agricultural period. In wave 2, the epidemic spread undetected in the rural areas, and people living in the rural areas had a higher incidence rate than those living in the urban areas (5.3 vs. 22.0 per 1 000 000). Furthermore, Rt was greater than 1 in the early stage of the two outbreak waves, and decreased substantially after massive non-pharmaceutical interventions were implemented. In China's 'new-normal' situation, development of targeted and effective intervention remains key for COVID-19 control in consideration of the potential threat of new coronavirus strains.

Substance and Internet use during the COVID-19 pandemic in China.

The coronavirus disease 2019 (COVID-19) has adversely influenced human physical and mental health, including emotional disorders and addictions. This study examined substance and Internet use behavior and their associations with anxiety and depression during the COVID-19 pandemic. An online self-report questionnaire was administered to 2196 Chinese adults between February 17 and 29, 2020. The questionnaire contained the seven-item Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9), questions on demographic information, and items about substance and Internet use characteristics. Our results revealed that males consumed less alcohol (p < 0.001) and areca-nut (p = 0.012) during the pandemic than before the pandemic. Age, gender, education status, and occupation significantly differed among increased substance users, regular substance users, and nonsubstance users. Time spent on the Internet was significantly longer during the pandemic (p < 0.001) and 72% of participants reported increased dependence on the Internet. Compared to regular Internet users, increased users were more likely to be younger and female. Multiple logistic regression analysis revealed that age <33 years (OR = 2.034, p < 0.001), increased substance use (OR = 3.439, p < 0.001), and increased Internet use (OR = 1.914, p < 0.001) were significantly associated with depression. Moreover, anxiety was significantly related to female gender (OR = 2.065, p < 0.001), "unmarried" status (OR = 1.480, p = 0.017), nonstudents (OR = 1.946-3.030, p = 0.001), and increased substance use (OR = 4.291, p < 0.001). Although there was a significant decrease in social substance use during the pandemic, more attention should be paid to increased Internet use. Increased Internet use was significantly associated with both anxiety and depression, and increased substance use was related to depression. Professional support should be provided to vulnerable individuals to prevent addiction.

COVID-19 and Tuberculosis Coinfection: An Overview of Case Reports/Case Series and Meta-Analysis.

Background: Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are two major infectious diseases posing significant public health threats, and their coinfection (aptly abbreviated COVID-TB) makes the situation worse. This study aimed to investigate the clinical features and prognosis of COVID-TB cases. Methods: The PubMed, Embase, Cochrane, CNKI, and Wanfang databases were searched for relevant studies published through December 18, 2020. An overview of COVID-TB case reports/case series was prepared that described their clinical characteristics and differences between survivors and deceased patients. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) for death or severe COVID-19 were calculated. The quality of outcomes was assessed using GRADEpro. Results: Thirty-six studies were included. Of 89 COVID-TB patients, 19 (23.46%) died, and 72 (80.90%) were male. The median age of non-survivors (53.95 ± 19.78 years) was greater than that of survivors (37.76 ± 15.54 years) (p < 0.001). Non-survivors were more likely to have hypertension (47.06 vs. 17.95%) or symptoms of dyspnea (72.73% vs. 30%) or bilateral lesions (73.68 vs. 47.14%), infiltrates (57.89 vs. 24.29%), tree in bud (10.53% vs. 0%), or a higher leucocyte count (12.9 [10.5-16.73] vs. 8.015 [4.8-8.97] × 109/L) than survivors (p < 0.05). In terms of treatment, 88.52% received anti-TB therapy, 50.82% received antibiotics, 22.95% received antiviral therapy, 26.23% received hydroxychloroquine, and 11.48% received corticosteroids. The pooled ORs of death or severe disease in the COVID-TB group and the non-TB group were 2.21 (95% CI: 1.80, 2.70) and 2.77 (95% CI: 1.33, 5.74) (P < 0.01), respectively. Conclusion: In summary, there appear to be some predictors of worse prognosis among COVID-TB cases. A moderate level of evidence suggests that COVID-TB patients are more likely to suffer severe disease or death than COVID-19 patients. Finally, routine screening for TB may be recommended among suspected or confirmed cases of COVID-19 in countries with high TB burden.

3D CNN classification model for accurate diagnosis of coronavirus disease 2019 using computed tomography images.

Purpose: The coronavirus disease (COVID-19) has been spreading rapidly around the world. As of August 25, 2020, 23.719 million people have been infected in many countries. The cumulative death toll exceeds 812,000. Early detection of COVID-19 is essential to provide patients with appropriate medical care and protecting uninfected people. Approach: Leveraging a large computed tomography (CT) database from 1112 patients provided by China Consortium of Chest CT Image Investigation (CC-CCII), we investigated multiple solutions in detecting COVID-19 and distinguished it from other common pneumonia (CP) and normal controls. We also compared the performance of different models for complete and segmented CT slices. In particular, we studied the effects of CT-superimposition depths into volumes on the performance of our models. Results: The results show that the optimal model can identify the COVID-19 slices with 99.76% accuracy (99.96% recall, 99.35% precision, and 99.65% F 1 -score). The overall performance for three-way classification obtained 99.24% accuracy and a macroaverage area under the receiver operating characteristic curve (macro-AUROC) of 0.9998. To the best of our knowledge, our method achieves the highest accuracy and recall with the largest public available COVID-19 CT dataset. Conclusions: Our model can help radiologists and physicians perform rapid diagnosis, especially when the healthcare system is overloaded.

Affordable measures to monitor and alarm nosocomial SARS-CoV-2 infection due to poor ventilation.

Since the coronavirus disease 2019 (COVID-19) outbreak, the nosocomial infection rate worldwide has been reported high. It is urgent to figure out an affordable way to monitor and alarm nosocomial infection. Carbon dioxide (CO2 ) concentration can reflect the ventilation performance and crowdedness, so CO2 sensors were placed in Beijing Tsinghua Changgung Hospital's fever clinic and emergency department where the nosocomial infection risk was high. Patients' medical records were extracted to figure out their timelines and whereabouts. Based on these, site-specific CO2 concentration thresholds were calculated by the dilution equation and sites' risk ratios were determined to evaluate ventilation performance. CO2 concentration successfully revealed that the expiratory tracer was poorly diluted in the mechanically ventilated inner spaces, compared to naturally ventilated outer spaces, among all of the monitoring sites that COVID-19 patients visited. Sufficient ventilation, personal protection, and disinfection measures led to no nosocomial infection in this hospital. The actual outdoor airflow rate per person (Qc ) during the COVID-19 patients' presence was estimated for reference using equilibrium analysis. During the stay of single COVID-19 patient wearing a mask, the minimum Qc value was 15-18 L/(s·person). When the patient was given throat swab sampling, the minimum Qc value was 21 L/(s·person). The Qc value reached 36-42 L/(s·person) thanks to window-inducted natural ventilation, when two COVID-19 patients wearing masks shared the same space with other patients or healthcare workers. The CO2 concentration monitoring system proved to be effective in assessing nosocomial infection risk by reflecting real-time dilution of patients' exhalation.

ATP biphasically modulates LLPS of SARS-CoV-2 nucleocapsid protein and specifically binds its RNA-binding domain.

SARS-CoV-2 is a highly contagious coronavirus causing the ongoing pandemic. Very recently its genomic RNA of ∼30 kb was decoded to be packaged with nucleocapsid (N) protein into phase separated condensates. Interestingly, viruses have no ability to generate ATP but host cells have very high ATP concentrations of 2-12 mM. A key question thus arises whether ATP modulates liquid-liquid phase separation (LLPS) of the N protein. Here we discovered that ATP not only biphasically modulates LLPS of the viral N protein as we previously found on human FUS and TDP-43, but also dissolves the droplets induced by oligonucleic acid. Residue-specific NMR characterization showed ATP specifically binds the RNA-binding domain (RBD) of the N protein with the average Kd of 3.3 ± 0.4 mM. The ATP-RBD complex structure was constructed by NMR-derived constraints, in which ATP occupies a pocket within the positive-charged surface utilized for binding nucleic acids. Our study suggests that ATP appears to be exploited by SARS-CoV-2 to promote its life cycle by facilitating the uncoating, localizing and packing of its genomic RNA. Therefore the interactions of ATP with the viral RNA and N protein might represent promising targets for design of drugs and vaccines to terminate the pandemic.

News from a postpandemic world

The article presents several news related to long-term effects of the coronavirus disease 2019 (COVID-19) pandemic. It highlights effects such as science and technology research budgets has classified as an arm of the national defense force;announcement of U.S. government related to spaceship designate for in-orbit medical treatment of COVID-19 patients;and changes in education with the use of remote, and technology-enhanced classrooms.

A SARS-CoV-2 vaccine candidate would likely match all currently circulating variants.

The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Many vaccine candidates focus on the Spike protein, as it is targeted by neutralizing antibodies and plays a key role in viral entry. Here we investigate the diversity seen in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences and compare it to the sequence on which most vaccine candidates are based. Using 18,514 sequences, we perform phylogenetic, population genetics, and structural bioinformatics analyses. We find limited diversity across SARS-CoV-2 genomes: Only 11 sites show polymorphisms in >5% of sequences; yet two mutations, including the D614G mutation in Spike, have already become consensus. Because SARS-CoV-2 is being transmitted more rapidly than it evolves, the viral population is becoming more homogeneous, with a median of seven nucleotide substitutions between genomes. There is evidence of purifying selection but little evidence of diversifying selection, with substitution rates comparable across structural versus nonstructural genes. Finally, the Wuhan-Hu-1 reference sequence for the Spike protein, which is the basis for different vaccine candidates, matches optimized vaccine inserts, being identical to an ancestral sequence and one mutation away from the consensus. While the rapid spread of the D614G mutation warrants further study, our results indicate that drift and bottleneck events can explain the minimal diversity found among SARS-CoV-2 sequences. These findings suggest that a single vaccine candidate should be efficacious against currently circulating lineages.