Perceived COVID-19-related stress drives home gardening intentions and improves human health in Taiwan.

The COVID-19 pandemic has added a layer of mental health problems and perceived stress. Home gardening is considered a good method to reduce perceived stress. The current research evidence is insufficient to understand the relationship and influencing factors between the intentions, behaviors, and benefits of home gardening during short-term COVID-19 events. Although the duration from the onset to stabilization of the outbreak lasted for only 1.5 months from May to June 2021 throughout Taiwan, the significant pandemic changes might have affected the perceived stress along with the intentions, behaviors, and benefits of home gardening. This study explored the relationship between pandemic stress and home gardening through online snowball sampling because of the strict social distancing regulations. A total of 1455 non-follow-up and internet questionnaires throughout Taiwan were collected during the wave onset, peak, easing, and stabilization stages. The questionnaire included questions on personal information, perceived pandemic stress, gardening intentions, gardening behaviors, and gardening benefits. This study showed that perceived stress increased from the pandemic onset to its peak, and decreased from the peak to stabilization stages. Home gardening intentions and behaviors also revealed similar trends. Higher pandemic-perceived stress directly increased home-gardening intentions and indirectly promoted home-gardening behaviors and benefits. Our findings indicated that home gardening is a positive element in reducing perceived stress. Lower gardening intentions and behaviors were observed when the high perceived stress was removed. This study suggests that home gardening was a valuable strategy for staying close to nature and obtaining multiple benefits during the peak pandemic period. Providing small-scale gardening activities and spaces is appropriate for obtaining gardening benefits and avoiding space abandonment after the pandemic. Providing seeds, seedlings, tools, knowledge, online home gardening programs, and small residential and food gardens is a valuable strategy for obtaining multiple benefits during the peak of the pandemic.

Management of Atopic Dermatitis During the COVID-19 Pandemic: Key Questions and Review of the Current Evidence.

Since the outbreak of COVID-19, management of atopic dermatitis (AD) has been widely discussed. Key issues include the risk of COVID-19 infection and related outcomes in AD patients, the efficacy and safety of COVID-19 vaccination in AD populations, and management of AD in the COVID-19 pandemic. Recent studies have shown that patients with AD have a slightly increased risk of COVID-19 infection but are not associated with a worse outcome than the non-AD population. COVID-19 vaccination is generally effective and safe in patients with AD. However, temporary discontinuation of certain systemic immunomodulatory agents after vaccination is suggested. During the pandemic, continuation of all immunomodulating agents is suggested, but these agents should be paused when patients with AD are infected with COVID-19 until recovery. Further studies are warranted to investigate the long-term interaction between AD and COVID-19 to aid clinical decisions during the pandemic.

Quality of care in the course of subcutaneous versus intravenous trastuzumab administration in patients with breast cancer: an integrated time-motion study with mixed-methods research.

OBJECTIVES: This study aimed to compare the time required and concerns raised by various perspectives of participants regarding administering subcutaneous and intravenous trastuzumab for patients with breast cancer (BC). DESIGN: This observational time-motion study design with mixed-methods research (cross-sectional surveys and semistructured interviews) was conducted. The time spent on preparing or administering trastuzumab by different healthcare professionals (HCPs) was recorded. The data were analysed by descriptive/inferential statistical analyses, followed by thematic analyses. SETTING: Outpatient and inpatient administration units of a single medical centre in Taiwan. PARTICIPANTS: The study included patients with early-stage BC who received subcutaneous or intravenous trastuzumab (n=93), and HCPs including two attending physicians, a nurse practitioner, two pharmacists and two nurses. RESULT: Based on the perspectives of patients and HCPs, the subcutaneous form of trastuzumab was more efficient, less expensive and produced less discomfort in outpatient units than inpatient units. More participants preferred the subcutaneous form over the intravenous form in both outpatient and inpatient units. Pharmacists and nurse practitioners spent threefold more time on patients when preparing and administering the intravenous form in both outpatient and inpatient units. The concerns raised by patients and HCPs varied in certain aspects, including the injection skills, speed, mental distress (eg, needle phobia) and pain associated with the subcutaneous form. Almost all patients preferred receiving the subcutaneous form in outpatient units after the initial COVID-19 outbreak. CONCLUSION: Patients with early-stage BC preferred receiving subcutaneous trastuzumab in outpatient units rather than inpatient units or the intravenous form before and after the COVID-19 outbreak. Such findings may serve as real-world evidence to facilitate better quality of care regarding administration of subcutaneous or intravenous trastuzumab in medical settings, and its feasible resolutions to balance the quality, concerns and efficiency of anticancer administration during the COVID-19 pandemic.

Emergence and Persistent Dominance of SARS-CoV-2 Omicron BA.2.3.7 Variant, Taiwan.

Since April 2022, waves of SARS-CoV-2 Omicron variant cases have surfaced in Taiwan and spread throughout the island. Using high-throughput sequencing of the SARS-CoV-2 genome, we analyzed 2,405 PCR-positive swab samples from 2,339 persons and identified the Omicron BA.2.3.7 variant as a major lineage within recent community outbreaks in Taiwan.

Analysis of psychological status and effect of psychological intervention in quarantined population during the epidemic of SARS-CoV-2.

ABSTRACT: During outbreaks of the coronavirus disease 2019 (COVID-19), many countries adopted quarantine to slow the spread of the virus of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Quarantine will cause isolation from families, friends, and the public, which consequently leads to serious psychological pressure with potentially long-lasting effects on the quarantined population. Experience of specific practices to improve the psychological status of the mandatory quarantined population was limited. The aim of this study was to investigate the psychological impact of mandatory quarantine, and evaluate the effect of psychological intervention on the quarantined population.We conducted a prospective cohort study to assess and manage the psychological status of a mandatory quarantined population in Beijing, China. A total of 638 individuals completed 2 questionnaires and were enrolled in this study, of which 372 participants accepted designed psychological intervention while other 266 participants refused it. The SCL-90 questionnaire was used to evaluate the psychological status and its change before and after the intervention. The differences of SCL-90 factor scores between participants and the national norm group were assessed by 2 samples t test. While the SCL-90 factor scores before and after intervention were compared with 2 paired samples t test.Compared with the Chinese norms of SCL-90, the participants had higher SCL-90 factor scores in most items of the SCL-90 inventory. The SCL-90 factor scores of participants with psychological intervention significantly decreased in somatization, obsessive-compulsive, depression, anxiety, phobic anxiety, paranoid ideation, and psychoticism. In contrast, most factor scores of the SCL-90 inventory changed little without statistical significance in participants without psychological intervention.Psychological problems should be emphasized in the quarantined individuals and professional psychological intervention was a feasible approach to improve the psychological status of the mandatory quarantined population in the epidemic of SARS-CoV-2.

Community transmission of COVID-19 outbreaks caused by SARS-CoV-2 Delta variant in 3 areas of Zhejiang, December 2021

Objective: To analyze epidemiological characteristics of COVID-19 outbreaks caused by SARS-CoV-2 Delta variant in 3 areas of Zhejiang province in December 2021.

Outbreak investigation in a COVID-19 designated hospital: The combination of phylogenetic analysis and field epidemiology study suggesting airborne transmission.

BACKGROUND: Healthcare-associated COVID-19 infections caused by SARS-CoV-2 have increased morbidity and mortality. Hospitals and skilled nursing facilities (SNFs) have been challenged by infection control and management. METHODS: This case study presents an outbreak investigation in a COVID-19-designated hospital and a hospital-based SNF. Real-time polymerase chain reaction (PCR) and other studies were performed on samples obtained from SNF residents, hospital patients, and healthcare workers (HCWs). The results of the laboratory tests and field epidemiological data were analyzed. Genome sequencing and phylogenetic analysis of SARS-CoV-2 were performed to identify the associations between cases. The tracer gas was released and recorded by a thermal imaging camera to investigate the spatial relations within clusters. RESULTS: During the outbreak, 29 COVID-19 infections in 3 clusters were identified through hospital-wide, risk-guided, and symptom-driven PCR tests. This included 12 HCWs, 5 patients, and 12 SNF residents who had been hospitalized for at least 14 days. Serology tests did not identify any cases among the PCR-negative individuals. The phylogenetic analysis revealed that viral strains from the 3 clusters shared a common mutation of G3994T and were phylogenetically related, which suggested that this outbreak had a common source rather than multiple introductions from the community. Linked cases exhibited vertical spatial distribution, and the sulfur hexafluoride release test confirmed a potential airborne transmission. CONCLUSIONS: This report addressed the advantage of a multi-disciplinary team in outbreak investigation. Identifying an airborne transmission within an outbreak highlighted the importance of regular maintenance of ventilation systems.

Short-term effect of internet-delivered mindfulness-based stress reduction on mental health, self-efficacy, and body image among women with breast cancer during the COVID-19 pandemic.

Background and aim: During the COVID-19 pandemic, an Internet-Mindfulness-Based Stress Reduction (iMBSR) program was delivered and may be better than an in-person approach. Our study evaluated the effects of iMBSR intervention on mental health, self-efficacy, and body image in women with breast cancer in Taiwan. Materials and methods: Sixty-seven women with breast cancer were allocated to a 6-week iMBSR (n = 41) program or a waitlist control group (n = 26), without heterogeneity between group characteristics. Patients from both groups were measured at baseline and postintervention using three scales: Depression, Anxiety, and Stress Scale (DASS-21), General self-efficacy scale, and Body Image Scale. Descriptive dataset analysis, paired t-test, and Student's t-test were used to evaluate the data. Results: Although iMBSR did not significantly improve depression and stress between groups, iMBSR could improve anxiety (Δmean: -2.0 vs. -0.4, p = 0.041) with medium effect sizes. Significant benefits were found for body image (Δmean: -3.6 vs. 0.9, p = 0.003) and self-efficacy (Δmean: 4.2 vs. 1.5, p = 0.004), with large effect sizes (Cohen's d = 0.73). Conclusion: Our preliminary study supports iMBSR as a program that can improve mental health, body image, and self-efficacy in women with breast cancer. During the COVID-19 pandemic, medical professionals can use Internet-based clinical health education.

The Uneven Short-Run Effects of the COVID-19 Pandemic on Foreign Direct Investment

This study examines short-run economic and business impacts of the COVID-19 pandemic as a global disruption event. The purpose is to build propositions about specific subnational FDI (Foreign Direct Investment) developments in the short-term of global disturbance. We approach the investigation by reviewing FDI outcomes in the year prior and in the first year of the pandemic, at the U.S. national and subnational levels, and through the lens of local characteristics and FDI outcomes in the state of New Hampshire. Our methods include distribution and frequency analyses on two sets of data: secondary data on FDI and trade at the state level, and primary data as direct observations on firm activities in New Hampshire. Our leading method is the evaluation of data aimed at triangulating and consequently generating a set of propositions that explain phenomena observed in relation to short-term effects of disruption. Our methodological tools consist of an in-focus instance of the phenomena in one state, as a particular case for verifying the validity of our propositions, and comparisons with available data across states to establish the reliability of the proposed consequences. Our analysis provides evidence for subnational heterogeneity of global disruption impact. Our interstate trend analysis and unique data on FDI-related activities in New Hampshire reveal how foreign businesses respond to the external shock of global disruption in the short-run. We use our insights to propose that established regional supply chains and differences in local advantages determine varying FDI outcomes across subnational locations. As a result, we set forth three calls-to-action for regional policymakers: the development of initiatives to support strong trade and FDI-outcomes at all times and in preparation for global disruption;the promotion and facilitation of firms' access to markets;and the implementation of actions that encourage the establishment of regional supply chains.

Trend of hand, foot, and mouth disease from 2010 to 2021 and estimation of the reduction in enterovirus 71 infection after vaccine use in Zhejiang Province, China.

BACKGROUND: Zhejiang, ranked in the top three in HFMD (hand, foot, and mouth disease) incidence, is located in the Yangtze River Delta region of southeast China. Since 2016, the EV71 vaccine has been promoted in Zhejiang Province. This study aimed to investigate the trend and seasonal variation characteristics of HFMD from 2010 to 2021 and estimate the reduction in enterovirus 71 infection after vaccine use. METHODS: The data on HFMD cases in Zhejiang Province from January 2010 to December 2021 were obtained from this network system. Individual information on cases and deaths was imported, and surveillance information, including demographic characteristics and temporal distributions, was computed by the system. The Joinpoint regression model was used to describe continuous changes in the incidence trend. The BSTS (Bayesian structural time-series models) model was used to estimate the monthly number of cases from 2017 to 2021 based on the observed monthly incidence during 2010-2016 by accounting for seasonality and long-term trends. The seasonal variation characteristics of HFMD pathogens were detected by wavelet analysis. RESULTS: From 2010 to 2021, the annual incidence rate fluctuated between 98.81 cases per 100,000 in 2020 and 435.63 cases per 100,000 in 2018, and 1711 severe HFMD cases and 106 fatal cases were reported in Zhejiang Province, China. The annual percent change (APC) in EV71 cases was -30.72% (95% CI: -45.10 to -12.50) from 2016 to 2021. The wavelet transform of total incidence and number of cases of the three pathogens all showed significant periodicity on the 1-year scale. The average 2-year scale periodicity was significant for the total incidence, EV71 cases and Cox A16 cases, but the other enterovirus cases showed significant periodicity on the 30-month scale. The 6-month scale periodicity was significant for the total incidence, EV71 case and Cox A16 case but not for the other enteroviruses case. The relative error percentage of the performance of the BSTS model was 0.3%. The estimated number of cases from 2017 to 2021 after the EV-A71 vaccines were used was 9422, and the reduction in the number of cases infected with the EV71 virus was 73.43% compared to 70.80% when the impact of the COVID-19 epidemic in 2020 was excluded. CONCLUSIONS: Since 2010, the incidence of EV71 infections has shown an obvious downward trend. All types of viruses showed significant periodicity on the 1-year scale. The periodicity of the biennial peak is mainly related to EV71 and Cox A16 before 2017 and other enteroviruses since 2018. The half-year peak cycle of HFMD was mainly caused by EV71 and Cox A6 infection. The expected incidence will be 2.76 times(include the cases of 2020) and 2.43 times(exclude the cases of 2020) higher than the actual value assuming that the measures of vaccination are not taken. EV71 vaccines are very effective and should be administered in the age window between 5 months and 5 years.

Prospects of Coffee Leaf against SARS-CoV-2 Infection.

In the current climate, many countries are in dire need of effective preventive methods to curb the Severe Acute Respiratory Syndrome Coronavirus Type 2 (SARS-CoV-2) pandemic. The purpose of this research is to screen and explore natural plant extracts that have the potential to against SARS-CoV-2 and provide alternative options for SARS-CoV-2 prevention and hand sanitizer or spray-like disinfectants. We first used Spike-ACE2 ELISA and TMPRSS2 fluorescence resonance energy transfer (FRET) assays to screen extracts from agricultural by-products from Taiwan with the potential to impede SARS-CoV-2 infection. Next, the SARS-CoV-2 pseudo-particles (Vpp) infection assay was tested to validate the effectiveness. We identified an extract from coffee leaf (Coffea Arabica), a natural plant that effectively inhibited wild-type SARS-CoV-2, and five Variants of Concern (Alpha, Beta, Gamma, Delta, and Omicron strain) from entering host cells. In an attempt to apply coffee leaf extract for hand sanitizer or spray-like disinfectants, we designed a skin-like gelatin membrane experiment. We showed that the high concentration of coffee leaf extract on the skin surface could block SARS-CoV-2 into cells more potently than 75% Ethanol, a standard disinfectant to inactivate SARS-CoV-2. Finally, LC-HRMS analysis was used to identify compounds such as caffeine, chlorogenic acid (CGA), quinic acid, and mangiferin that are associated with an anti-SARS-CoV-2 activity. Our results demonstrated that coffee leaf extract, an agricultural by-product effectively inhibits SARS-CoV-2 Vpp infection through an ACE2-dependent mechanism and may be utilized to develop products against SARS-CoV-2 infection.

A User-Centered Evaluation of a COVID-19 Intelligent Query System (COVID-IQS).

As the fight against COVID-19 continues, it is critical to discover and accumulate knowledge in scientific literature to combat the pandemic. In this work, we shared the experience in developing an intelligent query system on COVID-19 literature. We conducted a user-centered evaluation with 12 researchers in our institution and identified usability issues in four categories: distinct user needs, functionality errors, suboptimal information display, and implementation errors. Furthermore, we shared two lessons for building such a COVID-19 literature search engine. We will deploy the system and continue refining it through multiple phases of evaluation to aid in redesigning the system to accommodate different user roles as well as enhancing repository features to support collaborative information seeking. The successful implementation of the COVID-IQS can support knowledge discovery and hypothesis generation in our institution and can be shared with other institutions to make a broader impact.

Density Map-based vehicle counting in remote sensing images with limited resolution

Observing traffic flow is of great significance to contemporary urban management. Overhead images, as represented by remote sensing images, provide a major source of information about traffic flow. However, the spatial resolutions of most common high-resolution remote sensing images are often limited to 0.5 m and even below, which makes it unrealistic to count vehicles by means of widely used object detection methods. Therefore, to explore the potential of remote sensing data for studying global urban development and management, this paper introduces a density map-based vehicle counting method for remote sensing imagery with limited resolution. Density map-based models regard the vehicle counting task as estimating the density of vehicle targets in terms of pixel values. We propose an improved CNN-based network, called Congested Scene Recognition Network Minus (CSRNet—), that generates a density map of vehicles from the input remote sensing imagery. A new dataset, RSVC2021, which was generated from the public DOTA and ITCVD datasets, is also introduced for network training and testing. A benchmark on the RSVC2021 dataset is accordingly established and CSRNet— is selected as the baseline model for subsequent experiments. A set of GF-2 time series images with a resolution of 1 m taken before, during and after the COVID-19 epidemic lockdown covering Wuhan city are applied for real-world application testing. The testing results on both the RSVC2021 dataset and real satellite images confirm that, in terms of both the counting values and the visualized density maps, the proposed method achieves good performance and exhibits considerable application potential in this task. The generating codes of RSVC2021 dataset will be publicly available at https://github.com/YinongGuo/RSVC2021-Dataset.

Invariant in variants.

The coronavirus Covid-19 mutates quickly in the pandemic, leaves people struggling to verify and improve the effectiveness of the vaccine based on biochemistry. Is there any physical invariant in the variants of such kind of pathogen that could be taken advantage to ease the tensions? To this point, extensive numerical experiments based on continuity mechanics have been accomplished to discover the consistent vibration modes and the range of natural frequency of coronavirus Covid-19. Such invariant could help us in developing some flexible technique to deactivate the coronavirus, like as resonantly breaking the viral spike by ultrasound wave. The fundamental mechanisms governing such process are demonstrated via solving the coupled acoustic wave and elastic dynamic equations, after which the practical strategies are proposed to efficiently realize the technique concept.

Evolutionary Game Analysis of Co-Opetition Strategy in Energy Big Data Ecosystem under Government Intervention

This study discusses how to facilitate the barrier-free circulation of energy big data among multiple entities and how to balance the energy big data ecosystem under government supervision using dynamic game theory. First, we define the related concepts and summarize the recent studies and developments of energy big data. Second, evolutionary game theory is applied to examine the interaction mechanism of complex behaviors between power grid enterprises and third-party enterprises in the energy big data ecosystem, with and without the supervision of government. Finally, a sensitivity analysis is conducted on the main factors affecting co-opetition, such as the initial participation willingness, distribution of benefits, free-riding behavior, government funding, and punitive liquidated damages. The results show that both government supervision measures and the participants’ own will have an impact on the stable evolution of the energy big data ecosystem in the dynamic evolution process, and the effect of parameter changes on the evolution is more significant under the state of no government supervision. In addition, the effectiveness of the developed model in this work is verified by simulated analysis. The present model can provide an important reference for overall planning and efficient operation of the energy big data ecosystem.

Investigation and influencing factors about well-being level of elderly chronic patients during COVID-19 postpandemic period in Beijing.

ABSTRACT: The Corona Virus Disease 2019 (COVID-19) pandemic has huge impacts on the world, including human health and economic decline. The COVID-19 has severe infectivity, especially the elderly with chronic diseases will cause various complications after infection and accelerate the disease process. In addition, COVID-19 will also affect their mental health. Therefore, the mental health of elderly patients with chronic diseases cannot be ignored. The aim of this study was to investigate the well-being level of elderly people with chronic disease during COVID-19 postpandemic period in Beijing and analysis related influencing factors, so as to provide a basis for improving the well-being level of elderly chronic patients during the postpandemic period.Elderly patients with chronic diseases who met the inclusion criteria in 5 different administrative regions in Beijing were selected to carry out a questionnaire survey. The contents of the questionnaire included general data, the Memorial University of Newfoundland Happiness scale and the awareness situation of the COVID-19 pandemic. A total of 500 questionnaires were distributed by WeChat and 486 valid questionnaires were collected. The t test and one-way analysis of variance were used to compare Memorial University of Newfoundland Happiness scores between 2 or more groups, multiple linear regression analysis was used to conduct multiple factor analysis to explore the related factors about well-being level of elderly chronic patients.A total of 109 cases (22.43%) were evaluated high well-being level, 319 cases (65.64%) were evaluated moderate well-being level and 58 cases (11.93%) were evaluated low well-being according to the Memorial University of Newfoundland Happiness (MUNSH) scores rating. The multiple linear regression indicated that the education level, number of chronic diseases, medical expenses, frequency of children's visits, taking care of grandchildren or not, and group activity frequency significantly affected the well-being of patients with chronic diseases during COVID-19 postpandemic period in Beijing (P < .05).Most elderly patients with chronic diseases had moderate or above sense of well-being during postpandemic period, but we should still pay attention to the mental health of those elderly chronic patients with low education level, much comorbidity, more medical expenses, less visits by children, not take care of grandchildren and never participate in group activities.

Safety and immunogenicity of anti-SARS CoV-2 conjugate vaccine SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults: Phase IIb Clinical Trial (preprint)

Background: We report results of immunogenicity, safety and reactogenicity of SOBERANA 02 in a two-dose or three-dose heterologous scheme in adults in a phase IIb clinical trial. Method: This phase IIb trial was designed as parallel, multicentre, adaptive, double blind, randomized and placebo-controlled. Subjects (N=810) aged 19-80 years were randomized to receive two doses of the recombinant SARS CoV-2 receptor binding domain (RBD) conjugated to tetanus toxoid (SOBERANA 02) and a third dose of dimeric RBD (SOBERANA Plus) 28 days apart; two production batches of active ingredient of SOBERANA 02 were evaluated. Primary outcome was the percentage of seroconverted subjects with [≥]4-fold the anti-RBD IgG concentration. Secondary outcomes were safety, reactogenicity and neutralizing antibodies. Results: Seroconversion rate in vaccinees was respectively 76.3 and 96.8% after two or three doses, compared with 7.3% in placebo group. Anti-RBD IgG increased significantly after first and second dose of SOBERANA 02 respect to placebo group; and the third dose with SOBERANA Plus boosts the response compared to the second dose. Neutralizing IgG antibodies were detected against D614G and VOCs , {beta} and {delta}. Specific and functional antibodies were detected until 7-8 months after the third dose. The frequency of serious adverse events (AEs) associated with vaccination was very low (0.1%); with only one serious AE consistent with vaccination. Local pain was the most frequent AE. Conclusions: Two doses of SOBERANA 02 were well tolerated, safe an immunogenic in adults aged 19-80 years old. The heterologous combination with a third dose of SOBERANA Plus increased neutralizing antibodies, detectable 7-8 months after the third dose. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000347

Safety and Immunogenicity of anti-SARS CoV-2 vaccine SOBERANA 02 in homologous or heterologous scheme. (preprint)

Background SOBERANA 02 is a COVID19 conjugate vaccine candidate based on SARS CoV2 recombinant RBD conjugated to tetanus toxoid. SOBERANA Plus antigen is dimericRBD. Here we report safety, reactogenicity and immunogenicity from phase I and IIa clinical trials using two doses SOBERANA 02 (homologous protocol) and three doses (homologous) or heterologous (with SOBERANA Plus) protocols. Method We performed an open label, monocentric, sequential and adaptive phase I for evaluating safety, reactogenicity and exploring immunogenicity of SOBERANA 02 in two formulations (15 and 25 microg) in 40 subjects, 19 to 59 years old. Phase IIa was open label including 100 volunteers 19 to 80 years, receiving two doses of SOBERANA 02 25 microg. In both trials, half of volunteers received a third dose of SOBERANA 02, half received a heterologous dose of SOBERANA Plus 50 microg. Primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity evaluated by anti RBD IgG ELISA, molecular neutralization test of RBD:hACE2 interaction, live virus neutralization test and specific T cells response. Results The most frequent AE was local pain, other AEs had frequencies lower than 5%. No serious related AEs were reported. Phase IIa confirmed the safety results in 60 to 80 years subjects. In phase I SOBERANA 02 25 microg elicited higher immune response than SOBERANA 02 15 microg; in consequence, the higher dose progressed to phase IIa. Phase IIa results confirmed the immunogenicity of SOBERANA 02 25 microg. even in 60 to 80 age range. Two doses of SOBERANA02 25 microg elicited an immune response similar to that of the Cuban Convalescent Serum Panel; it was higher after both the homologous and heterologous third doses; the heterologous scheme showing a higher immunological response. Conclusions SOBERANA 02 was safe and immunogenic in persons aged 19 to 80 years, eliciting neutralizing antibodies and specific T cell response. Highest immune responses were obtained in the heterologous three doses protocol. Trial registry: https://rpcec.sld.cu/trials/RPCEC00000340 and https://rpcec.sld.cu/trials/RPCEC00000347

A randomized, double-blind phase I clinical trial of two recombinant dimeric RBD COVID-19 vaccine candidates: safety, reactogenicity and immunogenicity (preprint)

Background The Receptor Binding Domain (RBD) of the SARS-CoV-2 spike protein is the target for many COVID-19 vaccines. Here we report results for phase 1 clinical trial of two COVID-19 vaccine candidates based on recombinant dimeric RBD (d-RBD). Methods We performed a randomized, double-blind, phase I clinical trial in the National Centre of Toxicology in Havana. Sixty Cuban volunteers aged 19-59 years were randomized into three groups (20 subjects each): 1) FINLAY-FR-1 (50 mcg d-RBD plus outer membrane vesicles from N. meningitidis ); 2) FINLAY-FR-1A-50 mcg d-RBD (three doses); 3) FINLAY-FR-1A-25 mcg d-RDB (three doses). The FINLAY-FR-1 group was randomly divided to receive a third dose of the same vaccine candidate (homologous schedule) or of FINLAY-FR-1A-50 (heterologous schedule). The primary outcomes were safety and reactogenicity. The secondary outcome was vaccine immunogenicity. Humoral response at baseline and following each vaccination was evaluated using live-virus neutralization test, anti-RBD IgG ELISA and in-vitro neutralization test of RBD:hACE2 interaction. Results Most adverse events were of mild intensity (63.5%), solicited (58.8%), and local (61.8%); 69.4% with causal association with vaccination. Serious adverse events were not found. The FINLAY-FR-1 group reported more adverse events than the other two groups. After the third dose, anti-RBD seroconversion was 100%, 94.4% and 90% for the FINLAY-FR-1, FINLAY-FR-1A-50 and FINLAY-FR-1A-25 respectively. The in-vitro inhibition of RBD:hACE2 interaction increased after the second dose in all formulations. The geometric mean neutralizing titres after the third dose rose significantly in the group vaccinated with FINLAY-FR-1 with respect to the other formulations and the COVID-19 Convalescent Serum Panel. No differences were found between FINLAY-FR-1 homologous or heterologous schedules. Conclusions Vaccine candidates were safe and immunogenic, and induced live-virus neutralizing antibodies against SARS-CoV-2. The highest values were obtained when outer membrane vesicles were used as adjuvant. Trial registry https://rpcec.sld.cu/en/trials/RPCEC00000338-En