Peimine inhibits variants of SARS‐CoV‐2 cell entry via blocking the interaction between viral spike protein and ACE2

Coronavirus disease 2019 (COVID‐19) is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Several vaccines against SARS‐CoV‐2 have been approved;however, variants of concern (VOCs) can evade vaccine protection. Therefore, developing small compound drugs that directly block the interaction between the viral spike glycoprotein and ACE2 is urgently needed to provide a complementary or alternative treatment for COVID‐19 patients. We developed a viral infection assay to screen a library of approximately 126 small molecules and showed that peimine inhibits VOCs viral infections. In addition, a fluorescence resonance energy transfer (FRET) assay showed that peimine suppresses the interaction of spike and ACE2. Molecular docking analysis revealed that peimine exhibits a higher binding affinity for variant spike proteins and is able to form hydrogen bonds with N501Y in the spike protein. These results suggest that peimine, a compound isolated from Fritillaria, may be a potent inhibitor of SARS‐CoV‐2 variant infection. PRACTICAL APPLICATIONS: In this study, we identified a naturally derived compound of peimine, a major bioactive alkaloid extracted from Fritillaria, that could inhibit SARS‐CoV‐2 variants of concern (VOCs) viral infection in 293T/ACE2 and Calu‐3 lung cells. In addition, peimine blocks viral entry through interruption of spike and ACE2 interaction. Moreover, molecular docking analysis demonstrates that peimine has a higher binding affinity on N501Y in the spike protein. Furthermore, we found that Fritillaria significantly inhibits SARS‐CoV‐2 viral infection. These results suggested that peimine and Fritillaria could be a potential functional drug and food for COVID‐19 patients.

Exploring the role of Xingren on COVID‐19 based on network pharmacology and molecular docking

Since the outbreak of novel Coronavirus Pneumonia 2019 (COVID‐19), the role of Almonds (Xingren) in the protection and treatment of COVID‐19 is not clear. Network pharmacology and molecular docking were used to explore the potential mechanism and potential key targets of Xingren on COVID‐19. A total of nine common targets between them were obtained, and these targets were involved in multiple related processes of GO and KEGG pathway enrichment analysis. Molecular docking showed that licochalcone B has the best binding energy (−9.33 kJ·mol⁻¹) to PTGS2. They are maybe the important ingredient and key potential target. Its possible mechanism is to intervene anxiety disorder in the process of disease development, such as regulation of blood pressure, reactive oxygen species metabolic process, leishmaniasis peroxisome, and IL‐17 signaling pathway. PRACTICAL APPLICATIONS: Xingren is a traditional Chinese medicine that has been used and developed in China for many years. It contains a variety of active ingredients and also has the functions of relieving cough, relieving asthma, enhancing human immunity, delaying aging, regulating blood lipids, nourishing brain, and improving intelligence. In this article, the possible mechanisms of action and important targets of Xingren in the prevention and treatment of COVID‐19 were discussed through network pharmacology and molecular docking. We also found that active ingredient licochalcone B and the potential target PTGS2 are worthy of further research and analysis. At the same time, the study also provides a theoretical basis and reference for the prevention and treatment of COVID‐19 and the development of new drugs.

Repurposing CRISPR/Cas to Discover SARS-CoV-2 Detecting and Neutralizing Aptamers.

RNA aptamers provide useful biological probes and therapeutic agents. New methodologies to screen RNA aptamers will be valuable by complementing the traditional Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Meanwhile, repurposing clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated systems (Cas) has expanded their utility far beyond their native nuclease function. Here, CRISmers, a CRISPR/Cas-based novel screening system for RNA aptamers based on binding to a chosen protein of interest in a cellular context, is presented. Using CRISmers, aptamers are identified specifically targeting the receptor binding domain (RBD) of the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two aptamer leads enable sensitive detection and potent neutralization of SARS-CoV-2 Delta and Omicron variants in vitro. Intranasal administration of one aptamer, further modified with 2'-fluoro pyrimidines (2'-F), 2'-O-methyl purines (2'-O), and conjugation with both cholesterol and polyethylene glycol of 40 kDa (PEG40K), achieves effective prophylactic and therapeutic antiviral activity against live Omicron BA.2 variants in vivo. The study concludes by demonstrating the robustness, consistency, and potential broad utility of CRISmers using two newly identified aptamers but switching CRISPR, selection marker, and host species.

Oxalic acid blocked the binding of spike protein from SARS-CoV-2 Delta (B.1.617.2) and Omicron (B.1.1.529) variants to human angiotensin-converting enzymes 2.

An epidemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. Moreover, the emergence of SARS-CoV-2 variants of concern, such as Delta and Omicron, has seriously challenged the application of current therapeutics including vaccination and drugs. Relying on interaction of spike protein with receptor angiotensin-converting enzymes 2 (ACE2), SARS-CoV-2 successfully invades to the host cells, which indicates a strategy that identification of small-molecular compounds to block the entry is of great significance for COVID-19 prevention. Our study evaluated the potential efficacy of natural compound oxalic acid (OA) as an inhibitory agent against SARS-CoV-2 invasion, particular on the interaction of the receptor binding domain (RBD) of Delta and Omicron variants to ACE2. By employing a competitive binding assay in vitro, OA significantly blocked the binding of RBDs from Delta B.1.617.2 and Omicron B.1.1.529 to ACE2, but has no effect on the wide-type SARS-CoV-2 strain. Furthermore, OA inhibited the entries of Delta and Omicron pseudovirus into ACE2 high expressing-HEK293T cells. By surface plasmon resonance (SPR) assay, the direct bindings of OA to RBD and ACE2 were analyzed and OA had both affinities with RBDs of B.1.617.2 and B.1.1.529 and with ACE2. Molecular docking predicted the binding sites on the RBD-ACE2 complex and it showed similar binding abilities to both complex of variant Delta or Omicron RBD and ACE2. In conclusion, we provided a promising novel small-molecule compound OA as an antiviral candidate by blocking the cellular entries of SARS-CoV-2 variants.

Determination of 25 quaternary ammonium compounds in sludge by liquid chromatography-mass spectrometry.

With the pandemic of COVID-19, the application of quaternary ammonium compounds (QACs), which can be used in SARS-CoV-2 disinfection products, has increased substantially. QACs cumulated in sewer system are ultimately deposited and enriched in sludge. QACs in the environment can adversely affect human health and the environment. In this study, a liquid chromatography-mass spectrometry method was established for the simultaneous determination of 25 QACs in sludge samples. Ultrasonic extraction and filtration of the samples was performed using a 50 mM hydrochloric acid-methanol solution. The samples were separated by liquid chromatography and detected in multiple reaction monitoring mode. The matrix effects of the sludge on the 25 QACs ranged from - 25.5% to 7.2%. All substances showed good linearity in the range of 0.5-100 ng/mL, with all determination coefficients (R2) greater than 0.999. The method detection limits (MDLs) were 9.0 ng/g for alkyltrimethylammonium chloride (ATMAC), 3.0 ng/g for benzylalkyldimethylammonium chloride (BAC), and 3.0 ng/g for dialkyldimethylammonium chloride (DADMAC). The spiked recovery rates were in the range of 74-107%, while the relative standard deviations were in the range of 0.8-20.6%. Considering its sensitivity, accuracy, and easy operation, the proposed method in this study was used to determine 22 sludge samples collected from a comprehensive wastewater treatment plant. The results showed that the concentrations of ΣATMACs, ΣBACs, and ΣDADMACs were 19.684, 3.199, and 8.344 µg/g, respectively. The main components included ATMAC-C16, ATMAC-C18, ATMAC-C20, ATMAC-C22, BAC-C12, and DADMAC-C18:C18, with concentrations exceeding 1.0 µg/g. The concentration relationships of different components in the congeners showed that some components were of similar origin.

Association between meteorological factors and COVID-19 transmission in low- and middle-income countries: A time-stratified case-crossover study.

BACKGROUND: Evidence is limited regarding the association between meteorological factors and COVID-19 transmission in low- and middle-income countries (LMICs). OBJECTIVE: To investigate the independent and interactive effects of temperature, relative humidity (RH), and ultraviolet (UV) radiation on the spread of COVID-19 in LMICs. METHODS: We collected daily data on COVID-19 confirmed cases, meteorological factors and non-pharmaceutical interventions (NPIs) in 2143 city- and district-level sites from 6 LMICs during 2020. We applied a time-stratified case-crossover design with distributed lag nonlinear model to evaluate the independent and interactive effects of meteorological factors on COVID-19 transmission after controlling NPIs. We generated an overall estimate through pooling site-specific relative risks (RR) using a multivariate meta-regression model. RESULTS: There was a positive, non-linear, association between temperature and COVID-19 confirmed cases in all study sites, while RH and UV showed negative non-linear associations. RR of the 90th percentile temperature (28.1 °C) was 1.14 [95% confidence interval (CI): 1.02, 1.28] compared with the 50th percentile temperature (24.4 °C). RR of the10th percentile UV was 1.41 (95% CI: 1.29, 1.54). High temperature and high RH were associated with increased risks in temperate climate but decreased risks in tropical climate, while UV exhibited a consistent, negative association across climate zones. Temperature, RH, and UV interacted to affect COVID-19 transmission. Temperature and RH also showed higher risks in low NPIs sites. CONCLUSION: Temperature, RH, and UV appeared to independently and interactively affect the transmission of COVID-19 in LMICs but such associations varied with climate zones. Our results suggest that more attention should be paid to meteorological variation when the transmission of COVID-19 is still rampant in LMICs.

Nature-inspired catalytic asymmetric rearrangement of cyclopropylcarbinyl cation.

In nature, cyclopropylcarbinyl cation is often involved in cationic cascade reactions catalyzed by natural enzymes to produce a great number of structurally diverse natural substances. However, mimicking this natural process with artificial organic catalysts remains a daunting challenge in synthetic chemistry. We report a small molecule-catalyzed asymmetric rearrangement of cyclopropylcarbinyl cations, leading to a series of chiral homoallylic sulfide products with good to excellent yields and enantioselectivities (up to 99% enantiomeric excess). In the presence of a chiral SPINOL-derived N-triflyl phosphoramide catalyst, the dehydration of prochiral cyclopropylcarbinols occurs rapidly to generate symmetrical cyclopropylcarbinyl cations, which are subsequently trapped by thione-containing nucleophiles. A subgram-scale experiment and multiple downstream transformations of the sulfide products are further pursued to demonstrate the synthetic utility. Notably, a few heteroaromatic sulfone derivatives could serve as "covalent warhead" in the enzymatic inhibition of severe acute respiratory syndrome coronavirus 2 main protease.

Risk assessment of retinal vascular occlusion after COVID-19 vaccination.

Coronavirus disease 2019 (COVID-19) vaccines are associated with several ocular manifestations. Emerging evidence has been reported; however, the causality between the two is debatable. We aimed to investigate the risk of retinal vascular occlusion after COVID-19 vaccination. This retrospective cohort study used the TriNetX global network and included individuals vaccinated with COVID-19 vaccines between January 2020 and December 2022. We excluded individuals with a history of retinal vascular occlusion or those who used any systemic medication that could potentially affect blood coagulation prior to vaccination. To compare the risk of retinal vascular occlusion, we employed multivariable-adjusted Cox proportional hazards models after performing a 1:1 propensity score matching between the vaccinated and unvaccinated cohorts. Individuals with COVID-19 vaccination had a higher risk of all forms of retinal vascular occlusion in 2 years after vaccination, with an overall hazard ratio of 2.19 (95% confidence interval 2.00-2.39). The cumulative incidence of retinal vascular occlusion was significantly higher in the vaccinated cohort compared to the unvaccinated cohort, 2 years and 12 weeks after vaccination. The risk of retinal vascular occlusion significantly increased during the first 2 weeks after vaccination and persisted for 12 weeks. Additionally, individuals with first and second dose of BNT162b2 and mRNA-1273 had significantly increased risk of retinal vascular occlusion 2 years following vaccination, while no disparity was detected between brand and dose of vaccines. This large multicenter study strengthens the findings of previous cases. Retinal vascular occlusion may not be a coincidental finding after COVID-19 vaccination.

Luteolin inhibits spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) binding to angiotensin-converting enzyme 2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a respiratory illness that poses a serious threat to global public health. In an essential step during infection, SARS-CoV-2 uses the receptor-binding domain (RBD) of the spike (S) protein to engage with angiotensin-converting enzyme 2 (ACE2) in host cells. Chinese herbal medicines and their active components exhibit antiviral activity, with luteolin being a flavonoid that can significantly inhibit SARS-CoV infection. However, whether it can block the interaction between the S-protein RBD of SARS-CoV-2 and ACE2 has not yet been elucidated. Here, we investigated the effects of luteolin on the binding of the S-protein RBD to ACE2. By employing a competitive binding assay in vitro, we found that luteolin significantly blocked the binding of S-protein RBD to ACE2 with IC50 values of 0.61 mM, which was confirmed by the neutralized infection with SARS-CoV-2 pseudovirus in vivo. A surface plasmon resonance-based competition assay revealed that luteolin significantly affects the binding of the S-protein RBD to the ACE2 receptor. Molecular docking was performed to predict the binding sites of luteolin to the S-protein RBD-ACE2 complex. The active binding sites were defined based on published literature, and we found that luteolin might interfere with the mixture at residues including LYS353, ASP30, and TYR83 in the cellular ACE2 receptor and GLY496, GLN498, TYR505, LEU455, GLN493, and GLU484 in the S-protein RBD. These residues may together form attractive charges and destroy the stable interaction of S-protein RBD-ACE2. Luteolin also inhibits SARS-CoV-2 spike protein-induced platelet spreading, thereby inhibiting the binding of the spike protein to ACE2. Our results are the first to provide evidence that luteolin is an anti-SARS-CoV-2 agent associated with interference between viral S-protein RBD-ACE2 interactions.

COVID-19 risk perception and tourist satisfaction: A mixed-method study of the roles of destination image and self-protection behavior.

This study aimed to examine the effects of COVID-19 risk perception on negative destination image and self-protection behavior, and the resultant effects on tourist satisfaction. Hence, this study applied a continuous interpretive mixed-method design combining quantitative and qualitative analyses. A quantitative survey (n = 486) in the cities of Ningbo, Huangshan, and Chengdu, China, and 19 qualitative interviews were conducted online. The results of the quantitative study show that: (1) Risk perception and negative destination image are antecedent variables influencing tourist satisfaction, and (2) there are significant positive correlations between risk perception and negative destination image, risk perception and tourist self-protection behavior, and negative destination image and tourist self-protection behavior. Moreover, (3) negative destination image had a partial mediating effect between risk perception and satisfaction. Furthermore, to supplement the research data and expand the quantitative findings, this study further examined whether the above variables are related to tourist satisfaction, through in-depth interviews with tourists. The findings showed that COVID-19 risk perception, negative destination image, and self-protection behavior all affect tourist satisfaction. The findings provide valuable crisis management suggestions for the government and should contribute to the efforts of tourist destinations to build a healthy and safe image, thereby contributing to the sustainable development of tourism industries in the post-epidemic era.

Lessons from the stigma of COVID-19 survivors: A Marxist criticism appraisal.

Stigma refers to devalued stereotypes that create barriers for stigmatized individuals. During the COVID-19 pandemic, the stigmatization of survivors worsened existing inequalities and triggered mass hysteria. The paper delves into the stigmatization experienced by COVID-19 survivors and the role of Marxist criticism in analyzing this issue. The main findings from the empiricist tradition approach suggest that the perception of COVID-19 stigma is higher among those who are older, belong to ethnic minorities, lack social support, have manual occupations, and possess lower levels of education. The proposed destigmatization pathways include psychological counseling services, social support, and health education. Employing a Marxist perspective can aid in illuminating how economic practices and material conditions influence prevalent ideologies related to stigma. The stigmatization of COVID-19 survivors may be perceived as a consequence of social power inequality, although the current emphasis on individual characteristics as triggers for stigma may neglect the wider systemic forces in operation. Thus, it's crucial to establish improved social care policies to combat exploitation and oppression due to power imbalances. The ultimate objective of such an examination is to identify effective approaches to tackle and eradicate stigma regarding health-related concerns. An interdisciplinary approach integrating a pluralistic perspective would benefit investigating how social systems and individual attributes contribute to the exacerbation of social inequality and stigmatization.

Impacts of androgen deprivation therapy on the risks and outcomes of SARS-CoV-2 infection in patients with prostate cancer.

Studies have investigated the effects of androgen deprivation therapy (ADT) use on the incidence and clinical outcomes of coronavirus disease 2019 (COVID-19); however, the results have been inconsistent. We searched the PubMed, Medline, Cochrane, Scopus, and Web of Science databases from inception to March 2022; 13 studies covering 84 003 prostate cancer (PCa) patients with or without ADT met the eligibility criteria and were included in the meta-analysis. We calculated the pooled risk ratios (RRs) with 95% confidence intervals (CIs) to explore the association between ADT use and the infection risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and severity of COVID-19. After synthesizing the evidence, the pooled RR in the SARS-CoV-2 positive group was equal to 1.17, and the SARS-CoV-2 positive risk in PCa patients using ADT was not significantly different from that in those not using ADT (P = 0.544). Moreover, no significant results concerning the beneficial effect of ADT on the rate of intensive care unit admission (RR = 1.04, P = 0.872) or death risk (RR = 1.23, P = 0.53) were found. However, PCa patients with a history of ADT use had a markedly higher COVID-19 hospitalization rate (RR = 1.31, P = 0.015) than those with no history of ADT use. These findings indicate that ADT use by PCa patients is associated with a high risk of hospitalization during infection with SARS-CoV-2. A large number of high quality studies are needed to confirm these results.

Flare and change in disease activity among patients with stable rheumatoid arthritis following coronavirus disease 2019 vaccination: a prospective Chinese cohort study.

BACKGROUND: Vaccination has been shown effective in controlling the global coronavirus disease 2019 (COVID-19) pandemic and reducing severe cases. This study was to assess the flare and change in disease activity after COVID-19 vaccination in patients with stable rheumatoid arthritis (RA). METHODS: A prospective cohort of RA patients in remission or with low disease activity was divided into a vaccination group and a non-vaccination group based on their COVID-19 vaccination status. Each of them was examined every 3 to 6 months. In the vaccination group, disease activity was compared before and after vaccination. The rates of flare defined as disease activity scores based on 28-joint count (DAS28) >3.2 with ΔDAS28 ≥0.6 were compared between vaccination and non-vaccination groups. RESULTS: A total of 202 eligible RA patients were enrolled. Of these, 98 patients received no vaccine shot (non-vaccination group), and 104 patients received two doses of vaccine (vaccination group). The median time interval from pre-vaccination visit to the first immunization and from the second dose of vaccine to post-vaccination visit was 67 days and 83 days, respectively. The disease activity scores at pre-vaccination and post-vaccination visits in the vaccination group patients were similar. At enrollment, gender, RA disease course, seropositivity, and disease activity were comparable across the two groups. Flare was observed in five (4.8%) of the vaccination group patients and nine (9.2%) of the non-vaccination group patients at post-vaccination assessment (P = 0.221). In terms of safety, 29 (27.9%) patients experienced adverse events (AEs) after vaccination. No serious AEs occurred. CONCLUSIONS: COVID-19 vaccinations had no significant effect on disease activity or risk of flare in RA patients in remission or with low disease activity. Patients with stable RA should be encouraged to receive the COVID-19 vaccination.

Factors influencing loneliness among older people using homecare services during the COVID-19 pandemic.

BACKGROUND: Elderly homecare service users may reduce their level of social participation and interpersonal interactions due to physiological loss, which may lead to loneliness and depression over the years. However, there is a lack of research on loneliness among older people who use homecare services. The purpose of this study was to examine the factors influencing loneliness among older people using homecare services. METHODS: This is a longitudinal study conducted in communities in Central Taiwan, and data were collected using a structured questionnaire. The questionnaire was first administered as a pre-test to obtain baseline information about the participants, and the same questionnaire was administered as a post-test after 6 months to follow-up. The pre- and post-test questionnaires included five sections, that is, participant demographics, Brief Symptom Rating Scale, Interpersonal Interaction Scale (IIS), Frenchay Activities Index, and UCLA Loneliness Scale (UCLA). RESULTS: A total of 178 participants were recruited in this study. Results indicated that gender, whether participants eat alone or with others at dinner, social media use, perceived economic status, and IIS score were significantly correlated with the loneliness score on the UCLA. Furthermore, there was a significant increase in the loneliness score among male participants in the low loneliness group from baseline to 6 months follow-up. CONCLUSIONS: Gender, presence of others at dinner, social media use, perceived economic status, and interpersonal interaction skills are significant factors that influence loneliness among older people using homecare services. Men tend to experience higher levels of loneliness over time.

Uncovering the pharmacological mechanisms of Zizhu ointment against diabetic ulcer by integrating network analysis and experimental evaluation in vivo and in vitro.

Diabetic ulcer (DU) has been recognized as one of the most prevalent and serious complications of diabetes. However, the clinical efficacy of standard treatments for DU remains poor. Traditional Chinese medicine (TCM) shows a positive therapeutic effect on DU. Specifically, Zizhu ointment (ZZO) has been widely used to treat DU in long-term clinical practice, but the exact mechanism by which it promotes DU wound healing remains unknown. In this study, network analysis and high-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS) were conducted to identify the active compounds of ZZO. We detected isovalerylshikonin (ISO), mandenol, daidzein, kaempferol, and formononetin in both network analysis and UPLC-HRMS. Moreover, ZZO could ameliorate DU by regulating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) and inflammation signaling pathways, according to the results of KEGG analysis. We established a DU mouse model with a high-fat diet and streptozotocin injection in vivo to evaluate the network analysis result. The experimental results showed that ZZO could inhibit inflammation, remodel fibrous tissue, and promote angiogenesis in the DU area, facilitating wound healing in DU mice. Moreover, the PI3K/AKT signaling pathway was indeed activated by ZZO treatment, promoting macrophage M2 polarization. In addition, we used molecular docking technology to evaluate the binding sites between ZZO and the PI3K/AKT pathway. The results showed that ISO has a good binding interaction with AKT. Moreover, ISO promoted M2 polarization in macrophages in a dose-dependent manner in vitro. Our study found that ZZO could promote DU wound healing by inhibiting inflammation, which was achieved by macrophage M2 polarization through activating the PI3K/AKT pathway. Further studies have demonstrated that ISO plays major role in the above process. These findings provide a theoretical basis for further preclinical evaluation and lay a foundation for nano-gel compound treatment with ZZO.

A threshold effect of COVID-19 risk on oil price returns.

Using U.S. data, we investigate how the COVID-19 pandemic influences oil price returns in an asset pricing framework. Unlike earlier studies, we consider a threshold model to allow for the possibility that COVID-19 risk may not play a role until it reaches a certain level. Based on WTI crude oil spot price data from January 2020 to December 2021, our findings show that oil returns significantly decline with the daily number of COVID-19 deaths but only if the daily death toll exceeds approximately 2100. In addition, a more severe COVID-19 pandemic can substantially increase the exposure of oil returns to various systematic risk factors, which has not been documented in previous literature.

Adjustment of Immunosuppressants to Facilitate Anti-COVID-19 Antibody Production after mRNA Vaccination in Liver Transplant Recipients.

Liver transplant recipients are immunocompromised and have low immunogenicity to produce antibodies in anti-COVID-19 vaccination. Whether immunosuppressant adjustment could facilitate anti-COVID-19 antibody production in anti-COVID-19 mRNA vaccination is undetermined. Our patients were informed to temporarily suspend mycophenolate mofetil (MMF) or everolimus (EVR) for 2 weeks during both the 1st and 2nd doses of Moderna mRNA-1273 vaccine. A total of 183 recipients receiving two doses of Moderna mRNA-1273 vaccine were enrolled and grouped into tacrolimus monotherapy (MT, n = 41), and dual therapy with non-adjustment (NA, n = 23), single suspension (SS, n = 19) and double suspension (DS, n = 100) of MMF/EVR in two-dose mRNA vaccination. A total of 155 (84.7%) patients had a humoral response to vaccines in this study. The humoral response rates were 60.9%, 89.5%, 91.0% and 80.5% in NA, SS, DS, and MT group patients, respectively (p = 0.003). Multivariate analysis showed that favorable factors for humoral response were temporary suspension of MMF/EVR and monotherapy, and unfavorable factors were deceased donor liver transplantation, WBC count < 4000/uL, lymphocyte < 20% and tacrolimus trough level ≥ 6.8 ng/mL. In conclusion, temporary two-week suspension of anti-proliferation immunosuppressants could create a window to facilitate antibody production during anti-COVID-19 mRNA vaccination. This concept may be applied to other vaccinations in liver transplant recipients.