ABSTRACT
Background: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is recommended for patients with chronic liver diseases as the vaccine can prevent and/or reduce the severity of SARS-CoV-2 infection. However, we have little information on the often-reported liver-related adverse events (LrAEs) caused by the mRNA vaccine. Methods: We retrospectively investigated the frequency and details of severe LrAEs and changes in liver function tests in patients with chronic liver diseases. Results: Among 431 patients with chronic liver diseases, 416 (96.5%) had received the SARS-CoV-2 vaccine ≥ 2 times. Among the 345 patients included in the analysis, 6 (1.7%) had severe LrAEs;3 ascites, 2 increases in transaminases, and 1 an increase in total bilirubin. Multivariate analysis demonstrated that cirrhosis and autoimmune disease were risk factors for severe LrAEs. In contrast, the liver function reserve assessed by the Child-Pugh and ALBI scores did not markedly change after vaccination in patients with cirrhosis and/or autoimmune diseases despite a small increase in transaminase levels. Conclusion: SARS-CoV-2 mRNA vaccines, which were used in most of our patients, are safe in patients with chronic liver diseases, but the frequency of severe LrAEs is slightly increased in patients with cirrhosis and/or autoimmune diseases.
ABSTRACT
As long as the coronavirus disease 2019 (COVID-19) pandemic continues, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with altered antigenicity will emerge. The development of vaccines that elicit robust, broad, and durable protection against SARS-CoV-2 variants is urgently needed. We have developed a vaccine (rDIs-S) consisting of the attenuated vaccinia virus DIs strain platform carrying the SARS-CoV-2 S gene. rDIs-S induced neutralizing antibody and T-lymphocyte responses in cynomolgus macaques and human angiotensin converting enzyme 2 (hACE2) transgenic mice, and showed broad protection against SARS-CoV-2 isolates ranging from the early-pandemic strain (WK-521) to the recent Omicron BA.1 variant (TY38-839). Using a tandem mass tag (TMT) -based quantitative proteomic analysis of lung homogenates from hACE2 transgenic mice, we found that, among mice subjected to challenge infection with WK-521, vaccination with rDIs-S prevented protein expression related to the severe pathogenic effects of SARS-CoV-2 infection (tissue destruction, inflammation, coagulation, fibrosis, and angiogenesis) and restored protein expression related to immune responses (antigen presentation and cellular response to stress). Furthermore, long-term studies in mice showed that rDIs-S maintains S protein-specific antibody titers for at least 6 months after a 1st vaccination. Thus, rDIs-S appears to provide broad and durable protective immunity against SARS-CoV-2, including current and possibly future variants.
Subject(s)
Coronavirus Infections , Fibrosis , COVID-19 , Inflammation , Blood Coagulation Disorders, InheritedABSTRACT
We assessed whether the coronavirus disease 2019 (COVID-19) pandemic-related disruptions impacted the physical fitness of adolescent athletes. We reviewed the age-, sex-, and sports category-matched data of 78 adolescent athletes (divided into two groups: 2019 group = 37;2020 group = 41) from the clinical database and investigated their height, weight, body composition, flexibility muscle strength, and jump height. We also provided questionnaires to the teams' coaches to collect data on the duration of practice suspension due to the COVID-19 pandemic;the practice hours per week in August 2019, immediately after the suspension ended, and in August 2020;and the guidelines for the players after resuming their practice. For data analyses, we considered p ≤0.05 as statistically significant. The strength of knee flexion and extension was significantly lower in the 2020 group than in the 2019 group;there was no difference in the other physical fitness parameters. The practice duration in August 2019 and August 2020 was the same. COVID-19-related interruptions did not alter the athletes' jump height, upper-limb strength, and flexibility but reduced lower-limb muscle strength. We recommend that basic strength training protocols be followed to prevent sports-related injuries after such unexpected practice interruptions.
ABSTRACT
To analyze the molecular pathogenesis of SARS-CoV-2, a small animal model such as mice is needed: human ACE2, the receptor of SARS-CoV-2, needs to be expressed in the respiratory tract of mice. We conferred SARS-CoV-2 susceptibility in mice by using an adenoviral vector expressing hACE2 driven by an EF1α promoter with a leftward orientation. In this model, severe pneumonia like human COVID-19 was observed in SARS-CoV-2-infected mice, which was confirmed by dramatic infiltration of inflammatory cells in the lung with efficient viral replication. An early circulating strain of SARS-CoV-2 caused the most severe weight loss when compared to SARS-CoV-2 variants of concern, although histopathological findings, viral replication, and cytokine expression characteristics were comparable. We found that a distinct proteome of an early circulating strain infected lung characterized by elevated complement activation and blood coagulation, which were mild in other variants, can contribute to disease severity. Unraveling the specificity of early circulating SARS-CoV-2 strains is important in elucidating the origin of the pandemic.
Subject(s)
COVID-19ABSTRACT
Abstract It is still undetermined if the main infection route of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that leads to coronavirus disease 2019 (COVID-19), is infection through droplet, contact, or airborne transmission. However, confined spaces with poor ventilation are cited as a risk factor for group outbreaks, and there is growing interest in the effects of intervention through the appropriate operation of air-conditioning and sanitary equipment to reduce the risk of airborne transmission. This study first offers an outline of the characteristics of the novel coronavirus disease and the cluster outbreak case reports that have been clarified until now. Subsequently, we describe the appropriate operating conditions for building equipment that are effective in reducing the risk of infection and also highlight specificities for each building use based on the guidance provided by healthcare institutions and with reference to the standard recommendations by Western academic societies related to building equipment.
ABSTRACT
In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against coronavirus disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the treatment of this disease, and several approved drugs such as lopinavir have been evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication of SARS-CoV-2. The effective concentrations for 50% and 90% inhibition (EC50 and EC90) of nelfinavir were 1.13 {micro}M and 1.76 {micro}M respectively, the lowest of the nine HIV-1 protease inhibitors including lopinavir. The trough and peak serum concentrations of nelfinavir were three to six times higher than EC50 of this drug. These results suggest that nelfinavir is a potential candidate drug for the treatment of COVID-19 and should be assessed in patients with COVID-19.