Increased sTREM-1 plasma concentrations are associated with poor clinical outcomes in patients with COVID-19

Patients with sepsis display increased concentrations of sTREM-1 (soluble Triggering Receptor Expressed on Myeloid cells 1), and a phase II clinical trial focusing on TREM-1 modulation is ongoing. We investigated whether sTREM-1 circulating concentrations are associated with the outcome of patients with coronavirus disease 2019 (COVID-19) to assess the role of this pathway in COVID-19. This observational study was performed in two independent cohorts of patients with COVID-19. Plasma concentrations of sTREM-1 were assessed after ICU admission (pilot cohort) or after COVID-19 diagnosis (validation cohort). Routine laboratory and clinical parameters were collected from electronic patient files. Results showed sTREM-1 plasma concentrations were significantly elevated in patients with COVID-19 (161 [129–196] pg/ml) compared to healthy controls (104 [75–124] pg/ml; P<0.001). Patients with severe COVID-19 needing ICU admission displayed even higher sTREM-1 concentrations compared to less severely ill COVID-19 patients receiving clinical ward-based care (235 [176–319] pg/ml and 195 [139–283] pg/ml, respectively, P = 0.017). In addition, higher sTREM-1 plasma concentrations were observed in patients who did not survive the infection (326 [207–445] pg/ml) compared to survivors (199 [142–278] pg/ml, P<0.001). Survival analyses indicated that patients with higher sTREM-1 concentrations are at higher risk for death (hazard ratio = 3.3, 95%CI: 1.4–7.8). In conclusion, plasma sTREM-1 concentrations are elevated in patients with COVID-19, relate to disease severity, and discriminate between survivors and non-survivors. This suggests that the TREM-1 pathway is involved in the inflammatory reaction and the disease course of COVID-19, and therefore may be considered as a therapeutic target in severely ill patients with COVID-19.     

Neuroinflammation and COVID-19

Coronavirus disease 2019 (COVID-19) has caused a historic pandemic of respiratory disease. COVID-19 also causes acute and post-acute neurological symptoms, which range from mild, such as headaches, to severe, including hemorrhages. Current evidence suggests that there is no widespread infection of the central nervous system (CNS) by SARS-CoV-2, thus what is causing COVID-19 neurological disease? Here, we review potential immunological mechanisms driving neurological disease in COVID-19 patients. We begin by discussing the implications of imbalanced peripheral immunity on CNS function. Next, we examine the evidence for dysregulation of the blood-brain barrier during SARS-CoV-2 infection. Last, we discuss the role myeloid cells may play in promoting COVID-19 neurological disease. Combined, we highlight the role of innate immunity in COVID-19 neuroinflammation and suggest areas for future research.     

Of mitochondrion and COVID-19

COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19’s signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19.     

Insight into the biological impact of COVID-19 and its vaccines on human health

COVID-19 (coronavirus disease-2019) is a contagious illness that has been declared a global epidemic by the World Health Organization (WHO). The coronavirus causes diseases ranging in severity from the common cold to severe respiratory diseases and death. Coronavirus primarily affects blood pressure by attaching to the angiotensin converting enzyme 2 (ACE 2) receptor. This virus has an impact on multiple organ systems, including the central nervous system, immune system, cardiovascular system, peripheral nervous system, gastrointestinal tract, endocrine system, urinary system, skin, and pregnancy. For the prevention of COVID-19, various vaccines such as viral-like particle vaccines, entire inactivated virus vaccines, viral vector vaccines, live attenuated virus vaccines, subunit vaccines, RNA vaccines, and DNA vaccines are now available. Some of the COVID-19 vaccines are reported to cause a variety of adverse effects that range from mild to severe in nature. SARS-CoV-2 replication is controlled by the RNA-Dependent RNA-Polymerase enzyme (RdRp). The availability of FDA-approved anti-RdRp drugs (Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir) as potent drugs against SARS-CoV-2 that tightly bind to its RdRp may aid in the treatment of patients and reduce the risk of the mysterious new form of COVID-19 viral infection. RdRp inhibitors, such as remdesivir (an anti-Ebola virus experimental drug) and favipiravir (an anti-influenza drug), inhibit RdRp and thus slow the progression of COVID-19 and associated clinical symptoms, as well as significantly shorten recovery time. Molnupiravir, an orally active RdRp inhibitor and noval broad spectrum antiviral agent, is an isopropyl pro-drug of EIDD-1931 for emergency use. Galidesivir's in vitro and in vivo activities are limited to RNA of human public health concern. Top seeds for antiviral treatments with high potential to combat the SARS-CoV-2 strain include guanosine derivatives (IDX-184), setrobuvir, and YAK. The goal of this review is to compile scattered information on available COVID-19 vaccines and other treatments for protecting the human body from their harmful effects and to provide options for making better choices in a timely manner.     

新型冠状病毒疫苗研究策略分析

新型冠状病毒(SARS-CoV-2)是一种可引起人新型冠状病毒肺炎(COVID-19)的新发呼吸道病原体,与重症急性呼吸道综合症冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)同属于β-冠状病毒,具有较高的传染性和一定的致死率。2019年12月在我国武汉被发现,随后蔓延到我国大部分省份,给我国人民健康和经济发展造成巨大损失。疫苗接种是预防和控制传染病的常规和有效手段,国内外多个机构已启动COVID-19疫苗研究工作。文中基于SARS和MERS疫苗研究的经验和教训,对COVID-19疫苗的研究策略和需要注意的关键问题进行了阐述,为相关研究人员提供参考。     

Platforms for Personalized Polytherapeutics Discovery in COVID-19

The COVID-19 pandemic entered its third and most intense to date wave of infections in November 2020. This perspective article describes how combination therapies (polytherapeutics) are a needed focus for helping battle the severity of complications from SARS-CoV-2 infection. It outlines the types of systems that are needed for fast and efficient combinatorial assessment of therapeutic candidates. Proposed are micro-physiological systems using human iPSC as a format for tissue-specific modeling of infection, the use of gene-humanized zebrafish and C. elegans for combinatorial drug screens due to the animals being addressable in liquid multi-well formats, and the use of engineered pseudo-typing systems to safely model infection in the transgenic animals and engineered tissue systems.