Tissue injury and leukocyte changes in post-acute sequelae of SARS-CoV-2: review of 2833 post-acute patient outcomes per immune dysregulation and microbial translocation in long COVID.

A significant number of persons with coronavirus disease 2019 (COVID-19) experience persistent, recurrent, or new symptoms several months after the acute stage of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. This phenomenon, termed post-acute sequelae of SARS-CoV-2 (PASC) or long COVID, is associated with high viral titers during acute infection, a persistently hyperactivated immune system, tissue injury by NETosis-induced micro-thrombofibrosis (NETinjury), microbial translocation, complement deposition, fibrotic macrophages, the presence of autoantibodies, and lymphopenic immune environments. Here, we review the current literature on the immunological imbalances that occur during PASC. Specifically, we focus on data supporting common immunopathogenesis and tissue injury mechanisms shared across this highly heterogenous disorder, including NETosis, coagulopathy, and fibrosis. Mechanisms include changes in leukocyte subsets/functions, fibroblast activation, cytokine imbalances, lower cortisol, autoantibodies, co-pathogen reactivation, and residual immune activation driven by persistent viral antigens and/or microbial translocation. Taken together, we develop the premise that SARS-CoV-2 infection results in PASC as a consequence of acute and/or persistent single or multiple organ injury mediated by PASC determinants to include the degree of host responses (inflammation, NETinjury), residual viral antigen (persistent antigen), and exogenous factors (microbial translocation). Determinants of PASC may be amplified by comorbidities, age, and sex.

Seroprevalence of SARS-CoV-2 antibodies among Forcibly Displaced Myanmar Nationals in Cox's Bazar, Bangladesh 2020: a population-based cross-sectional study.

OBJECTIVES: The study aimed to determine the seroprevalence, the fraction of asymptomatic infections, and risk factors of SARS-CoV-2 infections among the Forcibly Displaced Myanmar Nationals (FDMNs). DESIGN: It was a population-based two-stage cross-sectional study at the level of households. SETTING: The study was conducted in December 2020 among household members of the FDMN population living in the 34 camps of Ukhia and Teknaf Upazila of Cox's Bazar district in Bangladesh. PARTICIPANTS: Among 860 697 FDMNs residing in 187 517 households, 3446 were recruited for the study. One individual aged 1 year or older was randomly selected from each targeted household. PRIMARY AND SECONDARY OUTCOME MEASURES: Blood samples from respondents were tested for total antibodies for SARS-CoV-2 using Wantai ELISA kits, and later positive samples were validated by Kantaro kits. RESULTS: More than half (55.3%) of the respondents were females, aged 23 median (IQR 14-35) years and more than half (58.4%) had no formal education. Overall, 2090 of 3446 study participants tested positive for SARS-CoV-2 antibody. The weighted and test adjusted seroprevalence (95% CI) was 48.3% (45.3% to 51.4%), which did not differ by the sexes. Children (aged 1-17 years) had a significantly lower seroprevalence 38.6% (95% CI 33.8% to 43.4%) compared with adults (58.1%, 95% CI 55.2% to 61.1%). Almost half (45.7%, 95% CI 41.9% to 49.5%) of seropositive individuals reported no relevant symptoms since March 2020. Antibody seroprevalence was higher in those with any comorbidity (57.8%, 95% CI 50.4% to 64.5%) than those without (47.2%, 95% CI 43.9% to 50.4%). Multivariate logistic regression analysis of all subjects identified increasing age and education as risk factors for seropositivity. In children (≤17 years), only age was significantly associated with the infection. CONCLUSIONS: In December 2020, about half of the FDMNs had antibodies against SARS-CoV-2, including those who reported no history of symptoms. Periodic serosurveys are necessary to recommend appropriate public health measures to limit transmission.

Humoral and Cellular Immune Responses of COVID-19 vaccines against SARS-Cov-2 Omicron variant: a systemic review.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has undergone multiple mutations since its emergence, and its latest variant, Omicron (B.1.1.529), is the most contagious variant of concern (VOC) which poses a major and imminent threat to public health. Since firstly reported by World Health Organization (WHO) in November 2021, Omicron variant has been spreading rapidly and has become the dominant variant in many countries worldwide. Omicron is the most mutated variant so far, containing 60 mutations in its genome, including 37 mutations in the S-protein. Since all current COVID-19 vaccines in use were developed based on ancestral SARS-CoV-2 strains, whether they are protective against Omicron is a critical question which has been the center of study currently. In this article, we systemically reviewed the studies regarding the effectiveness of 2- or 3-dose vaccines delivered in either homologous or heterologous manner. The humoral and cellular immune responses elicited by various vaccine regimens to protect against Omicron variant are discussed. Current understanding of the molecular basis underlying immune escape of Omicron was also analyzed. These studies indicate that two doses of vaccination are insufficient to elicit neutralizing antibody responses against Omicron variant. Nevertheless, Omicron-specific humoral immune responses can be enhanced by booster dose of almost all type vaccines in certain degree, and heterologous vaccination strategy may represent a better choice than homogenous regimens. Intriguingly, results of studies indicate that all current vaccines are still able to elicit robust T cell response against Omicron. Future focus should be the development of Omicron variant vaccine, which may induce potent humoral as well as cellular immune responses simultaneously against all known variants of the SARS-CoV-2 virus.

The role of CD4+FoxP3+ regulatory T cells in the immunopathogenesis of COVID-19: implications for treatment.

The severe cases of Coronavirus Disease 2019 (COVID-19) frequently exhibit excessive inflammatory responses, acute respiratory distress syndrome (ARDS), coagulopathy, and organ damage. The most striking immunopathology of advanced COVID-19 is cytokine release syndrome or "cytokine storm" that is attributable to the deficiencies in immune regulatory mechanisms. CD4+FoxP3+ regulatory T cells (Tregs) are central regulators of immune responses and play an indispensable role in the maintenance of immune homeostasis. Tregs are likely involved in the attenuation of antiviral defense at the early stage of infection and ameliorating inflammation-induced organ injury at the late stage of COVID-19. In this article, we review and summarize the current understanding of the change of Tregs in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and discuss the potential role of Tregs in the immunopathology of COVID-19. The emerging concept of Treg-targeted therapies, including both adoptive Treg transfer and low dose of IL-2 treatment, is introduced. Furthermore, the potential Treg-boosting effect of therapeutic agents used in the treatment of COVID-19, including dexamethasone, vitamin D, tocilizumab and sarilumab, chloroquine, hydroxychloroquine, azithromycin, adalimumab and tetrandrine, is discussed. The problems in the current study of Treg cells in COVID-19 and future perspectives are also addressed.

Global landscape of patents related to human coronaviruses.

At present, the COVID-19 pandemic is running rampant, having caused 2.18 million deaths. Characterizing the global patent landscape of coronaviruses is essential not only for informing research and policy, given the current pandemic crisis, but also for anticipating important future developments. While patents are a promising indicator of technological knowledge production widely used in innovation research, they are often an underused resource in biological sciences. In this study, we present a patent landscape for the seven coronaviruses known to infect humans. The information included in this paper provides a strong intellectual groundwork for the ongoing development of therapeutic agents and vaccines along with a deeper discussion of intellectual property rights under epidemic conditions. The results show that there has been a rapid increase in human coronavirus patents, especially COVID-19 patents. China and the United States play an outstanding role in global cooperation and patent application. The leading role of academic institutions and government is increasingly apparent. Notable technological issues related to human coronaviruses include pharmacochemical treatment, diagnosis of viral infection, viral-vector vaccines, and traditional Chinese medicine. Furthermore, a critical challenge lies in balancing commercial competition, enterprise profit, knowledge sharing, and public interest.

Traditional Chinese Medicine in the Treatment of Patients Infected with 2019-New Coronavirus (SARS-CoV-2): A Review and Perspective.

Currently, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, formerly known as 2019-nCoV, the causative pathogen of Coronavirus Disease 2019 (COVID-19)) has rapidly spread across China and around the world, causing an outbreak of acute infectious pneumonia. No specific anti-virus drugs or vaccines are available for the treatment of this sudden and lethal disease. The supportive care and non-specific treatment to ameliorate the symptoms of the patient are the only options currently. At the top of these conventional therapies, greater than 85% of SARS-CoV-2 infected patients in China are receiving Traditional Chinese Medicine (TCM) treatment. In this article, relevant published literatures are thoroughly reviewed and current applications of TCM in the treatment of COVID-19 patients are analyzed. Due to the homology in epidemiology, genomics, and pathogenesis of the SARS-CoV-2 and SARS-CoV, and the widely use of TCM in the treatment of SARS-CoV, the clinical evidence showing the beneficial effect of TCM in the treatment of patients with SARS coronaviral infections are discussed. Current experiment studies that provide an insight into the mechanism underlying the therapeutic effect of TCM, and those studies identified novel naturally occurring compounds with anti-coronaviral activity are also introduced.