We propose here that one of the potential mechanisms for the relapse of the COVID-19 infection could be a cellular transport pathway associated with the release of the SARS-CoV-2-loaded exosomes and other extracellular vesicles. It is possible that this "Trojan horse" strategy represents possible explanation for the reappearance of the viral RNA in the recovered COVID-19 patients 7-14 day post discharge, suggesting that viral material was hidden within such exosomes or extracellular vesicles during this "silence" time period and then started to re-spread again.

Without protective and/or therapeutic agents the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection known as coronavirus disease 2019 is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS‐CoV‐2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS‐CoV‐2 components could use to reach the CNS and PNS, utilizing the within‐body cross talk between organs. The majority of SARS‐CoV‐2–infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune‐mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood–endothelial barrier may be considered as the main route for SARS‐CoV‐2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

Although vaccination represents the most promising way to stop or contain the coronavirus disease 2019 (COVID-19) pandemic and safety and effectiveness of available vaccines were proven, a small number of individuals who received anti-SARS-CoV-2 vaccines developed a prothrombotic syndrome. Vaccine-induced immune thrombotic thrombocytopenia (VITT) can be triggered by the adenoviral vector-based vaccine, whereas lipid nanoparticle-mRNA-based vaccines can induce rare cases of deep vein thrombosis (DVT). Although the main pathogenic mechanisms behind this rare phenomenon have not yet been identified, both host and vaccine factors might be involved, with pathology at least in part being related to the vaccine-triggered autoimmune reaction. In this review, we are considering some aspects related to pathogenesis, major risk factors, as well as peculiarities of diagnosis and treatment of this rare condition.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face a microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (severe acute respiratory syndrome (SARS-CoV) and middle east respiratory syndrome (MERS-CoV)) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summarize the possible and logical answers to these questions.

The world population is still facing the second wave of the COVID-19 pandemic. Such a challenge requires complicated tools to control, namely vaccines, effective cures, and complementary agents. Here we present one candidate for the role of an effective cure and/or complementary agent: lactoferrin. It is the cross-talking mediator between many organs/cellular systems in the body. It serves as a physiological, immunological, and anti-microbial barrier, and acts as a regulator molecule. Furthermore, lactoferrin has receptors on most tissues cells, and is a rich source for bioactive peptides, particularly in the digestive system. In the past months, in vitro and in vivo evidence has accumulated regarding lactoferrin’s ability to control SARS-CoV-2 infectivity in different indicated scenarios. Also, lactoferrin or whey milk (of human or other mammal’s origin) is a cheap, easily available, and safe agent, the use of which can produce promising results. Pharmaceutical and/or food supplementary formulas of lactoferrin could be particularly effective in controlling the gastrointestinal COVID-19-associated symptoms and could limit the fecal-oral viral infection transmission, through mechanisms that mimic that of norovirus infection control by lactoferrin via induction of intestinal innate immunity. This natural avenue may be effective not only in symptomatic patients, but could also be more helpful in asymptomatic patients as a main or adjuvant treatment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing pandemic of coronavirus disease 2019 (COVID-19). The worldwide transmission of COVID-19 from human to human is spreading like wildfire, affecting almost every country in the world. In the past 100 years, the globe did not face microbial pandemic similar in scale to COVID-19. Taken together, both previous outbreaks of other members of the coronavirus family (SARS-CoV and MERS-CoV) did not produce even 1% of the global harm already inflicted by COVID-19. There are also four other CoVs capable of infecting humans (HCoVs), which circulate continuously in the human population, but their phenotypes are generally mild, and these HCoVs received relatively little attention. These dramatic differences between infection with HCoVs, SARS-CoV, MERS-CoV, and SARS-CoV-2 raise many questions, such as: Why is COVID-19 transmitted so quickly? Is it due to the some specific features of the viral structure? Are there some specific human (host) factors? Are there some environmental factors? The aim of this review is to collect and concisely summaries the possible and logic answers to these questions.

No abstract

The novel severe acute respiratory syndrome (SARS) coronavirus SARS-CoV-2 walks the planet causing the rapid spread of the CoV disease 2019 (COVID-19) that has especially deleterious consequences for the patients with underlying cardiovascular diseases (CVDs). Entry of the SARS-CoV-2 into the host cell involves interaction of the virus (via the receptor-binding domain (RBD) of its spike glycoprotein) with the membrane-bound form of angiotensin-converting enzyme 2 (ACE2) followed by the virus-ACE2 complex internalization by the cell. Since ACE2 is expressed in various tissues, such as brain, gut, heart, kidney, and lung, and since these organs represent obvious targets for the SARS-CoV-2 infection, therapeutic approaches were developed to either inhibit ACE2 or reduce its expression as a means of prevention of the virus entry into the corresponding host cells. The problem here is that in addition to be a receptor for the SARS-CoV-2 entry into the host cells, ACE2 acts as a key component of the renin-angiotensin-aldosterone system (RAAS) aimed at the generation of a cascade of vasoactive peptides coordinating several physiological processes. In RAAS, ACE2 degrades angiotensin II, which is a multifunctional CVD-promoting peptide hormone and converts it to a heptapeptide angiotensin-(1–7) acting as the angiotensin II antagonist. As protein multifunctionality is commonly associated with the presence of flexible or disordered regions, we analyze here the intrinsic disorder predisposition of major players related to the SARS-CoV-2 – RAAS axis. We show that all considered proteins contain intrinsically disordered regions that might have specific functions. Since intrinsic disorder might play a role in the functionality of query proteins and be related to the COVID-19 pathogenesis, this work represents an important disorder-based outlook of an interplay between the renin-angiotensin-aldosterone system and SARS-CoV-2. It also suggests that consideration of the intrinsic disorder phenomenon should be added to the modern arsenal of means for drug development.