Medical Hypotheses

Therapeutic applications of synthetic mRNA were proposed more than 30 years ago, and are currently the basis of one of the vaccine platforms used at a massive scale as part of the public health strategy to get COVID-19 under control. To date, there are no published studies on the biodistribution, cellular uptake, endosomal escape, translation rates, functional half-life and inactivation kinetics of synthetic mRNA, rates and duration of vaccine-induced antigen expression in different cell types. Furthermore, despite the assumption that there is no possibility of genomic integration of therapeutic synthetic mRNA, only one recent study has examined interactions between vaccine mRNA and the genome of transfected cells, and reported that an endogenous retrotransposon, LINE-1 is unsilenced following mRNA entry to the cell, leading to reverse transcription of full length vaccine mRNA sequences, and nuclear entry...

Research evidence suggests that adipocytes in obesity might facilitate SARS-CoV-2 replication, for it was only found in adipose tissue of individuals with overweight or obesity but not lean individuals who died from COVID-19. As lipid metabolism is key to adipocyte function, and viruses are capable of exploiting and manipulating lipid metabolism of host cells for their own benefit of infection, we hypothesize that adipocytes could not only impair host immune defense against viral infection, but also facilitate SARS-CoV-2 entry, replication and assembly as a reservoir to boost the viral infection in obesity...

Patients with diabetes often have severe hyperglycemia triggered by novel coronavirus disease 2019 (COVID-19). Insulin treatment should be the main approach to the control of acute hyperglycemia in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, clinical investigation found that insulin treatment is associated with a significant increase in mortality risk in patients with diabetes and SARS-CoV-2 infection. The reason for this high mortality rate remains obscure...

No abstract text is available yet for this article.

Migration to the lungs of an initial upper airway infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or other respiratory pathogens can lead to pneumonia, associated with progression from mild to severe symptoms. Chemical pneumonitis or bacterial pneumonia may be caused by the 'macroaspiration' of large volumes of oropharyngeal or gastroesophageal secretions into the lower respiratory tract. 'Microaspiration', i.e. , a similar mechanism but involving much smaller amounts of oropharyngeal secretions, is considered the pathogenetic mechanism for most pneumonias, including that associated with COVID-19...

Specific antibodies that humans acquire as a result of disease or after vaccination are needed to effectively suppress infection with a specific variant of SARS CoV-2 virus. The S protein of the D614G variant of coronavirus is used as an antigen in known vaccines to date. It is known that COVID-19 disease resulting from infection with this coronavirus can often be very dangerous to the health and lives of patients. In contrast, vaccines produce antibodies against an older version of the protein S-D614G (January 2020) and therefore have difficulty recognizing new variants of the virus...

No abstract text is available yet for this article.

Interferons (IFN), first described 1957 by Isaacs and Lindemann, are antiviral proteins generated in cells after viral infections. One of several interferon-induced effector mechanisms is the so called 2-5A / RNaseL system: Interferon is produced in the virus-affected cells and released. After binding to cell membrane receptors of adjacent cells, 2-5 A synthetase (oligoadenylate synthetase, OAS) is generated, attaches to dsRNA section areas of the viral RNA and catalyses the production of 2-5 oligoadenylates from ATP...

Restless Legs Syndrome (RLS) is characterized by bothersome leg discomfort accompanied by an urge to move to obtain relief and symptoms are worse at night and on lying down. There is at least partial and temporary relief with activity. It is also an opioid responsive disorder, often accompanied by iron deficiency with or without anemia, and inflammation may be a precipitating factor in some cases. We created two in-vivo opiate receptor knock out mouse models of RLS - a triple opiate receptor knock-out mouse and a mu opiate receptor knock-out mouse...

Finding effective drugs to treat SARS-CoV-2 infection as a complementary step to the extensive vaccination is of the great importance to overcome the current pandemic situation. It has been shown that some bio-active unsaturated fatty acids such as Arachidonic Acid (AA) can reduce the infection severity and even destroy the virus by disintegration of the virus lipid envelope. On the other hand, it has been reported that several designed peptides with an activity similar to the angiotensin converting enzyme 2 (ACE-2), which has a high affinity towards the novel corona virus spike protein, can inhibit the viral infection through concealing the spike proteins from the cell surfaces ACE-2...

SARS-CoV-2 infection intrigued medicine with diverse outcomes ranging from asymptomatic to severe acute respiratory syndrome (SARS) and death. After more than two years of pandemic, reports of reinfection concern researchers and physicists. Here, we will discuss potential mechanisms that can explain reinfections, including the aggravated ones. The major topics of this hypothesis paper are the disbalance between interferon and antibodies responses, HLA heterogeneity among the affected population, and increased proportion of cytotoxic CD4+ T cells polarization in relation to T follicular cells (Tfh) subtypes...

People living with HIV are more exposed to the adverse health effects of the worldwide COVID-19 pandemic. The pandemic's health and social repercussions may promote drug abuse and inadequate HIV management among this demographic. The coronavirus pandemic of 2019 (COVID-19) has caused unprecedented disruption worldwide in people's lives and health care. When the COVID-19 epidemic was identified, people with HIV faced significant obstacles and hurdles to achieving optimal care results. The viral spike protein (S-Protein) and the cognate host cell receptor angiotensin-converting enzyme 2 (ACE2) are both realistic and appropriate intervention targets...

The Chinese scenario, a rapid increase in the frequency of SARS-CoV-2 infections and sudden decline, is uncommon worldwide. Enormous differences in COVID-19 severity among individual countries are the striking findings of the pandemics. It has been demonstrated that a mild course of COVID-19 is associated with gastrointestinal symptoms, less inflammatory response, and better prognosis. The presence of SARS-CoV-2 was observed longer in the gastrointestinal tract than in respiratory swabs, promoting feco-oral transmissions and mild virus attenuation...

Fungal co-infections of coronavirus disease 2019 (COVID-19) are generally infrequent, but are more common among patients with hematological diseases or severe cases in the intensive care unit (ICU). As fungal infections often carry a high mortality rate, preventing their development is considered important for patients with COVID-19. Caspofungin covers Candida spp. and Aspergillus spp. as causative pathogens of fungal infections associated with COVID-19, and is known to have few side effects among antifungal drugs...

Since the inception of the pandemic, almost all countries have been testing Covid-19 via a swab test with one bar (combined OP and NP). They use the same bar - first an oropharynx swab and then a nasopharynx swab- This manner of application causes oropharengeal Covid-19 viruses to be inoculated into the nasopharynx and help grow Covid-19 disease infection in that area as well. We speculate that asymptomatic Covid- 19 carriers can be converted to pre-symptomatic people via auto-transmission iatrogenically. This highlights the critical role of asymptomatic cases in the progression of the ongoing pandemic...

Vaccinees experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines with different occurrence frequencies. Many of these adverse events are generally considered as associated with immune responses to the active vaccine components (antigens) and/or to possibly one or more of the vaccine excipients. Most of these vaccine adverse events are self-limiting and resolve within days. Many of these adverse events symptoms overlap symptoms associated with elevated histamine levels...

Dyskeratosis Congenita (DC) is a rare and heterogeneous disease. This disorder is resulted from a defect in the telomere maintenance in stem cells. Telomerase RNA component, shelterin complex, and telomerase reverse transcriptase are mutated in this disease. Many studies have previously confirmed shorter leukocyte telomere length in DC. On the other hand, the association between telomere length and Coronavirus disease 2019 (COVID-19) indicated that people with a short telomere background mostly show more severe symptoms related to COVID-19, and the mortality rate among them increases as well...

Recent studies have reported an impaired exercise response at cardiopulmonary exercise testing (CPET) during convalescence from coronavirus disease 2019 (COVID-19). In detail, these previous reports suggest the presence of functional limitations in a consistent proportion of COVID-19 survivors, in the absence of relevant alterations of ventilatory and gas exchange parameters at CPET. Therefore, deconditioning has been proposed as the main mechanism of the reduced peak oxygen uptake in this clinical setting...

The treatment of post-acute sequelae of Covid-19 (PASC) has been informed primarily by symptomatic parallels with other chronic inflammatory syndromes. This manuscript takes a more systemic approach by examining how a marginal deficiency of tetrahydrobiopterin (BH4) resulting from mutations of the GCH1 (GTP cyclohydrolase 1) gene may result in the uncoupling of inducible Nitric Oxide Synthase (iNOS) early in the initial response of the innate immune system to SARS-CoV-2. The resulting production of superoxide instead of nitric oxide leads to a self-perpetuating cycle of oxidative stress with the potential to impair numerous metabolic processes and damage multiple organ systems...

COVID-19 infection was mainly associated with respiratory symptoms, but lately, ischemic stroke (IS) has been reported in several cases. The incidence of IS in SARS-CoV-2 infection is increasing, and its mechanism is still not fully understood. Calcitonin gene-related peptide (CGRP) -the abundantly expressed protein in the peripheral and central nervous system- showed low expression in SARS-CoV-2 patients. This peptide is strongly implicated in regulating cerebral blood flow (CBF) and improving neurological deficits after cerebral arterial occlusion...