Medical hypotheses
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The new zoonotic coronavirus (SARS-CoV-2) responsible for coronavirus disease (COVID-19) is a new strain of coronavirus not previously seen in humans and which appears to come from bat species. It originated in Wuhan, Hubei Province, China, and spread rapidly throughout the world, causing over 5,569,679 global cases and 351,866 deaths in almost every country in the world, including Europe, particularly Italy. In general, based on existing data published to date, 80.9% of patients infected with the virus develop mild infection; 13.8% severe pneumonia; 4.7% respiratory failure, septic shock or multi-organ failure; 3% of these cases are fatal. ⋯ The arrival of SARS-CoV-2 in the lungs causes severe primary interstitial viral pneumonia that can lead to the "cytokine storm syndrome", a deadly uncontrolled systemic inflammatory response triggered by the activation of interleukin 6 (IL-6), whose effect is extensive lung tissue damage and disseminated intravascular coagulation (DIC), that are life-threatening for patients with COVID-19. In the absence of a therapy of proven efficacy, current management consists of off-label or compassionate use therapies based on antivirals, antiparasitic agents in both oral and parenteral formulation, anti-inflammatory drugs, oxygen therapy and heparin support and convalescent plasma. Like most respiratory viruses can function and replicate at low temperatures (i.e. 34-35 °C) and assuming viral thermolability of SARS-CoV-2, local instillation or aerosol of antiviral (i.e. remdesivir) in humid heat vaporization (40°-41 °C) in the first phase of infection (phenotype I, before admission), both in asymptomatic but nasopharyngeal swab positive patients, together with antiseptic-antiviral oral gargles and povidone-iodine eye drops for conjunctiva (0,8-5% conjunctival congestion), would attack the virus directly through the receptors to which it binds, significantly decreasing viral replication, risk of evolution to phenotypes IV and V, reducing hospitalization and therefore death.
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SARS-CoV-2, the agent of COVID-19, shares a lineage with SARS-CoV-1, and a common fatal pulmonary profile but with striking differences in presentation, clinical course, and response to treatment. In contrast to SARS-CoV-1 (SARS), COVID-19 has presented as an often bi-phasic, multi-organ pathology, with a proclivity for severe disease in the elderly and those with hypertension, diabetes and cardiovascular disease. Whilst death is usually related to respiratory collapse, autopsy reveals multi-organ pathology. ⋯ Our proposed mechanism of lung injury provides an explanation for early hypoxia without reduction in lung compliance and suggests a need for revision of treatment protocols to address vasoconstriction, thromboprophylaxis, and to minimize additional small airways and alveolar trauma via ventilation choice. Our model predicts long term sequelae of scarring/fibrosis in vessels, lungs, renal and cardiac tissue with protracted illness in at-risk individuals. It is hoped that our model stimulates review of current diagnostic and therapeutic intervention protocols, particularly with respect to early anticoagulation, vasodilatation and revision of ventilatory support choices.
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Perioperative neurocognitive disorders (PND) are highly prevalent after surgery, especially in aged patients. PND results in long-term morbidity and mortality with unclear pathophysiologic mechanisms. As a key hallmark of PND, surgery-induced neuroinflammation resulted from the invading of exogenous tracers into the cerebral parenchyma, causing hippocampal neuroinflammation and cognitive impairment. ⋯ Thus, we speculate that IL-32 may participate in the regulation of the surgery-induced neuroinflammation during the parthenogenesis of PND. The isoforms, spatio-temporal regulation of IL-32 may determine its pro- or anti-inflammation properties in parthenogenesis of PND. Therefore, IL-32 could be a putative therapeutic target for the prevention and reversal of PND in the future.
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Coronavirus Diseases-2019 (COVID-19) has caused a large global outbreak and has been declared as a pandemic by the World Health Organization (WHO). It has been proposed that COVID-19-related hyperinflammation and dysregulated immune response might play a critical role in developing a cytokine storm which usually progresses to a life-threatening acute lung injury or acute respiratory distress syndrome in infected individuals. ⋯ It is proposed that nebulized lidocaine might be beneficial in reducing cytokines, protecting patients' lungs and improving outcomes in COVID-19 patients when administered via inhalation as an adjunctive treatment for severe respiratory symptoms in patients fighting the novel Coronavirus. Additional investigation is warranted.
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Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents the largest current health challenge for the society. At the moment, the therapeutic strategies to deal with this disease are only supportive. It is well known that zinc (Zn) possesses a variety of direct and indirect antiviral properties, which are realized through different mechanisms. ⋯ Zn may also protect or stabilize the cell membrane which could contribute to blocking of the virus entry into the cell. On the other hand, it was demonstrated that Zn may inhibit viral replication by alteration of the proteolytic processing of replicase polyproteins and RNA-dependent RNA polymerase (RdRp) in rhinoviruses, HCV, and influenza virus, and diminish the RNA-synthesizing activity of nidoviruses, for which SARS-CoV-2 belongs. Therefore, it may be hypothesized that Zn supplementation may be of potential benefit for prophylaxis and treatment of COVID-19.