K. Farsalinos, R. Niaura, J. le Houezec, A. Barbouni, A. Tsatsakis, D. Kouretas, A. Vantarakis, K. Poulas
Toxicology Reports, 2020
As of 20 April, almost 1.7 million people globally have been diagnosed with Corona Virus Disease 2019 (COVID-19), a pandemic that has evolved from the emergence of a new coronavirus strain, acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in China. More than 170,000 deaths have been reported, while there are certainly many more cases of milder disease that have not been diagnosed and officially confirmed due to limited testing capacity in most countries. The pandemic is a global emergency due to the rapid transmission of the disease and the potential to overwhelm the healthcare systems, and is expected to have considerable economic and health impacts. Contributing factors and their possible role in the relatively high infection, death rates between countries and origin have recently been studied [1,2]. This new outbreak has been additionally evaluated for current knowledge on coronaviruses based on a short history to epidemiology, pathogenesis, clinical manifestation of the disease, as well as treatment and prevention strategies [3]. The search for potential protective and therapeutic antiviral strategies is of particular and urgent concern [4]. While in most cases, especially in young people without any comorbidities, the disease is expected to be relatively mild, there is a substantial proportion of patients who develop complications and need intensive care-unit support and mechanical ventilation. In one case series of 1099 patients in China [5], 6.1 % of cases suffered from the primary composite end-point of admission to an intensive care unit, use of mechanical ventilation, or death. Patients with severe disease typically present with dyspnea and hypoxemia shortly after disease initiation, and may quickly progress to respiratory failure, acute respiratory distress syndrome (ARDS) and multi-organ failure [6]. Predictors of adverse outcomes include elevated levels of inflammatory markers and pro-inflammatory cytokines. A study of 150 COVID-19 cases reported that elevated levels of C-reactive protein (CRP), ferritin and IL-6 were associated with death [7]. IL-6, an important pro-inflammatory cytokine, was elevated in fatal cases of COVID-19 in another study of 191 patients [8]. Another study of 452 patients reported that those with severe disease showed lymphocytopenia, neutrophilia, low levels of monocytes, eosinophils and basophils, and elevated levels of infectionrelated biomarkers and inflammatory cytokines [9]. Pathological examination of a case in China revealed bilateral diffuse alveolar damage, desquamation of pneumocytes, hyaline membrane formation and interstitial mononuclear inflammatory infiltrates [10]. Flow cytometry of peripheral blood revealed reduced levels of CD4+ and CD8+T cells, which however were hyper-activated, and elevated concentration of pro-inflammatory CCR6+ Th17 in CD4+T cells. Such findings are hallmarks of ARDS and resemble features observed in SARS and Middle Eastern Respiratory Syndrome [11,12]. Systemic vasculitis was also observed [10]. Therefore, it seems that immune dysregulation may be implicated in the pathophysiology of severe COVID-19.
Cited by 95 publications.
Field of study: Medicine