Host genetic diversity and genetic variations of SARS-CoV-2 in COVID-19 pathogenesis and the effectiveness of vaccination.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the outbreak of coronavirus disease 2019 (COVID-19), has shown a vast range of clinical manifestations from asymptomatic to life-threatening symptoms. To figure out the cause of this heterogeneity, studies demonstrated the trace of genetic diversities whether in the hosts or the virus itself. With this regard, this review provides a comprehensive overview of how host genetic such as those related to the entry of the virus, the immune-related genes, gender-related genes, disease-related genes, and also host epigenetic could influence the severity of COVID-19. Besides, the mutations in the genome of SARS-CoV-2 __leading to emerging of new variants__ per se affect the affinity of the virus to the host cells and enhance the immune escape capacity. The current review discusses these variants and also the latest data about vaccination effectiveness facing the most important variants.

Complement inhibition: A possible therapeutic approach in the fight against Covid-19.

The complement system, as a vital part of innate immunity, has an important role in the clearance of pathogens; however, unregulated activation of this system probably has a key role in the pathogenesis of acute lung injury, which is induced by highly pathogenic viruses (i.e. influenza A viruses and severe acute respiratory syndrome [SARS] coronavirus). The novel coronavirus SARS-CoV-2, which is the causal agent for the ongoing global pandemic of the coronavirus disease 2019 (Covid-19), has recently been spread to almost all countries around the world. Although most people are immunocompetent to SARS-CoV-2, a small group develops hyper-inflammation that leads to complications like acute respiratory distress syndrome, disseminated intravascular coagulation, and multi-organ failure. Emerging evidence demonstrates that the complement system exerts a crucial role in this inflammatory reaction. Additionally, patients with the severe form of Covid-19 show over-activation of the complement in their skin, sera, and lungs. This study aims to summarise current knowledge concerning the interaction of SARS-CoV-2 with the complement system and to critically appraise complement inhibition as a potential new approach for Covid-19 treatment.

Platelets in the perspective of COVID-19; pathophysiology of thrombocytopenia and its implication as prognostic and therapeutic opportunity.

Despite endorsed and exponential research to improve diagnostic and therapeutic strategies, efforts have not yet converted into a better prospect for patients infected with the novel coronavirus (2019nCoV), and still, the name of SARS-CoV-2 is coupled with numerous unanswered questions. One of these questions is concerning how this respiratory virus reduces the number of platelets (PLTs)? The results of laboratory examinations showed that about a quarter of COVID-19 cases experience thrombocytopenia, and more remarkably, about half of these patients succumb to the infection due to coagulopathy. These findings have positioned PLTs as a pillar in the management as well as stratifying COVID-19 patients; however, not all the physicians came into a consensus about the prognostic value of these cells. The current review aims to unravel the contributory role of PLTs s in COVID-19; and alsoto summarize the original data obtained from international research laboratories on the association between COVID-19 and PLT production, activation, and clearance. In addition, we provide a special focus on the prognostic value of PLTs and their related parameters in COVID-19. Questions on how SARS-CoV-2 induces thrombocytopenia are also responded to. The last section provides a general overview of the most recent PLT- or thrombocytopenia-related therapeutic approaches. In conclusion, since SARS-CoV-2 reduces the number of PLTs by eliciting different mechanisms, treatment of thrombocytopenia in COVID-19 patients is not as simple as it appears and serious cautions should be considered to deal with the problem through scrutiny awareness of the causal mechanisms.

COVID-19-related coagulopathy: A review of pathophysiology and pharmaceutical management.

December 2019 will never be forgotten in the history of medicine when an outbreak of pneumonia of unknown etiology in Wuhan, China sooner or later prompted the World Health Organization to issue a public health warning emergency. This is not the first nor will it be the last time that a member of ß-coronaviruses (CoVs) is waging a full-scale war against human health. Notwithstanding the fact that pneumonia is the primary symptom of the novel coronavirus (2019nCoV; designated as SARS-CoV-2), the emergence of severe disease mainly due to the injury of nonpulmonary organs at the shadow of coagulopathy leaves no choice, in some cases, rather than a dreadful death. Multiple casual factors such as inflammation, endothelial dysfunction, platelet and complement activation, renin-angiotensin-aldosterone system derangement, and hypoxemia play a major role in the pathogenesis of coagulopathy in coronavirus disease 2019 (COVID-19) patients. Due to the undeniable role of coagulation dysfunction in the initiation of several complications, assessment of coagulation parameters and the platelet count would be beneficial in early diagnosis and also timely prediction of disease severity. Although low-molecular-weight heparin is considered as the first-line of treatment in COVID-19-associated coagulopathy, several possible therapeutic options have also been proposed for better management of the disease. In conclusion, this review would help us to gain insight into the pathogenesis, clinical manifestation, and laboratory findings associated with COVID-19 coagulopathy and would summarize management strategies to alleviate coagulopathy-related complications.

Mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles in COVID-19-induced ARDS: Mechanisms of action, research progress, challenges, and opportunities.

In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan city, Hubei province, China. Rapidly escalated into a worldwide pandemic, it has caused an unprecedented and devastating situation on the global public health and society economy. The severity of recent coronavirus disease, abbreviated to COVID-19, seems to be mostly associated with the patients' immune response. In this vein, mesenchymal stromal/stem cells (MSCs) have been suggested as a worth-considering option against COVID-19 as their therapeutic properties are mainly displayed in immunomodulation and anti-inflammatory effects. Indeed, administration of MSCs can attenuate cytokine storm and enhance alveolar fluid clearance, endothelial recovery, and anti-fibrotic regeneration. Despite advantages attributed to MSCs application in lung injuries, there are still several issues __foremost probability of malignant transformation and incidence of MSCs-related coagulopathy__ which should be resolved for the successful application of MSC therapy in COVID-19. In the present study, we review the historical evidence of successful use of MSCs and MSC-derived extracellular vesicles (EVs) in the treatment of acute respiratory distress syndrome (ARDS). We also take a look at MSCs mechanisms of action in the treatment of viral infections, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if MSC therapy might be a promising therapeutic approach in COVID-19 patients.

The contributory role of lymphocyte subsets, pathophysiology of lymphopenia and its implication as prognostic and therapeutic opportunity in COVID-19.

The incidence of the novel coronavirus disease (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought daunting complications for people as well as physicians around the world. An ever-increasing number of studies investigating the characteristics of the disease, day by day, is shedding light on a new feature of the virus with the hope that eventually these efforts lead to the proper treatment. SARS-CoV-2 activates antiviral immune responses, but in addition may overproduce pro-inflammatory cytokines, causing uncontrolled inflammatory responses in patients with severe COVID-19. This condition may lead to lymphopenia and lymphocyte dysfunction, which in turn, predispose patients to further infections, septic shock, and severe multiple organ dysfunction. Therefore, accurate knowledge in this issue is important to guide clinical management of the disease and the development of new therapeutic strategies in patients with COVID-19. In this review, we provide a piece of valuable information about the alteration of each subtype of lymphocytes and important prognostic factors associated with these cells. Moreover, through discussing the lymphopenia pathophysiology and debating some of the most recent lymphocyte- or lymphopenia-related treatment strategies in COVID-19 patients, we tried to brightening the foreseeable future for COVID-19 patients, especially those with severe disease.

Low-dose radiotherapy (LD-RT) for COVID-19-induced pneumopathy: a worth considering approach.

PURPOSE: It seems that 2020 would be always remembered by the name of novel coronavirus (designated as SARS-CoV-2), which exerted its deteriorating effects on the health care, economy, education, and political relationships. In August 2020 more than eight hundred thousand patients lost their lives due to acute respiratory syndrome. In the limited list of therapeutic approaches, the effectiveness of low-dose radiation therapy (LD-RT) for curing inflammatory-related diseases have sparkled a light that probably this approach would bring promising advantages for COVID-19 patients. LD-RT owns its reputation from its ability to modulate the host inflammatory responses by blocking the production of pro-inflammatory cytokines and hampering the activity of leukocytes. Moreover, the cost-effective and availability of this method allow it to be applied to a large number of patients, especially those who could not receive anti-IL-6 treatments in low-income countries. But enthusiasm for applying LD-RT for the treatment of COVID-19 patients has been muted yet. CONCLUSION: In this review, we take a look at LD-RT mechanisms of action in the treatment of nonmalignant diseases, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if LD-RT might be a promising therapeutic approach in COVID-19 patients.

Laboratory findings in COVID-19 diagnosis and prognosis.

BACKGROUND: Since its first description, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), formerly known as 2019-nCoV, has attracted tremendous attention in a short period of time as the death toll and number of confirmed cases grows unceasingly. METHODS: To provide a better understanding of the importance of abnormal laboratory findings in COVID-19 diagnosis and prognosis, we searched the Scopus, PubMed, and Web of Science medical databases and selected 19 articles (totaling 2988 patients, 484 of whom [16.1%] had severe disease) that reported panels of laboratory examinations in patients with COVID-19. RESULTS: Although in vitro diagnostics, primarily using PCR- and ELISA-based methods, efficiently contribute to the etiological identification of SARS-CoV-2 infection, we suggest that laboratory medicine may also be of significant assistance when differentiating between severe and non-severe COVID-19. CONCLUSION: When we wrote this article, our ability to provide a definitive conclusion may have been adversely affected by some limitations, such as the low sample size, differently applied methods, dissimilar reference ranges, non-synchronized representations of results, and variety of the patients' panels. Despite the limitations, the analysis of the current scientific literature demonstrates the value of laboratory parameters as simple, rapid, and cost-effective biomarkers in COVID-19 patients.