Comment on Zamfir et al. Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases. Medicina 2022, 58, 874.

The SARS-CoV-2 spike protein mRNA-based vaccines have prevented countless mortality and morbidity, and have an excellent risk/benefit ratio. However, various adverse events may rarely occur after the BNT162b2 vaccine, like any other medical intervention. The COVID-19 itself and the spike protein produced endogenously by mRNA vaccines may have immunological, microenvironmental, prothrombotic, and neoplastic effects. As a contribution to the published report, we would like to share our experience regarding four cases in which myeloid neoplasms emerged following the vaccination. Conclusions: There is no doubt that vaccination could continue along the lines of established universal recommendations. Meanwhile, all hematological adverse events must be closely monitored and reported. Further efforts should be focused on the probable pathobiological mechanisms and causalities of spike protein-related toxicity and clonal myeloid disorders.

Effectiveness of Mesenchymal Stem Cell Therapy for COVID-19 Patients in the Intensive Care Unit: A Case-Control Study

Objective: Many methods are used in the treatment of coronavirus disease 2019 (COVID-19), which causes acute respiratory distress syndrome (ARDS), and there are conflicting reports in the literature regarding the results of mesenchymal stem cell (MSC) therapy, which is one of those methods. The aim of our study is to evaluate the effect of MSC treatment applied together with standard treatments on survival. Materials and Methods: This retrospective case-control study evaluates the survival effect of MSC treatment administered to patients treated in intensive care after the development of ARDS due to COVID-19 between March 2020 and March 2021. The age, gender, comorbid disease status, APACHE II score, and overall and comorbidity-based survival rates were compared between patients who received standard medical treatment (SMT) and patients who received MSC treatment together with SMT. Results: There were 62 patients in the group receiving only SMT and 81 patients in the group receiving SMT and MSC. No difference was observed between the groups in terms of age, gender, presence of comorbid diseases, or APACHE II scores. There were also no differences according to Kaplan-Maier analysis for the survival statuses of the groups. There was no serious adverse effect due to MSC treatment among these patients. Conclusion: Our study presents the largest case series in the literature, and it was observed that MSC treatment may not significantly affect overall survival or comorbid disease-based survival, in contrast to many other studies in the literature.

Human Ace D/I Polymorphism Could Affect the Clinicobiological Course of COVID-19.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), that is caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), has spread rapidly worldwide since December 2019. The SARS-CoV-2 virus has a great affinity for the angiotensin-converting enzyme-2 (ACE-2) receptor, which is an essential element of the renin-angiotensin system (RAS). This study is aimed at assessing the impact of the angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphisms, on the susceptibility and clinical outcomes of the COVID-19 immunoinflammatory syndrome. Patients and Methods. A total of 112 patients diagnosed with COVID-19 between 1 and 15 May 2020 were enrolled in the study. ACE gene allele frequencies were compared to the previously reported Turkish population comprised of 300 people. RESULTS: The most common genotype in the patients and control group was DI with 53% and II with 42%, respectively. The difference in the presence of the D allele between the patient and control groups was statistically significant (67% vs. 42%, respectively, p < 0.0001). Severe pneumonia was observed more in patients with DI allele (31%) than DD (8%) and II (0%) (p = 0.021). The mortality rate, time to defervescence, and the hospitalization duration were not different between the genotype groups. CONCLUSION: Genotype DI of ACE I/D polymorphism is associated with the infectious rate particularly severe pneumonia in this study conducted in the Turkish population. Therefore, ACE D/I polymorphism could affect the clinical course of COVID-19.

Convalescent plasma therapy in patients with COVID-19.

INTRODUCTION: Passive antibody therapy has been used to immunize vulnerable people against infectious agents. In this study, we aim to investigate the efficacy of convalescent plasma (CP) in the treatment of severe and critically ill patients diagnosed with COVID-19. METHOD: The data of severe or critically ill COVID-19 patients who received anti-SARS-CoV-2 antibody-containing CP along with the antiviral treatment (n = 888) and an age-gender, comorbidity, and other COVID-19 treatments matched severe or critically ill COVID-19 patients at 1:1 ratio (n = 888) were analyzed retrospectively. RESULTS: Duration in the intensive care unit (ICU), the rate of mechanical ventilation (MV) support and vasopressor support were lower in CP group compared with the control group (p = 0.001, p = 0.02, p = 0.001, respectively). The case fatality rate (CFR) was 24.7 % in the CP group, and it was 27.7 % in the control group. Administration of CP 20 days after the COVID-19 diagnosis or COVID-19 related symptoms were associated with a higher rate of MV support compared with the first 3 interval groups (≤5 days, 6-10 days, 11-15 days) (p=0.001). CONCLUSION: CP therapy seems to be effective for a better course of COVID-19 in severe and critically ill patients.

The clinical course of COVID-19 in hematopoietic stem cell transplantation (HSCT) recipients

Background/aim: The disease caused by SARS-CoV-2 was named as COVID-19. There is as yet insufficient information about the effects of HSCT on the clinical course of COVID-19. In the present study, we aimed to investigate the clinical course of COVID-19 in patients who had undergone HSCT. Materials and methods: We analyzed baseline characteristics, clinical course and findings of COVID-19, hospitalization and death rates, overall survival, and case fatality rates of HSCT recipients diagnosed with COVID-19 retrospectively. Results: 57.6% of the patients underwent AHSCT, and 42.4% underwent allo-HSCT. 60.6%, 27.3%, and 12.1% of the patients had mild, moderate, and severe COVID-19 or critical illness, respectively. Overall, 45.5% were hospitalized, 12.1% required intensive care, and 9.1% necessitated invasive mechanical ventilation. The total CFR was 9.1% in HSCT recipients, 22.2% in patients with active hematologic malignancy, and 4.2% in patients without active hematologic malignancy. Conclusion: It can be concluded that mortality of HSCT recipients is lower in patients whose primary disease is in remission compared to ones that are not in remission. Further studies with larger group patients are needed in order to delineate the effects of COVID-19 on HSCT patients.

Current community transmission and future perspectives on the COVID-19 process

Background/aim: COVID-19 syndrome due to the SARS-CoV-2 virus is a currently challenging situation ongoing worldwide. Since the current pandemic of the SARS-CoV-2 virus is a great concern for everybody in the World, the frequently asked question is how and when the COVID-19 process will be concluded. The aim of this paper is to propose hypotheses in order to answer this essential question. As recently demonstrated, SARS-CoV-2 RNAs can be reverse-transcribed and integrated into the human genome. Our main hypothesis is that the ultimate aim of the SARS-CoV-2 virus is the incorporation to human genome and being an element of the intestinal virobiota. Materials and methods: We propose that the SARS-CoV-2 genomic incorporation to be a part of human virobiota is essentially based on three pathobiological phases which are called as the 'induction', 'consolidation', and 'maintenance phases'. The phase of 'recurrence' complicates any of these three disease phases based on the viral load, exposure time, and more contagious strains and/or mutants. We have performed the 'random walk model' in order to predict the community transmission kinetics of the virus. Results: Chimerism-mediated immunotherapy at the individual and community level with the help of vaccination seems to be the only option for ending the COVID-19 process. After the integration of SARS-CoV-2 virus into the human genome via the induction, consolidation, and maintenance phases as an element of intestinal virobiota, the chimerism would be concluded. The 'viral load', the 'genomic strain of the SARS-CoV-2', and 'host immune reaction against the SARS-CoV-2' are the hallmarks of this long journey. Conclusion: Elucidation of the functional viral dynamics will be helpful for disease management at the individual- and community- based long-term management strategies.

Covid-19 scientific publications from Turkey

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak poses a major global threat to the public health worldwide. The infectious disease caused by the virus that affected the entire world was named as the Coronavirus disease-2019 (COVID-19). The knowledge regarding the wide clinico-biological aspects of the COVID-19 continues to evolve very rapidly, given the growing data from all over the world. During this complicated process, healthcare professionals have benefited from each other's experiences in combatting against the COVID-19 syndrome. COVID-19 related studies have been performed by a wide variety of research groups in Turkey as well as the rest of the world. The aim of this paper is to outline Turkish COVID-19 research indexed in the LitCovid system. LitCovid is a curated literature hub for tracking up-to-date scientific data about the SARS-CoV-2. COVID-19's first case was detected in Turkey, on March 11th, 2020. Six months after the first case was observed, the total number of COVID-19 patients was reported to be as 286,455, and the total number of deaths due to SARS-CoV-2 was 6895. The genetic sequence of the novel coronavirus showed significant identity to SARS-CoV and MERS-CoV. Numerous drugs including lopinavir/ritonavir, favipiravir, neuraminidase inhibitors, remdesivir, umifenovir, azithromycin, and chloroquine have been suggested for the management of COVID-19 although the exact treatment is yet to be determined.

Could Targeting HMGB1 be Useful for the Clinical Management of COVID-19 Infection?

Since the high mobility group box-1 (HMGB1) molecule had been recognized as a proinflammatory cytokine, which mediates endotoxin lethality of mice, there have been lots of papers about targeting the HMGB1 within the contexts of infection, inflammation, and cancer. The pathogenic impact of HMGB1 to the severe acute respiratory syndrome (SARS) and disease management with herbal formulations targeting this unique protein have already been proposed. However, the failure of the numerous current anti-viral therapies on the ongoing viral infections casts reappraisal of the possible interrelationships regarding the HMGB1 and SARS-CoV-2. COVID-19 pandemic due to the SARS-CoV-2 virus is a currently ongoing challenging global health crisis. There is still not any proven exact treatment of COVID-19 with high level of evidence. In this paper, we focused on the potential usage of external and/or inhalation preparation of antiviral/antibacterial herbal products capable of targeting HMGB1 for the clinical management candidates of the ongoing COVID-19 infection.

Ankaferd hemostat (ABS) as a potential mucosal topical agent for the management of COVID-19 syndrome based on its PAR-1 inhibitory effect and oestrogen content.

COVID-19 due to the SARS-CoV-2 infection is a multi-systemic immune syndrome affecting mainly the lungs, oropharyngeal region, and other vascular endothelial beds. There are tremendous ongoing efforts for the aim of developing drugs against the COVID-19 syndrome-associated inflammation. However, currently no specific medicine is present for the absolute pharmacological cure of COVID-19 mucositis. The re-purposing/re-positioning of already existing drugs is a very important strategy for the management of ongoing pandemy since the development of a new drug needs decades. Apart from altering angiotensin signaling pathways, novel drug candidates for re-purposing comprise medications shall target COVID-19 pathobiology, including pharmaceutical formulations that antagonize proteinase-activated receptors (PARs), mainly PAR-1. Activation of the PAR-1, mediators and hormones impact on the hemostasis, endothelial activation, alveolar epithelial cells and mucosal inflammatory responses which are the essentials of the COVID-19 pathophysiology. In this context, Ankaferd hemostat (Ankaferd Blood Stopper, ABS) which is an already approved hemostatic agent affecting via vital erythroid aggregation and fibrinogen gamma could be a potential topical remedy for the mucosal management of COVID-19. ABS is a clinically safe and effective topical hemostatic agent of plant origin capable of exerting pleiotropic effects on the endothelial cells, angiogenesis, cell proliferation and vascular dynamics. ABS had been approved as a topically applied hemostatic agent for the management of post-surgical/dental bleedings and healing of infected inflammatory mucosal wounds. The anti-inflammatory and proteinase-activated receptor axis properties of ABS with a considerable amount of oestrogenic hormone presence highlight this unique topical hemostatic drug regarding the clinical re-positioning for COVID-19-associated mucositis. Topical ABS as a biological response modifier may lessen SARS-CoV-2 associated microthrombosis, endothelial dysfunction, oropharyngeal inflammation and mucosal lung damage. Moreover, PAR-1 inhibition ability of ABS might be helpful for reducing the initial virus propagation and mocasal spread of COVID-19.

Perspectives for immune plasma treatment of COVID-19

Background/aim: The SARS-CoV-2 infection was declared as a pandemic by the World Health Organization (WHO) on March 11, 2020, and the death toll from COVID-19, which is the disease caused by SARS-CoV-2, has already surpassed that of many previous epidemics. A wide variety of treatment options are being considered for COVID-19, but there is still no definitive treatment or vaccine. This study aims to explain the background of convalescent plasma (CP) treatment and its relations with COVID-19 immunity, to define ideal treatment procedures, and to reveal present and future perspectives in the light of the rapidly growing data. Immunological basis of COVID-19-associated immune response and convalescent plasma as a treatment option: Since it has been shown that the impaired immune response of the host is one of the most important factors that increase the severity of the infection, treatment strategies to suppress aberrant immune activation are currently being considered. CP, which is derived from recently recovered patients and contains neutralizing antibodies and many other immune- modulatory substances, seems to be the most convenient strategy to restore normal immune function considering the fast spreading nature of the ongoing pandemic. Conclusion: Even though mechanisms of action of plasma therapy are not fully delineated, it was shown that it could lead to a reduction in mortality since other alternatives such as monoclonal antibodies or SARS-CoV-2 hyperimmunoglobulin require much more time and effort to be developed.

In vitro analysis of the renin-angiotensin system and inflammatory gene transcripts in human bronchial epithelial cells after infection with severe acute respiratory syndrome coronavirus.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a recently identified coronavirus family member that triggers a respiratory disease similar to severe acute respiratory syndrome coronavirus (SARS-CoV). SARS-CoV and SARS-CoV-2 are very similar to each other in many respects, such as structure, genetics, and pathobiology. We hypothesized that coronaviruses could affect pulmonary tissues via integration with the critical immune genes after their interaction with renin-angiotensin system (RAS) elements. The aim of the present bioinformatics study was to assess expression changes of the RAS and non-RAS genes, particularly immune response genes, in the lung epithelial cells after infection with SARS-CoV. METHODS: Linear regression, hierarchical clustering, pathway analysis, and network analysis were performed using the E-GEOD-17400 data set. RESULTS: The whole-genome expression data of the lung epithelial cells infected with SARS-CoV for 12, 24, and 48 hours were analyzed, and a total of 15 RAS family and 29 immune genes were found to be highly correlated with the exposure time to the virus in the studied groups. CONCLUSION: RAS genes are important at the initiation of the infections caused by coronavirus family members and may have a strong relationship with the exchange of immune genes in due course following the infection.

The effects of blood group types on the risk of COVID-19 infection and its clinical outcome

Background/aim: COVID-19 (Coronavirus disease of 2019) is an infectious disease outbreak later on declared as a pandemic, caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2). It spreads very rapidly and can result in severe acute respiratory failure. The clinical studies have shown that advanced age and chronic diseases increase the risk of infection. However, influence of the blood groups on COVID-19 infection and its outcome remains to be confirmed. The aim of this study is to investigate whether there exists a relationship between the blood groups of the patients and risk of SARS-CoV-2 infection and the clinical outcomes in COVID-19 patients Material and method: 186 patients with PCR confirmed diagnosis of COVID-19 were included in this study. Age, sex, blood groups, comorbidities, need for intubation and intensive care unit follow up and mortalities of the patients were analyzed retrospectively. 1881 healthy individuals, who presented to the Hacettepe University Blood Bank served as the controls. Results: The most frequently detected blood group was blood group A (57%) amongst the COVID-19 patients. This was followed by blood group O (24.8%). The blood group types did not affect the clinical outcomes. The blood group A was statistically significantly more frequent among those infected with COVID-19 compared to controls (57% vs. 38%, P < 0.001; OR: 2.1). On the other hand, the frequency of blood group O was significantly lower in the COVID-19 patients, compared to the control group (24.8% vs. 37.2%, P: 0.001; OR: 1.8). Conclusions: The results of the present study suggest that while the blood group A might have a role in increased susceptibility to the COVID-19 infection, the blood group O might be somewhat protective. However, once infected, blood group type does not seem to influence clinical outcome.

Convalescent (immune) plasma treatment in a myelodysplastic COVID-19 patient with disseminated tuberculosis.

During the ongoing COVID-19 pandemic due to the SARS-CoV-2 virus of which evidence-based medical paradigms cannot be easily applied; difficult clinical decisions shall be required particularly in the 'difficult-to-treat' cases of high risk group with associated comorbidities. Convalescent immune plasma therapy is a promising option as a sort of 'rescue' treatment in COVID-19 immune syndrome, where miraculous antiviral drugs are not available yet. In this report, we aim to convey our experience of multi-task treatment approach with convalescent immune plasma and anti-cytokine drug combination in a COVID-19 patient with extremely challenging comorbidities including active myeloid malignancy, disseminated tuberculosis and kidney failure.

Local Bone Marrow Renin-Angiotensin System and COVID-19

For the first time on December 31, 2019, 27 cases of pneumonia of unknown etiology were detected in Wuhan City, Hubei province, China. The factor that caused this clinic was called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). In the following days, WHO officially named the disease caused by the new coronavirus as Coronavirus Disease 2019 (COVID-19). Patients infected with SARS-CoV-2 mostly applied to health centers with symptoms of dry cough, shortness of breath and fever. some patients have developed death-causing complications such as organ failure, septic shock, pulmonary edema, severe pneumonia, and Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 infects patients by binding human Angiotensin Converting Enzyme 2 (ACE 2), causing to severe pneumonia and high mortality. Circulating RAS and local paracrin-autocrin-intracrin tissue-based RAS participate in numerous pathobiological events. Pro-inflammatory, pro-fibrotic, and pro-thrombotic consequences associated with local RAS activation have been detected at cellular and molecular level. Regenerative progenitor cell therapy in response to RAS-modulating pharmacotherapy in context of endothelial cell damage and regeneration emerged as an auxiliary therapy to improve regeneration of the vascular endothelium. The aim of this article is to evaluate the relationship between circulating and local angiotensin systems and COVID-19.