The investigation of host genetic variants of toll-like receptor 7 and 8 in COVID-19.

Toll-like receptors (TLRs) recognize infectious agents and play an important role in the innate immune system. Studies have suggested that TLR single nucleotide polymorphisms (SNPs) are associated with poor antiviral responses against SARS-CoV-2. Therefore, we aimed to investigate the relationship of TLR7 and TLR8 (SNPs) with COVID-19 disease prognosis. A total of 120 COVID-19 patients, 40 outpatients, 40 clinical ward patients and 40 intensive care unit (ICU) patients were included in the study. TLR7 (rs179009), TLR8-129 C/G (rs3764879) and TLR8 Met1Val (rs3764880) SNPs were genotyped using the PCR-RFLP method. In female patients, individuals carrying AG genotype and G allele for TLR8 Met1Val SNP were found at a higher frequency in patients hospitalized in the ICU than in patients followed in the clinical ward (p < 0.05). In terms of the other two SNPs, no significant difference was found between the groups in females. Furthermore, in male patients, A allele of TLR7 rs179009 SNP was at a higher frequency in patients who have at least one comorbidity than in patients who have no comorbidity (p < 0.05). Our results suggest that TLR8 Met1Val SNP is important in the COVID-19 disease severity in females. Furthermore, TLR7 rs179009 SNP is important in male patients in the presence of comorbid diseases.

Multi-omics insights into host-viral response and pathogenesis in Crimean-Congo hemorrhagic fever viruses for novel therapeutic target.

The pathogenesis and host-viral interactions of the Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) are convoluted and not well evaluated. Application of the multi-omics system biology approaches, including biological network analysis in elucidating the complex host-viral response, interrogates the viral pathogenesis. The present study aimed to fingerprint the system-level alterations during acute CCHFV-infection and the cellular immune responses during productive CCHFV-replication in vitro. We used system-wide network-based system biology analysis of peripheral blood mononuclear cells (PBMCs) from a longitudinal cohort of CCHF patients during the acute phase of infection and after one year of recovery (convalescent phase) followed by untargeted quantitative proteomics analysis of the most permissive CCHFV-infected Huh7 and SW13 cells. In the RNAseq analysis of the PBMCs, comparing the acute and convalescent-phase, we observed system-level host's metabolic reprogramming towards central carbon and energy metabolism (CCEM) with distinct upregulation of oxidative phosphorylation (OXPHOS) during CCHFV-infection. Upon application of network-based system biology methods, negative coordination of the biological signaling systems like FOXO/Notch axis and Akt/mTOR/HIF-1 signaling with metabolic pathways during CCHFV-infection were observed. The temporal quantitative proteomics in Huh7 showed a dynamic change in the CCEM over time and concordant with the cross-sectional proteomics in SW13 cells. By blocking the two key CCEM pathways, glycolysis and glutaminolysis, viral replication was inhibited in vitro. Activation of key interferon stimulating genes during infection suggested the role of type I and II interferon-mediated antiviral mechanisms both at the system level and during progressive replication.

Crimean-Congo hemorrhagic fever (CCHF) is an emerging disease that is increasingly spreading to new populations. The condition is now endemic in almost 30 countries in sub-Saharan Africa, South-Eastern Europe, the Middle East and Central Asia. CCHF is caused by a tick-borne virus and can cause uncontrolled bleeding. It has a mortality rate of up to 40%, and there are currently no vaccines or effective treatments available. All viruses depend entirely on their hosts for reproduction, and they achieve this through hijacking the molecular machinery of the cells they infect. However, little is known about how the CCHF virus does this and how the cells respond. To understand more about the relationship between the cell's metabolism and viral replication, Neogi, Elaldi et al. studied immune cells taken from patients during an infection and one year later. The gene activity of the cells showed that the virus prefers to hijack processes known as central carbon and energy metabolism. These are the main regulator of the cellular energy supply and the production of essential chemicals. By using cancer drugs to block these key pathways, Neogi, Elaldi et al. could reduce the viral reproduction in laboratory cells. These findings provide a clearer understanding of how the CCHF virus replicates inside human cells. By interfering with these processes, researchers could develop new antiviral strategies to treat the disease. One of the cancer drugs tested in cells, 2-DG, has been approved for emergency use against COVID-19 in some countries. Neogi, Elaldi et al. are now studying this further in animals with the hope of reaching clinical trials in the future.

[COVID-19 Co-infection in a patient with Crimean Congo Hemorrhagic Fever: A Case Report]. / Kirim Kongo Kanamali Atesi Hastasinda COVID-19 Ko-enfeksiyonu: Bir Olgu Sunumu.

Crimean-Congo Hemorrhagic Fever (CCHF) is an acute viral zoonotic disease. Coronavirus disease-2019 (COVID-19) is a newly emerging viral disease and it is caused by "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)". In this article, a case diagnosed with CCHF and COVID-19 coinfection confirmed by the polymerase chain reaction (PCR) method and its management was presented. A thirtyfive years old female patient admitted to the hospital with the complaint of fever for one day and common body pain. It was learned that three days before the onset of her complaints, she removed a tick adhering to the anterior abdominal wall with no precaution. Her body temperature was 38°C degrees and her respiratory rate was 22 per minute. The leucocyte count was 3660/mm³ and the platelet count was 138.000/mm³. It was determined that prothrombin time was 15.4 seconds, international normalized ratio (INR) was 1.35 seconds, and D-dimer level was 1310 ng/ml. The patient was hospitalized with prediagnosis of CCHF. Supportive treatment was started. On the second day at the clinical follow-up of the patient, complaints of sore throat and cough without sputum started. A combined nasopharyngeal and throat swab sample was taken from the patient because of the suspicion of COVID-19. COVID-19 PCR test result was reported as positive. Favipiravir treatment was started. The CCHF-PCR test, which was studied from the serum sample sent to the Microbiology Reference Laboratories was reported as positive. From the third day of favipiravir treatment; the patient did not have a fever and her complaints regressed. On the ninth day of her hospitalization, she was discharged. In this case; it is important to show that both diseases, especially in regions where CCHF disease is endemic, can be confused due to the similarity of the clinical picture with COVID-19 and to know that they can coexist.