The suppressor of cytokine signaling-1 (SOCS1) gene polymorphism and promoter methylation correlate with the course of COVID-19.

The suppressor of the cytokine signaling-1 (SOCS1) gene is a short sequence located on chromosome 16 that functions to induce an appropriate immune response and is an essential physiological regulator of interferon (IFN) signaling. In addition to comparing the global DNA and SOCS1 gene promoter methylation status between our patients with coronavirus disease 2019 (COVID-19) and healthy controls, this study demonstrates the effect of the SOCS1 rs33989964 polymorphism on patients with COVID-19. The study group included 139 patients diagnosed with COVID-19 in our hospital's clinics between June and December 2020, and the control group included 78 healthy individuals. After comparing the initial gene polymorphisms of the patients with the healthy control group, three separate clinical subgroups were formed. The gene polymorphism distribution and the methylation status of SOCS1 were examined in these clinical subgroups. Hypomethylation of the SOCS1 gene was observed in the COVID-19 patient group compared to the healthy control group (p = 0.001). Between the patients divided into two separate clinical subgroups, those with severe and mild infections, the Del/Del genotype of the SOCS1 gene was more common in patients with severe infection than in patients with mild infection (p = 0.018). Patients with the CA/CA and CA/Del genotypes were 0.201 times more likely to have a severe infection (95% CI: 0.057-0.716, p = 0.007). Having a non-Del/Del genotype was a protective factor against severe infection. The effect of the SOCS1 rs33989964 polymorphism and methylation status of the SOCS1 gene throughout the COVID-19 pandemic could be significant contributions to the literature.

A COVID-19 mystery: multisystem inflammatory syndrome in adults (MIS-A) associated with splenic rupture.

Severe inflammation and one or more extrapulmonary organ dysfunctions have been observed in those who had recently developed COVID-19, except for a macrophage activation syndrome-like picture. A 50-year-old female patient was admitted to the emergency department with fever and a history of COVID-19 infection. More than one area of hemophagocytosis was found in the bone marrow aspiration. The HLH-2004 protocol was started with neurological involvement and she underwent splenectomy due to massive intra-abdominal bleeding secondary to splenic laceration on the 3rd day. Multiple microthrombosis and infarcts were observed in the splenectomy specimen. At the 4th week of the treatment, she was discharged with oral agents. Splenic microthrombosis and splenic rupture due to "multisystem inflammatory syndrome in adults" are the most important findings of this report.

Could serum thrombocyte/lymphocyte (TLR), neutrophil/lymphocyte (NLR) and neutrophil/albumin (NAR) ratios be indicators of hospitalization and mortality in COVID-19?

Background and Objectives: Neutrophil / lymphocyte (NLR) and thrombocyte / lymphocyte ratios (TLR) are also a guiding factors in the prognostic evaluation of infectious diseases. Another parameter to determine inflammation and prognosis is albumin. This study was aimed to determine whether TLR, NLR and neutrophil / albumin ratios (NAR) are effective in predicting the severity and course of Corona Virus Disease-2019 (COVID-19). Materials and Methods: In this retrospective and cross-sectional study, a total of 1597 patients who were admitted to our hospital between 15.03.2020-1.06.2020, diagnosed with COVID-19 were evaluated. Results: In the estimation of the decision for hospitalization, TLR, NLR and NAR AUROC values were 0.596, 0.634, 0.602 for cutoff values 123.7, 2.3 and 839.5, respectively. In predicting mortality, TLR, NLR and NAR AURO sample size can be specified C values were 0.674, 0.821, 0.787 for cutoff values 168.1, 5.2 and 1303.4, respectively (p <0.001 for all). Conclusion: In our study, it was determined that TLR, NLR and NAR are independent predictors in making the decision of hospitalization and in determining the prognosis in patients who are decided to be hospitalized.

The effect of DNA repair gene variants on COVID-19 disease: susceptibility, severity, and clinical course.

Oxidative stress (OS), which leads to DNA damage, plays a role in the pathogenesis of Coronavirus disease 2019 (COVID-19). We aimed to evaluate the role of DNA repair gene variants [X-ray repair cross complementing 4 (XRCC4) rs28360071, rs6869366, and X-ray cross-complementary gene 1 (XRCC1) rs25487] in susceptibility to COVID-19 in a Turkish population. We also evaluated its effect on the clinical course of the disease. A total of 300 subjects, including 200 COVID-19 patients and 100 healthy controls, were included in this study. These variants were genotyped using polymerase chain reaction (PCR) and/or PCR-restriction fragment length polymorphism (RFLP) methods. The patients were divided into three groups: those with a mild or severe infection; those who died or lived at the 28-day follow-up; those who required inpatient treatment or intensive care. There were 87 women (43.5%) and 113 men (56.5%) in the patient group. Hypertension was the most common comorbidity (26%). In the patient group, XRCC4 rs6869366 G/G genotype and G allele frequency were increased compared to controls, while XRCC4 rs6869366 G/T and T/T genotype frequencies were found to be higher in controls compared to patients. For XRCC1 rs25487, the A/A and A/G genotypes were significantly associated with COVID-19 disease. All of the patients hospitalized in the intensive care unit had the XRCC4 rs6869366 G/G genotype. In this study, we evaluated for the first time the impact of DNA repair gene variants on COVID-19 susceptibility. Results suggested that XRCC4 rs6869366 and XRCC1 rs25487 were associated with COVID-19 suspectibility and clinical course.

Lateral flow assay (LFA) in the diagnosis of COVID-19-associated pulmonary aspergillosis (CAPA): a single-center experience.

BACKGROUND: Invasive pulmonary aspergillosis (IPA) is seen during coronavirus-2019 (COVID-19), has been reported in different incidences, and is defined as COVID-19-associated pulmonary aspergillosis (CAPA). Detection of galactomannan antigen is an important diagnostic step in diagnosing IPA. Enzyme-linked immunoassay (ELISA) is the most frequently used method, and lateral flow assay (LFA) is increasingly used with high sensitivity and specificity for rapid diagnosis. The present study aimed to compare the sensitivity of LFA and ELISA in the diagnosis of CAPA in COVID-19 patients followed in our hospital's ICU for pandemic (ICU-P). METHODS: This study included patients with a diagnosis of COVID-19 cases confirmed by polymerase chain reaction and were followed up in ICU-P between August 2021 and February 2022 with acute respiratory failure. The diagnosis of CAPA was based on the European Confederation of Medical Mycology (ECMM) and the International Society for Human and Animal Mycology 2020 (ECMM/ ISHAM) guideline. Galactomannan levels were determined using LFA and ELISA in serum samples taken simultaneously from the patients. RESULTS: Out of the 174 patients followed in the ICU-P, 56 did not meet any criteria for CAPA and were excluded from the analysis. The rate of patients diagnosed with proven CAPA was 5.7% (10 patients). A statistically significant result was obtained with LFA for the cut-off value of 0.5 ODI in the diagnosis of CAPA (p < 0.001). The same significant statistical relationship was found for the cut-off value of 1.0 ODI for the ELISA (p < 0.01). The sensitivity of LFA was 80% (95% CI: 0.55-1.05, p < 0.05), specificity 94% (95% CI: 0.89-0.98, p < 0.05); PPV 53% (95% CI: 0.28-0.79, p > 0.05) and NPV was 98% (95% CI: 0.95-1.01, p < 0.05). The risk of death was 1.66 (HR: 1.66, 95% CI: 1.02-2.86, p < 0.05) times higher in patients with an LFA result of ≥ 0.5 ODI than those with < 0.5 (p < 0.05). CONCLUSIONS: It is reckoned that LFA can be used in future clinical practice, particularly given its effectiveness in patients with hematological malignancies and accuracy in diagnosing CAPA.

Efficacy of the lactate dehydrogenase (LDH)/lymphocyte ratio (LLR) to reduce the need for X-ray in pregnant patients with COVID-19.

OBJECTIVES: Pregnancy carries a significant risk for coronavirus disease-2019 (COVID-19) due to natural immunosuppression. A previous study from our center has shown that the lactate dehydrogenase (LDH)/lymphocyte ratio (LLR) can be used in the early diagnosis of COVID-19 and predicting mortality. Based on this, we aimed to determine the effect of LLR on early detection of critical pregnant women and mortality in COVID-19. METHODS: The data of 145 patients who were admitted to our hospital between March and December 2020; diagnosed with COVID-19 and hospitalized, were retrospectively analyzed. RESULTS: The median gestation period was 31 weeks (range: 5-41), 30.3% (n: 44) gave birth and 68.3% (n: 99) were pregnant. Median LLR was 0.13 (range: 0.04-0.70). The rate of cough (47% vs. 22.8%; p=0.003) was found to be high in patients with LLR>0.13. The patients were divided into subgroups. The proportion of patients without active complaints was higher in the Q1, followed by the Q4. The proportion of patients with an initial complaint of cough increased as LLR from Q1 to Q4, the distribution of other complaints did not differ between the quartiles. CONCLUSIONS: The higher rate of cough in the group with high LLR indicates that it may be an important indicator of lung involvement during pregnancy. The highest rate of non-treatment follow-up in the lowest LLR group proved that the LLR value at the time of diagnosis can be used as an important clinical marker in pregnant women.

Enigma of COVID-19: is "multisystem inflammatory syndrome in adults" (MIS-A) predictable?

BACKGROUND: Severe inflammation and one or more extrapulmonary organ dysfunctions have been reported and this clinical picture is defined as "multisystem inflammatory syndrome in adults" (MIS-A) in severe coronavirus disease-2019 (COVID-19). We aimed to determine the effect of LDH/lymphocyte ratio (LLR) on the development of MIS-A. METHODS: The data of 2333 patients were retrospectively analyzed. RESULTS: MIS-A rate was found to be 9.9% and MIS-A related mortality was 35.3%. LRR level above 0.24 was found to predict MIS-A development with 70% sensitivity and 65.2% specificity. The risk of MIS-A development was found to be 3.64 times higher in those with LRR levels above 0.24 compared to those with 0.24 and below. In patients with MIS-A, LRR level above 0.32 predicts mortality with 78% sensitivity and 70% specificity. CONCLUSIONS: Early detection of MIS-A with high sensitivity and specificity in a practical ratio is very important in terms new studies.

Is There a Link between Circadian Clock Protein PERIOD 3 (PER3) (rs57875989) Variant and the Severity of COVID-19 Infection?

OBJECTIVE: Corona Virus Disease-2019 (COVID-19) has been among the major infectious events of the century. In today's literature where COVID-19 and host factor effects are frequently examined, we aimed to examine another factor: Circadian Clock Protein PERIOD 3 (PER3). There is a significant correlation between PER3 gene polymorphism and circadian rhythm disturbances and immune system dysregulation. METHODS: In our study, we recruited 200 patients diagnosed with COVID-19 in our hospital between April-June 2020, and 100 volunteers without known comorbidities to create a healthy control group. After comparing the initial gene polymorphisms of the patients with healthy controls, three separate clinical subgroups were formed. Gene polymorphism distribution and statistical significance were examined in the formed patient groups. RESULTS: No significant difference was found between the patient group and the healthy controls (P>0.05, for all). When patients were divided into two separate clinical subgroups as exitus/alive according to their last condition during their 28-day follow-up, the 4R/5R genotype was significantly more common in patients with a mortal course (P=0.007). The PER3 4R/5R genotype was found at a significantly higher rate in the group of patients with the need for intensive care (P=0.034). CONCLUSION: The 4R/5R genotype may be associated with the need for intensive care and mortality in COVID-19 patients. These important results will be a guide for future studies.

Investigation of MBL2 and NOS3 functional gene variants in suspected COVID-19 PCR (-) patients.

For COVID-19 (Coronavirus Disease-2019) cases, detecting host-based factors that predispose to infection is a very important research area. In this study, the aim is to investigate the MBL2 and NOS3 gene polymorphisms in COVID-19 patients with lung involvement, whose first nasopharyngeal PCR results were negative. Seventy-nine patients diagnosed with COVID-19 between April-June 2020 who were admitted to a university hospital, and 100 healthy controls were included. In the first statistical analysis performed between PCR-positive, CT-negative and PCR-negative, CT-positive patients; the AB of MBL2 genotype was significantly higher in the first group (p = 0.049). The B allele was also significantly higher in the same subgroup (p = 0.001). The absence of the AB genotype was found to increase the risk of CT positivity by 6.9 times. The AB genotype of MBL2 was higher in healthy controls (p = 0.006). The absence of the AB genotype was found to increase the risk of CT positivity; also, it can be used for early detection and isolation of patients with typical lung involvement who had enough viral loads, but whose initial PCR results were negative.

COVID-19 Pneumonia or Hypereosinophilic Syndrome?

Hypereosinophilic syndromes (HESs) are a group of disorders characterized by pathological proliferation of eosinophils. Diagnostic criteria include eosinophil count of 1,500/mm3 or higher, presence of organ involvement and exclusion of other causes of eosinophilia for at least 6 months. A 69-year-old male patient was referred to the pandemic clinic with a preliminary diagnosis of coronavirus disease 2019 (COVID-19) with fever and dyspnea. Computed tomography (CT) was compatible with COVID-19, nasopharyngeal swab polymerase chain reaction (PCR) was negative for two times. He had 20,000/mm3 eosinophilia and retrospective examinations showed that he have had eosinophilia for more than 1 year. Platelet-derived growth factor receptor alpha (PDGFRα) resulted positively. After starting parenteral methylprednisolone with a dose of 1 mg/kg, he was discharged with oral maintenance therapy. In outpatient follow-up, it was observed that eosinophilic pneumonia completely regressed. HES may occur with multiple system and organ involvement and findings. In the differential diagnosis of patients presenting with heart failure, pulmonary involvement and eosinophilia, HES must definitely be considered.

A new parameter in COVID-19 pandemic: initial lactate dehydrogenase (LDH)/Lymphocyte ratio for diagnosis and mortality.

BACKGROUND: COVID-19 (Coronavirus Disease-2019) is a pandemic disease, infecting more than 26.5 million people. Since there is no specific and effective treatment; early diagnosis and optimal isolation of the patient are of vital importance. Real-time polymerase chain reaction-based (RT-PCR) analyses do not achieve sufficient sensitivity in the diagnosis of the disease. METHODS: The data from 2217 patients diagnosed as COVID-19 between March 2020 and June 2020 and hospitalized or discharged with home isolation were retrospectively analyzed. Demographic data, comorbidities, PCR results, initial computed tomography (CT), laboratory values, Lactate Dehydrogenase (LDH)/Lymphocyte ratio, initial treatments and last status were recorded. The diagnostic sensitivity of LDH/Lymphocyte ratio, which is the main purpose of the study, was analyzed statistically. RESULTS: In order to test the effectiveness of LDH/Lymphocyte ratio for COVID-19 for diagnostic purposes, CT results were considered as gold standard. The area under the curve (AUC) was found to be 0.706 (p < 0.001; cut-off > 0.06) (Sensitivity: 76.4, specificity: 59.60). For the evaluation of LDH/Lymphocyte ratio in terms of survival, AUC was found to be 0.749 (p < 0.001; cut-off > 0.21) (Sensitivity: 70.59, specificity: 73.88). CONCLUSION: Studies based on radiological findings have demonstrated that CT involvement has higher sensitivity. LDH/Lymphocyte ratio was analyzed in terms of diagnosis and mortality with using specific CT involvement as gold standard method which was found to be a more sensitive due to PCR false negativity; 0.06 and 0.21 were obtained as cut off values for diagnosis and mortality.