Effects of COVID-19 Disease on DNA Damage, Oxidative Stress and Immune Responses.

Coronavirus disease 2019 (COVID-19) has posed a great threat to public health and has caused concern due to its fatal consequences over the last few years. Most people with COVID-19 show mild-to-moderate symptoms and recover without the need for special treatment, while others become seriously ill and need medical attention. Additionally, some serious outcomes, such as heart attacks and even stroke, have been later reported in patients who had recovered. There are limited studies on how SARS-CoV-2 infection affects some molecular pathways, including oxidative stress and DNA damage. In this study, we aimed to evaluate DNA damage, using the alkaline comet assay, and its relationship with oxidative stress and immune response parameters in COVID-19-positive patients. Our results show that DNA damage, oxidative stress parameters and cytokine levels significantly increased in SARS-CoV-2-positive patients when compared with healthy controls. The effects of SARS-CoV-2 infection on DNA damage, oxidative stress and immune responses may be crucial in the pathophysiology of the disease. It is suggested that the illumination of these pathways will contribute to the development of clinical treatments and to reduce adverse effects in the future.

Safety and immunogenicity of inactive vaccines as booster doses for COVID-19 in Türkiye: A randomized trial.

Protective neutralizing antibody titers reduce in time after COVID-19 vaccinations, as in individuals who have had COVID-19. This study aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as a booster dose after CoronaVac primary vaccination. This double-blind, randomized, controlled, phase II, multicenter study included healthy male and female adults (18-60 years) who were vaccinated with two doses of CoronaVac vaccine and did not exceed the duration of at least 90 days and a maximum of 270 days from the second dose of vaccination. Among 236 eligible volunteers, 222 were recruited for randomization between July 12, 2021 and September 10, 2021; 108 and 114 were randomized to the TURKOVAC and CoronaVac arms, respectively. The primary endpoint was adverse events (AEs) (ClinicalTrials.gov; Identifier: NCT04979949). On day 28, at the neutralizing antibody threshold of 1/6, the positivity rate reached 100% from 46.2% to 98.2% from 52.6% in the TURKOVAC and CoronaVac arms, respectively, against the Wuhan variant and the positivity rate reached 80.6% from 8.7% in the TURKOVAC arm vs. 71.9% from 14.0% in the CoronaVac arm against the Delta variant. IgG spike antibody positivity rate increased from 57.3% to 98.1% and from 57.9% to 97.4% in the TURKOVAC and CoronaVac arms, respectively. The TURKOVAC and CoronaVac arms were comparable regarding the frequency of overall AEs. Both vaccines administered as booster yielded higher antibody titers with acceptable safety profiles.

What is the context? The timing of the primary and booster doses for each vaccine differs.We aimed to evaluate the safety and immunogenicity of CoronaVac and TURKOVAC vaccines used as homologous booster dose after CoronaVac primary vaccination.What is new? The neutralizing antibody titers against the Wuhan variant decreased below 1/6- the seropositivity threshold value- in more than 55% of the participants 4 months after administration of two doses of CoronaVac vaccine.Immunogenicity was re-stimulated and the neutralizing antibody titers increased rapidly and markedly with the administration of the CoronaVac or TURKOVAC as a booster dose 4 months after the second dose.While the increase in neutralizing antibodies against the Wuhan variant was similar with both CoronaVac and TURKOVAC, more antibodies developed against the Delta variant with TURKOVAC.What is the impact? With the Hybrid COV-RAPEL TR study, after the primary vaccination consisting of two doses of inactivated vaccine, antibody titers decreased in the long term; however, higher antibody titers are achieved than the primary vaccination after the booster dose administered after 4­6 month interval.Booster application with TURKOVAC provides antibodies at least as much as the CoronaVac booster dose, with an acceptable safety profile.

Comparison of the Clinical and Laboratory Findings and Outcomes of Hospitalized COVID-19 Patients Who Were Either Fully Vaccinated with Coronavac or Not: An Analytical, Cross Sectional Study.

COVID-19 vaccines are highly protective against severe disease; however, vaccine breakthrough infections resulting in hospitalization may still occur in a small percentage of vaccinated individuals. We investigated whether the clinical and microbiological features and outcomes were different between hospitalized COVID-19 patients who were either fully vaccinated with Coronovac or not. All hospitalized COVID-19 patients who had at least one dose of Coronavac were included in the study. The oldest unvaccinated patients with comorbidities, who were hospitalized during the same period, were chosen as controls. All epidemiologic, clinical and laboratory data of the patients were recorded and compared between the fully vaccinated and unvaccinated individuals. There were 69 and 217 patients who had been either fully vaccinated with Coronavac or not, respectively. All breakthrough infections occurred in the first 3 months of vaccination. Fully vaccinated patients were older and had more comorbidities than unvaccinated patients. There were minor differences between the groups in symptoms, physical and laboratory findings, anti-spike IgG positivity rate and level, the severity of COVID-19, complications, and clinical improvement rate. The mortality rate of fully vaccinated patients was higher than the mortality rate in unvaccinated patients in univariate analysis, which was attributed to the fact that vaccinated patients were older and had more comorbidities. The severity and clinical outcomes of hospitalized patients with breakthrough COVID-19 after Coronavac vaccination were similar to those of unvaccinated patients. Our findings suggest that the immune response elicited by Coronovac could be insufficient to prevent COVID-19-related severe disease and death within 3 months of vaccination among elderly people with comorbidities.

COVID-19 Pandemisinin Ílk Dalgasında Bir Eğitim ve Araştırma Hastanesi Deneyimi: Yoğun Bakım Íhtiyacı ile Ílişkili Risk Faktörleri

Objective: In this study, we aimed to determine the characteristics of patients with COVID-19 pneumonia who were hospitalized in our hospital in the first wave of the pandemic and the factors affecting the need for intensive care. Methods: Patients aged 18 years and older, hospitalized with the diagnosis of COVID-19 between 01/04/2020- 30/06/2020 were included in the study. Demographic and clinical characteristics of the patients were reviewed retrospectively from their files. Multivariate logistic regression analysis was performed to evaluate the factors predicting the need for intensive care. Results: A total of 143 patients with COVID-19 pneumonia were included in the study. Eighty-nine of the patients (62.2%) were male;the mean age was 59±15 years. 59.2% of the patients had at least one comorbidity. Thirty-nine (27.2%) patients developed the need for intensive care during their follow-up. Ferritin>400ng/ml (p:0.003, odds ratio- OR:15.2, 95% confidence interval- CI:2.479-93.2), severe involvement on thorax computed tomography (CT) (p:0.0, OR:44.92, 95% CI:5.681-355.3) were independent risk factors affecting the need for intensive care. The mortality rate was 23.1% in all patients included in the study, and the mortality rate was 84.6% in patients who needed intensive care. Conclusions: In addition to typical pneumonia symptoms, ferritin values, thorax CT findings, can be used as indicators to distinguish patients who may need intensive care at an early stage. Considering these risks at the time of admission in the management of patients hospitalized with COVID-19 will lead to better results. Amaç: Bu çalışmada, pandeminin ilk dalgasında hastanemizde yatırılarak takip edilen COVID-19 pnömonili hastaların özelliklerini ve aynı zamanda yoğun bakım ihtiyacını etkileyen faktörleri belirlemeyi amaçladık. Yöntemler: Çalışmaya, 01 Nisan 2020-30 Haziran 2020 tarihleri arasında COVID-19 tanısı ile hastanede yatan, 18 yaş ve üstü hastalar dahil edildi. Hastaların demografik ve klinik özellikleri dosyalarından retrospektif olarak incelendi. Yoğun bakım ihtiyacını öngören faktörleri değerlendirmek için çok değişkenli lojistik regresyon analizi yapıldı. Bulgular: COVID-19 pnömonisi olan toplam 143 hasta çalışmaya dahil edildi. Hastaların 89 (%62.2)'u erkek, yaş ortalaması 59±15 olup %59.2'sinde en az bir komorbidite vardı. Takiplerinde yoğun bakım ihtiyacı gelişen 39 (%27.2) hasta oldu. Yoğun bakım ihtiyacını etkileyen bağımsız risk faktörleri olarak;ferritin>400ng/ml (p:0.003, "odds ratio" OR:15.2, %95 güven aralığı GA:2.479- 93.2), toraks bilgisayarlı tomografide (BT) ağır tutulum (p:0.0, OR:44.92, %95 GA:5.681- 355.3) saptandı. Çalışmaya dahil edilen tüm hastalarda mortalite oranı %23.1;yoğun bakım ihtiyacı olan hastalarda ise %84.6 olarak saptandı. Sonuçlar: Tipik pnömoni belirtilerine ek olarak, yoğun bakım ihtiyacı gelişebilecek hastaları erken evrede ayırt etmek için;ferritin değeri, toraks BT bulgusu gösterge olarak kullanılabilir. COVID-19 tanısı ile hastaneye yatırılan hastaların yönetiminde başvuru sırasındaki bu riskleri de dikkate almak daha iyi sonuçlar alınmasını sağlayacaktır.

Diagnostic performance of thorax CT in mildly symptomatic COVID-19 patients: The importance of atypical CT findings.

OBJECTIVE: Computed tomography of the thorax (Thorax CT) is frequently used to diagnose viral pneumonia in moderate to severe COVID-19 patients, but its diagnostic performance in mildly symptomatic COVID-19 patients is still unclear. Assessing the diagnostic performance of thorax CT in mildly symptomatic COVID-19 patients was the purpose of our study. METHODS: Mildly symptomatic and clinically stable, suspected COVID-19 patients scanned with Thorax CTs between March 11, 2020, and April 13, 2020, were included in this study. The sensitivity, specificity, positive and negative likelihood ratios, positive and negative predictive values, and the respective accuracies were calculated for diagnostic purposes. RESULTS: Among the 1119 patients enrolled in our study, abnormal thorax CT scans were 527 out of which 363/527 (68.9%) had typical CT features for COVID-19. According to analysis of typical COVID findings, sensitivity, specificity, positive predictive values, negative predictive value, and the accuracy of Thorax CTs with were 51.45%, 86.07%, 78.24%, 64.55%, and 68.99%, respectively. When typical CT findings and atypical CT findings were combined for the statistical analysis, the sensitivity, specificity, and accuracy observed 68.84%, 74%, and 71.49%. CONCLUSION: Diagnosing pneumonia can be challenging in mildly symptomatic COVID-19 patients since the Reverse Transcription Polymerase Chain Reaction test results, when compared with symptoms are not always evident. According to our study, thorax CT sensitivity was higher when atypical COVID-19 CT findings were included compared to those with typical COVID-19 CT findings alone. Our study which included the largest number of patients among all other similar studies indicates that not only typical but also atypical CT findings should be considered for an accured diagnosis of COVID-19 pneumonia.

Combined Metabolic Activators Accelerates Recovery in Mild-to-Moderate COVID-19.

COVID-19 is associated with mitochondrial dysfunction and metabolic abnormalities, including the deficiencies in nicotinamide adenine dinucleotide (NAD+ ) and glutathione metabolism. Here it is investigated if administration of a mixture of combined metabolic activators (CMAs) consisting of glutathione and NAD+ precursors can restore metabolic function and thus aid the recovery of COVID-19 patients. CMAs include l-serine, N-acetyl-l-cysteine, nicotinamide riboside, and l-carnitine tartrate, salt form of l-carnitine. Placebo-controlled, open-label phase 2 study and double-blinded phase 3 clinical trials are conducted to investigate the time of symptom-free recovery on ambulatory patients using CMAs. The results of both studies show that the time to complete recovery is significantly shorter in the CMA group (6.6 vs 9.3 d) in phase 2 and (5.7 vs 9.2 d) in phase 3 trials compared to placebo group. A comprehensive analysis of the plasma metabolome and proteome reveals major metabolic changes. Plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly improved in patients treated with CMAs as compared to placebo. The results show that treating patients infected with COVID-19 with CMAs lead to a more rapid symptom-free recovery, suggesting a role for such a therapeutic regime in the treatment of infections leading to respiratory problems.

Evaluation of Modified ATRIA Risk Score in Predicting Mortality in Hospitalized Patients With COVID-19.

BACKGROUND: As the Modified Anticoagulation and Risk Factors in Atrial Fibrillation Risk Score (M-ATRIA-RS) encompasses prognostic risk factors of novel coronavirus-2019 (COVID-19), it may be used to predict in-hospital mortality. We aimed to investigate whether M-ATRIA-RS was an independent predictor of mortality in patients hospitalized for COVID-19 and compare its discrimination capability with CHADS, CHA2DS2-VASc, and modified CHA2DS2-VASc (mCHA2DS2-VASc)-RS. METHODS: A total of 1,001 patients were retrospectively analyzed and classified into three groups based on M-ATRIA-RS, designed by changing sex criteria of ATRIA-RS from female to male: Group 1 for points 0-1 (n = 448), Group 2 for points 2-4 (n = 268), and Group 3 for points ≥5 (n = 285). Clinical outcomes were defined as in-hospital mortality, need for high-flow oxygen and/or intubation, and admission to intensive care unit. RESULTS: As the M-ATRIA-RS increased, adverse clinical outcomes significantly increased (Group 1, 6.5%; Group 2, 15.3%; Group 3, 34.4%; p <0.001 mortality for in-hospital). Multivariate logistic regression analysis showed that M-ATRIA-RS, malignancy, troponin increase, and lactate dehydrogenase were independent predictors of in-hospital mortality (p<0.001, per scale possibility rate for ATRIA-RS 1.2). In receiver operating characteristic (ROC) analysis, the discriminative ability of M-ATRIA-RS was superior to mCHA2DS2-VASc-RS and ATRIA-RS, but similar to that Charlson Comorbidity Index (CCI) score (AUCM-ATRIAvs AUCATRIA Z-test=3.14 p = 0.002, AUCM-ATRIAvs. AUCmCHA2DS2-VASc Z-test=2.14, p = 0.03; AUCM-ATRIAvs. AUCCCI Z-test=1.46 p = 0.14). CONCLUSIONS: M-ATRIA-RS is useful to predict in-hospital mortality among patients hospitalized with COVID-19. In addition, it is superior to the mCHA2DS2-VASc-RS in predicting mortality in patients with COVID-19 and is more easily calculable than the CCI score.

Seroprevalence of coronavirus disease 2019 (COVID-19) among health care workers from three pandemic hospitals of Turkey.

COVID-19 is a global threat with an increasing number of infections. Research on IgG seroprevalence among health care workers (HCWs) is needed to re-evaluate health policies. This study was performed in three pandemic hospitals in Istanbul and Kocaeli. Different clusters of HCWs were screened for SARS-CoV-2 infection. Seropositivity rate among participants was evaluated by chemiluminescent microparticle immunoassay. We recruited 813 non-infected and 119 PCR-confirmed infected HCWs. Of the previously undiagnosed HCWs, 22 (2.7%) were seropositive. Seropositivity rates were highest for cleaning staff (6%), physicians (4%), nurses (2.2%) and radiology technicians (1%). Non-pandemic clinic (6.4%) and ICU (4.3%) had the highest prevalence. HCWs in "high risk" group had similar seropositivity rate with "no risk" group (2.9 vs 3.5 p = 0.7). These findings might lead to the re-evaluation of infection control and transmission dynamics in hospitals.

The effect of moderate and severe COVID-19 pneumonia on short-term right ventricular functions: a prospective observational single pandemic center analysis.

It has been reported that myocardial damage and heart failure are more common in COVID-19 patients with severe symptoms. The aim of our study was to measure the right ventricular functions of COVID-19 patients 30 days after their discharge, and compare them to the right ventricular functions of healthy volunteers. Fifty one patients with COVID-19 and 32 healthy volunteers who underwent echocardiographic examinations were enrolled in our study. 29 patients were treated for severe and 22 patients were treated for moderate COVID-19 pneumonia. The study was conducted prospectively, in a single center, between 15 May 2020 and 15 July 2020. We analyzed the right ventricular functions of the patients using conventional techniques and two-dimensional speckle-tracking. Right ventricular end-diastolic and end-systolic area were statistically higher than control group. The right ventricular fractional area change (RVFAC) was significantly lesser in the patient group compared to the control group. Tricuspid annular plane systolic motion (TAPSE) was within normal limits in both groups, it was lower in the patient group compared to the control group. Pulmonary artery pressure was found to be significantly higher in the patient group. Right ventricular global longitudinal strain (RV-GLS) was lesser than the control group (- 15.7 [(- 12.6)-(- 18.7)] vs. - 18.1 [(- 14.8)-(- 21)]; p 0.011). Right ventricular free wall strain (RV-FWS) was lesser in the patient group compared to the control group (- 16 [(- 12.7)-(- 19)] vs - 21.6 [(- 17)-(- 25.3)]; p < 0.001). We found subclinical right ventricular dysfunction in the echocardiographies of COVID-19 patients although there were no risk factors.

The origin of SARS-CoV-2 in Istanbul: Sequencing findings from the epicenter of the pandemic in Turkey.

OBJECTIVE: Turkey is one of the latest countries that COVID-19 disease was reported, with the first case on March 11, 2020, and since then, Istanbul became the epicenter of the pandemic in Turkey. Here, we reveal sequences of the virus isolated from three different patients with various clinical presentations. METHODS: Nasopharyngeal swab specimens of the patients were tested positive for the COVID-19 by qRT-PCR. Viral RNA extraction was performed from the same swab samples. Amplicon based libraries were prepared and sequenced using the Illumina NextSeq platform. Raw sequencing data were processed for variant calling and generating near-complete genome sequences. All three genomes were evaluated and compared with other worldwide isolates. RESULTS: The patients showed various clinics (an asymptomatic patient, patient with mild disease, and with severe pulmonary infiltration). Amplicon-based next-generation sequencing approach successfully applied to generate near-complete genomes with an average depth of 2.616. All three viral genomes carried the D614G variant (G clade according to GISAID classification) with implications for the origin of a spread first through China to Europe then to Istanbul. CONCLUSION: Here, we report the viral genomes circulating in Istanbul for the first time. Further sequencing of the virus isolates may enable us to understand variations in disease presentation and association with viral factors if there is any. In addition, the sequencing of more viral genomes will delineate the spread of disease and will guide and ease the necessary measures taken to stem the spread of the novel coronavirus.