Abstract Background Literature with regard to coronavirus disease 2019 (COVID-19) associated morb... more Abstract Background Literature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage markers and their predictive value for survival among hospitalized subjects with COVID-19. Methods Forty-seven participants was included and grouped as: ‘COVID-19 patients before treatment’, ‘COVID-19 patients after treatment’, ‘COVID-19 patients under treatment in intensive care unit (ICU)’, and ‘controls’. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan–Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well. Results Serum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine–cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups ‘COVID-19 patients before treatment’ and ‘COVID-19 patients under treatment in ICU’. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22–30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00–2.52; p = 0.09). Conclusions Our findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.
BackgroundThe central role in the pathogenesis of severe acute respiratory syndrome coronavirus 2... more BackgroundThe central role in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), called as coronavirus disease 2019 (COVID-19), infection is attributed to angiotensin-converting enzyme 2 (ACE-2). ACE-2 expressing respiratory system involvement is the main clinical manifestation of the infection. However, literature about the association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and higher ACE-2 expressing kidney is very limited. In this study, we primarily aimed to investigate whether there is a kidney injury during the course of SARS-CoV-2 infection. The predictive value of kidney injury for survival was also determined.MethodsA total of 47 participants who met the inclusion criteria were included in the study. The participants were classified as ‘‘COVID-19 patients before treatment’’ ‘‘COVID-19 patients after treatment’’, ‘‘COVID-19 patients under treatment in ICU’’ and ‘‘controls’’. The parameters comorbidity...
The WHO-named Coronavirus Disease 2019 (COVID-19) infection had become a pandemic within a short ... more The WHO-named Coronavirus Disease 2019 (COVID-19) infection had become a pandemic within a short time period since it was detected in Wuhan. The outbreak required the screening of millions of samples daily and overwhelmed diagnostic laboratories worldwide. During this pandemic, the handling of patient specimens according to the universal guidelines was extremely difficult as the WHO, CDC and ECDC required cold chain compliance during transport and storage of the swab samples. The aim of this study was to compare the effects of two different storage conditions on the COVID-19 real-time PCR assay on 30 positive nasopharyngeal and/or oropharyngeal samples stored at both ambient temperature (22 ± 2 °C) and +4 °C. The results revealed that all the samples stored at ambient temperature remain PCR positive for at least six days without any false-negative result. In conclusion, transporting and storing these types of swab samples at ambient temperature for six days under resource-limited conditions during the COVID-19 pandemics are acceptable.
Expression levels of the major mammalian autophagy regulator Beclin 1 and its interaction with Bc... more Expression levels of the major mammalian autophagy regulator Beclin 1 and its interaction with Bcl-2 regulate the switch between autophagic cell survival and apoptotic cell death pathways. However, some of the regulators and the precise mechanisms of these processes still remain elusive. Bag-1 (Bcl-2 associated athanogene-1), a member of BAG family proteins, is a multifunctional pro-survival molecule that possesses critical functions in vital cellular pathways. Herein, we report the role of Bag-1 on Bcl-2/Beclin 1 crosstalk through indirectly interacting with Beclin 1. Pull-down experiments suggested a molecular interaction between Bag-1 and Beclin 1 in breast cancer cell lines. On the other hand, in vitro binding assays showed that Bag-1/Beclin 1 interaction does not occur directly but occurs through a mediator molecule. Bag-1 interaction with p-Beclin 1 (T119), indicator of early autophagy, is increased during nutrient starvation suggesting involvement of Bag-1 in the autophagic r...
The study investigated whether there is a male reproductive system coronavirus disease‐2019 (COVI... more The study investigated whether there is a male reproductive system coronavirus disease‐2019 (COVID‐19) phenomenon. Thirty participants who met the inclusion criteria were enrolled in the study between April and May 2020. The participants were assigned in one of the three groups including COVID‐19 patients before and after treatment, and controls. Presence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) within the semen samples was investigated. Additionally, participant's demographics, semen parameters and serum sex hormone levels were compared between the groups. SARS‐CoV‐2 was not detected within the semen samples. Sperm morphology and serum sex hormone levels were significantly different between the groups. In the post hoc analysis, sperm morphology was significantly lower in the COVID‐19 patients. Patients before treatment had significantly lower serum FSH, LH and T levels than controls. However, patients after treatment had similar serum FSH, LH and T levels with controls and patients before treatment. In our opinion, COVID‐19 and its treatment had no specific deteriorative effect on male sexual health at a short‐time period. In the patients before treatment, decreased serum of T, FSH and LH levels was consistent with acute patient stress due to COVID‐19. Similarly, it seems that decreased sperm morphology was associated with the acute fever.
ABSTRACTThere is a need to treat COVID-19 patients suffering from respiratory problems, resulting... more ABSTRACTThere is a need to treat COVID-19 patients suffering from respiratory problems, resulting in decreased oxygen levels and thus leading to mitochondrial dysfunction and metabolic abnormalities. Here, we investigated if a high oral dose of a mixture of Combined Metabolic Activators (CMA) can restore metabolic function and thus aid the recovery of COVID-19 patients. We conducted a placebo-controlled, open-label phase 2 study and a double-blinded phase 3 clinical trials to investigate the time of symptom-free recovery on ambulatory patients using a mixture of CMA consisting of NAD+ and glutathione precursors. The results of both studies showed that the time to complete recovery was significantly shorter in the CMA group (6.6 vs 9.3 days) in phase 2 and (5.7 vs 9.2 days) in phase 3 trials. A comprehensive analysis of the blood metabolome and proteome showed that the plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly ...
SummaryCOVID-19 is a viral respiratory disease caused by SARS-CoV-2 infection. Global efforts of ... more SummaryCOVID-19 is a viral respiratory disease caused by SARS-CoV-2 infection. Global efforts of genomic surveillance of the virus give chance to track the spread of the pandemic. Global emergence of some viral mutations called attention and various studies have been suggested about increased infectivity of the virus. Herein, we sequenced viral genomes isolated from 184 patients in Istanbul and analyzed clinical metadata for the investigation of any viral mutation which affects the disease course of the host. We did not detect any viral mutations affecting the disease outcome in our cohort. Besides, we observed intra-host mutations in 76% of the isolates. Insertion/deletion and stop-gain mutations are also significantly less common among intra-host variants compared to consensus viral genome mutations. Longitudinal genomic surveillance is essential for timely detection of any lineages that might affect clinical outcome, the performance of diagnostic assays, or even the immunological...
The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA i... more The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA in nasopharyngeal sample by RT-PCR. Recently, saliva samples has been suggested as an alternative due to being fast, reliable and non-invasive, rather than nasopharyngeal samples. We compared RT-PCR results in nasopharyngeal, oro-nasopharyngeal and saliva samples of COVID-19 patients. 98 of 200 patients were positive in RT-PCR analysis performed before the hospitalization. In day 0, at least one sample was positive in 67% of 98 patients. Positivity rate was 83% for both oro-nasopharyngeal and nasopharyngeal samples, while it was 63% for saliva samples (p<0.001). On day 5, RT-PCR was performed in 59 patients, 34% had at least one positive result. The positivity rate was 55% for saliva and nasopharyngeal samples, while it was 60% for oro-nasopharyngeal samples. Our study shows that the sampling saliva does not increase the sensitivity of RT-PCR tests at early stages of infection. However...
SUMMARYCOVID-19 is a global threat with an increasing number of infections. Research on IgG serop... more SUMMARYCOVID-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 3.6p=0.7), indicating the efficient implementation of protection measures in the hospitals in Turkey. These findings might lead to the re-evaluation of infecti...
Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal canc... more Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer‐free elderly controls, using next‐generation sequencing‐based multigene panel testing and multiplex ligation‐dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high‐risk BC patients and 26.4% of high‐risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two‐thirds of all pathogenic variants detected in high‐risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high‐risk BC patients (4.5%). BRCA1 exons 17‐18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC,...
ABSTRACTBackgroundThe new type of Coronavirus infection had become a pandemic in a very short per... more ABSTRACTBackgroundThe new type of Coronavirus infection had become a pandemic in a very short period since it was first seen in Wuhan. The outbreak had a negative impact on all health care systems throughout the world and overwhelmed the diagnostic laboratories as well. During the pandemic, handling patient specimens in accordance with the universal guidelines was troublesome as WHO, CDC and ECDC required cold chain compliance during transporting and storing the swap samples.Materials and methodsIn this study, we tested diagnostic performance of RT-PCR on 30 swab samples stored at ambient temperature and compared them with the samples stored at +4°C.ResultsOur results revealed that all the samples stored at ambient temperature remain PCR positive for at least five days. We did not see any false negativity.ConclusionIn conclusion, we report that transferring and storing of nasopharyngeal/oropharyngeal samples at ambient temperature could be possible in the resource-limited conditions...
Abstract Background Literature with regard to coronavirus disease 2019 (COVID-19) associated morb... more Abstract Background Literature with regard to coronavirus disease 2019 (COVID-19) associated morbidities and the risk factors for death are still emerging. In this study, we investigated the presence of kidney damage markers and their predictive value for survival among hospitalized subjects with COVID-19. Methods Forty-seven participants was included and grouped as: ‘COVID-19 patients before treatment’, ‘COVID-19 patients after treatment’, ‘COVID-19 patients under treatment in intensive care unit (ICU)’, and ‘controls’. Kidney function tests and several kidney injury biomarkers were compared between the groups. Cumulative rates of death from COVID-19 were determined using the Kaplan–Meier method. The associations between covariates including kidney injury markers and death from COVID-19 were examined, as well. Results Serum creatinine and cystatin C levels, urine Kidney Injury Molecule-1 (KIM-1)/creatinine ratio, and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), CKD-EPI cystatin C, and CKD-EPI creatinine–cystatin C levels demonstrated significant difference among the groups. The most significant difference was noted between the groups ‘COVID-19 patients before treatment’ and ‘COVID-19 patients under treatment in ICU’. Advancing age, proteinuria, elevated serum cystatin C, and urine KIM-1/creatinine ratio were all significant univariate correlates of death (p < 0.05, for all). However, only elevated urine KIM-1/creatinine ratio retained significance in an age, sex, and comorbidities adjusted multivariable Cox regression (OR 6.11; 95% CI: 1.22–30.53; p = 0.02), whereas serum cystatin C showing only a statistically non-significant trend (OR 1.42; 95% CI: 0.00–2.52; p = 0.09). Conclusions Our findings clearly demonstrated the acute kidney injury related to COVID-19. Moreover, urine KIM-1/creatinine ratio was associated with COVID-19 specific death.
BackgroundThe central role in the pathogenesis of severe acute respiratory syndrome coronavirus 2... more BackgroundThe central role in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), called as coronavirus disease 2019 (COVID-19), infection is attributed to angiotensin-converting enzyme 2 (ACE-2). ACE-2 expressing respiratory system involvement is the main clinical manifestation of the infection. However, literature about the association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and higher ACE-2 expressing kidney is very limited. In this study, we primarily aimed to investigate whether there is a kidney injury during the course of SARS-CoV-2 infection. The predictive value of kidney injury for survival was also determined.MethodsA total of 47 participants who met the inclusion criteria were included in the study. The participants were classified as ‘‘COVID-19 patients before treatment’’ ‘‘COVID-19 patients after treatment’’, ‘‘COVID-19 patients under treatment in ICU’’ and ‘‘controls’’. The parameters comorbidity...
The WHO-named Coronavirus Disease 2019 (COVID-19) infection had become a pandemic within a short ... more The WHO-named Coronavirus Disease 2019 (COVID-19) infection had become a pandemic within a short time period since it was detected in Wuhan. The outbreak required the screening of millions of samples daily and overwhelmed diagnostic laboratories worldwide. During this pandemic, the handling of patient specimens according to the universal guidelines was extremely difficult as the WHO, CDC and ECDC required cold chain compliance during transport and storage of the swab samples. The aim of this study was to compare the effects of two different storage conditions on the COVID-19 real-time PCR assay on 30 positive nasopharyngeal and/or oropharyngeal samples stored at both ambient temperature (22 ± 2 °C) and +4 °C. The results revealed that all the samples stored at ambient temperature remain PCR positive for at least six days without any false-negative result. In conclusion, transporting and storing these types of swab samples at ambient temperature for six days under resource-limited conditions during the COVID-19 pandemics are acceptable.
Expression levels of the major mammalian autophagy regulator Beclin 1 and its interaction with Bc... more Expression levels of the major mammalian autophagy regulator Beclin 1 and its interaction with Bcl-2 regulate the switch between autophagic cell survival and apoptotic cell death pathways. However, some of the regulators and the precise mechanisms of these processes still remain elusive. Bag-1 (Bcl-2 associated athanogene-1), a member of BAG family proteins, is a multifunctional pro-survival molecule that possesses critical functions in vital cellular pathways. Herein, we report the role of Bag-1 on Bcl-2/Beclin 1 crosstalk through indirectly interacting with Beclin 1. Pull-down experiments suggested a molecular interaction between Bag-1 and Beclin 1 in breast cancer cell lines. On the other hand, in vitro binding assays showed that Bag-1/Beclin 1 interaction does not occur directly but occurs through a mediator molecule. Bag-1 interaction with p-Beclin 1 (T119), indicator of early autophagy, is increased during nutrient starvation suggesting involvement of Bag-1 in the autophagic r...
The study investigated whether there is a male reproductive system coronavirus disease‐2019 (COVI... more The study investigated whether there is a male reproductive system coronavirus disease‐2019 (COVID‐19) phenomenon. Thirty participants who met the inclusion criteria were enrolled in the study between April and May 2020. The participants were assigned in one of the three groups including COVID‐19 patients before and after treatment, and controls. Presence of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) within the semen samples was investigated. Additionally, participant's demographics, semen parameters and serum sex hormone levels were compared between the groups. SARS‐CoV‐2 was not detected within the semen samples. Sperm morphology and serum sex hormone levels were significantly different between the groups. In the post hoc analysis, sperm morphology was significantly lower in the COVID‐19 patients. Patients before treatment had significantly lower serum FSH, LH and T levels than controls. However, patients after treatment had similar serum FSH, LH and T levels with controls and patients before treatment. In our opinion, COVID‐19 and its treatment had no specific deteriorative effect on male sexual health at a short‐time period. In the patients before treatment, decreased serum of T, FSH and LH levels was consistent with acute patient stress due to COVID‐19. Similarly, it seems that decreased sperm morphology was associated with the acute fever.
ABSTRACTThere is a need to treat COVID-19 patients suffering from respiratory problems, resulting... more ABSTRACTThere is a need to treat COVID-19 patients suffering from respiratory problems, resulting in decreased oxygen levels and thus leading to mitochondrial dysfunction and metabolic abnormalities. Here, we investigated if a high oral dose of a mixture of Combined Metabolic Activators (CMA) can restore metabolic function and thus aid the recovery of COVID-19 patients. We conducted a placebo-controlled, open-label phase 2 study and a double-blinded phase 3 clinical trials to investigate the time of symptom-free recovery on ambulatory patients using a mixture of CMA consisting of NAD+ and glutathione precursors. The results of both studies showed that the time to complete recovery was significantly shorter in the CMA group (6.6 vs 9.3 days) in phase 2 and (5.7 vs 9.2 days) in phase 3 trials. A comprehensive analysis of the blood metabolome and proteome showed that the plasma levels of proteins and metabolites associated with inflammation and antioxidant metabolism are significantly ...
SummaryCOVID-19 is a viral respiratory disease caused by SARS-CoV-2 infection. Global efforts of ... more SummaryCOVID-19 is a viral respiratory disease caused by SARS-CoV-2 infection. Global efforts of genomic surveillance of the virus give chance to track the spread of the pandemic. Global emergence of some viral mutations called attention and various studies have been suggested about increased infectivity of the virus. Herein, we sequenced viral genomes isolated from 184 patients in Istanbul and analyzed clinical metadata for the investigation of any viral mutation which affects the disease course of the host. We did not detect any viral mutations affecting the disease outcome in our cohort. Besides, we observed intra-host mutations in 76% of the isolates. Insertion/deletion and stop-gain mutations are also significantly less common among intra-host variants compared to consensus viral genome mutations. Longitudinal genomic surveillance is essential for timely detection of any lineages that might affect clinical outcome, the performance of diagnostic assays, or even the immunological...
The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA i... more The gold standard method in the diagnosis of SARS-CoV-2 infection is the detection of viral RNA in nasopharyngeal sample by RT-PCR. Recently, saliva samples has been suggested as an alternative due to being fast, reliable and non-invasive, rather than nasopharyngeal samples. We compared RT-PCR results in nasopharyngeal, oro-nasopharyngeal and saliva samples of COVID-19 patients. 98 of 200 patients were positive in RT-PCR analysis performed before the hospitalization. In day 0, at least one sample was positive in 67% of 98 patients. Positivity rate was 83% for both oro-nasopharyngeal and nasopharyngeal samples, while it was 63% for saliva samples (p<0.001). On day 5, RT-PCR was performed in 59 patients, 34% had at least one positive result. The positivity rate was 55% for saliva and nasopharyngeal samples, while it was 60% for oro-nasopharyngeal samples. Our study shows that the sampling saliva does not increase the sensitivity of RT-PCR tests at early stages of infection. However...
SUMMARYCOVID-19 is a global threat with an increasing number of infections. Research on IgG serop... more SUMMARYCOVID-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 3.6p=0.7), indicating the efficient implementation of protection measures in the hospitals in Turkey. These findings might lead to the re-evaluation of infecti...
Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal canc... more Inherited pathogenic variants account for 5% to 10% of all breast cancer (BC) and colorectal cancer (CRC) cases. Here, we sought to profile the pathogenic variants in 25 cancer susceptibility genes in Turkish population. Germline pathogenic variants were screened in 732 BC patients, 189 CRC patients and 490 cancer‐free elderly controls, using next‐generation sequencing‐based multigene panel testing and multiplex ligation‐dependent probe amplification testing. Pathogenic variants were detected in 17.2% of high‐risk BC patients and 26.4% of high‐risk CRC patients. More than 95% of these variants were clinically actionable. BRCA1/2 and mismatch repair genes (MLH1, MSH2 and MSH6) accounted for two‐thirds of all pathogenic variants detected in high‐risk BC and CRC patients, respectively. Pathogenic variants in PALB2, CHEK2, ATM and TP53 were also prevalent in high‐risk BC patients (4.5%). BRCA1 exons 17‐18 deletion and CHEK2 c.592+3A>T were the most common variants predisposing to BC,...
ABSTRACTBackgroundThe new type of Coronavirus infection had become a pandemic in a very short per... more ABSTRACTBackgroundThe new type of Coronavirus infection had become a pandemic in a very short period since it was first seen in Wuhan. The outbreak had a negative impact on all health care systems throughout the world and overwhelmed the diagnostic laboratories as well. During the pandemic, handling patient specimens in accordance with the universal guidelines was troublesome as WHO, CDC and ECDC required cold chain compliance during transporting and storing the swap samples.Materials and methodsIn this study, we tested diagnostic performance of RT-PCR on 30 swab samples stored at ambient temperature and compared them with the samples stored at +4°C.ResultsOur results revealed that all the samples stored at ambient temperature remain PCR positive for at least five days. We did not see any false negativity.ConclusionIn conclusion, we report that transferring and storing of nasopharyngeal/oropharyngeal samples at ambient temperature could be possible in the resource-limited conditions...
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