ABSTRACT
Background: The 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. Methods: A 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, serum creatinine and cystatin C levels, CKD-EPI eGFR levels, KIM-1 and NGAL levels, urine KIM-1/creatinine and NGAL/creatinine ratios were statistically compared between the groups. The associations between covariates including kidney disease indicators and death from COVID-19 were examined using Cox proportional hazard regression analysis. Results: Serum creatinine and cystatin C levels, urine KIM-1/creatinine levels, and CKD-EPI, CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C eGFR levels exhibited significant difference in the groups. The causes of the difference were more altered kidney function and increased acute kidney damage in COVID-19 patients before treatment and under treatment in ICU. Additionally, incidences of comorbidity and proteinuria in the urine analysis were higher in the COVID-19 patients under treatment in ICU group. Urine KIM-1/creatinine ratio and proteinuria were associated with COVID-19 specific death. Conclusions: We found that COVID-19 patients under treatment in ICU exhibited extremely higher levels of serum cystatin C, and urine KIM-1/creatinine and urine NGAL/creatinine ratios. These results clearly described the acute kidney damage by COVID-19 using molecular kidney damage markers for the first time in the literature. Lowered CKD-EPI, CKD-EPI cystatin C and CKD-EPI creatinine-cystatin C eGFR levels were determined in them, as well. Urine KIM-1/creatinine ratio and proteinuria were associated with COVID-19 specific death. In this regard, considering kidney function and kidney damage markers must not be ignored in the COVID-19 patients, and serial monitoring of them should be considered.
Subject(s)
Coronavirus Infections , Proteinuria , Kidney Diseases , Acute Kidney Injury , COVID-19ABSTRACT
COVID-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 escape of the virus.
Subject(s)
COVID-19ABSTRACT
As the COVID-19 pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to spread around the globe, effective vaccination protocols are under deployment. Alternatively, the use of convalescent plasma (CP) therapy relies on the transfer of the immunoglobulin repertoire of a donor that has recovered from the disease as a means of passive vaccination. While the lack of an effective antiviral treatment inadvertently increases the interest in CP products, initial clinical evaluation on COVID-19 patients revealed that critical factors determining the outcome of CP therapy need to be defined clearly if clinical efficacy is to be expected. Measurement of neutralizing activity against SARS-CoV-2 using live virus presents a reliable functional assay but the availability of suitable BSL3 facilities for live virus culture restricts its applicability. Instead, the use of pseudovirus particles containing elements from the SARS-CoV-2 virus is widely applied to determine the activity of CP or other neutralizing agents such as monoclonal antibodies. In this study, we present our approach to optimize GFP-encoding lentiviral particles pseudotyped with the SARS-CoV-2 Spike and Membrane proteins for use in neutralization assays. Our results show the feasibility of pseudovirus production using a C-terminal truncated Spike protein which is greatly enhanced by the incorporation of the D614G mutation. Moreover, we report that the use of sodium butyrate during lentiviral vector production dramatically increases pseudovirus titers. Analysis of CP neutralizing activity against particles pseudotyped with wildtype or D614G mutant Spike protein in the presence or absence the M protein revealed differential activity in CP samples that did not necessarily correlate with the amount of anti-SARS-CoV-2 antibodies. Our results indicate that the extent of neutralizing activity in CP samples depends on the quality rather than the quantity of the humoral immune responses and varies greatly between donors. Functional screening of neutralizing activity using pseudovirus-based neutralization assays must be accepted as a critical tool for choosing CP donors if clinical efficacy is to be maximized.
Subject(s)
COVID-19 , Severe Acute Respiratory SyndromeABSTRACT
BACKGROUND The characteristics of COVID-19 outbreak and high fatality rate of COVID-19 infection have attracted the attention of scientists due to the strong interactions between components of metabolic syndrome, metabolic abnormalities, and viral pathobiology of COVID-19. Combined metabolic cofactors supplementation (CMCS) consisting of L-serine, N-acetyl-L-cysteine (NAC), nicotinamide riboside (NR), and L-carnitine tartrate is being studied for the treatment of patients with COVID-19. METHODS We conducted a placebo-controlled, phase-2 clinical trial involving ambulatory COVID-19 patients. A total of 100 patients were randomly assigned on a 3:1 basis to hydroxychloroquine plus CMCS or hydroxychloroquine plus placebo. The total treatment period for the hydroxychloroquine was 5 days, and for the CMCS/placebo was 14 days. Clinical status was evaluated daily by phone, using a binomial scale for subject reported presence or absence for multiple COVID-19 related symptoms. Plasma samples for clinical chemistry analyses were collected on day 0 and day 14. RESULTS A total of 93 patients completed the trial. The combination of CMCS and hydroxychloroquine significantly reduced the average complete recovery time compared with hydroxychloroquine and placebo (6.6 days vs 9.3 days, respectively). Moreover, there was a significant reduction in ALT, AST and LDH levels on day 14 compared to day 0 in the hydroxychloroquine plus CMCS group. The adverse effects were uncommon and self-limiting. CONCLUSIONS In patients with mild-to-moderate COVID-19, CMCS resulted in a significant reduction in recovery time and liver enzymes associated with hepatic function compared to placebo. We observed that CMSC is associated with a low incidence of adverse events.
Subject(s)
Metabolic Diseases , COVID-19ABSTRACT
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 3.6 p=0.7), indicating the efficient implementation of protection measures in the hospitals in Turkey. These findings might lead to the re-evaluation of infection control and transmission dynamics in hospitals.
Subject(s)
COVID-19ABSTRACT
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, on 5th day, viral RNA detection rates in saliva were similar to nasopharyngeal and oro-nasopharyngeal samples. In conclusion, we suggest that, in patients receiving treatment, virus presence in saliva, in addition to the standard samples, is important to determine the isolation period and to control the transmission.
Subject(s)
COVID-19ABSTRACT
BackgroundThe 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{degrees}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 like pandemic.