•Four rapid antigen tests showed moderate sensitivity (< = 55 %) for SARS-CoV-2.•All tests were able to detect high infectious samples with high reliability (95 %).•Handling of all the assays poses ...to users to significant risk for contamination.
SARS-CoV-2 molecular diagnostics is facing material shortages and long turnaround times due to exponential increase of testing demand.
We evaluated the analytic performance and handling of four rapid Antigen Point of Care Tests (AgPOCTs) I-IV (Distributors: (I) Roche, (II) Abbott, (III) MEDsan and (IV) Siemens).
100 RT-PCR negative and 84 RT-PCR positive oropharyngeal swabs were prospectively collected and used to determine performance and accuracy of these AgPOCTs. Handling was evaluated by 10 healthcare workers/users through a questionnaire.
The median duration from symptom onset to sampling was 6 days (IQR 2–12 days). The overall respective sensitivity were 49.4 % (CI95 %: 38.9–59.9), 44.6 % (CI95 %: 34.3–55.3), 45.8 % (CI95 %: 35.5–56.5) and 54.9 % (CI95 %: 43.4−65.9) for tests I, II, III and IV, respectively. In the high viral load subgroup (containing >106 copies of SARS-CoV-2 /swab, n = 26), AgPOCTs reached sensitivities of 92.3 % or more (range 92.3 %–100 %). Specificity was 100 % for tests I, II (CI95 %: 96.3–100 for both tests) and IV (CI95 %: 96.3–100) and 97 % (CI95 %: 91.5–98.9) for test III. Regarding handling, test I obtained the overall highest scores, while test II was considered to have the most convenient components. Of note, users considered all assays, with the exception of test I, to pose a significant risk for contamination by drips or spills.
Besides some differences in sensitivity and handling, all four AgPOCTs showed acceptable performance in high viral load samples. However, due to the significantly lower sensitivity compared to RT-qPCR, a careful consideration of pro and cons of AgPOCT has to be taken into account before clinical implementation.
We report an imported case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant P.1 detected in an asymptomatic traveler who arrived in Italy on an indirect flight from Brazil. ...This case shows the risk for introduction of SARS-CoV-2 variants from indirect flights and the need for continued SARS-CoV-2 surveillance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Flavonoids are important secondary plant metabolites that have been studied for a long time for their therapeutic potential in inflammatory diseases because of their cytokine-modulatory effects. Five ...flavonoid aglycones were isolated and identified from the hydrolyzed aqueous methanol extracts of
L.,
Blanco, and
(L.) Nabelek. They were identified as taxifolin (
), pectolinarigenin (
), tangeretin (
), gardenin B (
), and hispidulin (
). These structures were elucidated based on chromatographic and spectral analysis. In this study, molecular docking studies were carried out for the isolated and identified compounds against SARS-CoV-2 main protease (Mpro) compared to the co-crystallized inhibitor of SARS-CoV-2 Mpro (α-ketoamide inhibitor (
), IC
= 66.72 µg/mL) as a reference standard. Moreover,
screening against SARS-CoV-2 was evaluated. Compounds
and
showed the highest virus inhibition with IC
12.4 and 2.5 µg/mL, respectively. Our findings recommend further advanced
and
studies of the examined isolated flavonoids, especially pectolinarigenin (
), tangeretin (
), and gardenin B (
), either alone or in combination with each other to identify a promising lead to target SARS-CoV-2 effectively. This is the first report of the activity of these compounds against SARS-CoV-2.
Within one year after its emergence, more than 108 million people acquired SARS-CoV-2 and almost 2·4 million succumbed to COVID-19. New SARS-CoV-2 variants of concern (VoC) are emerging all over the ...world, with the threat of being more readily transmitted, being more virulent, or escaping naturally acquired and vaccine-induced immunity. At least three major prototypic VoC have been identified, i.e. the United Kingdom, UK (B.1.1.7), South African (B.1.351) and Brazilian (B.1.1.28.1) variants. These are replacing formerly dominant strains and sparking new COVID-19 epidemics.
We studied the effect of infection with prototypic VoC from both B.1.1.7 and B.1.351 variants in female Syrian golden hamsters to assess their relative infectivity and virulence in direct comparison to two basal SARS-CoV-2 strains isolated in early 2020.
A very efficient infection of the lower respiratory tract of hamsters by these VoC is observed. In line with clinical evidence from patients infected with these VoC, no major differences in disease outcome were observed as compared to the original strains as was quantified by (i) histological scoring, (ii) micro-computed tomography, and (iii) analysis of the expression profiles of selected antiviral and pro-inflammatory cytokine genes. Noteworthy however, in hamsters infected with VoC B.1.1.7, a particularly strong elevation of proinflammatory cytokines was detected.
We established relevant preclinical infection models that will be pivotal to assess the efficacy of current and future vaccine(s) (candidates) as well as therapeutics (small molecules and antibodies) against two important SARS-CoV-2 VoC.
Stated in the acknowledgment.
Bacterial coinfections increase the severity of respiratory viral infections and were frequent causes of mortality in influenza pandemics but have not been well characterized in patients with ...coronavirus disease 2019 (COVID-19). The aim of this review was to identify the frequency and microbial etiologies of bacterial coinfections that are present upon admission to the hospital and that occur during hospitalization for COVID-19. We found that bacterial coinfections were present in <4% of patients upon admission and the yield of routine diagnostic tests for pneumonia was low. When bacterial coinfections did occur, Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae were the most common pathogens and atypical bacteria were rare. Although uncommon upon admission, bacterial infections frequently occurred in patients with prolonged hospitalization, and Pseudomonas aeruginosa, Klebsiella spp., and S. aureus were common pathogens. Antibacterial therapy and diagnostic testing for bacterial infections are unnecessary upon admission in most patients hospitalized with COVID-19, but clinicians should be vigilant for nosocomial bacterial infections.
Bacterial coinfections occur in <4% of patients who are hospitalized with COVID-19 and are usually caused by S. aureus, S. pneumoniae, and H. influenzae.Empirical antibacterial therapy and diagnostic testing for bacterial pathogens in patients hospitalized with COVID-19 are indicated only in those patients with critical illness, severe immunosuppression, radiographic findings suggestive of a bacterial pneumonia, or multiple laboratory parameters compatible with bacterial infection.Hospital-acquired infections are common among patients with prolonged hospitalization for COVID-19, and hospital-acquired pneumonia is most commonly caused by P. aeruginosa, Klebsiella spp., and S. aureus.Carbapenem-resistant Gram-negative infections are being increasingly reported in patients with COVID-19 requiring intensive care.
The new WHO reference standard allows for the definition of serum antibodies against various SARS-CoV-2 antigens in terms of binding antibody units (BAU/mL) and thus to compare the results of ...different ELISA systems. In this study, the concentration of antibodies (ABs) against both the S- and the N-protein of SARS-CoV-2 as well as serum neutralization activity were evaluated in three patients after a mild course of COVID-19. Serum samples were collected frequently during a period of over one year. Furthermore, in two individuals, the effects of an additional vaccination with a mRNA vaccine containing the S1-RBD sequence on these antibodies were examined. After natural infection, the antibodies (IgA, IgG) against the S1-protein remained elevated above the established cut-off to positivity (S-IgA 60 BAU/mL and S-IgG 50 BAU/mL, respectively) for over a year in all patients, while this was not the case for ABs against the N-protein (cut-off N-IgG 40 BAU/mL, N-IgA 256 BAU/mL). Sera from all patients retained the ability to neutralize SARS-CoV-2 for more than a year. Vaccination resulted in a rapid boost of antibodies to S1-protein but, as expected, not to the N-protein. Most likely, the wide use of the WHO reference preparation will be very useful in determining the individual immune status of patients after an infection with SARS-CoV-2 or after vaccination.
The recent SARS-CoV-2 pandemic has brought many questions over the origin of the virus, the threat it poses to animals both in the wild and captivity, and the risks of a permanent viral reservoir ...developing in animals. Animal experiments have shown that a variety of animals can become infected with the virus. While coronaviruses have been known to infect animals for decades, the true intermediate host of the virus has not been identified, with no cases of SARS-CoV-2 in wild animals. The screening of wild, farmed, and domesticated animals is necessary to help us understand the virus and its origins and prevent future outbreaks of both COVID-19 and other diseases. There is intriguing evidence that farmed mink infections (acquired from humans) have led to infection of other farm workers in turn, with a recent outbreak of a mink variant in humans in Denmark. A thorough examination of the current knowledge and evidence of the ability of SARS-CoV-2 to infect different animal species is therefore vital to evaluate the threat of animal to human transmission and reverse zoonosis.
The pandemic of the coronavirus disease 2019 (COVID-19) has become a global public health crisis. The symptoms of COVID-19 range from mild to severe, but the physiological changes associated with ...COVID-19 are barely understood. In this study, we performed targeted metabolomic and lipidomic analyses of plasma from a cohort of patients with COVID-19 who had experienced different symptoms. We found that metabolite and lipid alterations exhibit apparent correlation with the course of disease in these patients, indicating that the development of COVID-19 affected their whole-body metabolism. In particular, malic acid of the TCA cycle and carbamoyl phosphate of the urea cycle result in altered energy metabolism and hepatic dysfunction, respectively. It should be noted that carbamoyl phosphate is profoundly down-regulated in patients who died compared with patients with mild symptoms. And, more importantly, guanosine monophosphate (GMP), which is mediated not only by GMP synthase but also by CD39 and CD73, is significantly changed between healthy subjects and patients with COVID-19, as well as between the mild and fatal cases. In addition, dyslipidemia was observed in patients with COVID-19. Overall, the disturbed metabolic patterns have been found to align with the progress and severity of COVID-19. This work provides valuable knowledge about plasma biomarkers associated with COVID-19 and potential therapeutic targets, as well as an important resource for further studies of the pathogenesis of COVID-19.
Display omitted
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Three viral proteins, the spike protein (S) for attachment of virus to host cells, ...3-chymotrypsin-like cysteine protease (Mpro) for digestion of viral polyproteins to functional proteins, and RNA-dependent-RNA-polymerase (RdRp) for RNA synthesis are the most critical proteins for virus infection and replication, rendering them the most important drug targets for both antibody and chemical drugs. Due to its low-fidelity polymerase, the virus is subject to frequent mutations. To date, the sequence data from tens of thousands of virus isolates have revealed hundreds of mutations. Although most mutations have a minimum consequence, a small number of non-synonymous mutations may alter the virulence and antigenicity of the mutants. To evaluate the effects of viral mutations on drug safety and efficacy, we reviewed the biochemical features of the three main proteins and their potentials as drug targets, and analyzed the mutation profiles and their impacts on RNA therapeutics. We believe that monitoring and predicting mutation-introduced protein conformational changes in the three key viral proteins and evaluating their binding affinities and enzymatic activities with the U.S. Food and Drug Administration (FDA) regulated drugs by using computational modeling and machine learning processes can provide valuable information for the consideration of drug efficacy and drug safety for drug developers and drug reviewers. Finally, we propose an interactive database for drug developers and reviewers to use in evaluating the safety and efficacy of U.S. FDA regulated drugs with regard to viral mutations.
PDF
