ABSTRACT
Aptamers, nucleic acid ligands against specific targets, have emerged as drug candidates, sensors, imaging tools, and nanotechnology building blocks. The most successful method for their development has been SELEX (Systematic Evolution of Ligands by EXponential Enrichment), an iterative procedure that is labor- and time-intensive and often enriches candidates for criteria other than those desired. Here we present UltraSelex, a non-iterative method that combines biochemical partitioning, high-throughput sequencing, and computational background minimization through statistical rank modeling. This approach avoids the common bias for abundant sequences and selects high-affinity ligands, even if they are extremely scarce. In six independent UltraSelex experiments (three towards each target), we discovered high-affinity aptamers for a fluorogenic silicon rhodamine dye, and a protein target, the SARS-CoV-2 RNA-dependent RNA polymerase. These aptamers enabled live-cell RNA imaging and efficient enzyme inhibition, respectively. The wet-lab partitioning part of UltraSelex can be completed in a few hours, and including sequencing and rank modeling via a public web server, the identification of lead candidates can be accomplished in about one day. UltraSelex provides a rapid route to novel drug candidates and diagnostic tools with greatly improved performance.
ABSTRACT
COVID-19 has spread surprisingly fast worldwide, and new variants continue to emerge. Recently, the World Health Organization acknowledged a new mutant strain "Omicron", with children were accounting for a growing share of COVID-19 cases compared with other mutant strains. However, the clinical and immunological characteristics of convalescent pediatric patients after Omicron infection were lacking. In this study, we comparatively analyzed the clinical data from pediatric patients with adult patients or healthy children and the effects of SARS-CoV-2 vaccine on the clinical and immune characteristics in convalescent pediatric patients. Our results indicated that convalescent pediatric patients had unique clinical and immune characteristics different from those of adult patients or healthy children, and SARS-CoV-2 vaccination significantly affected on the clinical and immune characteristics and the prevention of nucleic acid re-detectable positive (RP) in convalescent patients. Our study further deepens the understanding of the impact of Omicron on the long-term health of pediatric patients and provides a valuable reference for the prevention and treatment of children infected with Omicron.
ABSTRACT
Introduction: Recent reports of potential harmful effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with Corona Virus Disease 2019 (COVID-19) have provoked great concern. Therefore, the safety of NSAIDs is still questioned. Methods: We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases from December 2019 to January 2021 to examine use prevalence for NSAIDs in general, as well as associated COVID-19 risk and outcomes. This study has been registered with PROSPERO (CRD42019132063) Results: We included 25 studies with a total of 101,215 COVID-19 patients. The use of NSAIDs in COVID-19 patients reached 19%. Exposure to NSAIDs was not associated with significantly increased risk of developing COVID-19 (odds ratio [OR]=0.98, 95% confidence interval [CI]: 0.78-1.24; I2=82%), hospitalization (OR=1.06, 95%CI: 0.76-1.48; I2=81%), mechanical ventilation (OR=0.71, 95%CI: 0.47-1.06; I2=38%), and length of hospital stay. Moreover, use of NSAIDs was significantly associated with better outcomes, including severity of COVID-19 (OR=0.79, 95%CI: 71-0.89; I2=0%) and death (OR=0.68, 95%CI: 0.52-0.89; I2=85%) in patients with COVID-19. Regarding safety outcomes, exposure to NSAIDs was associated with increased risk of stroke (OR=2.32, 95%CI: 1.04-5.2; I2=0%), but not with myocardial infraction (OR=1.49; p=0.66; I2=0%), overt thrombosis (OR=0.76, p=0.50; I2=28%) and major bleeding (p=0.61). Conclusion: Based on current evidence, exposure to NSAIDs is not linked to increased odds or exacerbation of COVID-19 in the general COVID-19 population. Furthermore, administration of NSAIDs might have better outcomes and survival benefits in the general COVID-19 population, although potentially increasing the risk of stroke. Use of NSAIDs might be safe and beneficial in COVID-19. Future observational and randomized control trials are needed for further confirmation.
Subject(s)
Hemorrhage , Thrombosis , Virus Diseases , Cardiomyopathies , Death , COVID-19 , StrokeABSTRACT
Introduction: Recent reports of potential harmful effects of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with Corona Virus Disease 2019 (COVID-19) have provoked great concern. Therefore, the safety of NSAIDs is still questioned.Methods We searched the PubMed, EMBASE, Cochrane Library and Web of Science databases from December 2019 to January 2021 to examine use prevalence for NSAIDs in general, as well as associated COVID-19 risk and outcomes. This study has been registered with PROSPERO (CRD42019132063)Results We included 25 studies with a total of 101,215 COVID-19 patients. The use of NSAIDs in COVID-19 patients reached 19%. Exposure to NSAIDs was not associated with significantly increased risk of developing COVID-19 (odds ratio [OR] = 0.98, 95% confidence interval [CI]: 0.78–1.24; I2 = 82%), hospitalization (OR = 1.06, 95%CI: 0.76–1.48; I2 = 81%), mechanical ventilation (OR = 0.71, 95%CI: 0.47–1.06; I2 = 38%), and length of hospital stay. Moreover, use of NSAIDs was significantly associated with better outcomes, including severity of COVID-19 (OR = 0.79, 95%CI: 71–0.89; I2 = 0%) and death (OR = 0.68, 95%CI: 0.52–0.89; I2 = 85%) in patients with COVID-19. Regarding safety outcomes, exposure to NSAIDs was associated with increased risk of stroke (OR = 2.32, 95%CI: 1.04–5.2; I2 = 0%), but not with myocardial infraction (OR = 1.49; p = 0.66; I2 = 0%), overt thrombosis (OR = 0.76, p = 0.50; I2 = 28%) and major bleeding (p = 0.61).Conclusion Based on current evidence, exposure to NSAIDs is not linked to increased odds or exacerbation of COVID-19 in the general COVID-19 population. Furthermore, administration of NSAIDs might have better outcomes and survival benefits in the general COVID-19 population, although potentially increasing the risk of stroke. Use of NSAIDs might be safe and beneficial in COVID-19. Future observational and randomized control trials are needed for further confirmation.
Subject(s)
COVID-19ABSTRACT
Background: COVID-19 cases with suspected returned-positive SRAS-CoV-2 tests following consecutive negative tests have been reported, but evidence-based explanations for this phenomenon is still lacking. We aimed to describe the clinical and laboratory characteristics of returned-positive COVID-19 patients during treatment in comparison with other patients.Methods: From January 20 to April 10, 2020, all COVID-19 inpatient with at least three RT-PCR SARS-CoV-2 tests in Renmin Hospital in Wuhan, China were enrolled. Patients with 2 consecutively negative RT-PCR results followed by a positive result were classified as returned-positive patients, and their characteristics and repeatedly measured laboratory results were compared with the rest of the patients. Linear mixed effects models were performed.Results: A total of 789 COVID-19 patients were included and 22.8% patients returned positive in RT-PCR SARS-CoV-2 test. No significant differences were found for general characteristics between the returned-positive and the control groups. The trends of inflammatory and immune factors including the third component of complement (C3), C-reactive protein, procalcitonin (PCT), IL-4, IL-6, the counts of lymphocyte, CD3+, CD8+, white blood cell and immunoglobulin levels during hospitalization were significantly different between the two groups. During the returned-positive period, C3, PCT, serum IgM, anti-SARS-CoV-2 IgM and anti-SARS-CoV-2 IgG were significantly higher in the returned-positive patients at certain time points.Conclusions: Returned-positive COVID-19 patients appeared to be more sever at admission, and had periodically higher levels in C3, PCT, serum IgM and two specific antibodies during hospitalization. This suggests that positive return of SARS-COV-2 could not be completely explained by false-negative testing and longer observation of these patients is warranted.
Subject(s)
COVID-19ABSTRACT
The clinical characteristics of patients with novel coronavirus disease (COVID-19) in Hunan Province are less understood. We analyzed retrospectively the epidemiological, clinical characteristics, and risk factors associated with severity of 113 confirmed COVID-19 cases in Yueyang, Hunan Province, China, from January 20, 2020, to March 8, 2020, and followed until April 13, 2020. Of the 113 confirmed cases, 92 (81.4%) were from or infected by patients from Hubei province. More than half (63) of patients with COVID-19 had no fever in the early stages of disease. 23% patients had no symptoms at the onset. As of March 8, 2020, 113 (100%) of 113 patients had met the discharge criteria, 0 (0%) patients died. Compared with the non-severe cases, severe cases were associated with older age or patients with comorbidities, secondary bacterial infections, and higher levels of C-reactive protein. Longer duration of virus clearance was associated with a higher risk of progression to critical status. Older patients or patients with comorbidities such as diabetes were more likely to have severe condition. Prompt and effective treatment and sufficient medical resources may still significantly reduce hospital-related transmissions and mortality.