ABSTRACT
We designed a protein biosensor that uses thermodynamic coupling for sensitive and rapid detection of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in serum. The biosensor is a switchable, caged luciferase-receptor-binding domain (RBD) construct that detects serum-antibody interference with the binding of virus RBD to angiotensin-converting enzyme 2 (ACE-2) as a proxy for neutralization. Our coupling approach does not require target modification and can better distinguish sample-to-sample differences in analyte binding affinity and abundance than traditional competition-based assays.
Subject(s)
Biosensing Techniques , COVID-19 , Antibodies, Neutralizing/chemistry , Antibodies, Viral/genetics , COVID-19/diagnosis , Humans , Neutralization Tests , SARS-CoV-2/genetics , Spike Glycoprotein, Coronavirus/chemistryABSTRACT
Amidst the COVID-19 pandemic, there is a need for further research on its manifestation in pregnant women, since they are particularly prone to respiratory pathogens, like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), due to physiological changes during pregnancy. Its effects on infants born to mothers with COVID-19 are also not well-studied, and more evidence is needed on vertical transmission of the disease from mother to infant and on the transmission of IgG/IgM antibodies between mother and infant. We aim to systematically review and evaluate the effects of COVID-19 among SARS-CoV-2-positive pregnant women in late pregnancy and neonates with SARS-CoV-2-positive pregnant mothers using blood assays to find indicators of maternal and neonatal complications. We searched for original published articles in Google Scholar, Medline (PubMed), and Embase databases to identify articles in the English language from December 2019 to July 20, 2020. Duplicate entries were searched by their titles, authors, date of publication, and Digital Object Identifier. The selected studies were included based on patient pregnancy on admission, pregnant mothers with laboratory-confirmed COVID-19 virus, maternal/neonatal complications, and blood test results. We excluded duplicate studies, articles where full text was not available, other languages than English, opinions, and perspectives. The meta-analysis using the Generalized Linear Mixed model was conducted using the "meta" and "metaprop" packages in R code. Of the 1,642 studies assessed for eligibility, 29 studies (375 mothers and neonates) were included. Preterm birth rate was 34.2%, and cesarean section rate was 82.7%. Maternal laboratory findings found elevated neutrophils (71.4%; 95% CI: 38.5-90.9), elevated CRP (67.7%; 95%: 50.6-81.1), and low hemoglobin (57.3%; 95% CI: 26.0-87.8). We found platelet count, lactate dehydrogenase, and procalcitonin to be less strongly correlated with preterm birth than between high neutrophil counts (P = 0.0007), low hemoglobin (P = 0.0188), and risk of preterm birth. There is little evidence for vertical transmission. Elevated procalcitonin levels (23.2%; 95% CI: 8.4-49.8) are observed in infants born to mothers with COVID-19, which could indicate risk for neonatal sepsis. These infants may gain passive immunity to COVID-19 through antibody transfer via placenta. These results can guide current obstetrical care during the current SARS-CoV-2 pandemic.
ABSTRACT
Importance: During the coronavirus disease 2019 (COVID-19) pandemic, eye care professionals caring for patients with sight-threatening diseases, such as glaucoma, have had to determine whether some patient appointments could safely get postponed, weighing the risk that the patient's glaucoma could worsen during the interim vs the morbidity risk of acquiring COVID-19 while seeking ophthalmic care. They also need to prioritize appointment rescheduling during the ramp-up phase (when pandemic-associated service reductions are eased). Objective: To describe a flexible and scalable scoring algorithm for patients with glaucoma that considers glaucoma severity and progression risk vs the presence of high-risk features for morbidity from COVID-19, using information from a large data repository. Design, Setting, and Participants: In this cross-sectional study, patients with upcoming clinic appointments for glaucoma from March 16, 2020, to April 16, 2020, at an academic institution enrolled in the Sight Outcomes Research Collaborative (SOURCE) Ophthalmology Electronic Health Record Data Repository were identified. A risk stratification tool was developed that calculated a glaucoma severity and progression risk score and a COVID-19 morbidity risk score. These scores were summed to determine a total score for each patient. Main Outcomes and Measures: Total scores and percentages of clinic appointments recommended for rescheduling. Results: Among the 1034 patients with upcoming clinic appointments for glaucoma, the mean (SD) age was 66.7 (14.6) years. There were 575 women (55.6%), 733 White individuals (71%), and 160 Black individuals (15.5%). The mean (SD) glaucoma severity and progression risk score was 4.0 (14.4) points, the mean (SD) COVID-19 morbidity risk score was 27.2 (16.1) points, and the mean (SD) total score was 31.2 (21.4) points. During pandemic-associated reductions in services, using total score thresholds of 0, 25, and 50 points would identify 970 appointments (93.8%), 668 appointments (64.6%), and 275 appointments (26.6%), respectively, for postponement and rescheduling. The algorithm-generated total scores also helped prioritize appointment rescheduling during the ramp-up phase. Conclusions and Relevance: A tool that considers the risk of underlying ophthalmic disease progression from delayed care receipt and the morbidity risk from COVID-19 exposure was developed and implemented, facilitating the triage of upcoming ophthalmic appointments. Comparable approaches for other ophthalmic and nonophthalmic care during the COVID-19 pandemic and similar crises may be created using this methodology.