Evaluation of pre-induction dynamic arterial elastance as an adjustable predictor of post-induction hypotension: A prospective observational study.

STUDY OBJECTIVE: Dynamic arterial elastance (Eadyn) has been suggested as a functional measure of arterial load. We aimed to evaluate whether pre-induction Eadyn can predict post-induction hypotension. DESIGN: Prospective observational study. PATIENTS: Adult patients undergoing general anesthesia with invasive and non-invasive arterial pressure monitoring systems. MEASUREMENTS: We collected invasive and non-invasive Eadyns (n = 38 in each), respectively. In both invasive and non-invasive Eadyns, pre-induction Eadyns were obtained during one-minute tidal and deep breathing in each patient before anesthetic induction. Post-induction hypotension was defined as a decrease of >30% in mean blood pressure from the baseline value or any absolute mean blood pressure value of <65 mmHg for 10 min after anesthetic induction. The predictabilities of Eadyns for the development of post-induction hypotension were tested using receiver-operating characteristic curve analysis. MAIN RESULTS: Invasive Eadyn during deep breathing showed significant predictability with an area under the curve (AUC) of 0.78 (95% Confidence interval [CI], 0.61-0.90, P = 0.001). But non-invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.49-0.81, P = 0.096) and deep breathing (AUC = 0.53, 95% CI, 0.36-0.70, P = 0.75), and invasive Eadyn during tidal breathing (AUC = 0.66, 95% CI, 0.41-0.74, P = 0.095) failed to predict post-induction hypotension. CONCLUSION: In our study, invasive pre-induction Eadyn during deep breathing -could predict post-induction hypotension. Despite its invasiveness, future studies will be needed to evaluate the usefulness of Eadyn as a predictor of post-induction hypotension because it is an adjustable parameter.

Current Advances in Paper-Based Biosensor Technologies for Rapid COVID-19 Diagnosis.

The global coronavirus disease 2019 (COVID-19) pandemic has had significant economic and social impacts on billions of people worldwide since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China, in November 2019. Although polymerase chain reaction (PCR)-based technology serves as a robust test to detect SARS-CoV-2 in patients with COVID-19, there is a high demand for cost-effective, rapid, comfortable, and accurate point-of-care diagnostic tests in medical facilities. This review introduces the SARS-CoV-2 viral structure and diagnostic biomarkers derived from viral components. A comprehensive introduction of a paper-based diagnostic platform, including detection mechanisms for various target biomarkers and a COVID-19 commercial kit is presented. Intrinsic limitations related to the poor performance of currently developed paper-based devices and unresolved issues are discussed. Furthermore, we provide insight into novel paper-based diagnostic platforms integrated with advanced technologies such as nanotechnology, aptamers, surface-enhanced Raman spectroscopy (SERS), and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas. Finally, we discuss the prospects for the development of highly sensitive, accurate, cost-effective, and easy-to-use point-of-care COVID-19 diagnostic methods.

Influenza viral infection is a risk factor for severe illness in COVID-19 patients: a nationwide population-based cohort study.

In order to prepare for the twindemic of influenza and SARS-CoV-2 infection, we investigated the association between influenza infection and subsequent severity of SARS-CoV-2 infection. A population-based nationwide cohort study was performed using data from the National Health Insurance Service (NHIS) in the Republic of Korea. This study included 274,126 individuals who underwent SARS-CoV-2 PCR testing between 20 January 2020 and 1 October 2020. Among these patients, 28,338 tested positive for SARS-CoV-2, and 4,003 of these individuals had a history of influenza. The control group was selected through 1:1 propensity score matching. In the group of 4,003 COVID-19-positive individuals with no history of influenza, 192 (4.8%) experienced severe illness from COVID-19 infection. In the group of 4,003 COVID-19-positive individuals with a history of influenza, 260 (6.5%) had severe illness from COVID-19, and the overall adjusted odds ratio (aOR) was 1.29 (95% confidence interval 1.04-1.59). Among the 4,003 COVID-19-positive individuals with a history of influenza, severe COVID-19 infection was experienced by 143 of 1,760 (8.1%) with an influenza history within 1 year before the onset of COVID-19, 48 of 1,129 (4.3%) between 1 and 2 years, and 69 of 1,114 (6.2%) between 2 and 3 years before COVID-19 onset, and the aORs were 1.54 (1.20-1.98), 1.19 (0.84-1.70), and 1.00 (0.73-1.37), respectively. In conclusion, individuals who had an influenza infection less than 1 year before COVID-19 infection were at an increased risk of experiencing severe illness from the SARS-CoV-2 infection. To control the public health burden, it is essential that effective public health control measures, which include influenza vaccination, hand washing, cough etiquette, and mask use are in place.

ZnO Nanowire-Based Early Detection of SARS-CoV-2 Antibody Responses in Asymptomatic Patients with COVID-19 (Adv. Mater. Interfaces 14/2022)

ZnO Nanowire Microplate for COVID-19 Antibody Responses In article number 2102046, Jung Kim, Chang-Seop Lee, Hong Gi Kim, and co-workers report the development of ZnO nanowire-fabricated microplate by a modified hydrothermal synthesis method for early detection of SARS-CoV-2 antibody response in asymptomatic patients with COVID-19 as well as symptomatic patients.

ZnO Nanowire-Based Early Detection of SARS-CoV-2 Antibody Responses in Asymptomatic Patients with COVID-19.

A serological immunoassay based on enzyme-linked immunosorbent assay (ELISA) is a crucial tool for screening and identification of human SARS-CoV-2 seroconversion. Various immunoassays are developed to detect the spike 1 (S1) and nucleocapsid (NP) proteins of SARS-CoV-2; however, these serological tests have low sensitivity. Here, a novel microplate (MP) is developed on which a ZnO nanowire (NW) is fabricated by a modified hydrothermal synthesis method. This plate is coated with SARS-CoV-2 NP and used as a fluorescent immunoassay (FIA) to detect antibodies specific for SARS-CoV-2 NP. Compared with the bare MP, the ZnO-NW MP binds high levels (up to 5 µg mL-1) of SARS-CoV-2 NP tagged to histidine without any surface treatment. A novel serological assay based on the ZnO-NW MP is more sensitive than a commercial immunoassay, enabling early detection (within <5 days of a reverse transcription polymerase chain reaction-confirmed COVID-19 infection) of anti-SARS-CoV-2 NP IgG antibodies in asymptomatic patients with COVID-19. This is the first assay to detect early antibody responses to SARS-CoV-2 in asymptomatic patients. Therefore, this serological assay will facilitate accurate diagnosis of COVID-19, as well as estimation of COVID-19 prevalence and incidence.

Rapid Biosensor of SARS-CoV-2 Using Specific Monoclonal Antibodies Recognizing Conserved Nucleocapsid Protein Epitopes.

Coronavirus disease 2019 (COVID-19), the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by symptoms such as fever, fatigue, a sore throat, diarrhea, and coughing. Although various new vaccines against COVID-19 have been developed, early diagnostics, isolation, and prevention remain important due to virus mutations resulting in rapid and high disease transmission. Amino acid substitutions in the major diagnostic target antigens of SARS-CoV-2 may lower the sensitivity for the detection of SARS-CoV-2. For this reason, we developed specific monoclonal antibodies that bind to epitope peptides as antigens for the rapid detection of SARS-CoV-2 NP. The binding affinity between antigenic peptides and monoclonal antibodies was investigated, and a sandwich pair for capture and detection was employed to develop a rapid biosensor for SARS-CoV-2 NP. The rapid biosensor, based on a monoclonal antibody pair binding to conserved epitopes of SARS-CoV-2 NP, detected cultured virus samples of SARS-CoV-2 (1.4 × 103 TCID50/reaction) and recombinant NP (1 ng/mL). Laboratory confirmation of the rapid biosensor was performed with clinical specimens (n = 16) from COVID-19 patients and other pathogens. The rapid biosensor consisting of a monoclonal antibody pair (75E12 for capture and the 54G6/54G10 combination for detection) binding to conserved epitopes of SARS-CoV-2 NP could assist in the detection of SARS-CoV-2 NP under the circumstance of spreading SARS-CoV-2 variants.

Versatile role of ACE2-based biosensors for detection of SARS-CoV-2 variants and neutralizing antibodies.

Since the beginning of the COVID-19 pandemic, accumulating mutations have led to marked changes in the genetic sequence of SARS-CoV-2. Of these, mutations in the spike (S) protein can alter the properties of the virus, particularly transmissibility and antigenicity. However, it is difficult to detect antigenic variants of the SARS-CoV-2 S protein by immunoassay. Here, we developed an ACE2-based biosensor designed to detect both SARS-CoV-2 S1 mutations and neutralizing antibodies. In "binding mode", the biosensor works by detecting binding of the S protein to an immobilized ACE2 receptor. The ACE2-based biosensor was able to detect S1 proteins of the alpha (500 pg/mL) and beta variants (10 ng/mL), as well as wild-type S1 (10 ng/mL), of SARS-CoV-2. The biosensor distinguished wild-type SARS-CoV-2 S1 from the S1 alpha and beta variants via color differences. In addition, a slight modification to the protocol enabled the ACE2-based biosensor to operate in "blocking mode" to detect neutralizing antibodies in serum samples from COVID-19 patients. Therefore, the ACE2-based biosensor is a versatile test for detecting wild-type S1, S1 mutants, and neutralizing antibodies against SARS-CoV-2. This approach to targeting both the mechanism by which SARS-CoV-2 enters host cells and the subsequent adaptive immune response will facilitate the development of various biosensors against SARS-CoV-2.

Development of a SARS-CoV-2-specific biosensor for antigen detection using scFv-Fc fusion proteins.

Coronavirus disease 2019 (COVID-19) is a newly emerged human infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In a global pandemic, development of a cheap, rapid, accurate, and easy-to-use diagnostic test is necessary if we are to mount an immediate response to this emerging threat. Here, we report the development of a specific lateral flow immunoassay (LFIA)-based biosensor for COVID-19. We used phage display technology to generate four SARS-CoV-2 nucleocapsid protein (NP)-specific single-chain variable fragment-crystallizable fragment (scFv-Fc) fusion antibodies. The scFv-Fc antibodies bind specifically and with high affinity to the SARS-CoV-2 NP antigen, but not to NPs of other coronaviruses. Using these scFv-Fc antibodies, we screened three diagnostic antibody pairs for use on a cellulose nanobead (CNB)-based LFIA platform. The detection limits of the best scFv-Fc antibody pair, 12H1 as the capture probe and 12H8 as the CNB-conjugated detection probe, were 2 ng antigen protein and 2.5 × 104 pfu cultured virus. This LFIA platform detected only SARS-CoV-2 NP, not NPs from MERS-CoV, SARS-CoV, or influenza H1N1. Thus, we have successfully developed a SARS-CoV-2 NP-specific rapid diagnostic test, which is expected to be a simple and rapid diagnostic test for COVID-19.

A novel rapid detection for SARS-CoV-2 spike 1 antigens using human angiotensin converting enzyme 2 (ACE2).

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), a newly emerging human infectious disease. Because no specific antiviral drugs or vaccines are available to treat COVID-19, early diagnostics, isolation, and prevention are crucial for containing the outbreak. Molecular diagnostics using reverse transcription polymerase chain reaction (RT-PCR) are the current gold standard for detection. However, viral RNAs are much less stable during transport and storage than proteins such as antigens and antibodies. Consequently, false-negative RT-PCR results can occur due to inadequate collection of clinical specimens or poor handling of a specimen during testing. Although antigen immunoassays are stable diagnostics for detection of past infection, infection progress, and transmission dynamics, no matched antibody pair for immunoassay of SARS-CoV-2 antigens has yet been reported. In this study, we designed and developed a novel rapid detection method for SARS-CoV-2 spike 1 (S1) protein using the SARS-CoV-2 receptor ACE2, which can form matched pairs with commercially available antibodies. ACE2 and S1-mAb were paired with each other for capture and detection in a lateral flow immunoassay (LFIA) that did not cross-react with SARS-CoV Spike 1 or MERS-CoV Spike 1 protein. The SARS-CoV-2 S1 (<5 ng of recombinant proteins/reaction) was detected by the ACE2-based LFIA. The limit of detection of our ACE2-LFIA was 1.86 × 105 copies/mL in the clinical specimen of COVID-19 Patients without no cross-reactivity for nasal swabs from healthy subjects. This is the first study to detect SARS-CoV-2 S1 antigen using an LFIA with matched pair consisting of ACE2 and antibody. Our findings will be helpful to detect the S1 antigen of SARS-CoV-2 from COVID-19 patients.

Comparative Analysis of Primer-Probe Sets for RT-qPCR of COVID-19 Causative Virus (SARS-CoV-2).

Coronavirus disease 2019 (COVID-19) is a newly emerging human infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV). Within 8 months of the outbreak, more than 10,000,000 cases of COVID-19 have been confirmed worldwide. Since human-to-human transmission occurs easily and the rate of human infection is rapidly increasing, sensitive and early diagnosis is essential to prevent a global outbreak. Recently, the World Health Organization (WHO) announced various primer-probe sets for SARS-CoV-2 developed at different institutions: China Center for Disease Control and Prevention (China CDC, China), Charité (Germany), The University of Hong Kong (HKU, Hong Kong), National Institute of Infectious Diseases in Japan (Japan NIID, Japan), National Institute of Health in Thailand (Thailand NIH, Thailand), and US CDC (USA). In this study, we compared the ability to detect SARS-CoV-2 RNA among seven primer-probe sets for the N gene and three primer-probe sets for the Orf1 gene. The results revealed that "NIID_2019-nCOV_N" from the Japan NIID and "ORF1ab" from China CDC represent a recommendable performance of RT-qPCR analysis for SARS-CoV-2 molecular diagnostics without nonspecific amplification and cross-reactivity for hCoV-229E, hCoV-OC43, and MERS-CoV RNA. Therefore, the appropriate combination of NIID_2019-nCOV_N (Japan NIID) and ORF1ab (China CDC) sets should be selected for sensitive and reliable SARS-CoV-2 molecular diagnostics.