Advances in Biosensing Technologies for Diagnosis of COVID-19.

The COVID-19 pandemic has severely impacted normal human life worldwide. Due to its rapid community spread and high mortality statistics, the development of prompt diagnostic tests for a massive number of samples is essential. Currently used traditional methods are often expensive, time-consuming, laboratory-based, and unable to handle a large number of specimens in resource-limited settings. Because of its high contagiousness, efficient identification of SARS-CoV-2 carriers is crucial. As the advantages of adopting biosensors for efficient diagnosis of COVID-19 increase, this narrative review summarizes the recent advances and the respective reasons to consider applying biosensors. Biosensors are the most sensitive, specific, rapid, user-friendly tools having the potential to deliver point-of-care diagnostics beyond traditional standards. This review provides a brief introduction to conventional methods used for COVID-19 diagnosis and summarizes their advantages and disadvantages. It also discusses the pathogenesis of COVID-19, potential diagnostic biomarkers, and rapid diagnosis using biosensor technology. The current advancements in biosensing technologies, from academic research to commercial achievements, have been emphasized in recent publications. We covered a wide range of topics, including biomarker detection, viral genomes, viral proteins, immune responses to infection, and other potential proinflammatory biomolecules. Major challenges and prospects for future application in point-of-care settings are also highlighted.

Coagulation Profile of COVID-19 Patients.

Coronavirus disease is a viral infection that can affect multiple systems and be expressed with many-or no-symptoms. The viral infection begins when the virus binds to the host's receptor and from that point on, it is transmitted to the rest of the body, where it causes inflammatory reactions. Among other tissues and systems, SARS-CoV-2 impacts the coagulation system, where it triggers the immunothrombotic response. Its effects are rather intense and can lead to many complications. COVID-19-associated coagulopathy is frequently observed in hospitalized patients, especially ICU patients, and can be proven detrimental. It is usually accompanied by other complications, such as sepsis-induced coagulopathy, disseminated intravascular coagulation and venous thromboembolism. Since all these conditions lead to poor prognosis for severely ill patients, thromboprophylaxis and coagulopathy prognosis are just as important as the therapeutic handling of these patients. Since the beginning of the pandemic, many biomarkers have been considered useful when trying to assess the thrombotic risk of hospitalized patients or evaluate the severity of their situation. At the same time, many drugs have already been tested-while others are still being trialed-in order to find the optimal therapy for each urgent situation.

Ultrasensitive aptamer-functionalized Cu-MOF fluorescent nanozyme as an optical biosensor for detection of C-reactive protein.

In the present work, an aptasensing method based on integration of RNA on Cu-MOF was developed for detection of C-Reactive Protein (CRP). Cu-MOF showed stimulated fluorescence and mimetic peroxidase enzymatic activity at the time and can be used as dual-signal transduction. CRP binding RNA was used as a highly selective recognition element and immobilized on the Cu-MOF. The immobilized RNA can block the peroxidase activity and fluorescence of the signal traducer probe. Adding CRP to the RNA/Cu-MOF will release RNA from the surface of Cu-MOF and recover both the stimulated fluorescence and peroxidase activity. A biosensor was built for detection of CRP using the two modes of transduction, either colorimetry or fluorometry. A dynamic linear range was obtained from 0.1 to 50 ng mL -1with a limit of detection (LOD) as small as 40 pg mL -1was calculated in fluorescence mode and 240 pg mL -1 as LOD in colorimetry mode. The LODs are lower than the LOD of nephelometric techniques used in clinical practice and is comparable to the normal clinical cutoff value in high-sensitivity CRP assays (1 µg/mL). The aptasensor was successfully applied for detection of CRP in Covid-19 patients with spike recoveries between 84 and 102% and RSD from 0.94% to 2.05%.

Integration of Multiple Interferometers in Highly Multiplexed Diagnostic KITs to Evaluate Several Biomarkers of COVID-19 in Serum.

In the present work, highly multiplexed diagnostic KITs based on an Interferometric Optical Detection Method (IODM) were developed to evaluate six Coronavirus Disease 2019 (COVID-19)-related biomarkers. These biomarkers of COVID-19 were evaluated in 74 serum samples from severe, moderate, and mild patients with positive polymerase chain reaction (PCR), collected at the end of March 2020 in the Hospital Clínico San Carlos, in Madrid (Spain). The developed multiplexed diagnostic KITs were biofunctionalized to simultaneously measure different types of specific biomarkers involved in COVID-19. Thus, the serum samples were investigated by measuring the total specific Immunoglobulins (sIgT), specific Immunoglobulins G (sIgG), specific Immunoglobulins M (sIgM), specific Immunoglobulins A (sIgA), all of them against SARS-CoV-2, together with two biomarkers involved in inflammatory disorders, Ferritin (FER) and C Reactive Protein (CRP). To assess the results, a Multiple Linear Regression Model (MLRM) was carried out to study the influence of IgGs, IgMs, IgAs, FER, and CRP against the total sIgTs in these serum samples with a goodness of fit of 73.01% (Adjusted R-Squared).

Predictive Value of MR-proADM in the Risk Stratification and in the Adequate Care Setting of COVID-19 Patients Assessed at the Triage of the Emergency Department.

In the past two pandemic years, Emergency Departments (ED) have been overrun with COVID-19-suspicious patients. Some data on the role played by laboratory biomarkers in the early risk stratification of COVID-19 patients have been recently published. The aim of this study is to assess the potential role of the new biomarker mid-regional proadrenomedullin (MR-proADM) in stratifying the in-hospital mortality risk of COVID-19 patients at the triage. A further goal of the present study is to evaluate whether MR-proADM together with other biochemical markers could play a key role in assessing the correct care level of these patients. Data from 321 consecutive patients admitted to the triage of the ED with a COVID-19 infection were analyzed. Epidemiological; demographic; clinical; laboratory; and outcome data were assessed. All the biomarkers analyzed showed an important role in predicting mortality. In particular, an increase of MR-proADM level at ED admission was independently associated with a threefold higher risk of IMV. MR-proADM showed greater ROC curves and AUC when compared to other laboratory biomarkers for the primary endpoint such as in-hospital mortality, except for CRP. This study shows that MR-proADM seems to be particularly effective for early predicting mortality and the need of ventilation in COVID-19 patients admitted to the ED.