The rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to the coronavirus disease 2019 (COVID-19) worldwide pandemic. This unprecedented situation has garnered worldwide attention. An effective strategy for controlling the COVID-19 pandemic is to develop highly accurate methods for the rapid identification and isolation of SARS-CoV-2 infected patients. Many companies and institutes are therefore striving to develop effective methods for the rapid detection of SARS-CoV-2 ribonucleic acid (RNA), antibodies, antigens, and the virus. In this review, we summarize the structure of the SARS-CoV-2 virus, its genome and gene expression characteristics, and the current progression of SARS-CoV-2 RNA, antibodies, antigens, and virus detection. Further, we discuss the reasons for the observed false-negative and false-positive RNA and antibody detection results in practical clinical applications. Finally, we provide a review of the biosensors which hold promising potential for point-of-care detection of COVID-19 patients. This review thereby provides general guidelines for both scientists in the biosensing research community and for those in the biosensor industry to develop a highly sensitive and accurate point-of-care COVID-19 detection system, which would be of enormous benefit for controlling the current COVID-19 pandemic.

Background: The pandemic of novel coronavirus disease 2019 (COVID-19) has become a serious public health crisis worldwide. The symptoms of COVID-19 vary from mild to severe among different age groups, but the physiological changes related to COVID-19 are barely understood. Methods: In this study, a high-resolution mass spectrometry (HRMS)-based lipidomic strategy was used to characterize the endogenous plasma lipids for cured COVID-19 patients with different ages and symptoms. These patients were further divided into two groups: those with severe symptoms or who were elderly and relatively young patients with mild symptoms. In addition, automated lipidomic identification and alignment was conducted by LipidSearch software. Multivariate and univariate analyses were used for differential comparison. Results: Nearly 500 lipid compounds were identified in each cured COVID-19 group through LipidSearch software. At the level of lipid subclasses, patients with severe symptoms or elderly patients displayed dramatic changes in plasma lipidomic alterations, such as increased triglycerides and decreased cholesteryl esters. Some of these differential lipids might also have essential biological functions. Furthermore, the differential analysis of plasma lipids among groups was performed to provide potential prognostic indicators, and the change in signaling pathways. Conclusions: Dyslipidemia was observed in cured COVID-19 patients due to the viral infection and medical treatment, and the discharged patients should continue to do consolidation therapy. This work provides valuable knowledge about plasma lipid markers and potential therapeutic targets of COVID-19 and essential resources for further research on the pathogenesis of COVID-19.

Little information is available for antibody levels against SARS‐CoV‐2 variants of concern induced by Omicron breakthrough infection and a third booster with an inactivated vaccine (InV) or Ad5‐nCoV in people with completion of two InV doses. Plasma was collected from InV pre‐vaccinated Omicron‐infected patients (OIPs), unvaccinated OIPs between 0 and 22 days, and healthy donors (HDs) 14 days or 6 months after the second doses of an InV and 14 days after a homogenous booster or heterologous booster of Ad5‐nCoV. Anti‐Wuhan‐, Anti‐Delta‐, and Anti‐Omicron‐receptor binding domain (RBD)‐IgG titers were detected using enzyme‐linked immunosorbent assay. InV pre‐vaccinated OIPs had higher anti‐Wuhan‐, anti‐Delta‐, and anti‐Omicron‐RBD‐IgG titers compared to unvaccinated OIPs. Anti‐Wuhan‐RBD‐IgG titers sharply increased in InV pre‐vaccinated OIPs 0–5 days postinfection (DPI), while the geometric mean titers (GMTs) of anti‐Delta‐ and anti‐Omicron‐RBD‐IgG were 3.3‐fold and 12.0‐fold lower. Then, the GMT of anti‐Delta‐ and anti‐Omicron‐RBD‐IgG increased to 35 112 and 28 186 during 11–22 DPI, about 2.6‐fold and 3.2‐fold lower, respectively, than the anti‐Wuhan‐RBD‐IgG titer. The anti‐Wuhan‐, anti‐Delta‐, and anti‐Omicron‐RBD‐IgG titers declined over time in HDs after two doses of an InV, with 25.2‐fold, 5.6‐fold, and 4.5‐fold declination, respectively, at 6 months relative to the titers at 14 days after the second vaccination. Anti‐Wuhan‐, anti‐Delta‐, and anti‐Omicron‐RBD‐IgG titers elicited by a heterologous Ad5‐nCoV booster were significantly higher than those elicited by an InV booster, comparable to those in InV pre‐vaccinated OIPs. InV and Ad5‐nCoV boosters could improve humoral immunity against Omicron variants. Of these, the Ad5‐nCoV booster is a better alternative.

Recent studies have highlighted observations regarding re-tested positivity (RP) of SARS-CoV-2 RNA in discharged COVID-19 patients, however, the immune mechanisms underlying SARS-CoV-2 RNA RP in immunocompetent patients remain elusive. Herein, we describe the case of an immunocompetent COVID-19 patient with moderate symptoms who was twice re-tested as positive for SARS-CoV-2 RNA, and the period between first and third viral RNA positivity was 95 days, longer than previously reported (18–25 days). The chest computed tomography findings, plasma anti-SARS-CoV-2 antibody, neutralizing antibodies (NAbs) titer, and whole blood transcriptic characteristics in the viral RNA RP patient and other COVID-19 patients were analyzed. During the SARS-CoV-2 RNA RP period, new lung lesions were observed. The COVID-19 patient with viral RNA RP had delayed seroconversion of anti-spike/receptor-binding domain (RBD) IgA antibody and NAbs and were accompanied with disappearance of the lung lesions. Further experimental data validated that NAbs titer was significantly associated with anti-RBD IgA and IgG, and anti-spike IgG. The RP patient had lower interferon-, T cells- and B cell-related genes expression than non-RP patients with mild-to-moderate symptoms, and displayed lower cytokines and chemokines gene expression than severe patients. Interestingly, the RP patient had low expression of antigen presentation-related genes and low B cell counts which might have contributed to the delayed anti-RBD specific antibody and low CD8+ cell response. Collectively, delayed antigen presentation-related gene expression was found related to delayed adaptive immune response and contributed to the SARS-CoV-2 RNA RP in this described immunocompetent patient.

Purpose The immunogenicity of SARS-CoV-2 vaccines is poor in kidney transplant recipients (KTRs). The factors related to poor immunogenicity to vaccination in KTRs are not well defined. Methods An observational study was conducted in KTRs and healthy individuals who had received two doses of SARS-CoV-2 inactivated vaccine. IgG antibodies against the receptor-binding domain found in the S1 subunit of the spike protein, and against nucleocapsid protein were measured using enzyme-linked immunosorbent assay. Receptor-binding domain (RBD)-angiotensin-converting enzyme 2 interaction-blocking antibodies were measured using commercial kits. T cell responses against the spike and nucleocapsid proteins were detected using enzyme-linked immunosorbent spot assay. Results No severe adverse effects were observed in KTRs after first or second dose of SARS-CoV-2 inactivated vaccine. IgG antibodies against the receptor- binding domain, and nucleocapsid protein were not effectively induced in a majority of KTRs after second dose of inactivated vaccine. Specific T cell immunity response was detectable in 32%-40% KTRs after second doses of inactivated vaccine. KTRs who developed specific T cell immunity were more likely to be female, and have lower levels of total bilirubin, unconjugated bilirubin, and blood tacrolimus concentration. Multivariate logistic regression analysis found that blood unconjugated bilirubin was significantly negatively associated with SARS-CoV-2 specific T cell immunity response in k KTRs. Conclusions Specific T cell immunity response could be induced in 32%-40% KTRs after two doses of inactivated vaccine. Blood unconjugated bilirubin was negatively associated with specific cellular immunity response in KTRs following vaccination.