Smartphone-Based Photothermal Lateral Flow Immunoassay Using Rhenium Diselenide Nanosheet.

Developing a rapid antibody-based detection method is of great importance for preventing and controlling the spread of coronavirus disease 2019 (COVID-19). Among the antibody-based methods for point-of-care (POC) detection, lateral flow immunoassay (LFIA) is the most widely used. However, LFIA still has the disadvantage of low sensitivity. In this work, an ReSe2 nanosheet with a thickness of 10-20 nm was prepared by liquid exfoliation and applied as the label in a photothermal LFIA due to its high photothermal conversion efficiency and high photothermal stability. An integrated detection device was introduced for rapid, on-site, and highly sensitive assay of the human antisevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike (S) protein IgG antibodies. The device mainly included a rhenium diselenide (ReSe2) nanosheet-based photothermal LFIA, a portable laser, and a smartphone with a portable thermal imager, which was used to record and analyze the thermal signal of the LFIA test zone. The human anti-SARS-COV-2 S protein IgG antibodies in buffer solution can be detected in a portable box within 10 min, with a thermal signal detection limit of 0.86 ng mL-1, which was 108-fold lower than that of the colorimetric signal. The integrated device can detect values as low as 2.76 ng mL-1 of the human anti-SARS-COV-2 S protein IgG antibodies in 50% serum. The integrated device showed great potential for rapid and home self-testing diagnosis of COVID-19.

An epithelial-immune circuit amplifies inflammasome and IL-6 responses to SARS-CoV-2.

Elevated levels of cytokines IL-1ß and IL-6 are associated with severe COVID-19. Investigating the underlying mechanisms, we find that while primary human airway epithelia (HAE) have functional inflammasomes and support SARS-CoV-2 replication, they are not the source of IL-1ß released upon infection. In leukocytes, the SARS-CoV-2 E protein upregulates inflammasome gene transcription via TLR2 to prime, but not activate, inflammasomes. SARS-CoV-2-infected HAE supply a second signal, which includes genomic and mitochondrial DNA, to stimulate leukocyte IL-1ß release. Nuclease treatment, STING, and caspase-1 inhibition but not NLRP3 inhibition blocked leukocyte IL-1ß release. After release, IL-1ß stimulates IL-6 secretion from HAE. Therefore, infection alone does not increase IL-1ß secretion by either cell type. Rather, bi-directional interactions between the SARS-CoV-2-infected epithelium and immune bystanders stimulates both IL-1ß and IL-6, creating a pro-inflammatory cytokine circuit. Consistent with these observations, patient autopsy lungs show elevated myeloid inflammasome gene signatures in severe COVID-19.

Is Ivermectin Effective in Treating COVID-19?

Coronavirus disease 2019 was first discovered in December 2019 and subsequently became a global pandemic with serious political, economic, and social implications worldwide. We urgently need to find drugs that can be effective against COVID-19. Among the many observational studies, ivermectin has attracted the attention of many countries. Ivermectin is a broad-spectrum antiparasitic drug that also has some antiviral effects. We reviewed studies related to ivermectin for the treatment of COVID-19 over the last 2 years (2019.12-2022.03) via search engines such as PubMed, Web of Science, and EBSCOhost. Seven studies showed a lower mortality rate in the ivermectin group than in the control group, six studies found that the ivermectin group had a significantly fewer length of hospitalization than the control group, and eight studies showed better negative RT-PCR responses in the IVM group than in the control group. Our systematic review indicated that ivermectin may be effective for mildly to moderately ill patients. There is no clear evidence or guidelines to recommend ivermectin as a therapeutic agent for COVID-19, so physicians should use it with caution in the absence of better alternatives in the clinical setting, and self-medication is not recommended for patients.

Integrating longitudinal clinical laboratory tests with targeted proteomic and transcriptomic analyses reveal the landscape of host responses in COVID-19.

The pathophysiology of coronavirus disease 19 (COVID-19) involves a multitude of host responses, yet how they unfold during the course of disease progression remains unclear. Here, through integrative analysis of clinical laboratory tests, targeted proteomes, and transcriptomes of 963 patients in Shanghai, we delineate the dynamics of multiple circulatory factors within the first 30 days post-illness onset and during convalescence. We show that hypercortisolemia represents one of the probable causes of acute lymphocytopenia at the onset of severe/critical conditions. Comparison of the transcriptomes of the bronchoalveolar microenvironment and peripheral blood indicates alveolar macrophages, alveolar epithelial cells, and monocytes in lungs as the potential main sources of elevated cytokines mediating systemic immune responses and organ damages. In addition, the transcriptomes of patient blood cells are characterized by distinct gene regulatory networks and alternative splicing events. Our study provides a panorama of the host responses in COVID-19, which may serve as the basis for developing further diagnostics and therapy.