A decoy microrobot that removes SARS-CoV-2 and its variants in wastewater.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can persist in wastewater for several days, has a risk of waterborne-human transmission. The emergence of SARS-CoV-2 variants with increased infection capacity further highlights the need to remove the virus and restrict its spread in wastewater. Here, we report a decoy microrobot created by camouflaging algae with cell membranes displaying angiotensin-converting enzyme 2 (ACE2) for effective elimination of SARS-CoV-2 and its variants. The decoy microrobots show fast self-propulsion (>85 µm/s), allowing for successful "on-the-fly" elimination of SARS-CoV-2 spike proteins and pseudovirus in wastewater. Moreover, relying on the robust binding between ACE2 and SARS-CoV-2 variants, the decoy microrobots exhibit a broad-spectrum elimination of virus with a high efficiency of 95% for the wild-type strain, 92% for the Delta variant, and 93% for the Omicron variant, respectively. Our work presents a simple and safe decoy microrobot aimed toward eliminating viruses and other environmental hazards from wastewater.

Integration and Reanalysis of Four RNA-Seq Datasets Including BALF, Nasopharyngeal Swabs, Lung Biopsy, and Mouse Models Reveals Common Immune Features of COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1ß and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

Engineered Cell Membrane-Derived Nanoparticles in Immune Modulation.

Immune modulation is one of the most effective approaches in the therapy of complex diseases, including public health emergency. However, most immune therapeutics such as drugs, vaccines, and cellular therapy suffer from the limitations of poor efficacy and adverse side effects. Fortunately, cell membrane-derived nanoparticles (CMDNs) have superior compatibility with other therapeutics and offer new opportunities to push the limits of current treatments in immune modulation. As the interface between cells and outer surroundings, cell membrane contains components which instruct intercellular communication and the plasticity of cytomembrane has significantly potentiated CMDNs to leverage our immune system. Therefore, cell membranes employed in immunomodulatory CMDNs have gradually shifted from natural to engineered. In this review, unique properties of immunomodulatory CMDNs and engineering strategies of emerging CMDNs for immune modulation, with an emphasis on the design logic are summarized. Further, this review points out some pressing problems to be solved during clinical translation and put forward some suggestions on the prospect of immunoregulatory CMDNs. It is anticipated that this review can provide new insights on the design of immunoregulatory CMDNs and expand their potentiation in the precise control of the dysregulated immune system.

Capturing Cytokines with Advanced Materials: A Potential Strategy to Tackle COVID-19 Cytokine Storm.

The COVID-19 pandemic, induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused great impact on the global economy and people's daily life. In the clinic, most patients with COVID-19 show none or mild symptoms, while approximately 20% of them develop severe pneumonia, multiple organ failure, or septic shock due to infection-induced cytokine release syndrome (the so-called "cytokine storm"). Neutralizing antibodies targeting inflammatory cytokines may potentially curb immunopathology caused by COVID-19; however, the complexity of cytokine interactions and the multiplicity of cytokine targets make attenuating the cytokine storm challenging. Nonspecific in vivo biodistribution and dose-limiting side effects further limit the broad application of those free antibodies. Recent advances in biomaterials and nanotechnology have offered many promising opportunities for infectious and inflammatory diseases. Here, potential mechanisms of COVID-19 cytokine storm are first discussed, and relevant therapeutic strategies and ongoing clinical trials are then reviewed. Furthermore, recent research involving emerging biomaterials for improving antibody-based and broad-spectrum cytokine neutralization is summarized. It is anticipated that this work will provide insights on the development of novel therapeutics toward efficacious management of COVID-19 cytokine storm and other inflammatory diseases.

Decoy nanoparticles protect against COVID-19 by concurrently adsorbing viruses and inflammatory cytokines.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the urgent need to rapidly develop therapeutic strategies for such emerging viruses without effective vaccines or drugs. Here, we report a decoy nanoparticle against COVID-19 through a powerful two-step neutralization approach: virus neutralization in the first step followed by cytokine neutralization in the second step. The nanodecoy, made by fusing cellular membrane nanovesicles derived from human monocytes and genetically engineered cells stably expressing angiotensin converting enzyme II (ACE2) receptors, possesses an antigenic exterior the same as source cells. By competing with host cells for virus binding, these nanodecoys effectively protect host cells from the infection of pseudoviruses and authentic SARS-CoV-2. Moreover, relying on abundant cytokine receptors on the surface, the nanodecoys efficiently bind and neutralize inflammatory cytokines including interleukin 6 (IL-6) and granulocyte-macrophage colony-stimulating factor (GM-CSF), and significantly suppress immune disorder and lung injury in an acute pneumonia mouse model. Our work presents a simple, safe, and robust antiviral nanotechnology for ongoing COVID-19 and future potential epidemics.