Rapid growth and high cloud-forming potential of anthropogenic sulfate aerosol in a thermal power plant plume during COVID lockdown in India (preprint)

The COVID lockdown presented a unique opportunity to study the anthropogenic emissions from different sectors under relatively cleaner conditions in India. The complex interplays of power production, industry, and transport could be dissected due to the significantly reduced influence of the latter two emission sources. Here, based on measurements of cloud condensation nuclei (CCN) activity and chemical composition of atmospheric aerosols during the lockdown, we report an episodic event showing rapid growth and high hygroscopicity of new aerosol particles formed in the SO2 plume from a large coal-fired power plant. These sulfate-rich particles had high CCN activity and number concentration, indicating high cloud-forming potential. Examining the sensitivity of CCN properties under relatively clean conditions over India provides important new clues to delineate contributions of different anthropogenic emission sectors and further to understand their perturbations of past and future climate forcing.

Discovering common pathogenetic processes between COVID-19 and sepsis by bioinformatics and system biology approach

Corona Virus Disease 2019 (COVID-19), an acute respiratory infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread rapidly worldwide, resulting in a pandemic with a high mortality rate. In clinical practice, we have noted that many critically ill or critically ill patients with COVID-19 present with typical sepsis-related clinical manifestations, including multiple organ dysfunction syndrome, coagulopathy, and septic shock. In addition, it has been demonstrated that severe COVID-19 has some pathological similarities with sepsis, such as cytokine storm, hypercoagulable state after blood balance is disrupted and neutrophil dysfunction. Considering the parallels between COVID-19 and non-SARS-CoV-2 induced sepsis (hereafter referred to as sepsis), the aim of this study was to analyze the underlying molecular mechanisms between these two diseases by bioinformatics and a systems biology approach, providing new insights into the pathogenesis of COVID-19 and the development of new treatments. Specifically, the gene expression profiles of COVID-19 and sepsis patients were obtained from the Gene Expression Omnibus (GEO) database and compared to extract common differentially expressed genes (DEGs). Subsequently, common DEGs were used to investigate the genetic links between COVID-19 and sepsis. Based on enrichment analysis of common DEGs, many pathways closely related to inflammatory response were observed, such as Cytokine-cytokine receptor interaction pathway and NF-kappa B signaling pathway. In addition, protein-protein interaction networks and gene regulatory networks of common DEGs were constructed, and the analysis results showed that ITGAM may be a potential key biomarker base on regulatory analysis. Furthermore, a disease diagnostic model and risk prediction nomogram for COVID-19 were constructed using machine learning methods. Finally, potential therapeutic agents, including progesterone and emetine, were screened through drug-protein interaction networks and molecular docking simulations. We hope to provide new strategies for future research and treatment related to COVID-19 by elucidating the pathogenesis and genetic mechanisms between COVID-19 and sepsis.

Engineering SARS-CoV-2 cocktail antibodies into a bispecific format improves neutralizing potency and breadth (preprint)

One major limitation of neutralizing antibody-based COVID-19 therapy is the requirement of costly cocktails to reduce antibody resistance. We engineered two bispecific antibodies (bsAbs) using distinct designs and compared them with parental antibodies and their cocktail. Single molecules of both bsAbs block the two epitopes targeted by parental antibodies on the receptor-binding domain (RBD). However, bsAb with the IgG-(scFv)2 design (14-H-06) but not the CrossMAb design (14-crs-06) increases antigen-binding and virus-neutralizing activities and spectrum against multiple SARS-CoV-2 variants including the Omicron, than the cocktail. X-ray crystallography and computational simulations reveal distinct neutralizing mechanisms for individual cocktail antibodies and suggest higher inter-spike crosslinking potentials by 14-H-06 than 14-crs-06. In mouse models of infections by SARS-CoV-2 and the Beta, Gamma, and Delta variants, 14-H-06 exhibits higher or equivalent therapeutic efficacy than the cocktail. Rationally engineered bsAbs represent a cost-effective alternative to antibody cocktails and a promising strategy to improve potency and breadth.

Synergetic measures needed to control infection waves and contain SARS-CoV-2 transmission (preprint)

The public and scientific discourse on how to mitigate the COVID-19 pandemic is often focused on the impact of individual protective measures, in particular on immunization by vaccination. In view of changing virus variants and conditions, however, it seems not clear if vaccination or any other single protective measure alone may suffice to contain the transmission of SARS-CoV-2. Here, we investigate the effectiveness and synergies of vaccination and different non-pharmaceutical interventions such as universal masking (surgical, N95/FFP2), distancing & ventilation, contact reduction, and testing & isolation as a function of compliance in the population. We find that it would be difficult to contain SARS-CoV-2 transmission by any individual measure as currently available under realistic conditions. Instead, we show how multiple synergetic measures can be and have to be combined to decrease and keep the effective reproduction number (Re) below unity, even for virus variants with increased basic reproduction number (R0). We suggest that the presented approach and results can be used to design and communicate efficient strategies for mitigating the COVID-19 pandemic, depending on R0 as well as the efficacy and compliance achieved with each protective measure. At vaccination rates around 70%, the combination and synergies of universal masking, distancing & ventilation, and testing & isolation with moderate compliances around 30% appear well suited to keep Re below 1 and prevent or suppress infection waves. Higher compliance or additional measures like contact reductions (confinement/lockdown) are required to effectively and swiftly break intense waves of infection. For schools, we find that the transmission of SARS-CoV-2 can be contained by 2-3 tests per week combined with distancing & ventilation and masking.

Aerosol transmission of COVID-19 and infection risk in indoor environments (preprint)

The role of aerosolized SARS-CoV-2 viruses in airborne transmission of COVID-19 is debated. The transmitting aerosol particles are generated through the breathing and vocalization by infectious subjects. Some authors state that this represents the dominant route of spreading, while others dismiss the option. Public health organizations generally categorize it as a secondary transmission pathway. Here we present a simple, easy-to-use spreadsheet algorithm to estimate the infection risk for different indoor environments, constrained by published data on human aerosol emissions, SARS-CoV-2 viral loads, infective dose and other parameters. We evaluate typical indoor settings such as an office, a classroom, a choir practice room and reception/party environments. These are examples, and the reader is invited to use the algorithm for alternative situations and assumptions. Our results suggest that aerosols from highly infective subjects can effectively transmit COVID-19 in indoor environments. This "highly infective" category represents about one fifth of the patients tested positive for SARS-CoV-2. We find that "super infective" subjects, representing the top few percent of positive-tested ones, plus an unknown fraction of less, but still highly infective, high aerosol-emitting subjects, may cause COVID-19 clusters (>10 infections), e.g. in classrooms, during choir singing and at receptions. The highly infective ones also risk causing such events at parties, for example. In general, active room ventilation and the ubiquitous wearing of face masks (i.e. by all subjects) may reduce the individual infection risk by a factor of five to ten, similar to high-volume HEPA air filtering. The most effective mitigation measure studied is the use of high-quality masks, which can drastically reduce the indoor infection risk through aerosols.

Distinct regimes of particle and virus abundance explain face mask efficacy for COVID-19 (preprint)

Airborne transmission is an important transmission pathway for viruses, including SARS-CoV-2. Regions with a higher proportion of people wearing masks show better control of COVID-19, but the effectiveness of masks is still under debate due to their limited and variable efficiencies in removing respiratory particles. Here, we analyze experimental data and perform model calculations to show that this contrast can be explained by the different abundance regimes between particles and viruses. Upon short-term exposure, respiratory particles are usually in a particle-rich regime, but respiratory viruses are often in a virus-limited regime where the numbers of viruses inhaled by susceptible people are below or close to the infectious dose. This virus-limited regime ensures mask efficacy and synergy of multiple preventive measures in reducing the infection risk.

Development and Evaluation of A CRISPR-based Diagnostic For 2019-novel Coronavirus (preprint)

Background: The recent outbreak of infections by the 2019 novel coronavirus (2019-nCoV), the third zoonotic CoV has raised great public health concern. The demand for rapid and accurate diagnosis of this novel pathogen brought significant clinical and technological challenges. Currently, metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR (RT-PCR) are the most widely used molecular diagnostics. Methods: 2019-nCoV infections were confirmed in 52 specimens by mNGS. Genomic information was analyzed and used for the design and development of an isothermal, CRISPR-based diagnostic for this novel virus. The diagnostic performance of CRISPR-nCoV was assessed and compared across three technology platforms (mNGS, RT-PCR and CRISPR). Results: 2019-nCoVs sequenced in our study were conserved with the Wuhan strain, and shared certain genetic similarity with SARS-CoV. A high degree of variation in the level of viral RNA was observed in clinical specimens. CRISPR-nCoV demonstrated a near single-copy sensitivity and great clinical sensitivity with a shorter turn-around time than RT-PCR. Conclusion: CRISPR-nCoV presents as a promising diagnostic option for the emerging pathogen.