Nasal spray of an IgM-like ACE2 fusion protein HH-120 accelerates SARS-CoV-2 clearance: A single-center propensity score-matched cohort study.

HH-120, a recently developed IgM-like ACE2 fusion protein with broad-spectrum neutralizing activity against all ACE2-utilizing coronaviruses, has been developed as a nasal spray for use as an early treatment agent to reduce disease progression and airborne transmission. The objective of this study was to evaluate the safety and efficacy of the HH-120 nasal spray in SARS-CoV-2-infected subjects. Eligible symptomatic or asymptomatic SARS-CoV-2-infected participants were enrolled in a single-arm trial to receive the HH-120 nasal spray for no longer than 6 days or until viral clearance at a single hospital between August 3 and October 7, 2022. An external control was built from real-world data of SARS-CoV-2-infected subjects contemporaneously hospitalized in the same hospital using a propensity score matching (PSM) method. After PSM, 65 participants in the HH-120 group and 103 subjects with comparable baseline characteristics in the external control group were identified. The viral clearance time was significantly shorter in participants receiving the HH-120 nasal spray than that in subjects of the control group (median 8 days vs. 10 days, p < 0.001); the difference was more prominent in those subgroup subjects with higher baseline viral load (median 7.5 days vs. 10.5 days, p < 0.001). The incidence of treatment-emergent adverse events and treatment-related adverse events of HH-120 group were 35.1% (27/77) and 3.9% (3/77), respectively. All the adverse events observed were mild, being of CTCAE grade 1 or 2, and transient. The HH-120 nasal spray showed a favorable safety profile and promising antiviral efficacy in SARS-CoV-2-infected subjects. The results from this study warrant further assessment of the efficacy and safety of the HH-120 nasal spray in large-scale randomized controlled clinical trials.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

Polydopamine Nanoparticles-Based Three-Line Lateral Flow Immunoassay for COVID-19 Detection.

Currently, the global trend of several hundred thousand new confirmed COVID-19 patients per day has not abated significantly. Serological antibody detection has become an important tool for the self-screening of people. While the most commonly used colorimetric lateral flow immunoassay (LFIA) methods for the detection of COVID-19 antibodies are limited by low sensitivity and a lack of quantification ability. This leads to poor accuracy in the screening of early COVID-19 patients. Therefore, it is necessary to develop an accurate and sensitive autonomous antibody detection technique that will effectively reduce the COVID-19 infection rate. Here, we developed a three-line LFIA immunoassay based on polydopamine (PDA) nanoparticles for COVID-19 IgG and IgM antibodies detection to determine the degree of infection. The PDA-based three-line LFIA has a detection limit of 1.51 and 2.34 ng/mL for IgM and IgG, respectively. This assay reveals a good linearity for both IgM and IgG antibodies detection and is also able to achieve quantitative detection by measuring the optical density of test lines. In comparison, the commercial AuNP-based LFIA showed worse quantification results than the developed PDA-based LFIA for low-concentration COVID-19 antibody samples, making it difficult to distinguish between negative and positive samples. Therefore, the developed PDA-based three-line LFIA platform has the accurate quantitative capability and high sensitivity, which could be a powerful tool for the large-scale self-screening of people.

Chinese expert consensus on intestinal microecology and management of digestive tract complications related to tumor treatment (version 2022).

The human gut microbiota represents a complex ecosystem that is composed of bacteria, fungi, viruses, and archaea. It affects many physiological functions including metabolism, inflammation, and the immune response. The gut microbiota also plays a role in preventing infection. Chemotherapy disrupts an organism's microbiome, increasing the risk of microbial invasive infection; therefore, restoring the gut microbiota composition is one potential strategy to reduce this risk. The gut microbiome can develop colonization resistance, in which pathogenic bacteria and other competing microorganisms are destroyed through attacks on bacterial cell walls by bacteriocins, antimicrobial peptides, and other proteins produced by symbiotic bacteria. There is also a direct way. For example, Escherichia coli colonized in the human body competes with pathogenic Escherichia coli 0157 for proline, which shows that symbiotic bacteria compete with pathogens for resources and niches, thus improving the host's ability to resist pathogenic bacteria. Increased attention has been given to the impact of microecological changes in the digestive tract on tumor treatment. After 2019, the global pandemic of novel coronavirus disease 2019 (COVID-19), the development of novel tumor-targeting drugs, immune checkpoint inhibitors, and the increased prevalence of antimicrobial resistance have posed serious challenges and threats to public health. Currently, it is becoming increasingly important to manage the adverse effects and complications after chemotherapy. Gastrointestinal reactions are a common clinical presentation in patients with solid and hematologic tumors after chemotherapy, which increases the treatment risks of patients and affects treatment efficacy and prognosis. Gastrointestinal symptoms after chemotherapy range from nausea, vomiting, and anorexia to severe oral and intestinal mucositis, abdominal pain, diarrhea, and constipation, which are often closely associated with the dose and toxicity of chemotherapeutic drugs. It is particularly important to profile the gastrointestinal microecological flora and monitor the impact of antibiotics in older patients, low immune function, neutropenia, and bone marrow suppression, especially in complex clinical situations involving special pathogenic microbial infections (such as clostridioides difficile, multidrug-resistant Escherichia coli, carbapenem-resistant bacteria, and norovirus).

Investor attention and the COVID-19 concept stocks in China's stock market

Purpose This paper investigates the impact of investor attention on the COVID-19 concept stocks in China's stock market from the perspectives of the macroeconomy, the stock market and the COVID-19 pandemic. Design/methodology/approach On the basis of controlling the time effects and individual fixed effects, this paper studies the impact of investor attention on the COVID-19 concept stocks in China's stock market through a set of fixed effect panel data models. Among them, investor attention focuses on macroeconomy, stock market and the COVID-19 pandemic, respectively, while stock indicators cover return, volatility and turnover. In addition, this paper also examines the heterogeneity influence of investor attention on the COVID-19 concept stocks from the perspective of time and stock classification. Findings Findings indicate that the attention to macroeconomy does not have a statistically significant effect on the return, unlike the attention to stock market and COVID-19 incident. Three types of investor attention have significant positive effects on the volatility and turnover rate. During the outbreak of the domestic epidemic, the impact of investor attention was significantly higher than that during the outbreak of the epidemic overseas. A finer-grained analysis shows that the attention to stock market has significantly increased the return of preventive type and treatment type stocks, while diagnostic-related stocks have been most affected by the attention to COVID-19 incident. Research limitations/implications The major limitation of this work is the construction of investor attention. Although Baidu index is widely used, investor attention can be assessed more accurately based on more unstructured data. In addition, the effect of the COVID-19 can also be investigated in a longer time domain. Further research can be combined with the dynamics of the COVID-19 pandemic to more comprehensively evaluate its impact on the stock market. Originality/value The research proves that investor attention plays an important role in stock pricing and provides empirical evidence on the behavioral foundations of the conceptual sector of the stock market under uncertainty. It also has practical implications for regulators and investors interested in conducting accurate asset allocation and risk assessment.

First isolation and identification of SARS-CoV-2 in Guangdong Province, China

In January 2020, Guangdong Province, China imported several suspected cases with SARS-CoV-2 from Wuhan City, Hubei Province. China, which were detected as SARS-CoV-2 positive in laboratory. To further understand the SARS-CoV-2 virulence, as well as drug development and epidemic prevention and control needs, we established a SARS-CoV-2 isolation procedure. Vero-E6 cells were infected with the positive bronchoalveolar-lavage sample. The cells were monitored daily for cytopathic effects using light microscopy. The presence of viral nucleic acid in the supernatant was detected by RT-PCR. RNA extracted from culture supernatants were used as a template to clone and sequence the genome. We used Illumina sequencing to characterize the virus genome and results showed that the isolated virus was SARS-CoV-2.

Artificial intelligence-assisted colorimetric lateral flow immunoassay for sensitive and quantitative detection of COVID-19 neutralizing antibody.

Currently, vaccination is the most effective medical measure to improve group immunity and prevent the rapid spread of COVID-19. Since the individual difference of vaccine effectiveness is inevitable, it is necessary to evaluate the vaccine effectiveness of every vaccinated person to ensure the appearance of herd immunity. Here, we developed an artificial intelligent (AI)-assisted colorimetric polydopamine nanoparticle (PDA)-based lateral flow immunoassay (LFIA) platform for the sensitive and accurate quantification of neutralizing antibodies produced from vaccinations. The platform integrates PDA-based LFIA and a smartphone-based reader to test the neutralizing antibodies in serum, where an AI algorithm is also developed to accurately and quantitatively analyze the results. The developed platform achieved a quantitative detection with 160 ng/mL of detection limit and 625-10000 ng/mL of detection range. Moreover, it also successfully detected totally 50 clinical serum samples, revealing a great consistency with the commercial ELISA kit. Comparing with commercial gold nanoparticle-based LFIA, our PDA-based LFIA platform showed more accurate quantification ability for the clinical serum. Therefore, we envision that the AI-assisted PDA-based LFIA platform with sensitive and accurate quantification ability is of great significance for large-scale evaluation of vaccine effectiveness and other point-of-care immunoassays.

Teaching Reform to the Biology Major During the COVID-19 Pandemic: A Study of the Method of Teaching Industrial Innovation and Entrepreneurial Talents.

The biology major has developed rapidly in recent years. Biology is a science that penetrates every aspect of human life and is one of the core majors in most agricultural colleges and universities. However, many teachers lack practical experience in the subject. To overcome this problem, in recent years, we have been trying to introduce new reforms into our teaching. This article provides some insight into the way that biology majors have been reformed, which will help educators in agricultural colleges and universities. At present, teachers implement the "Industrial Innovation and Entrepreneurship Talent Cultivation" (IIETC) model, but it is not clear whether this helps biology majors to master the course and improve their practical skills. In this study, the IIETC model is outlined, and the academic achievement and satisfaction of students taught under the IIETC model are assessed. A T-test is used to examine potential differences between IIETC and traditional teaching models. In-depth interviews and questionnaires were given to two groups of students who followed different teaching models as part of an exploratory study. The aim was to explore how effective IIETC is at helping biology majors master the course and improve students' wellbeing. Our results show that compared with traditional teaching methods, the IIETC model has a significant positive impact on the academic performance and happiness of biology students. Students trained under the IIETC model were more active and scored more highly in their final exams. They were more likely to feel that they had achieved success and happiness through the course (P = 0.03). The outcomes of this research reveal a novel teaching reform that improved students' enthusiasm for innovation and entrepreneurship during the ongoing COVID-19 pandemic. The effects are very encouraging and deserve further exploration and expansion in future work.

Analysis and forecast of marine economy development in China

Purpose>In recent years, China's marine industry has maintained rapid growth in general, and marine-related economic activities have continued to improve. The purpose of this research is to analyze the basic situation of China's marine economy development, identify the problems therein, forecast development trends and propose policy recommendations accordingly.Design/methodology/approach>This research conducts a comprehensive and detailed analysis of the development of China's marine economy with rich data in diversified aspects. The current situation of China's marine economy development is analyzed from the perspective of scale and structure, and the external and internal development environment of China's marine economy is discussed. With the application of measurement and prediction method such as trend extrapolation, exponential smoothing, grey forecasting and neural network method, the future situation of China's marine economy development is forecasted.Findings>In a complex environment where uncertainties at home and abroad have increased significantly, China's marine economy development suffers tremendous downward pressure in recent years. As China has achieved major achievements in the prevention and control of the COVID-19 epidemic, the marine economy development will gradually return to normal. It is estimated that the gross marine production value in 2022 will exceed 10 trillion yuan. China's marine economy will continue to maintain a steady growth trend in the future, and its development prospects will remain promising.Originality/value>This research explores the current situation and trends of China's marine economy development and puts forward policy recommendations to promote the steady and health development of China's marine economy accordingly.

Viral infection and transmission in a large, well-traced outbreak caused by the SARS-CoV-2 Delta variant.

The SARS-CoV-2 Delta variant has spread rapidly worldwide. To provide data on its virological profile, we here report the first local transmission of Delta in mainland China. All 167 infections could be traced back to the first index case. Daily sequential PCR testing of quarantined individuals indicated that the viral loads of Delta infections, when they first become PCR-positive, were on average ~1000 times greater compared to lineage A/B infections during the first epidemic wave in China in early 2020, suggesting potentially faster viral replication and greater infectiousness of Delta during early infection. The estimated transmission bottleneck size of the Delta variant was generally narrow, with 1-3 virions in 29 donor-recipient transmission pairs. However, the transmission of minor iSNVs resulted in at least 3 of the 34 substitutions that were identified in the outbreak, highlighting the contribution of intra-host variants to population-level viral diversity during rapid spread.

SARS-CoV-2 non-structural protein 6 triggers NLRP3-dependent pyroptosis by targeting ATP6AP1.

A recent mutation analysis suggested that Non-Structural Protein 6 (NSP6) of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a key determinant of the viral pathogenicity. Here, by transcriptome analysis, we demonstrated that the inflammasome-related NOD-like receptor signaling was activated in SARS-CoV-2-infected lung epithelial cells and Coronavirus Disease 2019 (COVID-19) patients' lung tissues. The induction of inflammasomes/pyroptosis in patients with severe COVID-19 was confirmed by serological markers. Overexpression of NSP6 triggered NLRP3/ASC-dependent caspase-1 activation, interleukin-1ß/18 maturation, and pyroptosis of lung epithelial cells. Upstream, NSP6 impaired lysosome acidification to inhibit autophagic flux, whose restoration by 1α,25-dihydroxyvitamin D3, metformin or polydatin abrogated NSP6-induced pyroptosis. NSP6 directly interacted with ATP6AP1, a vacuolar ATPase proton pump component, and inhibited its cleavage-mediated activation. L37F NSP6 variant, which was associated with asymptomatic COVID-19, exhibited reduced binding to ATP6AP1 and weakened ability to impair lysosome acidification to induce pyroptosis. Consistently, infection of cultured lung epithelial cells with live SARS-CoV-2 resulted in autophagic flux stagnation, inflammasome activation, and pyroptosis. Overall, this work supports that NSP6 of SARS-CoV-2 could induce inflammatory cell death in lung epithelial cells, through which pharmacological rectification of autophagic flux might be therapeutically exploited.

Food safety knowledge, attitudes, and eating behavior in the advent of the global coronavirus pandemic.

The objective of this study was to evaluate the relationships of food safety knowledge, attitude and eating behavior of consumers during national lockdowns in the advent of the COVID-19 pandemic. A total of 157 respondents completed the online survey using a structured questionnaire worldwide. Overall, the respondents exhibited good attitude and good knowledge towards public health including food safety especially on the importance of social distancing, mask wearing, well-balanced diet, physical exercise and personal hygiene, such as hand washing during the pandemic lockdowns. A Structural Equation Modeling (SEM) was used to test the relationships among food safety knowledge, attitude and behavior under the pandemic conditions. Results showed that attitude towards food safety under the coronavirus pandemic and lockdowns positively affected the eating behavior of the respondents, which exhibited a high ß (0.686) among the variables tested (p<0.05). Food safety knowledge was apparently not affected by the food safety behavior of the respondents.

Graph model under grey and unknown preferences for resolving conflicts on discharging Fukushima nuclear wastewater into the ocean

Ten years after the Fukushima nuclear accident, on April 13, 2021, the Japanese government announced the discharge of nuclear wastewater into the Pacific Ocean starting from the late 2022 or early 2023. The implementation of this decision would harm the local and global marine ecology because of the radioactive substances in the nuclear wastewater, which has also triggered strong opposition from the Japanese people and neighboring countries. The discharge of nuclear wastewater is a complicated process. In the context of the COVID-19, options of decision makers (DMs) must take into consideration existing global uncertainty, potentially leading to a slew of uncertain outcomes. A novel grey and unknown preference framework of the graph model for conflict resolution (GMCR) was proposed in this study to resolve the conflict of discharging nuclear wastewater in the ocean. Four forms of unknown preferences were defined for different grey stability definitions fully considering consider the possibility of choosing unknown results by DMs and increasing the diversity of equilibrium results. The equilibrium results the other alternative methods to discharge or continue to store nuclear waste are more conducive to the development of various DMs, and the consultation and cooperation of all DMs would ensure effective conflict resolution.

Point-of-need detection of pathogen-specific nucleic acid targets using magnetic particle spectroscopy.

The ongoing COVID-19 pandemic stresses the need for widely available diagnostic tests for the presence of SARS-CoV-2 in individuals. Due to the limited availability of vaccines, diagnostic assays which are cheap, easy-to-use at the point-of-need, reliable and fast, are currently the only way to control the pandemic situation. Here we present a diagnostic assay for the detection of pathogen-specific nucleic acids based on changes of the magnetic response of magnetic nanoparticles: The target-mediated hybridization of modified nanoparticles leads to an increase in the hydrodynamic radius. This resulting change in the magnetic behaviour in an ac magnetic field can be measured via magnetic particle spectroscopy (MPS), providing a viable tool for the accurate detection of target nucleic acids. In this work we show that single stranded DNA can be detected in a concentration-dependent manner by these means. In addition to detecting synthetic DNA with an arbitrary sequence in a concentration down to 500 pM, we show that RNA and SARS-CoV-2-specific DNA as well as saliva as a sample medium can be used for an accurate assay. These proof-of-principle experiments show the potential of MPS based assays for the reliable and fast diagnostics of pathogens like SARS-CoV-2 in a point-of-need fashion without the need of complex sample preparation.

Quantifying Air Pollutant Variations during COVID-19 Lockdown in a Capital City in Northwest China

In the context of the outbreak of coronavirus disease 2019 (COVID-19), strict lockdown policies were implemented to control nonessential human activities in Xi’an, northwest China, which greatly limited the spread of the pandemic and affected air quality. Compared with pre-lockdown, the air quality index and concentrations of PM2.5, PM10, SO2, and CO during the lockdown reduced, but the reductions were not very significant. NO2 levels exhibited the largest decrease (52%) during lockdown, owing to the remarkable decreased motor vehicle emissions. The highest K+ and lowest Ca2+ concentrations in PM2.5 samples could be attributed to the increase in household biomass fuel consumption in suburbs and rural areas around Xi’an and the decrease in human physical activities in Xi’an (e.g., human travel, vehicle emissions, construction activities), respectively, during the lockdown period. Secondary chemical reactions in the atmosphere increased in the lockdown period, as evidenced by the increased O3 level (increased by 160%) and OC/EC ratios in PM2.5 (increased by 26%), compared with pre-lockdown levels. The results, based on a natural experiment in this study, can be used as a reference for studying the formation and source of air pollution in Xi’an and provide evidence for establishing future long-term air pollution control policies.

Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates.

The coronavirus disease pandemic of 2019 (COVID-19) caused by the novel SARS-CoV-2 coronavirus resulted in economic losses and threatened human health worldwide. The pandemic highlights an urgent need for a stable, easily produced, and effective vaccine. SARS-CoV-2 uses the spike protein receptor-binding domain (RBD) to bind its cognate receptor, angiotensin-converting enzyme 2 (ACE2), and initiate membrane fusion. Thus, the RBD is an ideal target for vaccine development. In this study, we designed three different RBD-conjugated nanoparticle vaccine candidates, namely, RBD-Ferritin (24-mer), RBD-mi3 (60-mer), and RBD-I53-50 (120-mer), via covalent conjugation using the SpyTag-SpyCatcher system. When mice were immunized with the RBD-conjugated nanoparticles (NPs) in conjunction with the AddaVax or Sigma Adjuvant System, the resulting antisera exhibited 8- to 120-fold greater neutralizing activity against both a pseudovirus and the authentic virus than those of mice immunized with monomeric RBD. Most importantly, sera from mice immunized with RBD-conjugated NPs more efficiently blocked the binding of RBD to ACE2 in vitro, further corroborating the promising immunization effect. Additionally, the vaccine has distinct advantages in terms of a relatively simple scale-up and flexible assembly. These results illustrate that the SARS-CoV-2 RBD-conjugated nanoparticles developed in this study are a competitive vaccine candidate and that the carrier nanoparticles could be adopted as a universal platform for a future vaccine development.

The kinetics of viral load and antibodies to SARS-CoV-2.

OBJECTIVES: The aim was to understand persistence of the virus in body fluids the and immune response of an infected host to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), an agent of coronavirus disease 2019 (COVID-19). METHODS: We determined the kinetics of viral load in several body fluids through real time reverse transcription polymerase chain reaction, serum antibodies of IgA, IgG and IgM by enzyme-linked immunosorbent assay and neutralizing antibodies by microneutralization assay in 35 COVID-19 cases from two hospitals in Guangdong, China. RESULTS: We found higher viral loads and prolonged shedding of virus RNA in severe cases of COVID-19 in nasopharyngeal (1.3 × 106 vs 6.4 × 104, p < 0.05; 7∼8 weeks) and throat (6.9 × 106 vs 2.9 × 105, p < 0.05; 4∼5 weeks), but similar in sputum samples (5.5 × 106 vs 0.9 × 106, p < 0.05; 4∼5 weeks). Viraemia was rarely detected (2.8%, n = 1/35). We detected early seroconversion of IgA and IgG at the first week after illness onset (day 5, 5.7%, n = 2/35). Neutralizing antibodies were produced in the second week, and observed in all 35 included cases after the third week illness onset. The levels of neutralizing antibodies correlated with IgG (rs = 0.85, p < 0.05; kappa = 0.85) and IgA (rs = 0.64, p < 0.05; kappa = 0.61) in severe, but not mild cases (IgG, rs = 0.42, kappa = 0.33; IgA, rs = 0.32, kappa = 0.22). No correlation with IgM in either severe (rs = 0.17, kappa = 0.06) or mild cases (rs = 0.27, kappa = 0.15) was found. DISCUSSION: We revealed a prolonged shedding of virus RNA in the upper respiratory tract, and evaluated the consistency of production of IgG, IgA, IgM and neutralizing antibodies in COVID-19 cases.

Thymosin α1 therapy in critically ill patients with COVID-19: A multicenter retrospective cohort study.

BACKGROUND: COVID-19 characterized by refractory hypoxemia increases patient mortality because of immunosuppression effects. This study aimed to evaluate the efficacy of immunomodulatory with thymosin α1 for critical COVID-19 patients. METHODS: This multicenter retrospective cohort study was performed in 8 government-designated treatment centers for COVID-19 patients in China from Dec. 2019 to Mar. 2020. Thymosin α1 was administrated with 1.6 mg qd or q12 h for >5 days. The primary outcomes were the 28-day and 60-day mortality, the secondary outcomes were hospital length of stay and the total duration of the disease. Subgroup analysis was carried out according to clinical classification. RESULTS: Of the 334 enrolled COVID-19 patients, 42 (12.6%) died within 28 days, and 55 (16.5%) died within 60 days of hospitalization. There was a significant difference in the 28-day mortality between the thymosin α1 and non-thymosin α1-treated groups in adjusted model (P = 0.016), without obvious differences in the 60-day mortality and survival time in the overall cohort (P > 0.05). In the subgroup analysis, it was found that thymosin α1 therapy significantly reduced 28-day mortality (Hazards Ratios HR, 0.11, 95% confidence interval CI 0.02-0.63, P=0.013) via improvement of Pa02/FiO2 (P = 0.036) and prolonged the hospital length of stay (P = 0.024) as well as the total duration of the disease (P=0.001) in the critical type patients, especially those aged over 64 years, with white blood cell >6.8×109/L, neutrophil >5.3×109/L, lymphocyte < 0.73 × 109/L, PaO2/FiO2 < 196, SOFA > 3, and acute physiology and chronic health evaluation (APACHE) II > 7. CONCLUSION: These results suggest that treatment with thymosin α1 can markedly decrease 28-day mortality and attenuate acute lung injury in critical type COVID-19 patients.