The research progress of SARS-CoV-2 main protease inhibitors from 2020 to 2022.

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. The main protease (Mpro) of SARS-CoV-2 plays a central role in viral replication and transcription and represents an attractive drug target for fighting COVID-19. Many SARS-CoV-2 Mpro inhibitors have been reported, including covalent and noncovalent inhibitors. The SARS-CoV-2 Mpro inhibitor PF-07321332 (Nirmatrelvir) designed by Pfizer has been put on the market. This paper briefly introduces the structural characteristics of SARS-CoV-2 Mpro and summarizes the research progress of SARS-CoV-2 Mpro inhibitors from the aspects of drug repurposing and drug design. These information will provide a basis for the drug development of treating the infection of SARS-CoV-2 and even other coronaviruses in the future.

Safety and immunogenicity of heterologous boosting with orally aerosolised or intramuscular Ad5-nCoV vaccine and homologous boosting with inactivated vaccines (BBIBP-CorV or CoronaVac) in children and adolescents: a randomised, open-label, parallel-controlled, non-inferiority, single-centre study.

BACKGROUND: Heterologous booster immunisation with orally administered aerosolised Ad5-nCoV vaccine (AAd5) has been shown to be safe and highly immunogenic in adults. Here, we aimed to assess the safety and immunogenicity of heterologous booster immunisation with orally administered AAd5 in children and adolescents aged 6-17 years who had received two doses of inactivated vaccine (BBIBP-CorV or CoronaVac). METHODS: We did a randomised, open-label, parallel-controlled, non-inferiority study to assess the safety and immunogenicity of heterologous booster immunisation with AAd5 (0·1 mL) or intramuscular Ad5-nCoV vaccine (IMAd5; 0·3 mL) and homologous booster immunisation with inactivated vaccine (BBIBP-CorV or CoronaVac; 0·5 mL) in children (aged 6-12 years) and adolescents (aged 13-17 years) who had received two doses of inactivated vaccine at least 3 months earlier in Hunan, China. Children and adolescents who were previously immunised with two-dose BBIBP-CorV or CoronaVac were recruited for eligibility screening at least 3 months after the second dose. A stratified block method was used for randomisation, and participants were stratified by age and randomly assigned (3:1:1) to receive AAd5, IMAd5, or inactivated vaccine. The study staff and participants were not masked to treatment allocation. Laboratory and statistical staff were masked during the study. In this interim analysis, adverse events within 14 days and geometric mean titre (GMT) of serum neutralising antibodies on day 28 after the booster vaccination, based on the per-protocol population, were used as the primary outcomes. The analysis of non-inferiority was based on comparison using a one-sided 97·5% CI with a non-inferiority margin of 0·67. This study was registered at ClinicalTrials.gov, NCT05330871, and is ongoing. FINDINGS: Between April 17 and May 28, 2022, 436 participants were screened and 360 were enrolled: 220 received AAd5, 70 received IMAd5, and 70 received inactivated vaccine. Within 14 days after booster vaccination, vaccine-related adverse reactions were reported: 35 adverse events (in 13 [12%] of 110 children and 22 [20%] of 110 adolescents) in 220 individuals in the AAd5 group, 35 (in 18 [51%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 13 (in five [14%] of 35 children and eight [23%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. Solicited adverse reactions were also reported: 34 (13 [12%] of 110 children and 21 [10%] of 110 adolescents) in 220 individuals in the AAd5 group, 34 (17 [49%] of 35 children and 17 [49%] of 35 adolescents) in 70 individuals in the IMAd5 group, and 12 (five [14%] of 35 children and seven [20%] of 35 adolescents) in 70 individuals in the inactivated vaccine group. The GMTs of neutralising antibodies against ancestral SARS-CoV-2 Wuhan-Hu-1 (Pango lineage B) in the AAd5 group were significantly higher than the GMTs in the inactivated vaccine group (adjusted GMT ratio 10·2 [95% CI 8·0-13·1]; p<0·0001). INTERPRETATION: Our study shows that a heterologous booster with AAd5 is safe and highly immunogenic against ancestral SARS-CoV-2 Wuhan-Hu-1 in children and adolescents. FUNDING: National Key R&D Program of China.

International cruise research advances and hotspots: Based on literature big data

This paper makes a systematic visual analysis of cruise research literature collected in science network database from 1996 to 2019. The results show that: the overall number of published literature on cruise research is growing;North American states, Europe, and Asia are the main regions of cruise research. The evolutionary of theme development of cruise research has three stages, and the current hot topics of cruise research can be summarized as cruise tourism, luxury cruises, cruise passengers, destination ports, environmental and biological conservation, and cruise diseases. Future research in the cruise field are in the areas of cruise supply chain, technology in cruise, children's cruise experience, itinerary design, planning and optimization, brand reputation and luxury cruises, public transportation in destinations, environmental responsibility of passengers and corporate social responsibility, optimization of energy systems, climate change in relation to the cruise industry, the Chinese cruise market and risk management of cruise diseases.

Policy-driven or market-driven? A new perspective on the development of China's cruise industry

The past 15 years have witnessed the rapid development of China's cruise industry from scratch and the formation of a policy system in the cruise industry, reflecting the shift of the Chinese government's attitude towards the cruise industry from wait-and-see, recognition and encouragement to active support. The paper conducts a statistical analysis of 128 policies related to the cruise industry issued by China's administrative departments at all levels. It is found that the release of policies synchronizes with the development of the cruise industry, with each one providing feedback to the other. The policies do not show a time lag with respect to their effects. The evolution of policy types from macro-level guidance to concrete operation is rapid, with the policy structure gradually improving. The themes of the policies concentrate on five areas: cruise tourism services and products, port construction and development, cruise industry chain expansion, cruise industry environment and cruise industry management, which is in line with current characteristics of the development of China's cruise industry. However, there is still a lack of adequate policies to support and guide the industrial upgrading of cruise operation and cruise construction and its green and low-carbon development.

Safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster following three doses of CoronaVac: a multicentre, open-label, phase 4, randomised trial

Background Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster. Methods This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 1011 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 1011 viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group vs homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing. Findings Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% vs 9% and 14%, respectively;p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7–837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0–672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 [48·0–71·4];p<0·0001). Interpretation A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac. Funding National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan.

[Effect of Family Environment on Non-Suicidal Self-Injury Among Middle School Students During the COVID-19 Epidemic: The Mediating Role of Depression].

Objective: To study the current status of non-suicidal self-injury (NSSI) incidents among middle school students in Chengdu during the COVID-19 epidemic and to explore the mechanism of action of depression on the relationship between family environment and NSSI. Methods: Data were obtained from the Chengdu Positive Child Development (CDPD) cohort. In June and July 2020, after primary and secondary schools were reopened after the closure due to the COVID-19 epidemic, on-site questionnaire surveys were conducted with the Deliberate Self-Harm Inventory (DSHI), the Chinese Family Assessment Instrument (C-FAI), and Center for Epidemiologic Studies Depression Scale for Children (CES-DC), thereby obtaining the data of 3595 middle school students. Two-sample t-test and χ 2 test were used to compare the incidence of NSSI among middle school students of different grades and genders, and the Model 58 test of the SPSS PROCESS component was used to analyze the mediating effect of gender-mediated depression. Results: 1) The incidence of NSSI among middle school students in Chengdu during the COVID-19 epidemic was 49.67%. The incidence of NSSI among ninth-graders (80.70%) was significantly higher than those of the eighth graders (33.82%) and seventh graders (32.32%), and the incidence of NSSI among female middle school students (54.75%) was significantly higher than that of male students (44.52%). 2) Family environment ( r=0.34, P<0.001) and depression ( r=0.50, P<0.001) were positively correlated with NSSI. 3) Depression partially mediated the effect of family environment on NSSI, with the mediating effect accounting for 64.64% of the total effect. Compared with that of male students, the positive predictive effect between family environment and depression and that between depression and NSSI in female middle school students were more significant. Conclusion: During the COVID-19 pandemic, middle school students in Chengdu had a high incidence of NSSI, which indicates that the family environment should be improved, more attention should be given to gender differences, and early screening and intervention for depression should be strengthened to reduce the incidence of NSSI.

Comparison of the prophylactic antithrombotic effect of indobufen and warfarin in patients with nephrotic syndrome: a randomized controlled trial.

PURPOSE: The risk of thromboembolic events is elevated in patients with nephrotic syndrome, and warfarin use has been associated with an increased risk of bleeding. Indobufen, a selective cyclooxygenase-1 inhibitor, is currently being evaluated for the prevention of thromboembolic events in nephrotic syndrome. This study aimed to compare the efficacy and safety of indobufen with that of warfarin in patients with nephrotic syndrome. MATERIALS AND METHODS: This multicenter, randomized, three-arm, open-label, parallel controlled trial involved a total of 180 adult patients with nephrotic syndrome from four centers in China. Patients were randomly assigned to receive 100 mg indobufen (bid), 200 mg indobufen (bid), and 3 mg warfarin (qd) daily for 12 weeks. The primary endpoints included thromboembolic and bleeding events, while laboratory results and adverse events constituted secondary endpoints. RESULTS: No thromboembolic events occurred in the high-/low-dose indobufen and warfarin groups. Moreover, the use of a low dose of indobufen significantly reduced the risk of minor bleeding events compared with warfarin use (2% versus 18%, p < .05). Finally, adverse events were more frequent in warfarin-treated patients. CONCLUSIONS: This study found that indobufen therapy provided equivalent effects in preventing thromboembolic events compared with warfarin therapy, while low dose of indobufen was associated with a reduced risk of bleeding events, thus it should be recommended for the prevention of thromboembolic events in clinical practice in patients with nephrotic syndrome. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-17013428.

Impact of Social Isolation and Digital Divide on Mental Health and Wellbeing in Patients with Mental Health Disorders during COVID-19: A Multiple Case Study.

The positive relationship between social connections and mental health and wellbeing has been widely documented. During the initial stage of the pandemic, COVID-19 associated restrictions had given rise to social isolation that had a negative effect on individuals' mental health and wellbeing, particularly among patients with preexisting mental health disorders. To abridge physical distance, digital technology had become a primary method of communication and social engagement. However, not everyone had access to internet and devices required to connect online due to the digital divide, especially among marginalized populations. The purpose of this multiple case study was to explore experiences of social isolation and the digital divide among patients with mental health disorders, and its impact on their mental health and wellbeing. Our findings revealed that social isolation was the major contributing factor to the intensification of mental health symptoms, while the digital divide (e.g., financial constraints and low proficiency in digital technology) was recognized as a barrier to making social connections via digital technologies. Nurses should engage with communities and policymakers in developing strategies to address the social determinants of health disparities during the current pandemic, other disruptive pandemics and beyond.

Flexible Amperometric Immunosensor Based on Colloidal Quantum Dots for Detecting the Myeloperoxidase (MPO) Systemic Inflammation Biomarker.

Myeloperoxidase (MPO) has been demonstrated to be a biomarker of neutrophilic inflammation in various diseases. Rapid detection and quantitative analysis of MPO are of great significance for human health. Herein, an MPO protein flexible amperometric immunosensor based on a colloidal quantum dot (CQD)-modified electrode was demonstrated. The remarkable surface activity of CQDs allows them to bind directly and stably to the surface of proteins and to convert antigen-antibody specific binding reactions into significant currents. The flexible amperometric immunosensor provides quantitative analysis of MPO protein with an ultra-low limit of detection (LOD) (31.6 fg mL-1), as well as good reproducibility and stability. The detection method is expected to be applied in clinical examination, POCT (bedside test), community physical examination, home self-examination and other practical scenarios.

Safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster following three doses of CoronaVac: a multicentre, open-label, phase 4, randomised trial.

BACKGROUND: Aerosolised Ad5-nCoV is the first approved mucosal respiratory COVID-19 vaccine to be used as a booster after the primary immunisation with COVID-19 vaccines. This study aimed to evaluate the safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster. METHODS: This is an open-label, parallel-controlled, phase 4 randomised trial enrolling healthy adult participants (≥18 years) who had completed a two-dose primary immunisation and a booster immunisation with inactivated COVID-19 vaccines (CoronaVac only) at least 6 months before, in Lianshui and Donghai counties, Jiangsu Province, China. We recruited eligible participants from previous trials in China (NCT04892459, NCT04952727, and NCT05043259) as cohort 1 (with the serum before and after the first booster dose available), and from eligible volunteers in Lianshui and Donghai counties, Jiangsu Province, as cohort 2. Participants were randomly assigned at a ratio of 1:1:1, using a web-based interactive response randomisation system, to receive the fourth dose (second booster) of aerosolised Ad5-nCoV (0·1 mL of 1·0 × 1011 viral particles per mL), intramuscular Ad5-nCoV (0·5 mL of 1·0 × 1011 viral particles per mL), or inactivated COVID-19 vaccine CoronaVac (0·5 mL), respectively. The co-primary outcomes were safety and immunogenicity of geometric mean titres (GMTs) of serum neutralising antibodies against prototype live SARS-CoV-2 virus 28 days after the vaccination, assessed on a per-protocol basis. Non-inferiority or superiority was achieved when the lower limit of the 95% CI of the GMT ratio (heterologous group vs homologous group) exceeded 0·67 or 1·0, respectively. This study was registered with ClinicalTrials.gov, NCT05303584 and is ongoing. FINDINGS: Between April 23 and May 23, 2022, from 367 volunteers screened for eligibility, 356 participants met eligibility criteria and received a dose of aerosolised Ad5-nCoV (n=117), intramuscular Ad5-nCoV (n=120), or CoronaVac (n=119). Within 28 days of booster vaccination, participants in the intramuscular Ad5-nCoV group reported a significantly higher frequency of adverse reactions than those in the aerosolised Ad5-nCoV and intramuscular CoronaVac groups (30% vs 9% and 14%, respectively; p<0·0001). No serious adverse events related to the vaccination were reported. The heterologous boosting with aerosolised Ad5-nCoV triggered a GMT of 672·4 (95% CI 539·7-837·7) and intramuscular Ad5-nCoV triggered a serum neutralising antibody GMT of 582·6 (505·0-672·2) 28 days after the booster dose, both of which were significantly higher than the GMT in the CoronaVac group (58·5 [48·0-71·4]; p<0·0001). INTERPRETATION: A heterologous fourth dose (second booster) with either aerosolised Ad5-nCoV or intramuscular Ad5-nCoV was safe and highly immunogenic in healthy adults who had been immunised with three doses of CoronaVac. FUNDING: National Natural Science Foundation of China, Jiangsu Provincial Science Fund for Distinguished Young Scholars, and Jiangsu Provincial Key Project of Science and Technology Plan.

Acriflavine and proflavine hemisulfate as potential antivirals by targeting Mpro.

The evolving SARS-CoV-2 epidemic buffets the world, and the concerted efforts are needed to explore effective drugs. M^pro is an intriguing antiviral target for interfering with viral RNA replication and transcription. In order to get potential anti-SARS-CoV-2 agents, we established an enzymatic assay using a fluorogenic substrate to screen the inhibitors of M^pro. Fortunately, Acriflavine (ACF) and Proflavine Hemisulfate (PRF) with the same acridine scaffold were picked out for their good inhibitory activity against M^pro with IC₅₀ of 5.60 ± 0.29 µM and 2.07 ± 0.01 µM, respectively. Further evaluation of MST assay and enzymatic kinetics experiment in vitro showed that they had a certain affinity to SARS-CoV-2 M^pro and were both non-competitive inhibitors. In addition, they inhibited about 90 % HCoV-OC43 replication in BHK-21 cells at 1 µM. Both compounds showed nano-molar activities against SARS-CoV-2 virus, which were superior to GC376 for anti-HCoV-43, and equivalent to the standard molecule remdesivir. Our study demonstrated that ACF and PRF were inhibitors of M^pro, and ACF has been previously reported as a PL^pro inhibitor. Taken together, ACF and PRF might be dual-targeted inhibitors to provide protection against infections of coronaviruses.

Reciprocal Effect between Depressive Symptoms and Adolescent Non-suicidal self-injury before and after COVID-19: A Longitudinal Study (preprint)

Background Non-suicidal   self-injury (NSSI) is a common psychological and behavioral problem among   adolescents and has now become a major public health problem for adolescents.   Since the COVID-19 outbreak in 2019, it has caused various mental health   problems, such as anxiety, depression, and mental burnout, contributing to a   severe mental health crisis globally. Thus far, a few studies recorded the   temporal change in adolescents’ psychological status during the COVID-19   pandemic as well as that with the implementation of large-scale public health   intervention methods, and this study adds to the evidence. Methods Based on   the Chengdu Positive Child Development (CPCD) survey, the baseline dataset   was collected in December 2019, and the first follow-up of the CPCD was conducted   in July 2020. A total of 6,023 adolescents aged 10-19 were recruited from   five primary and middle schools. Two independent autoregressive cross-lagged   models were used to test the bidirectional relationship between NSSI and   depressive symptoms in adolescents; logistic regression analysis was used to   explore the predictors of NSSI implementation in adolescents with depressive   symptoms, which could provide an entry point for behavioral interventions to   NSSI. Results The   prevalence of depressive symptoms among our participants was 32.69% at   baseline, and 34.27% at follow-up. The occurrence rate of NSSI in adolescents   who may have depressive symptoms was 44.34%%, and that during the pandemic   was 53.44%. The difference was statistically significant (P <   0.05). The results of the binary logistic analysis showed that among   adolescents, gender, duration of the online class, depression mood, place of   residence, and self-perception of relationship with caregivers were the risk   factors for NSSI (or > 1, β> 0), and daily sleep hours positive mood   was the protective factor (or < 1, β< 0).  The lag effect of adolescent depression on   their NSSI behavior is significant, which means that based on controlling the   adolescent baseline NSSI, the deeper the adolescent depression degree, the   more frequent their NSSI behavior (β=0.26, P<0.01). At the same time,   adolescents' NSSI behavior also had a lagging effect on depressive symptoms,   and adolescents with self-injury behavior were more likely to be depressed (β=0.02, P<0.01). Depression and   NSSI are mutual(β=0.77,   P<0.05；β=0.27,   P<0.01). Conclusions The   increased depressive symptoms among adolescents exacerbated their NSSI   behaviors and hurt their mental health during COVID-19. Screening for   depression should be carried out early to serve as a warning sign in   preventing and reducing NSSI in adolescents.

Efficient inactivation of the contamination with pathogenic microorganisms by a combination of water spray and plasma-activated air.

The global pandemic caused by SARS-CoV-2 has lasted two and a half years and the infections caused by the viral contamination are still occurring. Developing efficient disinfection technology is crucial for the current epidemic or infectious diseases caused by other pathogenic microorganisms. Gas plasma can efficiently inactivate different microorganisms, therefore, in this study, a combination of water spray and plasma-activated air was established for the disinfection of pathogenic microorganisms. The combined treatment efficiently inactivated the Omicron-pseudovirus through caused the nitration modification of the spike proteins and also the pathogenic bacteria. The combined treatment was improved with a funnel-shaped nozzle to form a temporary relatively sealed environment for the treatment of the contaminated area. The improved device could efficiently inactivate the Omicron-pseudovirus and bacteria on the surface of different materials including quartz, metal, leather, plastic, and cardboard and the particle size of the water spray did not affect the inactivation effects. This study supplied a disinfection strategy based on plasma-activated air for the inactivation of contaminated pathogenic microorganisms.

Deep Learning Mask Face Recognition with Annealing Mechanism

Face recognition (FR) has matured with deep learning, but due to the COVID-19 epidemic, people need to wear masks outside to reduce the risk of infection, making FR a challenge. This study uses the FaceNet approach combined with transfer learning using three different sizes of validated CNN architectures: InceptionResNetV2, InceptionV3, and MobileNetV2. With the addition of the cosine annealing (CA) mechanism, the optimizer can automatically adjust the learning rate (LR) during the model training process to improve the efficiency of the model in finding the best solution in the global domain. The mask face recognition (MFR) method is accomplished without increasing the computational complexity using existing methods. Experimentally, the three models of different sizes using the CA mechanism have a better performance than the fixed LR, step and exponential methods. The accuracy of the three models of different sizes using the CA mechanism can reach a practical level at about 93%.

Clinical efficacy analysis of mesenchymal stem cell therapy in patients with COVID-19: A systematic review.

BACKGROUND: Currently, ongoing trials of mesenchymal stem cells (MSC) therapies for coronavirus disease 2019 (COVID-19) have been reported. AIM: In this study, we investigated whether MSCs have therapeutic efficacy in novel COVID-19 patients. METHODS: Search terms included stem cell, MSC, umbilical cord blood, novel coronavirus, severe acute respiratory syndrome coronavirus-2 and COVID-19, applied to PubMed, the Cochrane Controlled Trials Register, EMBASE and Web of Science. RESULTS: A total of 13 eligible clinical trials met our inclusion criteria with a total of 548 patients. The analysis showed no significant decrease in C-reactive protein (CRP) levels after stem cell therapy (P = 0.11). A reduction of D-dimer levels was also not observed in patients after stem cell administration (P = 0.82). Furthermore, interleukin 6 (IL-6) demonstrated no decrease after stem cell therapy (P = 0.45). Finally, we investigated the overall survival (OS) rate after stem cell therapy in COVID-19 patients. There was a significant improvement in OS after stem cell therapy; the OS of enrolled patients who received stem cell therapy was 90.3%, whereas that of the control group was 79.8% (P = 0.02). CONCLUSION: Overall, our analysis suggests that while MSC therapy for COVID-19 patients does not significantly decrease inflammatory markers such as CRP, D-dimer and IL-6, OS is improved.