Continuous evolution and emerging lineage of seasonal human coronaviruses: A multicenter surveillance study.

The seasonal human coronaviruses (HCoVs) have zoonotic origins, repeated infections, and global transmission. The objectives of this study are to elaborate the epidemiological and evolutionary characteristics of HCoVs from patients with acute respiratory illness. We conducted a multicenter surveillance at 36 sentinel hospitals of Beijing Metropolis, China, during 2016-2019. Patients with influenza-like illness (ILI) and severe acute respiratory infection (SARI) were included, and submitted respiratory samples for screening HCoVs by multiplex real-time reverse transcription-polymerase chain reaction assays. All the positive samples were used for metatranscriptomic sequencing to get whole genomes of HCoVs for genetical and evolutionary analyses. Totally, 321 of 15 677 patients with ILI or SARI were found to be positive for HCoVs, with an infection rate of 2.0% (95% confidence interval, 1.8%-2.3%). HCoV-229E, HCoV-NL63, HCoV-OC43, and HCoV-HKU1 infections accounted for 18.7%, 38.3%, 40.5%, and 2.5%, respectively. In comparison to ILI cases, SARI cases were significantly older, more likely caused by HCoV-229E and HCoV-OC43, and more often co-infected with other respiratory pathogens. A total of 179 full genome sequences of HCoVs were obtained from 321 positive patients. The phylogenetical analyses revealed that HCoV-229E, HCoV-NL63 and HCoV-OC43 continuously yielded novel lineages, respectively. The nonsynonymous to synonymous ratio of all key genes in each HCoV was less than one, indicating that all four HCoVs were under negative selection pressure. Multiple substitution modes were observed in spike glycoprotein among the four HCoVs. Our findings highlight the importance of enhancing surveillance on HCoVs, and imply that more variants might occur in the future.

English teachers' perceptions of emergency remote teaching: Emotional attitudes, professional identity, and coping strategies.

While the technology integration has been widely acknowledged, insufficient effort has been made to understand English teachers' perceptions of emergency remote teaching (ERT). Given English is the primary foreign language in China and English teachers' perceptions and adoptions of ERT impact the attainment of teaching and learning goals, this study inquired into experienced university English teachers' emotional attitudes, perceptions of the reconstructed professional identity, and their strategies to cope with difficulties when conducting ERT in the Chinese English teaching context. Semi-structured interviews were conducted both online and face-to-face with five experienced universities English teachers in China. The findings indicated a trajectory of teachers' attitudes toward ERT, namely, their attitudes were switched from doubt and rejection to fondness and attachment. Experienced English teachers adopted various strategies to cope with the difficulties and challenges they have encountered, including seeking support from their peers, students, and family, as well as self-regulated learning to sustain continuing professional development. During ERT, they have reconstructed their teacher identities. The study enriched peoples' understandings of English teachers' perceptions of the ERT by contextualizing the study in the Chinese educational context. Results can provide empirical evidence for policymakers and teacher trainers to make informed decisions regarding technical support and teachers' continuing professional development.

Detection of SARS-CoV-2 Antibodies in Oral Fluid Using a Magnetic Particle-Based Chemiluminescence Immunoassay - Beijing Municipality, China, 2021.

Introduction: Oral fluids (OFs) have been broadly used as non-invasive samples for evaluating protective IgG antibodies from natural infection or vaccination, especially in pediatric populations. Methods: Paired OF and serum were collected from both individuals who received a booster dose of the inactive coronavirus disease 2019 (COVID-19) vaccine as well as those who did not have a history of COVID-19 vaccination and infection (as the control group). The total human IgG antibody (HIgG) content was evaluated as a marker of OF sampling quality. An in-house adapted magnetic particle-based chemiluminescence immunoassay was used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody detection in the OF. The SARS-CoV-2 IgG antibody in the serum samples was detected using a commercial immunoassay. Results: In total, 579 paired OF and serum samples were collected. An additional 172 OF samples were collected from preschool children. The results indicated that the HIgG concentration in qualified OF samples should be higher than 0.3 µg/mL. Compared to the serum assay, the in-house OF immunoassay for detecting IgG antibodies against SARS-CoV-2 had 95.06% accuracy, 95.03% sensitivity, and 100% specificity. Conclusions: Overall, the in-house immunoassay for detecting SARS-CoV-2 IgG antibodies in OF showed high potential for application towards serological surveillance and immunization effect assessment after large-scale, inactive COVID-19 vaccination in China.

Key takeaways from China's success in eliminating malaria: leveraging existing evidence for a malaria-free world.

Although the total number of malaria cases and fatalities have declined globally since 2010, there were still 241 million malaria cases identified across 85 countries and territories in 2020. As the global malaria eradication process accelerates, more countries have launched their own initiatives of elimination. Notably, China achieved this goal by 2021, ending thousands of years of endemic. Undoubtedly, tremendous experience and vital lessons have been accrued en route to the malaria-free goal in malaria-eliminated countries including China. To enhance prospects of a malaria-free world by bridging the key evidence from a malaria-eliminated country to the contexts of affected, this personal view highlights concerted commitments and universal investment in healthcare, improved surveillance and response system, constant capacity building, demand-oriented scientific research, and multiway cooperation, which have helped China to eliminate this ancient scourge. We discuss how these key takeaways could be leveraged to different contexts. We also argue the long-term challenges and barriers on the pathway to malaria elimination and underline the needs for consistent efforts to maintain zero indigenous cases and prevent re-introduction of malaria. Through concerted efforts from global collaboration, a malaria-free world can become a reality.

Differential effects of macrophage subtypes on SARS-CoV-2 infection in a human pluripotent stem cell-derived model.

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19), with macrophages as one of the main cell types involved. It is urgent to understand the interactions among permissive cells, macrophages, and the SARS-CoV-2 virus, thereby offering important insights into effective therapeutic strategies. Here, we establish a lung and macrophage co-culture system derived from human pluripotent stem cells (hPSCs), modeling the host-pathogen interaction in SARS-CoV-2 infection. We find that both classically polarized macrophages (M1) and alternatively polarized macrophages (M2) have inhibitory effects on SARS-CoV-2 infection. However, M1 and non-activated (M0) macrophages, but not M2 macrophages, significantly up-regulate inflammatory factors upon viral infection. Moreover, M1 macrophages suppress the growth and enhance apoptosis of lung cells. Inhibition of viral entry using an ACE2 blocking antibody substantially enhances the activity of M2 macrophages. Our studies indicate differential immune response patterns in distinct macrophage phenotypes, which could lead to a range of COVID-19 disease severity.

[Application of oral fluid in SARS-CoV-2 nucleic acid and antibody detection].

This study aimed to explore the application value of new biological specimen oral fluid in SARS-CoV-2 nucleic acid and antibody detection. Oral fluid and paired respiratory and blood specimens from 7 confirmed cases of two COVID-19 cluster epidemic were collected in Beijing from October to November 2021. SARS-CoV-2 virus and IgG antibody were detected by real time PCR kits and serum antibody detection reagents, and SARS-CoV-2 IgG antibody in oral fluids was detected by a new established method of magnetic particle chemiluminescence. The results showed that the nucleic acid amplification test of SARS-CoV-2 on nasopharyngeal swabs, throat swabs and oral fluid specimens from 3 confirmed cases of COVID-19 was positive, among which the Ct value for ORF1a/b and N gene of oral fluid samples in 2 cases was close to that of throat swab, and the Ct value of oral fluid sample for 1 case was higher than that of throat swab. The complete genome sequence of one oral fluid specimen was obtained, which belonged to the VOC/Delta variant strain. The SARS-CoV-2 IgG antibodies of the paired oral fluid and serum were all positive, and the S/CO values of oral fluid were all lower than those of serum. The series of oral fluid results showed that SARS-CoV-2 IgG antibody level increased from 11 to 32 days after the onset of the disease.

Development of an Adeno-Associated Virus-Vectored SARS-CoV-2 Vaccine and Its Immunogenicity in Mice.

Owing to the outbreak of the novel coronavirus (SARS-CoV-2) worldwide at the end of 2019, the development of a SARS-CoV-2 vaccine became an urgent need. In this study, we developed a type 9 adeno-associated virus vectored vaccine candidate expressing a dimeric receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S protein) and evaluated its immunogenicity in a murine model. The vaccine candidate, named AAV9-RBD virus, was constructed by inserting a signal peptide to the N-terminus of two copies of RBD, spaced by a linker, into the genome of a type 9 adeno-associated virus. In vitro assays showed that HeLa cells infected by the recombinant AAV virus expressed high levels of the recombinant RBD protein, mostly found in the cell culture supernatant. The recombinant AAV9-RBD virus was cultured and purified. The genome titer of the purified recombinant AAV9-RBD virus was determined to be 2.4 × 1013 genome copies/mL (GC/mL) by Q-PCR. Balb/c mice were immunized with the virus by intramuscular injection or nasal drip administration. Eight weeks after immunization, neutralizing antibodies against the new coronavirus pseudovirus were detected in the sera of all mice; the mean neutralizing antibody EC50 values were 517.7 ± 292.1 (n=10) and 682.8 ± 454.0 (n=10) in the intramuscular injection group and nasal drip group, respectively. The results of this study showed that the recombinant AAV9-RBD virus may be used for the development of a SARS-CoV-2 vaccine.

The epidemiological features of pediatric viral respiratory infection during the COVID-19 pandemic in Taiwan.

BACKGROUND: Enhanced nonpharmaceutical interventions (NPIs) to prevent the Coronavirus Disease 2019 (COVID-19) have shown various levels of impact on common respiratory pathogens. We aimed to analyze the epidemiological changes seen in certain common respiratory viruses found in Taiwanese children (e.g., influenza virus, enterovirus, parainfluenza virus, adenovirus and respiratory syncytial virus (RSV)) after the implementation of public health measures, as well as interpret the possible meaning of these changes. METHODS: This retrospective observational study examined the viral isolation from children younger than 18 years at a medical center in central Taiwan during the period January 2015-December 2020, a time frame of six years. Viral isolations prior to the COVID-19 pandemic (January 2015-December 2019), along with those during the post-COVID-19 period (January-December 2020) were analyzed and compared. RESULTS: A total of 6899 throat swab samples were collected during the pre-pandemic period of 2015-2019, with 2681 of them having a positive result (38.86%). There were a total of 713 samples collected in 2020, with 142 of them showing positive results (19.92%). The overall positive rate of viral isolates significantly decreased in 2020 (p < 0.001). Declines in the isolation of the influenza virus, parainfluenza virus, adenovirus and enterovirus were observed. The RSV surprisingly became the leading isolate, with up to 47 (6.59%) instances in 2020, and showing an unusual peak in the winter of 2020. The rise began in September of 2020 and reached its plateau in November of that year. CONCLUSIONS: Most respiratory viruses decreased under NPIs regarding SARS-CoV-2. However, the RSV outbreak in the winter of 2020 had shown the limitation of current NPIs. Possible explanations have been discussed in details and public preventive measures should be reinforced for RSV, particularly amongst people having young children both at home and in care centers.

The combined regimens of antiviral therapy might not be useful for the viral clearance of severe COVID-19 cases.

BACKGROUND: Severe COVID-19 caused by SARS-CoV-2 should closely be cared because of the relatively high mortality rate. If SARS-CoV-2 could be cleared as soon as possible, the mortality rate might lower. In the present study, we analyzed factors which might be related to the clearance of SARS-CoV-2. METHODS: One hundred and twenty-eight severe COVID-19 cases were enrolled. All of them had been isolated and treated at Shenzhen Third People's Hospital because they were positive for nucleic acid of SARS-CoV-2 tested by qRT-PCR. Their baseline clinical characteristics and antiviral regimens were collected and analyzed, respectively. RESULTS: Of the 128 enrolled severe COVID-19 cases, unfortunately 3 died. The mean viral duration of all patients was 23.5 (range 17-32) days. All patients achieved viral clearance during 9 weeks. 13.4% of patients achieved viral clearance within 2 weeks, and 63.0% of patients achieved viral clearance within 4 weeks. The combined regimens of three or more antiviral drugs, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 2 weeks. The use of arbidol, the use of invasive mechanical ventilation, and late admission might be related to the delay of viral clearance within 4 weeks. Patients often had a prolonged course of COVID-19 and hospitalization, and were more likely transferred to intensive care unit (ICU) for treatment, if they could not clear SARS-CoV-2 during 23 days. CONCLUSION: Severe COVID-19 cases should be admitted to hospital as soon as possible. The combined regimens of three or more antiviral drugs might not be useful for viral clearance, and should be performed carefully and cautiously.

Probiotics use is associated with improved clinical outcomes among hospitalized patients with COVID-19.

BACKGROUND AND AIMS: Currently, there are no definitive therapies for coronavirus disease 2019 (COVID-19). Gut microbial dysbiosis has been proved to be associated with COVID-19 severity and probiotics is an adjunctive therapy for COIVD-19. However, the potential benefit of probiotics in COVID-19 has not been studied. We aimed to assess the relationship of probiotics use with clinical outcomes in patients with COVID-19. METHODS: We conducted a propensity-score matched retrospective cohort study of adult patients with COVID-19. Eligible patients received either probiotics plus standard care (probiotics group) or standard care alone (non-probiotics group). The primary outcome was the clinical improvement rate, which was compared among propensity-score matched groups and in the unmatched cohort. Secondary outcomes included the duration of viral shedding, fever, and hospital stay. RESULTS: Among the propensity-score matched groups, probiotics use was related to clinical improvement rates (log-rank p = 0.028). This relationship was driven primarily by a shorter (days) time to clinical improvement [difference, -3 (-4 to -1), p = 0.022], reduction in duration of fever [-1.0 (-2.0 to 0.0), p = 0.025], viral shedding [-3 (-6 to -1), p < 0.001], and hospital stay [-3 (-5 to -1), p = 0.009]. Using the Cox model with time-varying exposure, use of probiotics remained independently related to better clinical improvement rate in the unmatched cohort. CONCLUSION: Our study suggested that probiotics use was related to improved clinical outcomes in patients with COVID-19. Further studies are required to validate the effect of probiotics in combating the COVID-19 pandemic.

Current status of traditional Chinese medicine for the treatment of COVID-19 in China.

An ongoing outbreak of severe respiratory illness and pneumonia caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2) commenced in December 2019, and the disease was named as coronavirus disease 2019 (COVID-19). Soon after, scientists identified the characteristics of SARS-CoV-2, including its genome sequence and protein structure. The clinical manifestations of COVID-19 have now been established; and nucleic acid amplification is used for the direct determination of the virus, whereas immunoassays can determine the antibodies against SARS-CoV-2. Clinical trials of several antiviral drugs are ongoing. However, there is still no specific drugs to treat COVID-19. Traditional Chinese medicine (TCM) was used in the treatment of COVID-19 during the early stages of the outbreak in China. Some ancient TCM prescriptions, which were efficacious in the treatment of severe acute respiratory syndrome (SARS) in 2002-03 and the influenza pandemic (H1N1) of 2009, have been improved by experienced TCM practitioners for the treatment of COVID-19 based on their clinical symptoms. These developed new prescriptions include Lianhua Qingwen capsules/granules, Jinhua Qinggan granules and XueBiJing injection, among others. In this review, we have summarized the presenting features of SARS-CoV-2, the clinical characteristics of COVID-19, and the progress in the treatment of COVID-19 using TCMs.

Effects of novel Coronavirus pneumonia pandemic on the spread of multidrug-resistant Acinetobacter in ICU

OBJECTIVE: To investigate the effect of novel coronavirus pneumonia pandemic on multidrug-resistant Acinetobacter baumannii transmission in intensive care units(ICU) and to provide reference for the guidance of nosocomial infection prevention and control. METHODS: Data of multidrug-resistant A. baumannii in ICU1, ICU2 and neurosurgery ICU from Jan. 2019 to Aug. 2020 were collected. Contact times between healthcare workers and environmental surfaces, clearance rate of fluorescent marker in the culture of environment specimens before and after the novel coronavirus pneumonia outbreak, number of free colonies and number of MDR-AB were detected, and the correlation between MDR-AB detection rate of the environment and MDR-AB the infection rate were analyzed by using Pearson correlation analysis. RESULTS: The high-frequency contact surfaces in ICU were bed bars(43.59 times), quilts(39.58 times), treatment vehicles(30.83 times), vein tubes(27.46 times), nursing station table tops(27.20 times) and hand sterilized buttons(26.40 times). The clearance rate of fluorescent marker after novel coronavirus pneumonia outbreak was 81.35%, which was significantly higher than that before the new coronavirus-infected pneumonia epidemic outbreak(P<0.001), with the rate of 56.57%. The detection rate and infection rate of MDR-AB in the environment after new coronavirus-infected pneumonia epidemic were 5.40% and 1.80%, respectively, which were significantly lower than that before the epidemic(P<0.001). Pearson correlation analysis showed that the detection rate of MDR-AB in the ICU environment was positively correlated with the MDR-AB infection rate of patients(r=0.850, P=0.002). CONCLUSION: Methods of novel coronavirus pneumonia epidemic prevention promoted the implementation of environmental sanitation, disinfection and isolation measures, cut off the transmission route of multidrug-resistant A. baumannii, and played a positive role in the prevention and control of infection.

Early risk factors for extrapulmonary organ injury in adult COVID-19 patients.

BACKGROUND: The novel 2019 coronavirus (COVID-19) has caused a global pandemic, and often leads to extrapulmonary organ injury. However, the risk factors for extrapulmonary organ injury are still unclear. We aim to explore the risk factors for extrapulmonary organ injury and the association between extrapulmonary organ injury and the prognosis in COVID-19 patients. METHODS: We implemented a single-center, retrospective, observational study, in which a total of 349 confirmed COVID-19 patients admitted to Tongji Hospital from January 25, 2020, to February 25, 2020, were enrolled. We collected demographic, clinical, laboratory, and treatment data from electronic medical records. Potential risk factors for extrapulmonary organ injury of COVID-19 patients were analyzed by a multivariable binary logistic model, and multivariable Cox proportional hazards regression model was used for survival analysis in the patients with extrapulmonary organ injury. RESULTS: The average age of the included patients was 61.73±14.64 years. In the final logistic model, variables including aged 60 or older [odds ratio (OR) 1.826, 95% confidence interval (CI): 1.060-3.142], acute respiratory distress syndrome (ARDS) (OR 2.748, 95% CI: 1.051-7.185), lymphocytes count lower than 1.1×109/L (OR 0.478, 95% CI: 0.240-0.949), level of interleukin-6 (IL-6) greater than 7 pg/mL (OR 1.664, 95% CI: 1.005-2.751) and D-Dimer greater than 0.5 µg/mL (OR 2.190, 95% CI: 1.176-4.084) were significantly associated with the extrapulmonary organ injury. Kaplan-Meier curve and log-rank test showed that the probabilities of survival for patients with extrapulmonary organ injury were significantly lower than those without extrapulmonary organ injury. Multivariate Cox proportional hazards model showed that only myocardial injury (P=0.000, HR: 5.068, 95% CI: 2.728-9.417) and circulatory system injury (P=0.000, HR: 4.076, 95% CI: 2.216-7.498) were the independent factors associated with COVID-19 patients' poor prognosis. CONCLUSIONS: Older age, lymphocytopenia, high level of D-Dimer and IL-6, and the severity of lung injury were the high-risk factors of extrapulmonary organ injury in COVID-19 patients. Myocardial and circulatory system injury were the most important risk factors related to poor outcomes of COVID-19 patients. It may help clinicians to identify extrapulmonary organ injury early and initiate appropriate treatment.

Network pharmacology and RNA-sequencing reveal the molecular mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Up to 20%-30% of patients hospitalized with COVID-19 have evidence of cardiac dysfunction. Xuebijing injection is a compound injection containing five traditional Chinese medicine ingredients, which can protect cells from SARS-CoV-2-induced cell death and improve cardiac function. However, the specific protective mechanism of Xuebijing injection on COVID-19-induced cardiac dysfunction remains unclear. METHODS: The therapeutic effect of Xuebijing injection on COVID-19 was validated by the TCM Anti COVID-19 (TCMATCOV) platform. RNA-sequencing (RNA-seq) data from GSE150392 was used to find differentially expressed genes (DEGs) from human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. Data from GSE151879 was used to verify the expression of Angiotensin I Converting Enzyme 2 (ACE2) and central hub genes in both human embryonic-stem-cell-derived cardiomyocytes (hESC-CMs) and adult human CMs with SARS-CoV-2 infection. RESULTS: A total of 97 proteins were identified as the therapeutic targets of Xuebijing injection for COVID-19. There were 22 DEGs in SARS-CoV-2 infected hiPSC-CMs overlapped with the 97 therapeutic targets, which might be the therapeutic targets of Xuebijing injection on COVID-19-induced cardiac dysfunction. Based on the bioinformatics analysis, 7 genes (CCL2, CXCL8, FOS, IFNB1, IL-1A, IL-1B, SERPINE1) were identified as central hub genes and enriched in pathways including cytokines, inflammation, cell senescence and oxidative stress. ACE2, the receptor of SARS-CoV-2, and the 7 central hub genes were differentially expressed in at least two kinds of SARS-CoV-2 infected CMs. Besides, FOS and quercetin exhibited the tightest binding by molecular docking analysis. CONCLUSION: Our study indicated the underlying protective effect of Xuebijing injection on COVID-19, especially on COVID19-induced cardiac dysfunction, which provided the theoretical basis for exploring the potential protective mechanism of Xuebijing injection on COVID19-induced cardiac dysfunction.

[Reuse process of positive pressure powered air-filter protective hoods].

OBJECTIVE: To establish reuse process of positive pressure powered air-filter protective hoods during coronavirus disease 2019 (COVID-19) epidemic. METHODS: The procedure of pretreatment, storage, recovery, cleaning, disinfection and sterilization process of positive pressure powered air-filter protective hoods, which were used in the treatment of COVID-19 infection patients was established in Central Sterile Supply Department of the hospital. The cleaning and disinfection effects of the protective hoods after treatment were examined by magnifying glass method, residual protein detection method, real-time PCR, and agar pour plate method. RESULTS: Twenty five used protective hoods underwent totally 135 times of washing, disinfecting and sterilizing procedures. After washing, all the protein residue tests and COVID-19 nucleic acid tests showed negative results. After sterilizing, all the protective hoods met sterility requirement. All the tested protective hoods were undamaged after reprocessing. CONCLUSIONS: The established reuse procedures for used positive pressure powered air-filter protective hoods are safe.

[Comparison of three medical goggle sterilizing approaches].

OBJECTIVE: To compare three sterilizing methods for reusable medical goggles. METHODS: A total of 180 medical goggles of the same brand and same model were randomly divided into three groups. In group A the goggles were first soaked with 2000 mg/L chlorine-containing disinfectant and then cleaned manually; goggles in other two groups were sterilized using pre-programmed automatic spray cleaning and disinfection machine, the disinfection program was set to 90 ℃ for 5 min in group B and 70 ℃ for 30 min in group C. The quality of the sterilization was monitored by visual inspection with luminous magnifying glass and residual protein detection assay. User satisfaction on cleanliness of medical goggles, clarity of mirror surface and suitability of elastic bands was investigated with questionnaire survey. RESULTS: The qualification rates verified by visual inspection were 82.4%, 84.6%and 98.3%in group A, B and C, respectively, the qualification rate in group C was significantly higher than those in group B and group C (all P<0.05). The qualification rates verified by residual protein detection assay were 96.7%, 100.0%and 100.0%in group A, B and C, respectively (P>0.05). A total of 54 questionnaires were submitted for the survey. The satisfaction rates were 100.0%, 90.7%and 94.4% for cleanliness of medical goggles, clarity of mirror surface and suitability of elastic bands, respectively. CONCLUSIONS: Machinery sterilization set 70 ℃ for 30 min has better cleaning and sterilizing effects for reusable medical goggles.

Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2.

Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies. Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages.