Development of Highly Potent Noncovalent Inhibitors of SARS-CoV-2 3CLpro

The 3C-like protease (3CLpro) is an essential enzyme for the replication of SARS-CoV-2 and other coronaviruses and thus is a target for coronavirus drug discovery. Nearly all inhibitors of coronavirus 3CLpro reported so far are covalent inhibitors. Here, we report the development of specific, noncovalent inhibitors of 3CLpro. The most potent one, WU-04, effectively blocks SARS-CoV-2 replications in human cells with EC50 values in the 10-nM range. WU-04 also inhibits the 3CLpro of SARS-CoV and MERS-CoV with high potency, indicating that it is a pan-inhibitor of coronavirus 3CLpro. WU-04 showed anti-SARS-CoV-2 activity similar to that of PF-07321332 (Nirmatrelvir) in K18-hACE2 mice when the same dose was administered orally. Thus, WU-04 is a promising drug candidate for coronavirus treatment. A novel oral noncovalent inhibitor of 3C-like protease, named WU-04, was developed as a promising drug candidate for COVID-19 treatment.

The relationship between the sources of confidence in overcoming major public health events and the improvement of medical students' professional identity: mediation by medical students' attention to major public health events. (preprint)

Background The prevalence of COVID-19 highlights the shortage of medical human resources, and improving medical students' professional identity is a key condition to improve this situation. The sources of confidence in overcoming major public health events and medical students' attention to major public health events were key factors affecting their professional identity, but no study has yet investigated the mediating role of medical students' attention to major public health events in the relationship between them. This study aims to investigate the relationship among these three in medical university students in Hunan Province.Methods This was a cross-sectional survey of 2,960 medical students’ questionnaires collected from three universities in Hunan Province. An intermediary model was established to evaluate the role of medical students' attention to major public health events in the sources of confidence in overcoming major public health events and the improvement of medical students' professional identity.Results The sources of confidence in overcoming major public health events, medical students' attention to national crisis events, the improvement of medical students' professional identity were positively associated with each other (β = 0.328 ~ 0.464, P < 0.001). The mediating effect accounted for 23.3% of the total effect and 30.4% of the direct effect. Medical students' attention to major public health events plays a partial mediating role in the relationship between the sources of confidence to overcome major public health events and the improvement of medical students' professional identity.Conclusions This study found that the sources of confidence in overcoming major public health events, medical students' attention to national crisis events have a signifcant predictive effect on the improvement of medical students' professional identity. Medical students' attention to major public health events mediated the relationship between the sources of confidence to overcome major public health events and the improvement of medical students' professional identity. The findings have emphasize the theoretical and practical significance of professional identity education for medical students.

Comorbidities Diminish the Likelihood of Seropositivity After SARS-CoV-2 Vaccination (preprint)

BackgroundThe impact of chronic health conditions (CHC) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. MethodsWe assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated adult residents of Jefferson County, Kentucky, USA from April 2021 through August 2021. Serostatus was determined by qualitative analysis of SARS-CoV-2 specific Spike IgG antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples. ResultsOf the 5,178 fully vaccinated participants, 51 were seronegative and 5,127 were seropositive. Chronic kidney disease (CKD) and autoimmune disease showed highest association with negative serostatus in fully vaccinated individuals. The absence of any CHC was strongly associated with positive serostatus. The risk of negative serostatus increased as the total number of pre-existing CHCs increased. Similarly, use of 2 or more CHC related medications was associated with seronegative status. ConclusionsPresence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. Absence of any CHC was protective and increased the likelihood of a positive serological response. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.

Association of T lymphocytes level and clinical severity in patients of COVID-19 in Shenzhen China

To explore the correlation between T lymphocytes and clinical severity in patients of COVID-19. A total of 183 COVID-19 patients were recruited in Shenzhen Third People's Hospital from January 11 to February 16, 2020. According to the clinical classification criteria, they were divided into severe group (46 cases) and non-severe (137cases). T lymphocyte counts, lymphocyte subpopulation, IL-6 levels, and clinical outcomes were compared between the two groups. Compared with the non-severe group, the lymphocyte count, T lymphocyte count, T lymphocyte percentage, CD4+ T lymphocyte count, CD4+ T lymphocyte percentage, CD8+ T lymphocyte count, and CD8+ T lymphocyte percentage were lower in the severe group (p < 0.05). Compared with the non-severe group, IL-6 were higher in the severe group (p < 0.05). Compared with admission, the T lymphocyte count, CD4+ T lymphocyte count, and CD8+ T lymphocyte count were significantly increased upon discharge in severe patients, non-severe patients and all patients. Multivariate Logsitic regression analysis showed CD4+ T lymphocyte count (OR −0.011;95% CI −0.041 to −0.001;p = 0.011), CD8+ T lymphocyte count (OR −0.14;95% CI −0.048 to −0.003;p = 0.013) were closely correlated with the clinical severity in patients of COVID-19. Multivariate Logsitic regression analysis also showed CD4+ T lymphocyte count (OR −0.012;95% CI −3.177 to 0.261;p = 0.021), CD8+ T lymphocyte count (OR −0.019;95% CI −5.852 to 0.115;p = 0.004) were independent predictors of disease progressing to the composite endpoint. Subgroup analysis for critically ill patients: The T lymphocyte count, CD4+ T lymphocyte count, and CD8+ T lymphocyte count remained low in the death patients. The T lymphocyte count, CD4+ T lymphocyte count, and CD8+ T lymphocyte count recovered soon in the discharged patients. In the event of COVID-19 infection, the T-lymphoid system is the primary activated immune system. The T lymphocytes, CD4+ T lymphocytes, CD8+ T lymphocytes continued to be low may be significantly related to the deterioration of the disease, and may indicate a poor prognosis. [ABSTRACT FROM AUTHOR] Copyright of European Journal of Inflammation (Sage Publications, Ltd.) is the property of Sage Publications, Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Comparative Efficacy and Safety of the Moxibustion for the Treatment of Coronavirus Disease 2019 (COVID-19): Protocol for a Systematic Review and Meta-analysis. (preprint)

Background Coronavirus disease 2019 (COVID-19) has spread from its origins to the world and become a pandemic since late 2019. It predominantly damages the lungs and causes diffuse alveolar injury with edema, cellular fibroblasts and hyaline membrane formation, resulting in acute respiratory insufficiency, respiratory failure, sepsis, acute heart injury, heart failure and other severe complications. It is also reported that moxibustion can effectively modify the negative emotions and relieve the symptoms of chest distress and impaired appetite for the patient with COVID-19. The main objective of current research is to make an assessment for effectiveness and safety of the moxibustion as an important complementary and alternative therapeutic method for COVID-19.Methods and analysis Articles for the systematic literature will be located at the MEDLINE, OVID, EMBASE, CNKI, CBM, NTR, Chi CTR databases. With no restriction about language, manual search will be conducted for potential eligible articles as supplements. Any randomized controlled trials (RCTs) with any moxibustion interventions issued by the therapeutic regimen on all patients diagnosed with COVID-19 will be included. We will include the published studies with no restriction about language. All study records of the title and abstract identified by the search strategies will be directly imported and assessed based on the eligibility criteria. Risk of individual studies for the methodological quality of eligible RCTs will be assessed with the tool from the Cochrane Collaboration’s risk of bias tool.Discussion The purpose of this study is to conduct a systematic review and meta-analysis of the efficacy and safety of moxibustion as a complementary and alternative treatment for COVID-19.No studies have investigated whether moxibustion will relieve clinical symptoms and shorten the length of hospitalization time.To the best of our knowledge, this is the first systematic review and meta-analysis program designed to update the currently available evidence. Despite the fact of controversial views in using moxibustion, if this study confirms its efficacy and safety, it could provide a better guide for clinical practice around the world.Systematic review registrationPROSPERO CRD42020176572.

Clinical Management of Gynecological Cancer Patients During COVID-19 Epidemic

During the epidemic of COVID-19, the routine clinical treatment for gynecological cancer patients has been disturbed due to the redistribution of medical resource. Due to the systemic immunosuppression caused by the malignancy and anticancer treatments, gynecological cancer patients are more susceptible to COVID-19. With the improvement of the epidemic, the treatment needs of gynecological cancer patients are extremely strong. During this special period, it should carefully identify fever and respiratory symptoms of gynecological cancer patients receiving chemotherapy, immunotherapy and operations. Therefore, it is quite necessary to carry out comprehensive clinical management. We introduce a clinical management of gynecological cancer patients in three aspects of outpatient, in-hospital and out-of-hospital management during this period, in order to maximize the treatment of tumors and effectively prevent COVID-19.

Effects of Different Anti-hypertensive Drugs on Hospitalized Patients With COVID-19 and Hypertension in China (preprint)

Background and aims: Calcium channel blockers (CCBs) and angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are commonly used in the treatment of hypertension. However, it is still not clear whether there are differences among different anti-hypertensive drugs in the treatment of patients with coronavirus disease 2019 (COVID-19) and hypertension. Herein, we aimed to assess the relation between different anti-hypertensive medications and COVID-19 outcomes. Materials and methods: We conducted a retrospective analysis of 58 hypertensive patients with COVID-19 who were treated with different anti-hypertensive drugs and reviewed the clinical data obtained from electronic medical records, including epidemiological, clinical, laboratory, and the treatment and progression of the disease. Results: There was no obvious difference in clinical prognosis after using any anti-hypertensive drugs in patients with COVID-19 and hypertension, but the different anti-hypertensive drugs were associated with the use of non-invasive ventilator treatment at admission comparing two groups between ACEIs/ARBs and CCBs+ACEIs/ARBs. Conclusion: there is no evidence showing that the different use of anti-hypertensive drugs is related to outcomes of patients with COVID-19 and hypertension, even between single drug regimen and combined therapy (with at least two anti-hypertensive drugs as combined therapy).

Analysis of 4 imaging features in patients with COVID-19 (preprint)

Background: The aim of this was to analyze 4 chest CT imaging features of patients with coronavirus disease 2019 (COVID-19) in Shenzhen, China so as to improve the diagnosis of COVID-19. Methods: Chest CT of 34 patients with COVID-19 confirmed by the nucleic acid test (NAT) were retrospectively analyzed. Analyses were performed to investigate the pathological basis of four imaging features(“feather sign”,“dandelion sign”,“pomegranate sign”, and “rime sign”) and to summarize the follow-up results. Results: There were 22 patients (65.2 %) with typical “feather sign”and 18 (52.9%) with “dandelion sign”, while few patients had “pomegranate sign” and “rime sign”. The “feather sign” and “dandelion sign” were composed of stripe or round ground-glass opacity(GGO), thickened blood vessels, and small-thickened interlobular septa. The “pomegranate sign” was characterized as follows: the increased range of GGO, the significant thickening of the interlobular septum, complicated with a small amount of punctate alveolar hemorrhage. The “rime sign” was characterized by numerous alveolar edemas. Microscopically, the wall thickening, small vascular proliferation, luminal stenosis, and occlusion, accompanied by interstitial infiltration of inflammatory cells, as well as numerous pulmonary interstitial fibrosis and partial hyaline degeneration were observed. Repeated chest CT revealed the mediastinal lymphadenectasis in one patient. Re-examination of the NAT showed another positive anal swab in two patients. Conclusion: “Feather sign” and “dandelion sign” were typical chest CT features in patients with COVID-19; “pomegranate sign” was an atypical feature, and “rime sign” was a severe feature. In clinical work, accurate identification of various chest CT signs can help to improve the diagnostic accuracy of COVID-19 and reduce the misdiagnosis or missed diagnosis rate.

Rapid development of an inactivated vaccine for SARS-CoV-2 (preprint)

The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3g or 6 g per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans. One Sentence SummaryA purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology

ECMO application of patients with Critical Corona Virus Disease 2019 and fulminant myocarditis / 中华实验和临床病毒学杂志

Objective To evaluate the clinical experience of extracorporeal membrane oxygenation (ECMO) treatment on two cases of infection with the critical Corona Virus Disease 2019 (COVID-19) complicated by fulminant myocarditis (FM) . Methods This study selects two COVID-19 cases comorbid with fulminant myocarditis and had been treated with ECMO in Shenzhen Third People's Hospital from January 2020 to February 2020. We compare the index of inflammation, immunization, D-dimer and lactic acid before and after ECMO treatment in 24 and 96 hours, cardiopulmonary function before and after ECMO treatment in 24, 48, 72, 96 hours,. We also analyze the complications and clinical outcomes of the two cases during the ECMO treatment. Results Both patients were elderly obese men with chronic cardiopulmonary disease. Comparing the laboratory test results and imaging data of the two patients, the acute lung injury score, oxygenation index, albumin level, hypersensitive C-reactive protein, lactate and lactate dehydrogenase levels in 2 patients after ECMO treatment were improved as compared with those before ECMO treatment. Finally, case 1 died of multiple organ failure and his cardiac function continued to deteriorate, while, case 2 successfully withdrew and his cardiac function gradually improved. Conclusions For critical COVID-19 patients with fulminant myocarditis, ECMO treatment can improve pulmonary function in the short term, provide valuable time for rescuing COVID-19 patients with fulminant myocarditis.

First Case of COVID-19 Complicated with Fulminant Myocarditis: A case Report and Insights (preprint)

Background: Coronavirus Disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. Case presentation: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission. He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of interleukin-6 was 272.40 pg/ml. Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia. Laboratory test results for viruses that cause myocarditis were all negative. The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/ml. Moreover, the LVEF of the patient gradually recovered to 68%. The patient died of aggravation of secondary infection on the 33rd day of hospitalization. Conclusion: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure. This is the first report of COVID-19 complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

Anti-hypertensive Angiotensin II receptor blockers associated to mitigation of disease severity in elderly COVID-19 patients (preprint)

Summary Background The novel coronavirus (CoV) severe acute respiratory syndrome (SARS)-CoV-2 outbreak started at the end of 2019 in Wuhan, China, and spread over 100 countries. SARS-CoV-2 uses the membrane protein Angiotensin I converting enzyme 2(ACE2) as a cell entry receptor. Indeed, it was reported that the balance of Renin-Angiotensin System (RAS), regulated by both ACE and ACE2, was altered in COVID-19 patients. It is controversial, however, whether commonly used anti-hypertensive drugs Angiotensin I converting enzyme inhibitor (ACEI) and Angiotensin II receptor blocker (ARB) shall be continued in the confirmed COVID-19 patients. This study was designed to investigate any difference in disease severity between COVID-19 patients with hypertension comorbidity. The included COVID-19 patients used ACEI, ARB, calcium channel blockers (CCB), beta blockers (BB), or thiazide to treat preexisting hypertension prior to the hospital were compared to patients who did not take any of those drugs. Methods In this multicentre retrospective study, clinical data of 511 COVID-19 patients were analyzed. Patients were categorized into six sub-groups of hypertension comorbidity based on treatment using one of anti-hypertension drugs (ACEI, ARB, CCB, BB, thiazide), or none. A meta-analysis was performed to evaluate the use of ACEI and ARB associated with pneumonia using published studies. Findings Among the elderly (age>65) COVID-19 patients with hypertension comorbidity, the risk of COVID-19-S (severe disease) was significantly decreased in patients who took ARB drugs prior to hospitalization compared to patients who took no drugs (OR=0.343, 95% CI 0.128-0.916, p=0.025). The meta-analysis showed that ARB use has positive effects associated with morbidity and mortality of pneumonia. Interpretation Elderly (age>65) COVID-19 patients with hypertension comorbidity who are taking ARB anti-hypertension drugs may be less likely to develop severe lung disease compared to patients who take no anti-hypertension drugs. Funding National Natural Science Foundation of China, Chinese Academy of Medical Sciences

Reinfection could not occur in SARS-CoV-2 infected rhesus macaques (preprint)

A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence SummaryNeutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.

Rhesus macaques can be effectively infected with SARS-CoV-2 via ocular conjunctival route (preprint)

The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1x106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.

First Case of COVID-19 Infection with Fulminant Myocarditis Complication: Case Report and Insights (preprint)

Background: The Coronavirus Disease 2019 (COVID-19) has been demonstrated as the cause of pneumonia. Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis. Case Presentation: A 63-year-old male was admitted with pneumonia and cardiac symptoms. He was genetically confirmed as COVID-19 by testing sputum on the first day of admission. He also had an elevated troponin-I (Trop I) level and diffuse myocardial dyskinesia along with decreased left ventricular ejection fraction (LVEF) on echocardiography. The highest level of Interleukin 6 was 272.40pg/ml. Bedside chest radiograph had typical ground-glass changes of viral pneumonia. The laboratory test results of virus that can cause myocarditis are all negative. The patient conformed to the diagnostic criteria of Chinese expert consensus statement for fulminant myocarditis. After receiving antiviral therapy and mechanical life support, the Trop I reduced to 0.10 g/L, and Interleukin 6 was 7.63 pg/ml. Meanwhile the LVEF of the patient gradually recovered to 68%. Conclusion: COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure, and this is the first case of COVID-19 infection complicated with fulminant myocarditis. The mechanism of cardiac pathology caused by COVID-19 needs further study.

Trends in Transmissibility of 2019 Novel Coronavirus-infected Pneumonia in Wuhan and 29 Provinces in China (preprint)

Background The 2019 coronavirus disease (COVID-19) represents a sig- nificant p ublic h ealth t hreat g lobally. H ere w e d escribe e fforts to compare epidemic growth, size and peaking time for countries in Asia, Europe, North America, South America and Australia in the early epidemic phase. Methods Using the time series of cases reported from January 20, 2020 to February 13, 2020 and transportation data from December 1, 2019 to January 23, 2020 we have built a novel time-varying growth model to predict the epidemic trend in China. We extended our method, using cases reported from January 26, 2020 - or the date of the earliest case reported, to April 9, 2020 to predict future epidemic trend and size in 41 countries. We estimated the impact of control measures on the epidemic trend. Results Our time-varying growth model yielded high concordance in the predicted epidemic size and trend with the observed figures in C hina. Among the other 41 countries, the peak time has been observed in 28 countries before or around April 9, 2020; the peak date and epidemic size were highly consistent with our estimates. We predicted the remaining countries would peak in April or May 2020, except India in July and Pakistan in August. The epidemic trajectory would reach the plateau in May or June for the majority of countries in the current wave. Countries that could emerge to be new epidemic centers are India, Pakistan, Brazil, Mexico, and Russia with a prediction of 105 cases for these countries. The effective reproduction number Rt displayed a downward trend with time across countries, revealing the impact of the intervention remeasures i.e. social distancing. Rt remained the highest in the UK (median 2.62) and the US (median 2.19) in the fourth week after the epidemic onset. Conclusions New epidemic centers are expected to continue to emerge across the whole world. Greater challenges such as those in the healthcare system would be faced by developing countries in hotspots. A domestic approach to curb the pandemic must align with joint international efforts to effectively control the spread of COVID-19. Our model promotes a reliable transmissibility characterization and epidemic forecasting using the incidence of cases in the early epidemic phase.

Protection of Rhesus Macaque from SARS-Coronavirus challenge by recombinant adenovirus vaccine (preprint)

A recombinant adenovirus vaccine against the SARS Coronavirus (SARS-CoV) was constructed, which contains fragments from the S, N, and Orf8 genes. Rhesus Macaques immunized with the recombinant adenovirus generated antigen-specific humoral and cellular response. Furthermore, the vaccine provided significant protection against subsequent live SARS-CoV challenge. In contrast, three out of four monkeys immunized with placebo suffered severe alveolar damage and pulmonary destruction.

The Pathogenicity of 2019 Novel Coronavirus in hACE2 Transgenic Mice (preprint)

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) caused the Corona Virus Disease 2019 (COVID-19) cases in China has become a public health emergency of international concern (PHEIC). Based on angiotensin converting enzyme 2 (ACE2) as cell entry receptor of SARS-CoV, we used the hACE2 transgenic mice infected with SARS-CoV-2 to study the pathogenicity of the virus. Weight loss and virus replication in lung were observed in hACE2 mice infected with SARS-CoV-2. The typical histopathology was interstitial pneumonia with infiltration of significant lymphocytes and monocytes in alveolar interstitium, and accumulation of macrophages in alveolar cavities. Viral antigens were observed in the bronchial epithelial cells, alveolar macrophages and alveolar epithelia. The phenomenon was not found in wild type mice with SARS-CoV-2 infection. The pathogenicity of SARS-CoV-2 in hACE2 mice was clarified and the Kochs postulates were fulfilled as well, and the mouse model may facilitate the development of therapeutics and vaccines against SARS-CoV-2.