Characterization of a mouse-adapted strain of bat severe acute respiratory syndrome-related coronavirus.

Bats carry genetically diverse severe acute respiratory syndrome-related coronaviruses (SARSr-CoVs). Some of them utilize human angiotensin-converting enzyme 2 (hACE2) as a receptor and cannot efficiently replicate in wild-type mice. Our previous study demonstrated that the bat SARSr-CoV rRsSHC014S induces respiratory infection and lung damage in hACE2 transgenic mice but not wild-type mice. In this study, we generated a mouse-adapted strain of rRsSHC014S, which we named SMA1901, by serial passaging of wild-type virus in BALB/c mice. SMA1901 showed increased infectivity in mouse lungs and induced interstitial lung pneumonia in both young and aged mice after intranasal inoculation. Genome sequencing revealed mutations in not only the spike protein but the whole genome, which may be responsible for the enhanced pathogenicity of SMA1901 in wild-type BALB/c mice. SMA1901 induced age-related mortality similar to that observed in SARS and COVID-19. Drug testing using antibodies and antiviral molecules indicated that this mouse-adapted virus strain can be used to test prophylactic and therapeutic drug candidates against SARSr-CoVs. IMPORTANCE The genetic diversity of SARSr-CoVs in wildlife and their potential risk of cross-species infection highlights the importance of developing a powerful animal model to evaluate the antibodies and antiviral drugs. We acquired the mouse-adapted strain of a bat-origin coronavirus named SMA1901 by natural serial passaging of rRsSHC014S in BALB/c mice. The SMA1901 infection caused interstitial pneumonia and inflammatory immune responses in both young and aged BALB/c mice after intranasal inoculation. Our model exhibited age-related mortality similar to SARS and COVID-19. Therefore, our model will be of high value for investigating the pathogenesis of bat SARSr-CoVs and could serve as a prospective test platform for prophylactic and therapeutic candidates.

[Expert recommendations for the diagnosis and treatment of interstitial lung disease caused by novel coronavirus pneumonia].

COVID-19 is an acute infectious disease caused by a newly discovered coronavirus (SARS-CoV2). COVID-19 may manifest bilateral interstitial pneumonia on imaging. About 30%-60% of patients present varying degrees of interstitial changes, while most patients have a good prognosis. Since there's little practical instruct on treating interstitial lung disease (ILD) caused by COVID-19, we present this file as references for all the colleagues fighting with this disease. The primary findings on CT are bilateral, peripheral ground-glass opacities (GGO) and consolidation. Inter-/intra-lobular septal thickening are also common. Subpleural lines and traction bronchiectasis can be seen in some cases which indicate the presence of interstitial fibrosis. Images of severe cases are similar with those in advanced stage of nonspecific interstitial pneumonia (NSIP) and organizing pneumonia (OP). COVID-19 could present the typical two phases of diffuse alveolar damage: acute and proliferative phase on pathology. Massive pulmonary interstitial fibrosis may also be present. HRCT is the best radiological approach for the diagnosis and differential diagnosis of COVID-19, and to assess the presence of ILD. Periodical CT following-up is recommended for patients who present interstitial manifestations. Biomarkers such as KL-6, SP-D, RAGE may also helpful on evaluating the severity of interstitial fibrosis and therapeutic response. We do not suggest applying pulmonary function tests and 6-minute walking test on patients in active stage of the disease. The primary treatments in acute phase are antiviral therapy and supportive treatment. We do not suggest routine use of corticosteroids, while on patients with excessive activation of inflammatory response or rapid progression of lung lesions, a low to medium dosage of corticosteroids could be applied for a short course. Pirfenidone and Nintedanib are encouraged to apply on patients in reparative phase with evidence of progressing fibrosis. Low to medium dosage of corticosteroids is also feasible on patients with NSIP or OP manifestation in this phase, with a relatively longer course. Chinese traditional medicine and rehabilitation medicine may also helpful. Lung transplant surgery is an option for severe pulmonary fibrosis patients. Patients should receive CT following-up after be discharged from hospital, especially those whose pulmonary exudation is not well absorbed. We suggest a routine following-up on month 1, 4 and 10 after discharging, and an extended period for those who have developed irreversible interstitial fibrosis.

Experimental infection of a newly emerging Korean type I porcine reproductive and respiratory syndrome virus isolate in colostrum-deprived pigs.

BACKGROUND: Recently, new emergence of type I PRRSV has been reported in Korea by several research groups. Although specific subgroups of type I PRRSVs in Korea were observed in the previous phylogenetic analysis, there is a lack of information about the virulence of type I PRRSV recently isolated in Korea. METHODS: One type I PRRSV isolate (G2446, 3 times passaged in primarily cultured pulmonary macrophages) in Korea was experimentally infected in colostrum-deprived pigs. The pathological and serological evaluations were performed and compared to type II PRRSV strain (CP07-401-9, 5 times passaged in MARC-145 cell lines)-infected pigs, for 21 days post challenge (dpc). RESULTS: The pneumonia found in gross examination was more severe in type I PRRSV-infected pigs than type II PRRSV-infected pigs. Both groups showed bronchointerstitial pneumonia, mild multifocal perivascular lymphohistiocytic myocarditis and lymphadenopathy at 14 dpc. However, the unique histopathologic lesions were not found in the pigs experimentally infected with a Korean type I PRRSV isolate, when compared to previous data about classical pathology of PRRSV. The PRRS-specific antibodies were detected in the first week after challenge and viremia continued at least until 21 dpc in both groups. CONCLUSION: The gross and histopathologic lesion in this study indicated that Korean type I PRRSV strain (G2446) caused classical PRRSV-specific lesions. Although this study evaluated one representative strain of Korean type I PRRSV, the results may provide information regarding the pathogenicity of type I PRRSV recently emerged in Korea.