A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

Is replacing red meat with other protein sources associated with lower risks of coronary heart disease and all-cause mortality? A meta-analysis of prospective studies.

CONTEXT: A high amount of red meat consumption has been associated with higher risks of coronary heart disease (CHD) and all-cause mortality in a single food-exposure model. However, this model may overlook the potentially differential influence of red meat on these outcomes depending on the foods replaced by red meat. OBJECTIVE: A PRISMA-compliant meta-analysis of prospective observational studies was performed to quantify the risks of CHD and all-cause mortality associated with the replacement of total, unprocessed, or processed red meat with fish/seafood, poultry, dairy, eggs, nuts, and legumes. DATA SOURCES: The PubMed and Web of Science databases were searched to identify relevant articles published in any language from database inception to October 30, 2021. DATA EXTRACTION: The prospective observational studies were considered relevant if they reported relative risks (RRs) and 95%CIs for the associations of interest. DATA ANALYSIS: Thirteen articles were included. A random-effects model was used to estimate the summary RRs and 95%CIs for the associations of interest. Replacing total red meat with poultry (RR, 0.88, 95%CI, 0.82-0.96; I2 = 0%), dairy (RR, 0.90, 95%CI, 0.88-0.92; I2 = 0%), eggs (RR, 0.86, 95%CI, 0.79-0.94; I2 = 7.1%), nuts (RR, 0.84, 95%CI, 0.74-0.95; I2 = 66.8%), or legumes (RR, 0.84, 95%CI, 0.74-0.95; I2 = 7.3%) was associated with a lower risk of CHD, whereas substituting fish/seafood (RR, 0.91, 95%CI, 0.79-1.04; I2 = 69.5%) for total red meat was not associated with the risk of CHD. The replacement of total red meat with fish/seafood (RR, 0.92, 95%CI, 0.89-0.96; I2 = 86.9%), poultry (RR, 0.92, 95%CI, 0.90-0.95; I2 = 61.6%), eggs (RR, 0.91, 95%CI, 0.87-0.95; I2 = 33.8%), or nuts (RR, 0.92, 95%CI, 0.87-0.97; I2 = 81.9%) was associated with a lower risk of all-cause mortality, whereas the substitution of dairy (RR, 0.97, 95%CI, 0.93-1.01; I2 = 33.9%) or legumes (RR, 0.97, 95%CI, 0.93-1.01; I2 = 53.5%) for total red meat was not associated with the risk of all-cause mortality. Lower risks of CHD and all-cause mortality were more consistently observed for processed red meat replacements than for unprocessed red meat replacements. The results did not materially change when the analyses of total, processed, and unprocessed red meat were restricted to the studies that used a uniform substitution amount per unit of 1 serving/d. CONCLUSION: Keeping red meat, particularly processed red meat, consumption to a minimum along with increasing healthier alternative protein sources to replace red meat in the diet may contribute to the prevention of CHD and premature death. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42021259446.