1 These authors contributed equally to this work. Highlights• A comprehensive genome and codon usage analysis of SARS-CoV-2 was performed.• SARS-CoV-2 has a distinct genome composition in relation to other βCoV strains.• The overall codon usage in SARS-CoV-2 is slightly biased.• Most of the highly frequent codons are A-and U-ending codons.• Different codon preferences in SARS-CoV-2 genes in relation to human ones were found.• These differences are due to codon usage preferences. J o u r n a l P r e -p r o o f Abstract An outbreak of atypical pneumonia caused by a novel Betacoronavirus (βCoV), named SARS-CoV-2 has been declared a public health emergency of international concern bythe World Health Organization. In order to gain insight into the emergence, evolution and adaptation of SARS-CoV-2 viruses, a comprehensive analysis of genome composition and codon usage of βCoV circulating in China was performed. A biased nucleotide composition was found for SARS-CoV-2 genome. This bias in genomic composition is reflected in its codon and amino acid usage patterns. The overall codon usage in SARS-CoV-2 is similar among themselves and slightly biased. Most of the highly frequent codons are A-and U-ending, which strongly suggests that mutational bias is the main force shaping codon usage in this virus. Significant differences in relative synonymous codon usage frequencies among SARS-CoV-2 and human cells were found. These differences are due to codon usage preferences.

Bovine coronavirus (BCoV) is a recognized cause of severe neonatal calf diarrhea, with a negative impact on animal welfare, leading to economic losses to the livestock industry. Cattle production is one of the most important economic sectors in Uruguay. The aim of this study was to determine the frequency of BCoV infections and their genetic diversity in Uruguayan calves and to describe the evolutionary history of the virus in South America. The overall detection rate of BCoV in Uruguay was 7.8% (64/824): 7.7% (60/782) in dairy cattle and 9.5% (4/42) in beef cattle. The detection rate of BCoV in samples from deceased and live calves was 10.0% (6/60) and 7.6% (58/763), respectively. Interestingly, there was a lower frequency of BCoV detection in calves born to vaccinated dams (3.3%, 8/240) than in calves born to unvaccinated dams (12.2%, 32/263) (OR: 4.02, 95%CI: 1.81-8.90; p = 0.00026). The frequency of BCoV detection was higher in colder months (11.8%, 44/373) than in warmer months (1.5%, 3/206) (OR: 9.05, 95%CI: 2.77-29.53, p = 0.000013). Uruguayan strains grouped together in two different lineages: one with Argentinean strains and the other with Brazilian strains. Both BCoV lineages were estimated to have entered Uruguay in 2013: one of them from Brazil (95%HPD interval: 2011 and the other from Argentina (95%HPD interval: 2010-2014). The lineages differed by four amino acid changes, and both were divergent from the Mebus reference strain. Surveillance should be maintained to detect possible emerging strains that can clearly diverge at the antigenic level from vaccine strains.

Neonatal calf diarrhea (NCD) and mortality cause significant losses to the dairy industry. The preweaning dairy calf mortality risk in Uruguay is high (15.2%); however, causes for these losses are largely unknown. This study aimed to assess whether various pathogens were associated with NCD and death in Uruguayan dairy calves and whether these infections, diarrhea, or deaths were associated with the failure of transfer of passive immunity (FTPI). Contemporary diarrheic (n = 264,) and non-diarrheic (n = 271) 1-to 30-day-old calves from 27 farms were sampled. Feces were analyzed by antigen-capture ELISA for Cryptosporidium spp., rotavirus, bovine coronavirus, and Escherichia coli F5+, RT-PCR for bovine astrovirus (BoAstV), and bacterial cultures for Salmonella enterica. Blood/serum was analyzed by RT-PCR or antigen-capture ELISA for bovine viral diarrhea virus (BVDV). Serum of ≤ 8-day-old calves (n = 95) was assessed by refractometry to determine the concention of serum total proteins (STP) as an indicator of FTPI. Whether the sampled calves died before weaning was recorded. At least one pathogen was detected in 65.4% of the calves, and this percentage was significantly higher in diarrheic (83.7%) versus non-diarrheic (47.6%) calves. Unlike the other pathogens, Cryptosporidium spp. and rotavirus were associated with NCD. Diarrheic calves, calves infected with any of the pathogens, and calves infected with rotavirus had significantly lower concentrations of STP. Diarrheic calves had higher chances of dying before weaning than non-diarrheic calves. Diarrheic calves infected with S. enterica were at increased risk of mortality. Controlling NCD, salmonellosis, cryptosporidiosis, and rotavirus infections, and improving colostrum management practices would help to reduce calf morbi-mortality in dairy farms in Uruguay.