Full Genome Nobecovirus Sequences From Malagasy Fruit Bats Define a Unique Evolutionary History for This Coronavirus Clade.

Bats are natural reservoirs for both Alpha- and Betacoronaviruses and the hypothesized original hosts of five of seven known zoonotic coronaviruses. To date, the vast majority of bat coronavirus research has been concentrated in Asia, though coronaviruses are globally distributed; indeed, SARS-CoV and SARS-CoV-2-related Betacoronaviruses in the subgenus Sarbecovirus have been identified circulating in Rhinolophid bats in both Africa and Europe, despite the relative dearth of surveillance in these regions. As part of a long-term study examining the dynamics of potentially zoonotic viruses in three species of endemic Madagascar fruit bat (Pteropus rufus, Eidolon dupreanum, Rousettus madagascariensis), we carried out metagenomic Next Generation Sequencing (mNGS) on urine, throat, and fecal samples obtained from wild-caught individuals. We report detection of RNA derived from Betacoronavirus subgenus Nobecovirus in fecal samples from all three species and describe full genome sequences of novel Nobecoviruses in P. rufus and R. madagascariensis. Phylogenetic analysis indicates the existence of five distinct Nobecovirus clades, one of which is defined by the highly divergent ancestral sequence reported here from P. rufus bats. Madagascar Nobecoviruses derived from P. rufus and R. madagascariensis demonstrate, respectively, Asian and African phylogeographic origins, mirroring those of their fruit bat hosts. Bootscan recombination analysis indicates significant selection has taken place in the spike, nucleocapsid, and NS7 accessory protein regions of the genome for viruses derived from both bat hosts. Madagascar offers a unique phylogeographic nexus of bats and viruses with both Asian and African phylogeographic origins, providing opportunities for unprecedented mixing of viral groups and, potentially, recombination. As fruit bats are handled and consumed widely across Madagascar for subsistence, understanding the landscape of potentially zoonotic coronavirus circulation is essential for mitigation of future zoonotic threats.

The COVID-19 epidemic in Madagascar: clinical description and laboratory results of the first wave, march-september 2020.

BACKGROUND: Following the first detection of SARS-CoV-2 in passengers arriving from Europe on 19 March 2020, Madagascar took several mitigation measures to limit the spread of the virus in the country. METHODS: Nasopharyngeal and/or oropharyngeal swabs were collected from travellers to Madagascar, suspected SARS-CoV-2 cases and contact of confirmed cases. Swabs were tested at the national reference laboratory using real-time RT-PCR. Data collected from patients were entered in an electronic database for subsequent statistical analysis. All distribution of laboratory-confirmed cases were mapped, and six genomes of viruses were fully sequenced. RESULTS: Overall, 26,415 individuals were tested for SARS-CoV-2 between 18 March and 18 September 2020, of whom 21.0% (5,553/26,145) returned positive. Among laboratory-confirmed SARS-CoV-2-positive patients, the median age was 39 years (IQR: 28-52), and 56.6% (3,311/5,553) were asymptomatic at the time of sampling. The probability of testing positive increased with age with the highest adjusted odds ratio of 2.2 [95% CI: 1.9-2.5] for individuals aged 49 years and more. Viral strains sequenced belong to clades 19A, 20A and 20B indicative of several independent introduction of viruses. CONCLUSIONS: Our study describes the first wave of the COVID-19 in Madagascar. Despite early strategies in place Madagascar could not avoid the introduction and spread of the virus. More studies are needed to estimate the true burden of disease and make public health recommendations for a better preparation to another wave.

The zoonotic potential of bat-borne coronaviruses.

Seven zoonoses - human infections of animal origin - have emerged from the Coronaviridae family in the past century, including three viruses responsible for significant human mortality (SARS-CoV, MERS-CoV, and SARS-CoV-2) in the past twenty years alone. These three viruses, in addition to two older CoV zoonoses (HCoV-229E and HCoV-NL63) are believed to be originally derived from wild bat reservoir species. We review the molecular biology of the bat-derived Alpha- and Betacoronavirus genera, highlighting features that contribute to their potential for cross-species emergence, including the use of well-conserved mammalian host cell machinery for cell entry and a unique capacity for adaptation to novel host environments after host switching. The adaptive capacity of coronaviruses largely results from their large genomes, which reduce the risk of deleterious mutational errors and facilitate range-expanding recombination events by offering heightened redundancy in essential genetic material. Large CoV genomes are made possible by the unique proofreading capacity encoded for their RNA-dependent polymerase. We find that bat-borne SARS-related coronaviruses in the subgenus Sarbecovirus, the source clade for SARS-CoV and SARS-CoV-2, present a particularly poignant pandemic threat, due to the extraordinary viral genetic diversity represented among several sympatric species of their horseshoe bat hosts. To date, Sarbecovirus surveillance has been almost entirely restricted to China. More vigorous field research efforts tracking the circulation of Sarbecoviruses specifically and Betacoronaviruses more generally is needed across a broader global range if we are to avoid future repeats of the COVID-19 pandemic.