The origins of viruses: discovery takes time, international resources, and cooperation

Revealing the origins of SARS-CoV-2 is a prerequisite for cutting off the virus from the root and preventing future spillover of the virus. This work is of great significance in infection disease prevention and control in the face of Disease X.¹ Although scientists around the world are searching very hard, the origins of SARS-CoV-2 remain elusive. In fact, for many infectious pathogens, although their origins have been traced back decades, the debate around the origins remains alive.

HIV is a good first example. The first official report about AIDS was made on June 5, 1981, by the US Centers for Disease Control and Prevention. 5 years later, Nahmias and colleagues² discovered a human serum sample collected in Léopoldville (now Kinshasa, Democratic Republic of the Congo) in early 1959 that suggested exposure to HIV. Phylogenetic analysis subsequently suggested that an HIV ancestor had been introduced to Africa before 1959,³ and a relatively recent report, from 2008, revealed that the HIV-1 M group originated in about 1908 (CI 1884–1924) and has been circulating in the population for about 100 years.⁴

In 2004, human coronavirus HKU1 (HCoV-HKU1) was identified from a patient with pneumonia who returned to Hong Kong from Shenzhen, China.⁵ However, since then, HCoV-HKU1 positive signals have been detected across the globe and spanning decades: in specimens from Australian children that were collected in 2004,⁶ in respiratory specimens collected in Connecticut, USA, in 2001–02,⁷ in Finnish children in 1996–98,⁸ and in nasopharyngeal swab samples from children in Brazil that were frozen in 1995.⁹

The virus that causes severe fever with thrombocytopenia syndrome, SFTSV, was discovered in Henan province, China, in 2009.¹⁰ This discovery prompted SFTSV testing of samples obtained from patients in Jiangsu province, China, who had similar clinical manifestations in 2007 but whose aetiology was elusive, with positive results.¹¹ Other researchers tested serum samples from six patients with fever and thrombocytopenia in Yixing County, Jiangsu province, China, in 1996. And on the basis of epidemiological, clinical, and retrospective serological studies, the pathogen in this small cluster was confirmed to be SFTSV. ¹²

MERS-CoV was first reported in a Saudi Arabian man, aged 60 years, who died in 2012.¹³ The transmission route of this virus from animals to humans is not well understood, but dromedary camels are considered the major intermediate host of MERS-CoV,¹⁴ and bats are thought to be reservoir hosts. The discovery of antibodies in serum samples collected in 2003 indicates that MERS-CoV, or a closely related virus, had been prevalent in dromedary camels in the region long before the first MERS case was identified in humans. Alagaili and colleagues¹⁵ have proved that MERS-CoV had been circulating in camels since at least 1992 and can be phylogenically classified into clades related to human disease outbreaks. In 2014, researchers tested 189 stored dromedary camel serum samples collected in Egypt in 1997 and in Sudan and Somalia in 1983–84. 81% of the samples had neutralising antibodies against MERS-CoV, suggesting long-term virus circulation in these animals.¹⁶

As these cases show, tracing the origins of a virus requires long-term and extensive sample accumulation, which can take several years or decades. The geographical origins of a virus might not rely on an initial sick patient, and in some cases the index patient might never be found. Real-time RT-PCR and high-throughput sequencing technologies will help clarify the origins of emerging viruses, and in-depth research needs to be carried out from epidemiology, genomics, aetiology, and serology to lay the foundation for research on intermediate animal hosts, virus sources, and the transition of a virus into the human population. Patients with similar symptoms before the pandemic should therefore be re-evaluated,¹⁷ and stored samples from a broad geographical area should be re-tested. Blood and tissue banks are important resources for retrospective serological or genomics studies, especially by looking into the epidemiology of the disease in countries or regions where evidence of the virus has appeared in blood samples or environmental samples before the outbreak. Comprehensive genomic studies in animal species that are susceptible to the virus are necessary to identify the natural or intermediate hosts. Finally, the experience of on-going progress with HIV, HCoV-HKU1, SFTSV, and MERS-CoV origin studies shows that open-mindedness and close international cooperation are pivotal for tracing the origins of any viruses. Stay away from politicisation of the origins of the COVID-19 causative agents, and work together globally for science.

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We declare no competing interests. YT and WL contributed equally to this Correspondence.