University of Pretoria-led study reveals COVID-19 Delta variants transmitted from humans to animals

A team of scientists from the University of Pretoria (UP) has published the only study from Africa that entailed genomic One Health investigations which reveal that Delta variants of COVID-19 were transmitted from humans to animals

One Health is an approach that recognises that the health of people is closely connected to the health of animals and a shared environment.  Close contact with animals and their environment provides opportunities for diseases to spread between animals and people.

The team of transdisciplinary scientists found that reverse zoonotic transmission of COVID-19 from asymptomatic animal handlers at a private zoo in Gauteng posed a risk to big cats kept in captivity. Transmission of the Delta variant to these animals could result in more severe disease. The animals tested PCR positive for up to seven weeks after becoming sick. “This extended period of potential virus shedding poses a risk of infection to animals in close proximity and possibly humans. The animals were therefore placed in quarantine until they tested negative,” the scientists said.  

The study, titled ‘SARS-CoV-2 Reverse Zoonoses to Pumas and Lions, South Africa’, was led by Professor Marietjie Venter, Head of the Zoonotic, Arbo- and Respiratory Virus Programme at UP’s Department of Medical Virology; and Professor Katja Koeppel, Associate Professor of Wildlife Health at the University’s Faculty of Veterinary Science. The findings of the study were recently published in Viruses journal.

Members of the veterinary team taking clinical samples from a lion to test for COVID-19.

Postdoctoral students Dr Adriano Mendes and Dr Amy Strydom of the Zoonotic, Arbo- and Respiratory Virus Programme were responsible for the initial diagnoses and genomic investigations of the human and animal cases; while Dr Lia Rotherham and Professor Misheck Mulumba, Director of the Agricultural Research Council Onderstepoort Veterinary Research Campus, confirmed the diagnoses. 

“In 2020, the team tested the faeces of two pumas that had previously shown signs of anorexia, diarrhoea and nasal discharge,” Prof Koeppel explained. “They tested positive for COVID-19, and exhibited mild symptoms. They were medicated and made a full recovery after 23 days. Unfortunately, we could not carry out an investigation into the source or the specific variant involved in the outbreak. The samples were diagnosed by real-time PCR at the time of the outbreak, but when we tried to sequence the sample a year later, there was insufficient RNA left for genome sequencing.” 

A year later, during South Africa’s third wave of the COVID-19 pandemic, the team conducted a study on three sick lions at the same zoo. “The lions had breathing problems as well as runny noses and a dry cough for up to 15 days,” Prof Koeppel said. “A persistent cough was seen between five and 15 days, with two lions experiencing difficulty breathing. One lioness developed pneumonia that did not respond to antibiotics.” Respiratory swabs were submitted to Prof Venter’s programme, where the cases were investigated. 

Staff and lions were monitored in the weeks that followed for the presence of SARS-CoV-2 and, within 15 to 25 days, all three lions made a full recovery. “A One Health investigation into the source of infection was conducted on 12 staff members who had been in direct or indirect contact with the lions,” Prof Venter said. “Swab and serum testing were carried out.”

Members of the Department of Medical Virology taking blood from a zoo staff member to test for COVID-19 antibodies.

One staff member who had direct contact with the lions and another who had indirect contact tested PCR positive for SARS-CoV-2 two weeks after the start of the lion disease course. All three lions were PCR positive. “These two individuals and three other staff members also tested positive for anti-spike IgG antibodies,” Prof Venter said. “None of the staff interviewed reported any recent symptoms of COVID-19; however, the zoo keeper developed mild symptoms the following day and was confirmed positive.”

More tests were done. “This data suggests that SARS-CoV-2 was circulating among staff during the time that the lions got sick, and suggests that those with direct contact with the animals were likely responsible for the reverse zoonotic transmission.”

Genome sequencing was conducted on the humans and three lions, and tests revealed that each of the infections was a Delta variant. The two pumas and three lions presented with respiratory illness that was similar to COVID-19 in humans. The animals did not respond to antibiotic treatment but recovered after treatment with anti-inflammatory drugs and supportive care.

“Detection of viral RNA in the upper respiratory tract and the faeces, coupled with the fact that the pumas and lions had symptoms, reveal that this virus is able to infect these animals via a natural infection route,” Prof Venter said.

These outbreaks are at least the third and fourth of this kind in which SARS-CoV-2 has been shown to transmit between humans and captive large felines, “although the current study is the only one that reports on genomic One Health investigations of Delta variants transmitted from humans to animals, and the only one reported so far in Africa,” Prof Venter added. 

Members of the Zoonotic, Arbo- and Respiratory Virus team analysing COVID-19 samples in the lab.

The scientists said the timeline of infections of the lions from a COVID-positive human is difficult to estimate as all staff members were asymptomatic during the outbreak. They said that reverse zoonotic transmission of SARS-CoV-2 from asymptomatic animal handlers pose a risk to large felines kept in captivity. 

The scientists stress that precautions such as vaccinating staff, wearing masks when entering cages and preparing food, infection control through use of disinfectants, and distance barriers for members of the public should be put in place at zoos. 

“This is to protect potentially endangered species from getting infected and dying,” Prof Venter and Prof Koeppel said. “These measures are also important because of the risk of new variants emerging if the virus establishes itself in other animal reservoirs; these variants could be transmitted back to humans.” Members of the public are also urged to be aware of the possibility of infecting their pet cats and dogs if they have COVID-19. 

“A One Health approach – where human and animal health specialists as well as environmental specialists work together – is essential to investigate and prevent zoonotic disease transmission,” the scientists said.

Researchers

• 

  Professor Marietjie Venter

  Professor Marietjie Venter joined the University of Pretoria (UP) in 2006 and established a research programme on neurological arboviruses and respiratory viruses, in the Department Medical Virology.
  In 2009, she became Co-director of the Centre for Respiratory Diseases and Meningitis at the National Institute for Communicable Diseases (NICD) of South Africa. She then worked for two years for the US Centers for Disease Control and Prevention, and the Global Disease Detection Centre in South Africa as One Health and Emerging Disease Programme Director. Prof Venter maintained a part-time joint appointment with UP to continue her research programme and supervised postgraduate students between 2009 and 2016, first as an associate professor and later as a full professor. In 2016 she took up a full-time position as a full professor in medical virology and as Head of the Zoonotic Arbo- and Respiratory Virus Programme (ZARV).
  Prof Venter holds a BSc in Molecular Biology, Genetics and Microbiology from UP and a PhD in Medical Virology from the University of the Witwatersrand (2003) with a focus on the respiratory syncytial virus (RSV). She also received postdoctoral training on the West Nile virus at the National Institute for Allergy and Infectious Diseases in the US (2003).
  Prof Venter established a One Health programme in the Department of Medical Virology that focuses on detecting and describing emerging and zoonotic vector-borne and respiratory viruses. There is close collaboration between the ZARV medical virology group in the medical school, veterinarians, veterinary pathologists and clinicians as well as entomologists. This collaboration has been extremely productive in describing the molecular epidemiology of vector-borne and respiratory viruses.
  The Department of Medical Virology has a state-of-the-art biosafety level 3 laboratory, which was funded and commissioned in 2011, and which has been the core infrastructure for Prof Venter’s research programme. She co-founded the steering committee of the Centre for Viral Zoonoses, which was launched around this infrastructure in 2015 and stretches across three faculties.
  In terms of far-reaching impact, Prof Venter says her research programme focuses on developing diagnostic tools and syndromic surveillance programmes for detecting novel and common pathogens, discovering new viruses, and defining the importance of zoonotic and human viruses with epidemic and pandemic potential. Vector-borne viruses associated with neurological symptoms – such as the West Nile and Zika viruses as well as respiratory viruses such as influenza A and coronaviruses – have been some of the most important emerging epidemic- and pandemic-prone viruses. “Our capacity to detect and respond to emerging diseases using a One Health approach and defining the clinical epidemiology and genomics has been very topical during the COVID 19 pandemic,” she says.
  Since 2020, Prof Venter has been part of several COVID-19 investigations, specifically the genomic surveillance network with the University of KwaZulu-Natal as well as the National Health Laboratory Service, NICD, the Universities of Cape Town and the Free State. Apart from working closely with UP’s Faculty of Veterinary Science, her research programme also works with clinicians in Kalafong and Steve Biko hospitals to detect acute febrile disease of unknown origin, respiratory viruses and zoonotic infections.
  Prof Venter holds the position of vice-president for Africa for the World Society of Virology and is a member of the international One Health Platform Scientific Advisory Board. She is the principal investigator for a study on febrile disease of unknown origin with or without neurological signs for the African network for improved diagnostics and epidemiology of common and emerging viruses. In addition, she is the principal investigator for South Africa on the Long-term Europe-African Research Network (LEARN) study of the LEAP-Agri Initiative, which is funded by the EU and administered by the National Research Foundation. It is a One Health initiative for the development of molecular and serological tools for the surveillance of arboviruses in animals and human, and is being conducted in collaboration with Wageningen University in the Netherlands and the Friedrich-Loeffler Institut in Greifswald, Germany.
  Over the past year, Prof Venter’s programme took up the ANDEMIA respiratory virus work package at UP in collaboration with the NICD and the Robert Koch Institute in Germany. The ANDEMIA network study has allowed the researchers to carry out active surveillance and define the correlates of disease for both zoonotic and common pathogens. “We obtained additional funding through the G7 as part of the ANDEMIA grant to investigate COVID-19 genomics, seroprevalence and infection risk in healthcare workers as well as co-infections. We are also investigating reverse zoonotic transmission from humans to wildlife.”
  Dutch virologist Dr Ab Osterhaus, founder of the One Health Platform, inspires Prof Venter’s research efforts. He and his team described several viruses including the original SARS coronavirus. He also actively involves many young scientists such as Prof Venter in international networks to promote One Health aimed at detecting and preventing potential zoonotic disease outbreaks and pandemics. Prof Venter says she has also been inspired by several African scientists who have dedicated their lives to fighting infectious diseases in their home countries.
  The professor says that she has had several role models and mentors throughout her career, but that Prof Barry Schoub, former director of the NICD, stands out for her. He dedicated his career to fighting infectious diseases through research, by supporting his staff and by advising policy nationally and globally. Prof Schoub was both Prof Venter’s PhD mentor and supervisor at the NICD and has maintained an interest in her career.
  She has always been motivated to improve the lives of humans and animals by investigating the viral causes of respiratory and neurological infections through virus discovery, molecular epidemiology, pathogenesis research and the development of diagnostic tools and preventative strategies such as vaccines.
  “I have been involved in vaccine research over the years, and have found it to be very rewarding,” she says. “For instance, the West Nile virus vaccine was licensed for horses after we proved that it protects against lineage two variants that are dominant in South Africa.” She says she would like to focus some of her work in this area again, trying to find vaccines for viruses that have the potential to cause epidemics and spread internationally.
  Prof Venter says her research matters because it focuses on improving the ability to detect, respond and control important viruses such as RSV, influenza, COVID-19, the West Nile virus and emerging arboviruses, thereby contributing to the international health regulations for countries to respond to zoonotic viruses and the United Nations Sustainable Development Goals 3: Good health and well-being.
  For school learners or undergraduates who are interested in her field of study, Prof Venter says that a career in virology offers opportunities to work in the field of public health or as a laboratory scientist internationally or locally. She adds that virologists get to investigate unsolved diseases, discover new viruses and develop technologies that can save lives and improve health for humans and animals.
  In her spare time, Prof Venter is a competitive dressage rider, a member of the South African Warmblood Society and a breeder of warmblood horses.
  
  
  

  More from this Researcher