Revealed: how the immune system fights back against COVID-19

Thursday, 19 March, 2020

Revealed: how the immune system fights back against COVID-19

Researchers at Melbourne’s Peter Doherty Institute for Infection and Immunity have mapped immune responses from one of Australia’s first novel coronavirus (COVID-19) patients, showing the body’s ability to fight the virus and recover from the infection.

The researchers were able to test blood samples at four different time points in an otherwise healthy woman in her 40s, who presented with COVID-19 and had mild-to-moderate symptoms requiring hospital admission. Published in the journal Nature Medicine is a detailed report of how the patient’s immune system responded to the virus — the first time that broad immune responses to COVID-19 have been reported, according to co-author Dr Oanh Nguyen.

“We looked at the whole breadth of the immune response in this patient using the knowledge we have built over many years of looking at immune responses in patients hospitalised with influenza,” Dr Nguyen said.

“Three days after the patient was admitted, we saw large populations of several immune cells, which are often a tell-tale sign of recovery during seasonal influenza infection, so we predicted that the patient would recover in three days, which is what happened.”

The research team was able to do this research so rapidly thanks to SETREP-ID (Sentinel Travellers and Research Preparedness for Emerging Infectious Disease), led by Royal Melbourne Hospital Infectious Diseases Physician Dr Irani Thevarajan at the Doherty Institute. SETREP-ID is a platform that enables a broad range of biological sampling to take place in returned travellers in the event of a new and unexpected infectious disease outbreak, which is exactly how COVID-19 started in Australia.

“When COVID-19 emerged, we already had ethics and protocols in place so we could rapidly start looking at the virus and immune system in great detail,” Dr Thevarajan said.

“Already established at a number of Melbourne hospitals, we now plan to roll out SETREP-ID as a national study.”

Working together with influenza immunology researcher Professor Katherine Kedzierska, a laboratory head at the Doherty Institute, the team were able to dissect the immune response leading to successful recovery from COVID-19, which might be the secret to finding an effective vaccine.

“We showed that even though COVID-19 is caused by a new virus, in an otherwise healthy person a robust immune response across different cell types was associated with clinical recovery, similar to what we see in influenza,” Prof Kedzierska said.

“This is an incredible step forward in understanding what drives recovery of COVID-19. People can use our methods to understand the immune responses in larger COVID-19 cohorts, and also understand what’s lacking in those who have fatal outcomes.”

Dr Thevarajan said current estimates show more than 80% of COVID-19 cases are mild to moderate, and understanding the immune response in these mild cases is very important research.

“We hope to now expand our work nationally and internationally to understand why some people die from COVID-19, and build further knowledge to assist in the rapid response of COVID-19 and future emerging viruses,” she said.

Meanwhile, researchers from the University of Valencia and the FISABIO foundation have managed to sequence the complete genome of three samples from patients infected with COVID-19 — said to be the first sequences of the virus obtained in Spain. This complete genome sequencing adds to the efforts being made by laboratories worldwide to find out what the transmission routes have been and how the different lineages of the virus have spread.

“The primary objective is to identify more reliably the focal points and transmission chains of the coronavirus,” said lead researcher Fernando González Candelas. “The main conclusion of the analysis of the first samples is that the strains come from different transmission routes.”

The samples were sequenced using MinIOn, a third-generation sequencer from Oxford Nanopore Technologies. The sequences are already accessible in the GISAID Initiative database, a public consortium dedicated to the study of the influenza virus; the Nextstrain platform, which makes it possible to see the spatial and temporal progression of the pandemic from the more than 500 genomes deposited since last December by 40 countries; and the Genbank database of genetic sequences from the US National Institutes of Health.

The researchers have determined that one of the strains analysed is related to other European strains. “The next step will be to analyse sequences of more samples of patients from the hospitals of the Valencian Community in order to check the links between them and with the transmission chains established by the epidemiology specialist personnel,” Fernando González explained.

The analysis of viral genomes allows scientists to know the ways in which the virus has entered the community and how it is transmitted at this time, which will help health authorities to better control the spread of the virus. In addition, the sequencing of the virus genome indicates the mutations that the virus has suffered since the epidemic began; the conclusion that has been reached is that, until now, no mutation associated with increased virulence, lethality or any interesting property from a clinical point of view has been found.

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