A patient infected with an early variant of COVID-19 has been cured after 411 days by using neutralising monoclonal antibodies.
The 59-year-old male patient could not clear infection due to having a weakened immune system following a kidney transplant.
New research detailing the case is published in the journal Clinical Infectious Diseases by Dr Luke Blagdon Snell and colleagues, from King's and Guy's and St Thomas' NHS Foundation Trust, London.
The team used nanopore technology to discover cases of persistent infection, and to analyse the SARS-CoV-2 virus to see which treatments could be the most effective for patients. The details of this case was first presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Lisbon, Portugal.
The patient originally tested positive in December 2020 and continued to test positive until January 2022 despite receiving three doses of the COVID vaccine. The team conduced a detailed genetic analysis of the virus. This revealed that the patient's infection was a persistent infection with an early COVID variant – a variation of the original Wuhan variant that was dominant in the UK in the later months of 2020. Analysis found the patient's virus had multiple mutations since he was first infected.
Researchers used detailed genetic analysis using nanopore technology to rapidly identify the variant of the COVID virus that patients are infected with. With this information they identified mutations that made treatments ineffective and were then able to choose the best treatment options. In another case, a 45-year old woman with HIV infection had failed treatment with casirivimab/imdevimab (Regeneron) antibodies. Rapid analysis of the COVID virus showed it had developed mutations giving it resistance to these antibodies – the patient was offered another treatment (Paxlovid) and eventually cleared the virus.
The continual emergence of new variants has rendered successive neutralising antibody treatments ineffective. There are no effective neutralising antibody treatments for the omicron subvariants available in the UK or Europe.
Some new variants of the virus are resistant to all the antibody treatments available in the UK and Europe. Some people with weakened immune systems are still at risk of severe illness and becoming persistently infected. We are still working to understand the best way to protect and treat them.– Dr Luke Snell, from the School of Immunology & Microbial Sciences
The team also presented the case of a patient with a weakened immune system persistently infected with COVID-19, who required repeated hospitalisation and was close to death when he was one of the first patients to be cured with a combination of antiviral treatments.
The 60-year-old man, who had a past medical history of blood cancer, first tested positive in April 2022. He had received four vaccinations against COVID-19, with the last vaccine administered in February 2022, and had never (to his knowledge) had COVID prior to April 2022.
Over the subsequent four months, he was admitted to hospital four times with COVID-19 symptoms. During his first two admissions he was treated with the standard antiviral (remdesivir) for unwell patients with COVID-19 to no effect. During the third admission, he required intensive care admission and was treated with a range of therapies including high doses of antibody therapy against COVID (sotrovimab 1000mg) and a five-day course of the COVID antiviral (Paxlovid), along with further treatment to suppress inflammation in his lungs (steroids and baricitinib).
During the fourth admission, various tests showed a decline in the patient's condition, with widespread COVID-related lung disease and he was ventilated for the first time on day 99. Doctors believed his condition was terminal.
The medical team at St. Thomas' Hospital decided to try treatment with two antivirals – a combination which had not previously been tried or reported - Paxlovid and remdesivir, and it was started on day 109 for 10 days. This combination had not existed before.
The viral load in the patient's samples decreased during treatment, and he first became COVID negative on day 119. Over the next four weeks his need for supplementary oxygen declined then stopped. CT scans of his lungs, 19 days after treatment, showed significant improvement with only mild COVID-like changes. He was discharged on day 145. Today, some six weeks after discharge, he remains well, COVID negative, and resuming his life at home.
Dr Snell concludes: "This case suggests using two antivirals may successfully treat chronic COVID-19, which can occur in those with weakened immune systems who become persistently infected. This is especially important now COVID variants have become resistant to the antibody therapies previously used to neutralise the virus. Further evidence is urgently needed to confirm the best treatments for persistent SARS-CoV-2 infection."
