Longest documented Covid-19 infection alerts to risks of vaccine-resistant mutations

MADRID, (EUROPA PRESS). – After detecting the longest known chronic SARS-CoV-2 infection, lasting 613 days, experts from the University of Amsterdam, in the Netherlands, warn of the risk of developing new potentially immunoevasive SARS-CoV-2 variants due to infections persistent in immunosuppressed patients.

The research will be presented at the European Society for Clinical Microbiology and Infectious Diseases (ESCMID) World Congress, ESCMID (formerly ECCMID), which will be held next week in Barcelona, ​​Spain, from April 27 to 30. It is the work of doctoral student Magda Vergouwe, from the Center for Experimental and Molecular Medicine (CEMM) at the University Medical Center Amsterdam (UMC Amsterdam), and her colleagues.

The authors describe the prolonged viral evolution in a patient infected with SARS-CoV-2 for 613 days, which gave rise to a new highly mutated variant. To the authors’ knowledge, this is the longest-lasting SARS-CoV-2 infection to date, although several cases lasting hundreds of days had previously been recorded.

While healthy patients infected with SARS-CoV-2 can clear the virus over a period of days to weeks, an immunocompromised individual can develop a persistent infection with prolonged viral replication and evolution.

For example, the initial emergence of the omicron variant is believed to have originated in an immunocompromised individual, highlighting the importance of close genomic surveillance in this patient population.

Furthermore, the use of targeted immune pressure, including novel antiviral and/or monoclonal antibody therapies, may further promote the emergence of escape viral variants.

CASE DESCRIPTION

Vergouwe and colleagues describe in their report a 72-year-old immunocompromised male patient who was admitted to the University Medical Center Amsterdam in February 2022 with a SARS-CoV-2 infection. Due to a history of allogeneic stem cell transplantation as treatment for overlapping myelodysplastic and myeloproliferative syndrome, he was defined as immunocompromised.

This was complicated by the development of post-transplant lymphoma for which he received rituximab, which depletes all available B cells, including those that normally produce antibodies directed against SARS-CoV-2. Previously, she had received multiple allogeneic stem cell transplants for the treatment of myelodysplastic and myeloproliferative overlap syndrome.

Additionally, he had already received multiple SARS-CoV-2 vaccines without a measurable SARS-CoV-2 IgG antibody response at the time of hospital admission. Routine genomic surveillance showed infection with the SARS-CoV-2 Ómicron variant BA.1.17. He received treatment with the targeted anti-SARS-CoV-2 antibody sotrovimab, the anti-IL6 antibody sarilumab, and dexamethasone without clinical response.

Follow-up sequencing of SARS-CoV-2 showed the development of the known sotrovimab resistance mutation S:E340K as early as 21 days after receiving the sotrovimab infusion.

SARS-CoV-2-specific T cell activity and the development of anti-spike antibodies in the first month were minimal, indicating that the patient’s immune system was not capable of clearing the virus. Prolonged infection led to the emergence of a new immune-evasive variant due to extensive evolution within the host. Ultimately, the patient died due to a relapse of his hematological status after remaining positive for SARS-CoV-2 with high viral loads for a total of 613 days.

Fortunately, there had been no documented transmission with the highly mutated variant to secondary cases in the community.

In more detail, the 613 days following the initial detection of SARS-CoV-2 were characterized by multiple virus-related and non-virus-related symptomatic episodes, requiring hospital admissions.

Persistent SARS-CoV-2 infection caused the patient to have prolonged periods of isolation during hospital admission and increased use of personal protective materials, which greatly reduced his self-reported quality of life.

Complete genome sequencing of SARS-CoV-2 was performed on 27 nasopharyngeal samples, collected between February 2022 and September 2023. It revealed more than 50 nucleotide mutations compared to contemporary globally circulating BA.1 variants with multiple substitutions of amino acids, including the ACE-2 receptor binding site substitutions S:L452M/K and S:Y453F. Additionally, several deletions developed in the N-terminal domain of the spike indicative of immune escape.

“This case highlights the risk of persistent SARS-CoV-2 infections in immunocompromised individuals, as unique viral variants may emerge due to extensive intra-host evolution,” the authors say.

Thus, they underline the importance of continuing genomic surveillance of the evolution of SARS-CoV-2 in immunocompromised individuals with persistent infections, given the potential threat to public health posed by the possible introduction of escape viral variants into the community.

Although close surveillance is necessary, the authors emphasize that there must be a balance between protecting the population against possible new variants and humane supportive care at home for seriously ill patients near the end of life.

Possible solutions include increased awareness of potential risks, combined with diagnostic testing accessible to known contacts (family) as soon as they develop relevant symptoms.

This should be combined with genomic surveillance to assess the threat to public health, together with professionals in this field.

The authors highlight that although there may be an increased risk of developing new variants in immunocompromised patients, not all new variants in these patients will become a new variant of concern (VOC) for the community. The underlying mechanisms involved in the development of a VOC are much more complex, as they also depend on factors in the population surrounding the patient, including the prevalence of B- and T-cell-related immunity.

“The duration of SARS-CoV-2 infection in this case described is extreme, but prolonged infections in immunocompromised patients are much more frequent compared to the general community. Other work by our team includes the description of a cohort of infections Prolonged infections in immunocompromised patients in our hospital with durations of infection varying between 1 month and 2 years However, from the point of view of the general public, prolonged infections remain rare, since the immunocompromised population only represents a fraction. very small percentage of the total population”, he concluded.