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had developed a new variant (with more than 50 mutations)

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had developed a new variant (with more than 50 mutations)

An extraordinary clinical case emerges from the Netherlands, where a 72-year-old man died after living with Covid-19 for 613 days, the longest period of infection ever documented. During this time, the virus has undergone significant evolutions, resulting in a highly mutated and potentially immuno-evasive variant. The case will be discussed in detail at the ESCMID Global Congress 2024, a major event in clinical microbiology and infectious diseases.

The case

The Dutch man, who suffered from serious underlying conditions, including myelodysplastic-myeloproliferative syndrome treated with an allogeneic stem cell transplant, was extremely immunocompromised. Further complicating his clinical picture was diffuse large B-cell lymphoma, treated with rituximab, a drug that eliminates both normal and malignant B cells. This drastically reduced his ability to produce antibodies against Sars-Cov-2, despite him having received multiple doses of the vaccine.

The evolution of the virus

During his hospitalization at the University of Amsterdam Medical Center, treatment with monoclonal antibodies and other antiviral drugs was attempted, without success in eradicating the virus. At 21 days after treatment, a mutation in the virus was evident that conferred resistance to sotrovimab, the monoclonal antibody used. Sequencing of the virus revealed over 50 mutations compared to contemporary Omicron variants, including significant changes in the Spike protein, relevant to the virus’s ability to bypass the immune system.

What does he teach

This case is particularly significant for several reasons. First, it demonstrates how in a severely immunocompromised patient, Covid-19 can not only persist but also evolve in ways that can evade commonly activated immune defenses. Furthermore, the case highlights the risks associated with the possibility of immune-evasive variants emerging from similar clinical contexts, similar to what is believed to have happened with the Omicron variant. Although the virus variant in this patient did not cause transmissions to secondary cases, its development raises concerns about the ability of persistent infections to generate new variants that challenge existing protection mechanisms.

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