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Researchers Document Longest Known COVID-19 Infection, Occult Infection

Lasting 505 days, investigators documented the longest known COVID-19 infection. The research, presented at ECCMID, also found one of the first cases of occult COVID-19, in which a patient who tests negative is later found to have ongoing COVID-19.

New research, presented at this week’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID), identified what is believed to be the longest known COVID-19 infection. A London patient PCR-tested positive for 505 days before their subsequent death.

The investigators, from King’s College London and Guy’s and St Thomas’s NHS, studied 9 COVID-19 patients to evaluate how the virus changes over time in immunocompromised persons. When presenting their research at ECCMID in Lisbon, Portugal from April 23-26, 2022, they detailed one of the first occult COVID-19 infections.

Occult infection is classified as a patient believed to be cleared of the virus, seemingly confirmed by negative COVID-19 tests, but who is later found to have an ongoing infection. “The patient was symptomatic and tested positive for Covid before recovering,” the investigators explained. “They then tested negative several times before developing Covid symptoms again several months later. A PCR test was positive and genome sequencing of the virus at this point showed the infection was caused by the Alpha variant, which had by then been eliminated from the UK, suggesting the virus had been present in the body ever since the initial infection but remained undetected.”

The investigators recruited immunocompromised COVID-19 patients from March 2020-December 2021. The patients had weakened immune systems due to solid organ transplantation, HIV, cancer, or medical therapies for comorbidities. The 9 study participants tested positive for COVID-19 for at least 8 weeks. Average infection length was 73 days, but 2 of the patients had persistent infections for over 1 year.

“We wanted to investigate which mutations arise, and if variants evolve, in these people with persistent infection,” said first author, Dr. Luke Blagdon Snell, of Guy’s and St Thomas’s NHS Foundation Trust. “Some of these variants transmit more easily between people, cause more severe disease, or make the vaccines less effective. One theory is that these viral variants evolve in individuals whose immune systems are weakened from illness or medical treatments like chemotherapy, who can have persistent infection with SARS-CoV-2.

After conducting regular sampling and genetic analysis, the investigators found 5 of the 9 patients developed 1 or more mutations seen in COVID-19 variants of concern. A few of the participants developed multiple mutations correlated with variants of concern, such as Alpha, Delta, and Omicron. One individual harbored 10 mutations that were later identified in the Alpha, Gamma, and Omicron variants of concern.

“This provides evidence that mutations found in variants of concern do arise in immunocompromised patients and so supports the idea that new variants of the viruses may develop in immunocompromised individuals,” the investigators said. “It is important to note, however, that none of the individuals in our work developed new variants that became widespread variants of concern.”

Of the 9 immunocompromised COVID-19 patients, 5 recovered. 2 cleared the infection without treatment, 2 cleared the infection with antibody therapies and antivirals, and 1 is currently living with ongoing infection. At their last follow-up, earlier this year, this 1 participant had been infected for 412 days. The patient was treated with monoclonal antibodies, but if this does not succeed in clearing the infection, they will likely surpass the 505 day longest-known infection.

The investigators noted that occult infections have previously been recorded in Ebola and hepatitis B patients. Occult COVID-19 is different from “long covid,” in which the virus is cleared but certain debilitating symptoms, such as fatigue, persist.