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    Home > Active Ingredient News > Infection > The longest new crown infection in the world: After recovering from cancer, she struggled with the new crown for 335 days

    The longest new crown infection in the world: After recovering from cancer, she struggled with the new crown for 335 days

    • Last Update: 2021-11-04
    • Source: Internet
    • Author: User
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    ▎Editor of WuXi AppTec's content team In March 2021, Maryland, USA, which had just recovered from the cold winter, encountered a new round of new crown epidemic growth
    .

    For Dr.
    Veronique Nussenblatt, an infectious disease expert working here at the National Institutes of Health (NIH), the headache is not only the rising curve of new cases, but also the patients before him
    .

    This female patient is 47 years old.
    Lying on the hospital bed, she coughs from time to time and is short of breath
    .

    The results of the new crown test showed that she had a large number of new crown viruses in her body
    .

    But unlike other patients with new coronary pneumonia around, this patient has not been infected recently: her symptoms have lasted for more than 300 days, and she is the longest known patient with new coronary pneumonia
    .

    Recently, the "Science" website reported this rare case, and the research paper has also been published on the preprint platform (not yet peer reviewed)
    .

    What has changed in the human body during the nearly one year period? From her, what clues to the evolution of the virus can we find? On May 2020, Dr.
    Nussenblatt met this patient
    .

    About 10 days before that, the patient had symptoms such as fever, headache, cough, and nasal congestion
    .

    As the symptoms continued, she came to the NIH clinical center, and the diagnosis was new coronary pneumonia
    .

    After reviewing the patient’s past medical history, Dr.
    Nussenblatt realized that the patient’s condition was somewhat special: she was not only a type 2 diabetes patient, but also a cancer survivor
    .

    Three years ago, she suffered from diffuse large B-cell lymphoma and received CAR-T therapy.
    This emerging therapy uses modified T cells to recognize antigens on the surface of cancer cells and successfully cleared her lymphoma
    .

    The fly in the ointment is that this radical treatment also hinders her B cell development
    .

    For such immunocompromised people who lack sufficient B cells, ordinary infections may also pose a more serious threat
    .

    Fortunately, the condition of this new crown patient is not that serious
    .

    After a month of recovery with plasma and immunoglobulin treatment, the patient was discharged from the hospital
    .

    However, she did not fully recover.
    She was also accompanied by low-grade fever, intermittent cough, and needed supplemental oxygen
    .

    In the following months, she was regularly tested for COVID-19, and the results always fluctuated between negative and weakly positive
    .

    Since the symptoms are relatively mild, from the results of the new crown test, the weak positive is more likely to be caused by non-viable virus fragments
    .

    After all, for most people, the RNA of the new coronavirus may still be detected several months after infection, but the live virus is generally undetectable 10 days after the onset of symptoms
    .

    In this way, the patient repeats between negative and positive, and the symptoms sometimes disappear
    .

    Until March of this year, her respiratory symptoms significantly worsened
    .

    Her C-reactive protein level rose, this acute protein in plasma appeared in large quantities when the body was infected; at the same time, the new coronavirus load also increased significantly
    .

    As a result, she was once again admitted to the NIH ward due to new coronary pneumonia
    .

    At this time, remdesivir (remdesivir) has been approved by the FDA for the treatment of new coronary pneumonia
    .

    So Dr.
    Nussenblatt used a 10-day course of remdesivir, supplemented by high-titer recovery plasma treatment
    .

    Soon, the patient's condition improved significantly
    .


    2.
    At this time, Dr.
    Nussenblatt and colleagues no longer need to worry too much about the patient's safety, so they shifted their focus to scientific research
    .

    They believe that there must be more clues about the new coronavirus in this patient who puzzled them
    .

    The first thing to be clear is whether the patient suffered from the new coronavirus infection again after recovering in the winter, or is the virus in her body always present and has not been completely eliminated at all? To answer this question, genetic sequencing of the virus in the patient is essential
    .

    Leading this work are NIH molecular virologist Dr.
    Elodie Ghedin and computational biologist Dr.
    Allison Roder
    .

    The treatment team still retains the virus samples from the patient's first visit, so they were able to sequence the whole genome of the virus from May last year and March this year
    .

    The results showed that the two groups of viruses that had passed more than 300 days belonged to the same strain, that is to say, the virus never left the patient
    .

    ▲The phylogenetic tree of virus sequencing in May last year and March of this year (picture source: reference [2]) As we mentioned earlier, the new coronavirus has a limited survival time in most patients
    .

    But this patient belongs to a population with low immunity, and her own immune system is not enough to kill the virus during the first infection.

    .

    As a result, the low-load virus was looming in the body, lurking for 10 months, until it broke out again
    .

    Similar situations have also been reported before
    .

    In December last year, an article in the "New England Journal of Medicine" reported a case of a 45-year-old immunocompromised person.
    The new crown virus survived in his body for 5 months until it eventually caused his death
    .

    The patient in this article has been carrying the new coronavirus for more than 300 days.
    This is also the patient known to have been infected with the new coronavirus for the longest time
    .


    3.
    Through this patient, what we see is the evolution of the new coronavirus in the human body
    .

    In the course of nearly a year of evolution, what mutations did the virus undergo? How did these mutations affect the characteristics and spread of the virus? Through the comparison of viral gene sequences, the research team found two interesting gene deletions
    .

    One of them is located on the RNA encoding the spike protein, resulting in the loss of the specific N-terminal domain of the spike protein
    .

    We know that the spike protein is the site used by the new coronavirus to bind to host cells, and the deletion of the N-terminal domain makes some specific antibodies ineffective
    .

    The reason for the deletion of the N-terminal domain in the immunocompromised population is still unclear, but previously, Professor Ravindra Gupta, an epidemiologist at the University of Cambridge, found in a study that immunocompromised hosts receiving (antibody-rich) convalescent plasma therapy are prone to this Class mutations, so the sensitivity to neutralizing antibodies is reduced
    .

    The experience of the patients in this article provides new evidence for this phenomenon
    .

    Image source: 123RF In the view of Professor Gupta, this phenomenon reminds us that we need to be extra cautious in the treatment of patients with immunocompromised COVID-19
    .

    For example, it is not clear whether the monoclonal antibody therapy currently used will also accelerate the evolution of the virus in such patients
    .

    Therefore, it is very important to avoid infection as much as possible for people with low immunity
    .

    This is not only to protect their lives, but also to avoid the emergence of new mutations-Professor Gupta has previously proposed that the alpha mutant of the new coronavirus, which first appeared in the UK and became the world's main strain, may initially be in the body of people with low immunity.
    Appeared
    .

    For the NIH team, the mutation related to the spike protein is important, but they are more interested in another mutation that is not related to the spike protein: 497 nucleotides are missing, and the regions encoding the accessory proteins ORF7b and ORF8 are lost.
    Completely delete
    .

    This is the first time that such a large-scale gene deletion has been found in an immunocompromised person
    .

    ▲497 nucleotide deletions involved in encoding ORF7b and ORF8 proteins (picture source: reference [2]) Although they are not located on the spike protein, the ORF8 protein also plays an important role in the virus invading the human body
    .

    For example, in June this year, a study by the Sun Yat-Sen University team found that ORF8 protein can induce immune escape
    .

    The deletion of the gene encoding the ORF8 protein in the patient in this article may be the result of natural selection: when the new coronavirus invades patients with low immunity, it does not need the ORF8 protein to evade the immune system; on the contrary, the virus that lacks the ORF8 protein replicates faster , Have an advantage in the competition-this is exactly the trend that the research team in this article has observed in the virus samples of patients
    .

    This phenomenon also reminds us that the long-term evolution of the new coronavirus in some immunocompromised patients may also produce other mutations that are conducive to the spread of the virus.
    Therefore, the changes in the virus in patients with chronic new coronary pneumonia need to be extra vigilant
    .


    Fourth, this is obviously not a problem that Dr.
    Nussenblatt's patient needs to worry about.
    Her long and twists and turns of the new crown story still ushered in a gratifying ending
    .

    After receiving 11 days of hospitalization in March this year, her lung function improved and her blood C-reactive protein was significantly reduced
    .

    In the end, counting from the day of her first visit to the doctor, she was infected with the new crown virus for 335 days.
    Since then, her multiple new crown tests have been negative, and the sequelae have gradually subsided
    .

    For Dr.
    Nussenblatt and other researchers, a new and attractive research path has been paved
    .

    The threat posed by the continuous mutation of the new crown virus keeps us shrouded in dark clouds.
    The clues to the evolution of the virus from such special patients may help us to find the direction of understanding and fighting against the mutation of the virus
    .

    Source of title picture: 123RF Reference material: [1] A cancer survivor had the longest documented COVID-19 infection.
    Here's what scientists learned.
    Retrieved Oct 19, 2021 from https:// survivor-had-longest-documented-covid-19-infection-here-s-what-scientists-learned[2] Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion.
    MedRxiv preprint doi: https://doi.
    org/10.
    1101/2021.
    10.
    02.
    21264267[3] Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host.
    N Engl J Med 2020; DOI: 10.
    1056/NEJMc2031364[4] The ORF8 protein of SARS-CoV-2 mediates immune evasion through down-regulating MHC-Ι.
    PNAS (2021); https://doi.
    org/10.
    1073/pnas.
    2024202118
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