Covid 19 persistence for over a year - confirmed case in immunocompromised patient

Pyrrhus

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Here's the report:

Year-long COVID-19 infection reveals within-host evolution of SARS-CoV-2 in a patient with B cell depletion (Nussenblatt et al., 2021 - preprint)
https://www.medrxiv.org/content/10.1101/2021.10.02.21264267v2.full.pdf

Nussenblatt et al 2021 said:
Background:
B-cell depleting therapies may lead to protracted disease and prolonged viral shedding in individuals infected with SARS-CoV-2. Viral persistence in the setting of immunosuppression raises concern for viral evolution.

Methods:
Amplification of sub-genomic transcripts for the E gene (sgE) was done on nasopharyngeal samples over the course of 355 days in a patient infected with SARS-CoV-2 who had previously undergone CAR T cell therapy and had persistently positive SARS-CoV-2 nasopharyngeal swabs. Whole genome sequencing was performed on samples from the patient’s original presentation and 10 months later.

Results:
Over the course of almost a year, the virus accumulated a unique in-frame deletion in the amino-terminal domain of the spike protein, and complete deletion of ORF7b and ORF8, the first report of its kind in an immunocompromised patient. Also, minority variants that were identified in the early samples—reflecting the heterogeneity of the initial infection—were found to be fixed late in the infection. Remdesivir and high-titer convalescent plasma treatment were given, and the infection was eventually cleared after 335 days of infection.

Conclusions:
The unique viral mutations found in this study highlight the importance of analyzing viral evolution in protracted SARS-CoV-2 infection, especially in immunosuppressed hosts, and the implication of these mutations in the emergence of viral variants
 

Pyrrhus

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A similar report, from last year, of coronavirus persistence in an immunocompromised patient:

Severe COVID-19 virus reactivation following treatment for B cell acute lymphoblastic leukemia (Lancman et al., 2020)
https://doi.org/10.1186/s13045-020-00968-1

The interesting thing about this case is the fact that the person had a coronavirus infection, appeared to have recovered, and two-months later re-started her immunosuppressive therapy.

As soon as she started her immunosuppressive therapy, the virus suddenly re-appeared, showing that the virus had not, in fact, disappeared during the two months that she tested negative on PCR, and had instead persisted inside her body.

Excerpt:
SARS-CoV-2 has infected millions of people worldwide, but little is known at this time about second infections or reactivation. Here, we report a case of a 55-year-old female undergoing treatment for CD20+ B cell acute lymphoblastic leukemia who experienced a viral reactivation after receiving rituximab, cytarabine, and dasatinib.

She was initially hospitalized with COVID-19 in April and developed a high antibody titer with two negative nasal polymerase chain reaction (PCR) swabs for SARS-CoV-2 on discharge.

After recovery, she resumed treatment in June for her leukemia, which included rituximab, cytarabine, and dasatinib. She promptly lost her COVID-19 antibodies, and her nasal PCR turned positive in June.

She developed a severe COVID-19 pneumonia with lymphopenia, high inflammatory markers, and characteristic bilateral ground-glass opacities on chest CT, requiring high-flow nasal cannula and transfer to the intensive care unit. She received steroids, anticoagulation, and convalescent plasma, and within 48 h she was off oxygen. She was discharged home in stable condition several days later.

Given the short time frame from leukemia treatment to PCR positivity and the low case rate in mid-June in New York City, reinfection appears to have been unlikely and SARS-CoV-2 reactivation is a possible explanation. This case illustrates the risks of treating recently recovered COVID-19 patients with immunosuppressive therapy, particularly lymphocyte- and antibody-depleting therapy, and raises new questions about the potential of SARS-CoV-2 reactivation.
 

Pyrrhus

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And another case of coronavirus persistence in an immunocompromised patient:

Severe clinical relapse in an immunocompromised host with persistent SARS-CoV-2 infection (Reuken et al., 2021)
https://doi.org/10.1038/s41375-021-01175-8

In this case the patient caught the coronavirus in April 2020, right after a rituximab treatment. She was hospitalized and recovered.

Four months later, her COVID symptoms returned and she was hospitalized. Multiple PCR tests from the nose and throat were all negative. Only when she was admitted to the ICU, where they finally extracted lung fluid, did they finally detect the coronavirus persisting in the lungs.

Excerpt:
In this brief report, we present the case of a female patient with a rituximab-treated B-cell lymphoma with severe relapse 4 months after moderate COVID-19 due to SARS-CoV-2.

We present the case of a 56-year old woman who was diagnosed with a follicular lymphoma (grade 2–3a, stage IV, bone marrow >50%) in 2019. The patient was started on a combination therapy with rituximab (375 mg/m2) and bendamustine (90 mg/m2) for six cycles, followed by single-agent rituximab (375 mg/m2 IV every 8 weeks) after achieving complete remission. The last treatment occurred on March 16th [2020].

On April 2nd [2020], she developed a 38.4 °C fever without other symptoms. After 10 days, she felt shortness of breath and dry cough, and she was admitted to the hospital. A low-dose-CT chest scan revealed ground glass opacities. RT-PCR SARS-CoV2 testing on a nasal-throat-swab was positive. [...] Decreased counts of white blood cells (4.2 × 109/L) and lymphocytes (0.53 × 109/L) were detected. [...] notably, no B-cells were detectable.

Six days after hospitalization, she had no further symptoms. RT-PCR tests for SARS-CoV-2 remained negative, and the patient was discharged from the hospital.
[...]
Unexpectedly, 4 months later, her symptoms of dry cough and intermittent fever re-appeared. Outpatient care with two nasal-throat swabs revealed negative RT-PCR results. However, her fever increased, and she developed fatigue and was re-admitted to the hospital. Her chest CT showed radiographic signs indicative of COVID-19. Three SARS-CoV-2 RT-PCR tests of nasal-throat swabs and induced sputum remained negative.
[...]
In the following days, her respiratory situation deteriorated, and she was transferred to the ICU. [...] Because the pathogen remained unknown, a bronchoscopy was performed directly after intubation, and broncho-alveolar lavage finally confirmed the presence of SARS-CoV2-RNA.
[...]
Given the suspected relapse of the SARS-CoV-2 infection, a molecular and immunological work-up was performed. Since a SARS-CoV-2 positive swab of the first episode was stored in our biobank, we were able to sequence and compare both samples. [...] Both isolates belonged to the same SARS-CoV-2 strain. These results suggest that the virus has persisted and evolved within the patient during the last four months.
 

Zebra

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Hi, @Pyrrhus

Thank you, as always, for posting such informative articles.

As someone "living" with ME/CFS I suppose I shouldn't be surprised, but I do find this viral persistence terrifying.

I feel for all those having to make hard decisions about treatment with immunosuppression during a pandemic that is still raging around the world.
 

Pyrrhus

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And another report:

Evolution of a globally unique SARS-CoV-2 Spike E484T monoclonal antibody escape mutation in a persistently infected, immunocompromised individual (Halfmann et al., 2022)
https://www.medrxiv.org/content/10.1101/2022.04.11.22272784v1

Abstract:
Prolonged infections in immunocompromised individuals may be a source for novel SARS-CoV-2 variants, particularly when both the immune system and antiviral therapy fail to clear the infection, thereby promoting adaptation.

Here we describe an approximately 16-month case of SARS-CoV-2 infection in an immunocompromised individual.

Following monotherapy with the monoclonal antibody Bamlanivimab, the individual’s virus was resistant to this antibody via a globally unique Spike amino acid variant (E484T) that evolved from E484A earlier in infection. With the emergence and spread of the Omicron Variant of Concern, which also contains Spike E484A, E484T may arise again as an antibody-resistant derivative of E484A.
(spacing added)
 
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Jesus 3 seperate case studies.

So it's just like ME, the host system either keeps a lid on the dormant virus or it doesn't. I am truly screwed if I get this.

Wow it was resistant? Yikes!

To think we have pax and it appears to work just fine but nobody can get a hold of it.
 

SWAlexander

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More findings on COVID-19

Changes in the Incidence of Retinal Vascular Occlusions After COVID-19 Diagnosis
Key Points
Question Does the incidence of retinal vascular occlusions change after COVID-19 infection?

Findings This cohort study of 432 515 patients diagnosed with COVID-19 found that the incidence of retinal vein occlusions, but not retinal artery occlusions, appeared to increase in the 6 months after COVID-19 diagnosis.

Meaning Patients with COVID-19 infection may have an increased risk of retinal vein occlusion in the 6 months after infection, similar to the increased risk of systemic vascular damage associated with COVID-19, and clinicians need to consider this factor when evaluating these patients.


Abstract

Importance COVID-19 is associated with systemic vascular damage; however, the risk posed to the retinal vasculature remains incompletely understood.

Objective To assess if there is a change in the incidence of retinal vascular occlusions after COVID-19 infection.

Design, Setting, and Participants This cohort study at an integrated health care organization (Kaiser Permanente Southern California) included patients without a history of retinal vascular occlusion who were diagnosed with COVID-19 infection between January 20, 2020, and May 31, 2021. Patients were excluded if they had a history of retinal artery occlusions (RAOs) or retinal vein occlusions (RVOs) more than 6 months before their COVID-19 diagnosis or if they were enrolled in Kaiser Permanente Southern California for less than 6 months before COVID-19 diagnosis.

Exposures COVID-19 infection.

Main Outcomes and Measures The change in the average biweekly incidence of new RAOs and RVOs after COVID-19 diagnosis. Adjusted incidence rate ratios (IRRs) were calculated to compare the incidence of retinal vascular occlusions before and after COVID-19 diagnosis after accounting for baseline demographic characteristics, medical history, and hospitalization.

Results A total of 432 515 patients diagnosed with COVID-19 infection were included in this study. The mean (SD) age was 40.9 (19.2) years, and 231 767 patients (53.6%) were women. Sixteen patients had an RAO (crude incidence rate, 3.00 per 1 000 000 patients), and 65 had an RVO (crude incidence rate, 12.20 per 1 000 000 patients) in the 6 months after COVID-19 diagnosis. The incidence of new RVOs was higher in the 6 months after COVID-19 infection compared with the 6 months before infection after adjusting for age; sex; self-reported race and ethnicity; body mass index; history of diabetes, hypertension, or hyperlipidemia; and hospitalization (adjusted IRR, 1.54; 95% CI, 1.05-2.26; P = .03). There was a smaller increase in the incidence of RAOs after COVID-19 diagnosis (IRR, 1.35; 95% CI, 0.64-2.85; P = .44). The peak incidence of RAOs and RVOs occurred 10 to 12 weeks and 6 to 8 weeks after COVID-19 diagnosis, respectively.

Conclusions and Relevance The findings of this study suggest that there was an increase in the incidence of RVOs after COVID-19 infection; however, these events remain rare, and in the absence of randomized controls, a cause-and-effect relationship cannot be established. Further large, epidemiologic studies are warranted to better define the association between retinal thromboembolic events and COVID-19 infection.
Continue: https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2790988