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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.
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.
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.
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
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.
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 .
On April 2nd , 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.
(spacing added)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.