Leukaemia Patient Carried SARS-CoV-2 RNA for 127 Days in Fatal Case

Most people infected with SARS-CoV-2 clear the virus within one to two weeks, their immune systems erasing traces of viral RNA from the respiratory tract long before symptoms fully resolve. A newly published case report in Respirology Case Reports describes the opposite extreme: a 69-year-old woman with chronic lymphocytic leukaemia whose nasopharyngeal samples continued to yield positive RT-PCR results for 127 days after the onset of her COVID-19 symptoms. The case, documented by clinicians treating the patient, offers a stark illustration of how a profoundly compromised immune system can permit the virus to persist for more than four months, ultimately with fatal consequences.

Chronic lymphocytic leukaemia, or CLL, is a malignancy characterised by the progressive accumulation of monoclonal lymphocytes bearing a distinctive immunophenotype — cells that are CD5-positive, CD19-positive, CD20-dim, CD23-positive and express dim surface immunoglobulin — in the peripheral blood, bone marrow and lymphoid tissues. Unlike many other chronic lymphoproliferative disorders, CLL is defined as much by its immunological consequences as by its malignant ones. Patients frequently present with immune disturbances and recurrent infections, a feature that makes the disease particularly dangerous in the era of a novel respiratory virus. The leukaemic cells crowd out functional immune components, and the humoral arm of the immune system is often left strikingly weakened.

The patient in this report had been diagnosed with CLL four years before she presented with fever. For the two years preceding her COVID-19 illness, she had been receiving ibrutinib, a targeted Bruton tyrosine kinase inhibitor used as maintenance therapy. While ibrutinib has transformed the management of CLL, it adds another layer of immunosuppression to a disease already defined by immune dysfunction. When her symptoms began, a computed tomography scan of the chest revealed a pattern of ground-glass opacities, the hazy radiological signature familiar to clinicians throughout the pandemic, and RT-PCR testing confirmed SARS-CoV-2 infection.

What followed was a clinical course that departed sharply from the expected trajectory. Two weeks after the patient had clinically recovered, repeat RT-PCR testing remained positive. Twenty-eight days later, she returned to medical attention with fever and weakness. On admission, her clinicians discontinued ibrutinib, a common practice for patients with COVID-19 intended to minimise potential drug-related complications and reduce the burden of immunosuppression. She was treated with dexamethasone to manage inflammation and remdesivir as antiviral therapy, both standard interventions for hospitalised COVID-19 patients aimed at curbing viral replication and blunting the cytokine-driven tissue damage that characterises severe disease.

Despite this conventional therapeutic arsenal, the virus would not retreat. Serial RT-PCR tests performed on nasopharyngeal aspirates continued to detect the SARS-CoV-2 genome, with positivity persisting up to 127 days after symptom onset. Throughout this period, the patient remained under quarantine and home observation. Laboratory findings captured the depth of her illness: a white blood cell count of 50 × 10⁹ per litre with 88 percent lymphocytes, reflecting the leukaemic burden; a C-reactive protein level of 200 mg/L and an erythrocyte sedimentation rate of 119 mm/hour, markers of vigorous systemic inflammation; and elevated liver enzymes, with alanine aminotransferase at 87 U/L and aspartate aminotransferase at 75 U/L. Eventually, on day 127, her oxygen saturation declined, and she died in the intensive care unit.

The authors of the report attribute this extraordinary duration of viral shedding to the profound immunodeficiency associated with CLL, further compromised by ongoing chemotherapy and ibrutinib therapy. Central to this vulnerability is hypogammaglobulinemia, a hallmark of CLL in which levels of protective antibodies — IgG, IgA and IgM — fall below the thresholds needed for effective host defence. These immunoglobulins are crucial for neutralising SARS-CoV-2 and preventing its dissemination within the body. When the humoral immune system cannot mount a competent antibody response against the virus, viral replication proceeds unchecked, and shedding continues for months rather than weeks. The patient’s failure to seroconvert, noted by the authors, aligns with a growing body of evidence showing that CLL patients mount suboptimal antibody responses to SARS-CoV-2 infection.

This immunological failure helps explain a broader and troubling pattern. Early reports from China indicated that individuals with cancer are more susceptible to SARS-CoV-2, although initial data on the prevalence and features of COVID-19 across different cancers, including CLL, were limited. Subsequent studies have shown that patients with CLL are more likely to experience severe COVID-19, with higher rates of hospitalisation, intensive care unit admission and mortality compared to the general population. Advanced age compounds the risk, and this patient’s 69 years, combined with ongoing chemotherapy, placed her in a particularly precarious position. Prolonged viral shedding has been documented in other immunocompromised individuals as well, but the distinguishing feature of this case, according to the authors, is the demonstration that early cessation of targeted therapy combined with standard antiviral and corticosteroid administration was entirely insufficient to halt continuous viral replication, ultimately leading to fatal hypoxemia by day 127.

The case also raises uncomfortable questions about the limits of standard COVID-19 therapy in immunocompromised hosts. Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA-dependent RNA polymerase, and dexamethasone, a corticosteroid that dampens the inflammatory cascade, were developed and validated largely in populations with intact immune systems. In a patient who cannot generate neutralising antibodies, the report suggests, these treatments may not suffice to achieve viral clearance. The authors point instead to monoclonal antibodies such as casirivimab and imdevimab, which have shown promise in facilitating rapid viral clearance in CLL patients grappling with persistent infections. By supplying exogenous neutralising antibodies, such therapies can in principle substitute for the humoral response the patient’s own body cannot mount, offering a potential therapeutic avenue where conventional regimens fall short.

Supportive measures aimed at correcting the underlying antibody deficiency may hold similar promise. The authors highlight intravenous immunoglobulin infusions, which replenish circulating IgG and can provide passive immunity against a broad range of pathogens, as an intervention that may improve outcomes among CLL patients infected with SARS-CoV-2. Cited literature includes a reported case of long-lasting SARS-CoV-2 infection with post-COVID-19 chronic interstitial pneumonia in a CLL patient treated successfully with intravenous immunoglobulin, suggesting that addressing hypogammaglobulinemia directly can alter the course of otherwise intractable infections. Robust monitoring of viral shedding in such patients is also emphasised, both to guide therapy and to minimise potential transmission risks from prolonged carriers — a public health consideration, since immunocompromised individuals who harbour replicating virus for months are also environments in which new variants can emerge.

The report’s authors conclude that the prevalence, clinical characteristics and outcomes of COVID-19 in CLL patients have yet to be fully established, and that preliminary data from large patient series remain valuable for understanding and managing these cases. Their central message is a call for tailored strategies that go beyond remdesivir and dexamethasone, particularly given the high mortality linked to comorbidities in this population. For clinicians, the case is a reminder that a positive RT-PCR test in an immunocompromised patient is not merely a lingering molecular echo of a resolved infection; it can reflect genuinely ongoing viral replication. For virologists, it is a vivid demonstration of the delicate equilibrium between host immunity and viral persistence — an equilibrium that, when the immune system fails, can stretch a two-week illness into a 127-day ordeal with a fatal end.

Subject of Research: Prolonged SARS-CoV-2 RNA shedding in a chronic lymphocytic leukaemia patient with impaired antibody responses

Article Title: Persistent SARS‐CoV‐2 RNA Positivity in a Chronic Lymphocytic Leukaemia Patient for 127 Days After Disease Onset: A Case Report

Article References: Khamseh, F., Moghtader‐Mojdehi, A.-H., Nemati, Z., & Haghighi, M. (2026). Persistent SARS ‐ CoV ‐2 RNA Positivity in a Chronic Lymphocytic Leukaemia Patient for 127 Days After Disease Onset: A Case Report. Respirology Case Reports, 14(10), Article e70767. https://doi.org/10.1002/rcr2.70767

Image Credits: AI Generated

DOI: 10.1002/rcr2.70767

Keywords: SARS-CoV-2, chronic lymphocytic leukaemia, viral shedding, immunodeficiency, hypogammaglobulinemia, ibrutinib, remdesivir, dexamethasone, RT-PCR, monoclonal antibodies, COVID-19, case report