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With input from Dr Monica Vasudev
1110: First Reinfection Death Could have been due to underlying high IL-6 levels
Dutch woman dies after contracting COVID-19 twice, the first reported reinfection death
- An elderly Dutch woman, aged 89, has become the first known person to die from contracting COVID-19 twice.
- The woman in Netherlands suffered from a Waldenströms macroglobulinemia. [WM].
- Her immune system was compromised owing to the cell-depleting therapy that was given to her.
- The patient was initially admitted earlier this year with severe cough and fever, and had tested positive for COVID-19.
- She was discharged after five days when besides some persisting fatigue, her symptoms subsided completely.
- Two days into chemotherapy treatment, about 59 days after the onset of the first COVID-19 episode, she developed fever, cough and difficulty breathing. She again tested positive for COVID-19. There were no antibodies in her blood system when tested on days four and six. Her condition worsened on day eight and she died two weeks later.
- The case is reported by Maastricht University Medical Center in the Netherlands wrote in a paper accepted for publication in the journal Clinical Infectious Diseases.
- When the samples from both the cases were investigated, investigators found that the genetic makeup of the two viruses was different.
- Some cases of reinfection have been reported from across the world. The most recent has been the case of a 25-year-old resident of Nevada in the United States. According to researchers in The Lancet Infectious Diseases, the man tested positive for COVID-19 in April and again in June, showing symptoms in both cases including sore throat, cough, headache, nausea, and diarrhea. He had no underlying health conditions; however, like the Dutch woman, he suffered a more severe episode the second time. Unlike the Dutch woman; however, he developed a measurable antibody response after the second episode.
- A 33-year-old man from Hong Kong was the first person reported to have contracted the infection twice. He got re-infected 4.5 months after the initial infection, showing no symptoms the second time round.
- The higher levels of angiogenic cytokines in patients with WM point to a role of angiogenesis in WM.
- C-C motif ligand 5 (CCL5) a chemokine, granulocyte colony-stimulating factor, and soluble interleukin (IL)-2 receptor are raised in patients with WM; IL-8 and epidermal growth factor levels are lower in comparison with healthy controls.
- CCL5 expression is higher in the BM microenvironment amomg patients with WM, compared to controls.
- CCL5 levels correspond with disease aggressiveness, and there appears to be a functional correlation between CCL5 and IL-6 levels.
- IL-6, a proinflammatory cytokine, is mainly produced by BM stromal cell and plays a role in normal and malignant B-cell biology.
- CCL5 stimulates IL-6 secretion from BM stromal cells by binding to a receptor C-C motif receptor 3 (CCR3) and induction of GLI2, a transcription factor via the PI3K-AKT-B-p65 pathway.
- The enhanced IL-6 production leads to increased IgM production by WM malignant cells via the JAK/STAT pathway.
- The CCL5– IL-6 interaction may be a mechanism by which the WM cells and BM stromal cells stimulate each other; the WM cells produce CCL5, which stimulates the stromal cells to produce IL-6, and IL-6 goes on to syimulate IgM production by the WM cells.
- IgM is a mediator of WM morbidity.
- Other cytokines that are increased in WM include B-lymphocyte stimulator and macrophage inflammatory protein-1 alpha.
[Clinical Lymphoma, Myeloma & Leukemia, Vol. 13, No. 2, 218-21]
- She might have recovered
- But, baseline IL-6 could have remained high
- Reinfection might have precipitated IL-6 storm.
Dr KK Aggarwal
President CMAAO, HCFI and Past National President IMA