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

1. An elderly Dutch woman, aged 89, has become the first known person to die from contracting COVID-19 twice.
2. The woman in Netherlands suffered from a Waldenströms macroglobulinemia. [WM].
3. Her immune system was compromised owing to the cell-depleting therapy that was given to her.
4. The patient was initially admitted earlier this year with severe cough and fever, and had tested positive for COVID-19.
5. She was discharged after five days when besides some persisting fatigue, her symptoms subsided completely.
6. 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.
7. 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.
8. When the samples from both the cases were investigated, investigators found that the genetic makeup of the two viruses was different.
9. 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.
10. 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.

[Source: https://www.wxii12.com/]

Discussion

1. The higher levels of angiogenic cytokines in patients with WM point to a role of angiogenesis in WM.
2. 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.
3. CCL5 expression is higher in the BM microenvironment amomg patients with WM, compared to controls.
4. CCL5 levels correspond with disease aggressiveness, and there appears to be a functional correlation between CCL5 and IL-6 levels.
5. IL-6, a proinflammatory cytokine, is mainly produced by BM stromal cell and plays a role in normal and malignant B-cell biology.
6. 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.
7. The enhanced IL-6 production leads to increased IgM production by WM malignant cells via the JAK/STAT pathway.
8. 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.
9. IgM is a mediator of WM morbidity.
10. 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]

Hypothesis

1. She might have recovered
2. But, baseline IL-6 could have remained high
3. Reinfection might have precipitated IL-6 storm.

Dr KK Aggarwal

President CMAAO, HCFI and Past National President IMA