Immunosuppression-the suppression of immunity-is used to treat people with severe forms of cancer, blood diseases, and internal organ transplantation. In bone marrow transplants or chimeric T cell therapy, doctors specifically inhibit patients’ immune system so that the donor cells can take root. If immunosuppression is not carried out, the human immune system will destroy the donor cells, perceiving them as foreign genetic agents.

The body of patients with suppressed immunity is more challenging to cope with coronavirus infection. Doctors of the Memorial Cancer Center studied the dynamics of this process. Sloan-Kettering (New York, USA).

The condition of cancer patients at the beginning of the coronavirus pandemic

At the height of the COVID-19 pandemic spring wave, doctors studied in detail the course of the disease in 20 patients with immunosuppression:

Average age

61 years

(range 35 – 77 years old)

Percentage of men

55%

Primary disease/number of cases

Acute leukemia

20%

Chronic leukemia

5%

Lymphoma

40%

Multiple myeloma

35%

Bone marrow transplantation was performed in 80% of patients. This operation is performed to restore the hematopoietic organs destroyed by cancer. Hematopoietic stem cells are isolated from the donor’s bone marrow, which is injected into patients then. After entering the body, these cells will give rise to other cells of hematopoiesis.

From bone marrow transplant surgery to COVID-19 infection, this group of patients took a different time:

Elapsed time from the day of surgery

Percentage of patients

> 2 years

31%

1 — 2 years

19%

3 months — 1 year

25%

< 100  days

25%

Treatment with chimeric T cells was conducted in 10% of patients. This type of therapy is used when a malignant degeneration of human B cells occurs, and lymphomas and leukemias develop. Reborn B cells express a protein on their membrane that hides them from the immune system’s cells. For treatment, doctors isolate immune cells, T cells, from the patient’s blood. These cells are then genetically engineered so that they can find degenerated malignant cells and destroy them. Then these genetically modified (chimeric) T cells are injected back into the patient. At this point, immunosuppressive therapy is performed so that the patient’s immune system does not destroy the resulting chimeric T cells.

The remaining 10% of patients received other treatment. However, their immunity was just as suppressed as in the other groups. Doctors do not specify the details of this group.

At the time of COVID-19 disease, 75% of patients received active treatment or chemotherapy.

The course of coronavirus infection in patients with suppressed immunity

COVID-19 was diagnosed on average 3 days after the onset of symptoms. None of the patients had an asymptomatic coronavirus infection. Mild severity of the disease was observed in 30% of cases. The average is 15%, and severe form – in 55% of patients.

95% of patients were hospitalized. 75% received treatment. Within the first 30 days, 20% died.

Medical treatment was carried out, taking into account individual characteristics. Some patients were treated with multiple medications.

Medication Percentage of patients treated
Hydroxychloroquine

65%

Remdesivir

10%

Azithromycin

25%

Plasma transfusion of recovering patients with COVID-19

40%

Tocilizumab

25%

Corticosteroids (dexamethasone)

45%

Acetylcysteine (N-Acetyl-L-Cysteine)

5%

 

The expression of live coronavirus particles and production of antibodies

Doctors at the cancer center regularly collected phlegm samples from the nasopharynx of immunocompromised patients with COVID-19. Then the specialists continued their research in the laboratory. They hooked the obtained samples to cell cultures and incubated them at 37 degrees Celsius for a week. Experts then studied each cell culture and looked to see if the virus had developed. If the coronavirus turned out to be viable and multiplied, then experts sequenced (decoded) the viral genome to compare it with the world phylogenetic tree of SARS-CoV-2.

As a result, it was found that the viable SARS-CoV-2 virus is excreted on average for 51 days in immunocompromised patients. Range of values: 12-82 days. The authors of the study claim that these data correspond to chronic coronavirus infection.

It was also found that in 13 cases, there was a mutation of the virus. These cases are marked “+” in the figure:

In the final analysis, the researchers tested for the presence of antibodies in patients. Antibodies were produced only in 7 out of 15 cases — 47%.

Conclusion

The cancer center staff demonstrated that patients with a weakened immune system could distinguish viable virus for several months. Due to the chronic nature of the disease and long-term treatment, the virus evolves faster. It becomes resistant to antibodies when transfused into the plasma of recovering patients.

Also, in a significant proportion of cases, patients with immunosuppression do not produce antibodies to coronavirus infection.

The researchers recommend updating the Centers for Disease Control and Prevention’s guidelines on precautions for managing this category of patients.

Source

Shedding of Viable SARS-CoV-2 after Immunosuppressive Therapy for Cancer

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