To study: Novel risk factors for coronavirus disease-associated mucormycosis (CAM): a case-control study during the epidemic in India. Crédit d’image : Kateryna Kon/Shutterstock.com
What is mucormycosis?
Mucormycosis is a sporadic fungal disease caused by angio-invasive fungi of the order Mucorales and occurs almost exclusively opportunistically in immunocompromised patients. This disease quickly causes destruction and death of rhino-orbital-brain tissue, which often extends to the lungs, skin, digestive tract, or even the systemic circulation.
The incidence of mucormycosis has recently increased to more than double its normal rate due to its prevalence in patients with coronavirus disease 2019 (COVID-19) in India. This suggests that COVID-19 is a risk factor for mucormycosis, either due to the weakened immune system or as an indirect consequence of therapies, such as corticosteroids, which have been used in the management of COVID-19.
Not only is mucormycosis itself life threatening, but the high cost of treatment requires rigorous efforts to prevent it.
India has had high rates of mucormycosis even before the COVID-19 pandemic, which is about 70 times the global prevalence. This increased incidence of mucormycosis could be due to humidity and high ambient temperatures in this country, as well as the prevalence of diabetes. Rural areas in India have often been particularly vulnerable to mucormycosis.
Previous studies indicate that men, usually in their 40s and 50s, are more likely than women to be affected by mucormycosis. Recently, the onset of mucormycosis has occurred about 3 weeks after the onset of symptoms of COVID-19, with the nose and orbital cavities usually affected first.
Most COVID-19 patients with mucormycosis reported poor blood sugar control, were on systemic corticosteroid therapy, or had diabetes. These factors were absent in only one patient in the present study, unlike previous reports where a minority of cases, up to 33% in some reports, did not have any of these risk factors.
Interaction of risk factors
Sporangiospores and fungal hyphae are usually destroyed by neutrophils and macrophages of the innate immune system. The activity of these immune cells then triggers an adaptive immune response, which is evidenced by activation of Th-17 cells and stronger activity of neutrophils. In the nasopharynx, neutrophils are activated prematurely with relatively low numbers of T, B and natural killer (NK) lymphocytes.
This abnormal pattern is clearly observable during week 2 of COVID-19 infection, which may explain the spike in mucormycosis cases during this period following the onset of COVID-19. Additionally, the invasive nature of fungi can be exacerbated by endothelial cell abnormalities and vascular damage associated with this viral infection.
Hyperglycemia is an inhibitor of neutrophil and chemotaxis activity, macrophage phagocytosis and NK cell degranulation. This condition also upregulates the expression of the glucose-regulated protein (GRP78) on the surface of cells, which is an invasion factor for Mucorales. The highest risk of mucormycosis has been observed in people with blood sugar levels above 400 mg / dL.
Long-term use of corticosteroids also increases the risk of mucormycosis, as these drugs suppress the activity of macrophages and neutrophils and promote hyperglycemia. Thus, postprandial blood sugar measurement is essential for blood sugar control during steroid therapy, unless it is used in the short term, especially in people with higher HbA1C levels before onset. processing.
Mucormycosis associated with COVID-19 is almost eight times more common in patients on corticosteroid therapy. This should not preclude the appropriate use of steroids in severe cases of COVID-19, where they have been shown to save lives; however, it should serve as a warning against their use in mild cases of COVID-19.
Zinc is an essential micronutrient that is safe and inexpensive as a supplement. It is essential for the proper functioning of the immune system, reduces the secretion of pro-inflammatory cytokines, prevents excessive lymphopenia, and alleviates inflammation of the airways in COVID-19. Zinc use has been linked to a reduced risk of mucormycosis in COVID-19 patients.
The severity of COVID-19 vs the risk of mucormycosis
While more than one in three COVID-19 patients with mucormycosis had a history of severe COVID-19 in the present study, previous studies reported severe COVID-19 in up to 75% of patients with associated mucormycosis to coronavirus disease (CAM). This discrepancy will have to be deepened by prospective studies in order to eliminate survival and selection bias.
However, ferritin levels are elevated in severe cases of COVID-19, including those with mucormycosis. This is an important observation because the Rhizopus species depend on iron for their pathogenesis and growth.
Other risk factors
The use of surgical and / or tissue masks for long periods of time has been associated with a higher incidence of mucormycosis because Rhizopus tolerates high temperatures and humidity.
The risk of mucormycosis associated with coronavirus disease depends on the type of mask as well as the duration of use. * represents a significant difference compared to the use of the N95 mask during
Using a mask for an hour increases the temperature of the skin around the mouth, while respiratory tract infections are more common with using a cloth mask compared to no masks or other types of masks. This risk could be related to ineffective mask cleaning, improper reuse of masks, or simply because they retain moisture.
On the other hand, the use of a mask can be an indicator of increased exposure to dust or soil containing spores. These preliminary results need to be explored further.
Repeated nasopharyngeal swab testing has been associated with an increased risk of mucormycosis, which may be analogous to cutaneous mucormycosis seen at local trauma sites. Steam inhalation did not show such an association.
What are the implications?
This is the first large-scale study comparing cases and controls to identify risk factors for mucormycosis associated with COVID-19. Notably, controls for this study were collected from a single center, which may have influenced the results, as cases are often treated with different protocols at different centers. The retrospective nature of the study may also have influenced the results due to missing data.
Overall, the authors found CAM to be strongly associated with diabetes, poor glycemic control, and systemic steroid use. The need for oxygen supplementation or hospitalization for COVID-19 has not been shown to increase the risk.
The use of a cloth mask for prolonged periods and repeated nasopharyngeal swab testing were found to be risk factors for fungal infection for the first time in this study. In contrast, N95 masks were protective against CAMs.
If confirmed by further research, appropriate modification recommendations should be made to reduce the incidence of this life-threatening complication of COVID-19.
medRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behavior, or treated as established information.