"Importance of fungal infections TX amid COVID-19 spike"

Sung-Yeon Cho, a professor of at the Catholic Univ. of Korea Seoul St. Mary's Hospital

Immunocompromised patients are vulnerable to fungal infections…higher risks to patients with severe diseases amid infectious diseases resurgence

Reimbursement discussions are difficult despite the introduction of effective new drugs…"More treatment options are in need"

Sung-Yeon Cho, a professor of at the Catholic Univ.

 

of Korea Seoul St.

 

Mary

"Fungal infections usually occur in immunocompromised patients and have a high fatality rate.

 

Because fungal infections can be fatal to patients, especially during the resurgence of infectious diseases, such as COVID-19, it is of paramount importance to secure various treatment options." During a recent meeting with Daily Pharm, Sung-Yeon Cho, a professor in the Department of Infectious Diseases at the Catholic University of Korea Seoul St.

 

Mary's Hospital, suggested potential improvements to treatment settings for fungal infections in South Korea.

 

In August, the number of patients hospitalized for severe COVID-19 symptoms was a record high for this year, and concerns about the pandemic increased, posing threats to public healthcare due to fungal infections.

 

The U.S.

 

Center for Disease Control and Prevention (CDC) has designated September 16-20, 2024, as 'Fungal Disease Awareness Week' and notifies the importance of managing fungal infections.

 

The most reported fungal infections are COVID-19 associated pulmonary aspergillosis (CAPA), COVID-19 associated mucormycosis (CAM), and Candida auris.

 

These diseases worsen the prognosis of immunocompromised patients, leading to death.

 

As infectious diseases resurge, the emphasis on fungal disease management and treatment becomes increasingly important.

 

However, there are unresolved issues regarding the timely treatment of Korean patients, as the focus of governmental support has been on antibiotics among antimicrobials, and patient access to treatments is limited.

 

European and U.S.

 

guidelines suggest Vfend (voriconazole) and Cresemba (isavuconazonium) as first-line treatments for invasive CAPA.

 

Cresemba won the Ministry of Food and Drug Safety (MFDS) approval in 2020 and it has been listed as the 'National Essential Drug.' However, it still has unmet medical needs because it is not reimbursed by national health insurance.

 

This is in contrast with Cresemba's reimbursable status in Europe, the UK, Hong Kong, Taiwan, and China.

 

Cho strongly suggested that fungal infections can be fatal to immunocompromised patients, and thus, patient access to treatments must be improved.

 

Fungal infections, the fatality rate↑ in patients with COVID-19 CAPA is categorized as the highest-ranked, 'Critical Priority Group,' in the WHO-published 'Fungal Priority Pathogen List.' It shows the highest antifungal tolerability, mortality, and occurrence rate.

 

CAPA is a variety of fungal infections induced by the 'aspergillosis' fungus, which exists in nature.

 

Patients with respiratory diseases or are immunocompromised can commonly contract 'invasive CAPA.' Invasive CAPA is the most serious form of CAPA, usually occuring in immunocompromised patients.

 

It commonly invades the lungs but can induce infections in any part of the body.

 

"Fungus exists naturally, but infections do not happen when the immune system normally works.

 

Patients receiving anticancer therapies, with a lowered number of neutrophils in white blood cells or taking extended steroids are vulnerable to fungal infections, " Cho said.

 

"COVID-19-associated infections reduce normally working protective mechanism of upper/lower respiratory airways and make the body susceptible to all secondary infections related to the respiratory system," Cho added.

 

Based on the results of a study involving 2427 patients with severe COVID-19 symptoms, 4.6% of all hospitalized patients and 11.2% of intensive care unit patients had CAPA infections.

 

The median value of time it takes until CAPA diagnosis was 9.5 days.

 

In particular, corticosteroid use in throughout the body has increased the risk of CAPA infections in COVID-19 patients.

 

30-day mortality was found to be higher in CAPA-infected patients (30%) than in patients with severe COVID-19 symptoms who are CAPA-negative (7.2%).

 

"Fungal infections have a high mortality rate because they commonly occur in patients with lowered white blood cell neutrophils, who have undergone anticancer therapies, who are taking extended steroids, and who are immunocompromised.

 

The mortality rate for CAPA is 30%.

 

It is known to be up to 100% when not diagnosed," Cho said.

 

"The rate of contracting CAPA is reported to be approximately 15-25% of COVID-19 patients who are hospitalized in intensive care units in South Korea.

 

Since there are cases where CAPA is not diagnosed, depending on institutes and patient sizes, the incidence rate is reported to be as low as 5% and up to 50%.

 

The CAPA mortality rate differs on diagnosis," Cho added.

 

A previous study indicated the seriousness of fungal infections, showing that CAPA has a similar incidence rate and mortality rate in patients with viral infections, including severe influenza infections, besides COVID-19.

 

WHO recommends physicians always consider the possibility of fungal infections when treating patients.

 

Effective treatments have emerged, but are 'pie in the sky' The importance of fungal infection treatment has been emphasized, but patient access to new drugs is limited in South Korea.

 

Voriconazole, a class of Azole, and Cresemba are prescribed as a first-line treatment of CAPA.

 

Antifungal agents are used in patients who are likely to have COVID-19-associated CAM, besides CAPA.

 

However, discussions about the reimbursable status of those agents are still challenging.

 

Antibiotics include antimicrobials effective for treating germs, antifungals effective for treating fungus, and antivirals effective for treating virus.

 

Among these, antifungals and antiviral agents are not included in the scope of the 'Cost-Effectiveness Evaluation Waiver System.' During the COVID-19 pandemic, the government included antimicrobials in the 'Cost-Effectiveness Evaluation Waiver System.' However, it sees that expanding the scope to antifungals does not meet the gravity and urgency standards.

 

As a result, some are advocating for reimbursement of new antifungal drugs, citing the increasing incidence rate of fungal infections is on the rise worldwide, including in South Korea.

 

However, reimbursement for new antifungals has not been made lately.

 

"Voriconazole is a treatment with extended proof of superior effects in treating CAPA than other antifungals, based on accumulated data since the 1990s.

 

However, there are concerns of extended treatments depending on the patient's immune conditions and refractory due to antifungal tolerance," Cho said.

 

"Cresemba is in high demand among patients likely to have multiple infections as it is effective in treating broad spectrum fungal infections as well as improved safety profiles," Cho added, "Drug interactions that may occur in antifungals of Azole class is 2-10, whereas in Cresemba is as low as 1-1.5.

 

It has the advantage of administering to patients with severe symptoms who are taking multiple drugs." Cresemba proved non-equivalence to the first-line treatment, voriconazole, and it is regarded as having a broader antifungal spectrum.

 

Additionally, Cresemba significantly reduced the most typical adverse reactions of antifungals, such as liver toxicity and photosensitivity, to almost none.

 

"The biggest reason for delayed reimbursement listing of antifungals is finance, but low awareness of infectious diseases can also be attributed.

 

Although antifungals may be crucial to patients, they are not on the priority list," Cho said, "Reimbursement listing of antifungals is often being delayed because people think it is substitutable despite the fact that none are substitutable." "There should be no cases where good new drugs with confirmed clinical data and recommended by global guidelines cannot be prescribed in 2024 due to systemic issues," Cho emphasized, "The reimbursement criteria must be improved considering that patients who need antifungals have life-threatening severe infections."