In severely ill COVID-19 patients, some kinds of fungi can thrive in the intestines, exacerbating the virus's characteristic inflammation and leading to an outsized immune response against the fungi for up to 1 year after infection, suggests a study published yesterday in Nature Immunology.

Weill Cornell Medicine and New York Presbyterian researchers analyzed blood samples from patients with severe COVID-19, finding immunoglobulin G (IgG) antibodies against fungi commonly found in the gut and an increase in neutrophil immune cells in the lungs.

They then used mouse models to confirm that fungi in the gut, especially strains of Candida albicans yeast, provoked the production of more neutrophils in the blood and lungs. The mice also had signs of inflammation when infected with SARS-CoV-2.

No immediate implications for treatment

Patient blood samples showed signs of persistent immune-system changes believed to be related to long COVID. At 1 year postinfection, the blood still contained antifungal antibodies, and stem cells that give rise to neutrophils were primed to attack fungi.

Severe and long COVID-19 were not thought to involve fungal blooms in the intestines that, in addition to the virus, can impact patient’s immunity.

The immune protein interleukin-6, induced by fungi, seemed to increase levels of both neutrophils in the lungs and fungal antibodies. The use of IL-6 blockers or antifungal drugs in patients or mice, however, reduced levels of neutrophils and fungal antibodies. Patients treated with the anti-inflammatory drug tocilizumab saw sustained reductions in IgG antibodies against both C albicans and neutrophil progenitors.

"Severe and long COVID-19 were not thought to involve fungal blooms in the intestines that, in addition to the virus, can impact patient’s immunity," senior author Iliyan Iliev, PhD, of Weill Cornell Medicine, said in a college news release.

The authors said the findings don't change the guidelines for treating severe or long COVID, but they may someday lead to tailored treatment, such as the use of antifungal antibodies to identify patients eligible for a therapy targeting the fungi or the immunologic changes they trigger. The antifungal antibodies may also be a marker of increased risk of long COVID or other infectious inflammatory conditions.

An analysis published by the Washington Post yesterday, based on modeling projections and the situation unfolding in Mozambique, suggests that climate change and demographic growth could put 5 billion more people at risk for malaria by 2040.

The analysis said longer transmission seasons and migration of mosquitoes to new latitudes threaten to undo years of progress. The new report also said Mozambique and other countries with highest malaria burden also have some of the world’s fastest-growing populations.

Of the 5 billion more people expected to be at higher risk in 2040, 1 billion are in Africa. The Post also estimates that 330 million people in South America could be at risk by 2070. The report notes that changing climate patterns not only encourage mosquito habitats, but also make it difficult to time control measures, such as indoor spraying.

The report provided detailed projections for different regions. In the United States, for example, warming temperatures and increased rainfall could lengthen malaria transmission seasons in some areas of the South, posing a threat where there is no population immunity—factors that could lead to higher morbidity and mortality.

Support for tools to battle resistant malaria

In another malaria development, Ocean Biomedical announced today that one of its scientists, Jonathan Kurtis, MD, has received a $1 million Falk Medical Research Trust Transformational Award to further the development of a new class of antimalaria drug candidates.

The program—focused on three key targets in the malaria parasite’s blood stage—includes a small-molecule drug candidate for treating severe malaria and an antibody for short-term prevention. The company said the tools are designed to address growing resistance to current artemisinin-based therapies.

AstraZeneca today announced that the US Food and Drug Administration (FDA) has agreed to review its application for the option for its FluMist flu vaccine to be self- or caregiver-administered, which if approved will be the first vaccine available for self-administration or by caregivers, offering another option for flu vaccination.

In a statement, the company said its application is supported by a usability study that confirmed that people ages 18 and older can self-administer or give the vaccine to people ages 2 though 49 years old when given instructions, but not other guidance.

AstraZeneca said it expects a decision from the FDA during the first quarter of 2024, which would pave the way for its availability through that new route for the United States' 2024-25 flu season.

The ability for individuals and parents to choose where to administer an injection-free flu vaccine could help increase access and, subsequently, vaccination rates.

Ravi Jhaveri, MD, professor of pediatrics and an infectious disease specialist at Northwestern University School of Medicine in Chicago, said the self-administered option leverages FluMist's unique attributes and provides a convenient new choice. He is also a scientific consultant to AstraZeneca on issues related to FluMist. "Vaccination rates for children and adults under 50 years of age declined in the 2022-2023 flu season, highlighting a need for more accessible solutions," he said. "The ability for individuals and parents to choose where to administer an injection-free flu vaccine could help increase access and, subsequently, vaccination rates, and greatly benefit those most impacted by this serious and contagious respiratory illness."

This article was edited on October 26 to more accurately reflect Dr Jhaveri's professional affiliations.

Today in JAMA Internal Medicine researchers from the National Library of Medicine and the National Institutes of Health describe a small reduction in post-COVID condition (PCC or long COVID) among US adults ages 65 and older who were treated with either the antiviral drug nirmatrelvir (Paxlovid) or molnupiravir (Lagevrio).

The studies were based on Medicare enrollees diagnosed as having COVID-19 from January to September 2022. Prescription of nirmatrelvir or molnupiravir was considered to be indicative of COVID-19 infection, as at-home testing was widely available during the study period.

PCC was defined as any new occurrence (not present prior to COVID-19 diagnosis) of 11 noted symptoms from 4 to 12 weeks after infection, including fatigue, difficulty breathing, heart palpitations, and memory problems.

Antivirals less protective in women

In a cohort of 313,262 participants, 51,658 took nirmatrelvir during acute infection, and 8,089 took molnupiravir. PCC incidence was 11.8% among patients receiving nirmatrelvir, 13.7% for molnupiravir, and 14.5% for neither. The absolute risk reduction was 2.7% for nirmatrelvir and 0.8% for molnupiravir.

The effect was smaller among females, Asian, Black, and Hispanic race, and patients with lower incomes. The hazard ratio for females compared to males was 0.89 compared to 0.84 for nirmatrelvir, and 0.95 compared to 0.88 for molnupiravir.

"The current approved use of the 2 drugs is for the prevention of severe acute COVID-19," the authors wrote. "Our findings suggest that they may also have a role in preventing PCC."

Our findings suggest that they may also have a role in preventing PCC.

Notably, the authors said vaccination status was not included in any final analysis. Though the study showed a smaller benefit to the approved antivirals than previous studies, it is one of the largest studies to look at the effect of the drugs on PCC.