CD8 cells offer clues on how COVID-19 causes persistent lung disease

COVID-19 can cause a sustained alteration of the airway immune landscape in patients with persistent lung disease, “with evidence of cell death and tissue repair linked to the ongoing activation of cytotoxic T cells,” according to research published in the journal Immunity.

The 38-patient study looked at the relationship between the immune system respiratory pathology after COVID-19 infection, by analysing the immune cell and proteomic composition of the airways and peripheral blood in previously hospitalised patients who showed lung abnormalities more than 3 months post discharge.

According to the authors, compared to healthy individuals the post-COVID-19 airways “showed substantial increases in activated CD8+ and CD4+ tissue-resident memory (Trm) cells, and an altered monocyte pool,” while “the airway proteome was also distinct from that observed in healthy individuals, with elevation in proteins associated with ongoing cell death, loss of barrier integrity and immune cell recruitment”.

Also of note, these airway abnormalities did not seem to alter the proteome or immune cells of the matched peripheral blood, and “the scale of these alterations was not linked to the initial severity of disease while in hospital and were heterogenous”.

“Our post-COVID-19 data support the concept that sustained activation of CD8 Trm cells in the airways long after recovery from acute disease contributes to the ongoing damage to the respiratory epithelium, resulting in airway disease,” the authors concluded.

They also suggested that “the involvement of the immune response in different aspects of ongoing respiratory disease post-COVID-19 suggests that … recovery could be accelerated using immunomodulatory treatments”.

How to CREATE a pulmonary fibrosis research network

A unique Australian training scheme for early-career researchers in pulmonary fibrosis, the CREATE Program, has made impressive achievements on a limited budget, a review suggests.

The program set up by the NHMRC’s Centre of Research Excellence in Pulmonary Fibrosis (CRE-PF) has provided funding opportunities, mentoring programs and educational opportunities as well as fostering a connected, supportive research community for respiratory early career researchers, according to a paper published in BMC Medical Education.

The progam has brought together respiratory physicians, physiotherapists, basic scientists and epidemiologist/health economists in CREATE group activities including conference symposia and events, virtual research meetings and a WhatsApp group.

However the program has faced challenges such as limited funding, busy schedules of researchers and the  COVID-19 pandemic, that have made it difficul to build a cohesive group

“In the process of developing this program, there have been many lessons learned which are transferrable to other academic disciplines,” the CRE-PF organisers said.

“In order for this type of program to succeed, we have found that it is critical to leverage and strategically distribute funding, seek and respond to feedback from the participants you are aiming to support, be flexible and nimble in response to changing international circumstances and group needs and to invest resources into building networks to support ECRs into the future.”

Fast track approval plan for biologics

The Therapeutic Goods Administration (TGA) is seeking feedback on a proposed priority pathway for assessment of certain novel and life-saving biologics that could see them approved within six months.

The proposed ‘Priority Review’ pathway will offer a faster formal assessment pathway for new or new use biologicals for people with a life-threatening disease or seriously debilitating condition. Under the proposals released for consultation a biologic would have to fulfil an unmet clinical need or offer a clinically significant improvement over already approved therapeutic goods to be eligible for fast track review.

According to the TGA, the priority pathway will only be open to biologics that have substantial evidence demonstrating that it “provides a major therapeutic advantage in patient outcomes when compared to existing treatments as defined by a magnitude well beyond the minimum threshold of clinical significance.”

This will require endpoints that directly demonstrate clinical benefit such as overall survival and progression-free survival for oncology-based biologicals, the TGA says.

The TGA says the pathway will build on the lessons learned from existing fast track review pathways offered by regulatory bodies such as the European Medicines Agency (150 days) and the FDA (six months).

“This will allow consumers with life-threatening diseases or seriously debilitating conditions to access these treatments in less time if the assessment results in a decision by the TGA to include the biological in the Australian Register of Therapeutic Goods (ARTG),” it says.