Sustainable immune dysregulation because of COVID-19 in non-hospitalized patients

Overview

• Post By :


• Source: University of Alabama at Birmingham


• Date: 31 Dec,2020

COVID-19, which has killed 1.7 million people globally, doesn’t follow a uniform path.

Others, especially those with comorbidities, can create severe clinical disease with atypical pneumonia and multiple system organ failure.

Since the first cases were reported in December 2019, the SARS-CoV-2 virus that causes COVID-19 has surged into a pandemic, with cases and deaths still mounting. Ongoing observational clinical studies have become a priority to better understand how this previously unknown virus behaves, and findings from this study can better inform treatment and vaccine design.

University of Alabama at Birmingham researchers, led by first-author Jacob”Jake” Files and co-senior authors Nathan Erdmann, M.D., Ph.D., and Paul Goepfert, M.D., have reported their observational study,”Sustained cellular immune dysregulation in individuals recovering from SARS-CoV-2 infection,” published in the Journal of Clinical Investigation.

In a comment about the UAB study, published in the same issue, Phillip Mudd, M.D., Ph.D., and Kenneth Remy, M.D., both of Washington University, wrote,”The value of these studies to offer context to the interpretation of immune responses generated by participants at COVID-19 vaccine trials, including how those reactions change over time, cannot be over-emphasized. This information will be key in potential modifications to existing COVID-19 vaccines and treatments.”

The UAB researchers obtained blood samples and clinical data in 46 hospitalized COVID-19 patients and 39 non-hospitalized people who had recovered from supported COVID-19 disease. Both groups were compared to healthy, COVID-19-negative controls. Significantly, most people in the hospitalized group had active SAR-CoV-2 viruses in their blood and were at the hospital at the time of sample collection.

From the blood samples, researchers were able to separate specific immune cell subsets and examine cell surface markers. From this complex information, immunologists can analyze how each individual’s immune system is reacting during illness and during convalescence. Some of the results can show whether immune cells have been activated and exhausted by the disease.

Additionally, the researchers could test changes over time, in two ways. The first was observing changes in surface markers over time, defined as days since the onset of symptoms for non-hospitalized samples. The second was directly comparing the frequencies of these markers between the first and second clinic visits for non-hospitalized patients who had blood samples collected at two successive timepoints.

The most surprising finding involved non-hospitalized patients. While the UAB researchers saw upregulated activation markers in hospitalized patients, they also found several activation and fatigue markers were expressed at higher frequencies in non-hospitalized convalescent samples.

Looking at these markers over time, it was apparent that immune dysregulation in the non-hospitalized people did not quickly resolve. Furthermore, the dysregulation of T cell activation and exhaustion markers in the non-hospitalized cohort was more pronounced in the elderly. “To our knowledge,” the researchers reported,”this is the first description of sustained immune dysregulation due to COVID-19 in a big group of non-hospitalized convalescent patients.”

For details of the comprehensive look at immune cells subsets during and after COVID-19 disease in hospitalized and non-hospitalized people, see the analysis, which contains an in-depth characterization of the activation and fatigue phenotype of CD4+ T cells, CD8+ T cells and B cells.

The T and B cells from the patient cohorts had phenotypes consistent with activation and cellular exhaustion throughout the first two weeks of disease. And at the non-hospitalized people, the activation markers and cellular fatigue increased over time.

These findings illustrate the persistent nature of the adaptive immune system changes that have been noted in COVID-19 and suggest longer-term effects that may shape the maintenance of immunity to SARS-CoV-2.”

Phillip Mudd, M.D., Ph.D., and Kenneth Remy, M.D., Washington University

A question now being researched, the UAB researchers say, is whether these observed immunologic changes are associated with symptoms experienced well beyond the acute infection, often described as”Long COVID.”