摘要：Three studies suggest that covid-19 can age different parts of the immune system, possibly triggering symptoms of long covid – but the effects may be reversible

PEOPLE who survive severe covid-19 appear to end up with a prematurely-aged immune system and other persistent immunological problems, which may be the underlying cause of long covid.

The immune response to acute covid-19 is now well understood, but the longer-term effects are only just coming to light. The preliminary results from three studies looking into these long-term effects were reported last month at a virtual conference hosted by the UK Coronavirus Immunology Consortium and the British Society for Immunology. Together they suggest that the immune system gets a nasty hangover from the virus, but that it may be reversible.

In one study, Niharika Duggal at the University of Birmingham, UK, and her colleagues studied the immune systems of 46 people who had been hospitalised with severe covid-19. Three months after discharge, a significant number showed signs of premature immunosenescence: an age-related decline in the ability to mount an immune response. “We have seen a number of different features of accelerated immune ageing,” says Duggal.

This included a loss of naive B- and T-cells, which are immature immune cells that have yet to be called into action against a pathogen. Duggal says they also saw another sign of immune ageing: accumulation of memory B- and T-cells, which remain in circulation after an infection, ready to respond to reinfection. Additionally, there was also an excess of senescent T-cells, which can secrete damaging chemicals, driving inflammation that may underlie many age-related diseases.

The subjects were aged between 30 and 68. Their immune systems were compared with a similar group who hadn’t had covid-19. Immunosenescence usually starts around age 60, but the survivors under 60 showed signs of it, says Duggal.

Cause or effect?

This fits with what we already know about premature immune ageing. Earlier studies have shown that traumatic injuries and chronic diseases can age the immune system prematurely. This is the first study to suggest that a viral infection can do so too.

Given the design of the study, however, it isn’t possible to rule out that the survivors became severely ill because they already had prematurely-aged immune systems. Immune age varies widely between individuals; somebody who is 40 years old can have an immune age of anything between 20 and 60.

“Is it cause or effect?” says team leader Janet Lord, also at the University of Birmingham. “Probably a bit of both, as an analysis of people in the UK Biobank who developed covid showed they were biologically 10 to 14 years older.”

In a separate study, Verena Kaestele at the University of Manchester, UK, looked at neutrophils in about 50 people who experienced severe covid-19.

Neutrophils are general-purpose immune cells that patrol the body, destroying invading bacteria. They also promote inflammation, and are activated by viruses, including SARS-CoV-2.

Neutrophils usually constitute up to two-thirds of all white blood cells in the body. During an infection, their numbers increase rapidly and fall back to baseline after the infection has cleared. In some people with acute covid-19 neutrophil levels were elevated to 90 per cent of all white blood cells. “That cannot be healthy,” says Tracy Hussell at the University of Manchester, who oversaw the study.

Demand for neutrophils is so high in these people that the bone marrow can’t keep up and ends up cranking out immature neutrophils, which aren’t fully functional and may contribute to the severity of disease, according to Kaestele.

About half of the people in the study survived. Of these, Kaestele found that around a third had elevated and dysfunctional neutrophils up to 9 months after discharge from hospital. It is possible that this neutrophil imbalance contributes to long covid symptoms, says Kaestele. For example, there is some evidence that neutrophils promote excessive blood clotting, one symptom of long covid.

A third study found persistent changes in gene expression in the immune systems of some people with covid-19. The cause and effect of these changes isn’t yet known, says Aimee Hanson at the University of Cambridge, who presented the research. But they may also be related to long covid.

“We have seen a number of different features of accelerated immune ageing”

All three studies are at an early stage and more data is needed to fully explain long covid. The good news is that interventions, such as exercise and diet, have been shown to reverse immunosenescence, so if severe covid-19 does cause premature ageing, the health consequences aren’t necessarily irreversible.