For more than a year now, daily life has felt like Russian roulette for people living with severely compromised immune systems.

The gradual end of Covid testing, mask mandates, social distancing, and self-isolation requirements between March and May last year marked a watershed moment in the pandemic when most of us were able to resume normal life.

But for the 500,000 in the UK living with diseases or relying on drugs that impair their immune response, it has been a frightening time.

Some have continued shielding voluntarily as Covid rates climbed to record highs driven by the combination of the highly-transmissible Omicron strain and the removal of restrictions which had previously helped to curtail it.

They had good reason to be nervous.

READ MORE: 'Reassuring' study finds that 90 per cent of Covid cases in immunocompromised were mild or asymptomatic

Early data from the Glasgow-led Octave trial back in 2021 suggested that half of immunocompromised patients generated little or no antibodies even after two Covid vaccine doses.

This left important questions unanswered, however.

The Herald: Evidence of T cell response after two vaccine doses (HC = healthy control; OCTAVE = trial participant average; HD = haemodialysis)Evidence of T cell response after two vaccine doses (HC = healthy control; OCTAVE = trial participant average; HD = haemodialysis) (Image: Nature Medicine)

It was possible that they still had protection from T cells, which are more important in defending against severe disease.

It was also unclear which patient groups were at highest risk of severe infections and death.

The updated findings - based on a larger sample size - finally shed some light on this.

While 39% of participants had little or no antibody response, the majority (88%) did produce T cells.

READ MORE: Charity 'seriously concerned' over lack of protections for severely immunocompromised 

This dovetails with data showing that 90% of known Covid cases in immuno-compromised patients were mild or asymptomatic.

The results were particularly reassuring for patients with ulcerative colitis or Crohn's disease - autoimmune conditions which cause inflammation in the bowel and digestive tract.

Of the 104 patients in the study who had either condition, were double-vaccinated, and tested positive for Covid, only one - a Crohn's patient, who survived - required hospital treatment.

The Herald: Some people have continued to live in self-imposed lockdown due to health conditions following the rapid increase in Covid rates from 2022 onwards, as restrictions endedSome people have continued to live in self-imposed lockdown due to health conditions following the rapid increase in Covid rates from 2022 onwards, as restrictions ended (Image: PA)

For others, infection rates were low (possibly due to shielding) but much more likely to be severe or fatal.

This was the case particularly for patients with kidney failure, ANCA-associated vasculitis (AAV) who use the drug rituximab, and patients who had undergone stem cell transplants or CAR-T therapy for cancer.

For example, all three known Covid infections in double-vaccinated CAR-T patients resulted in severe disease.

READ MORE: How well do Covid infections protect against future illness? 

There was also evidence of changing trends over time: of the 107 cases identified among study participants during the Delta wave, there were eight deaths and 23 severe infections, whereas Omicron resulted in 327 cases but only 17 were severe and two fatal.

However, the researchers note that it is "not possible to disentangle" how much of this is down to Omicron itself being less pathogenic and how much is due to the fact that the Omicron era coincided with the rollout of vaccine boosters and Covid antivirals. 

Covid is no longer the threat it once was - even for the immunocompromised. 

But a minority remain at much higher risk than the rest of the population.

The goal of the Octave study was to identify them; the job of policymakers is to ensure they are not left behind in our 'new normal'.