Issue #107: Pre-Omicron and longest history of Long COVID

Written by Nobel Laureate Professor Peter Doherty

A recently published study reaches back to the very beginnings of the COVID-19 clinical story and tells us something of what happened to 2,469 patients from Wuhan, China, who were hospitalised between January 27 and May 29, 2020, then examined up to two years later. The median age at discharge in 2020 was 57 years and 46% were women. Described as ‘survivors’, they were presumably - given the pressure that the Wuhan clinical community was under at that time - very ill at time of hospital admission. And this was, of course, way before there were vaccines or effective antiviral drug treatments.

Thinking about where we were in our understanding of COVID-19 during the first quarter of 2020, the disease seemed primarily to be a severe form of viral pneumonia. It wasn’t influenza - the imaging specialists were seeing what they described as atypical ‘ground glass opacities’ in the lung - but it was clearly a respiratory problem. Somewhat later, virologists found that COVID-19 (unlike influenza) is often, if not always, a systemic infection, with the virus being distributed around the body in the blood.

Then it was realised that COVID-19 can also be a thrombo-embolic, or blood clotting disease. At least some of that respiratory distress can, it seems, reflect the presence of micro-clots in the tiny capillaries of the lung alveolar circulation. Right at the beginning, though,clinicians did not know that cheap, readily available therapeutics like the anticoagulant heparin and the anti-inflammatory dexamethasone could help to save lives and potentially minimise any permanent damage to body organs. This early series may thus represent a worst-case scenario, at least for disease caused by the original Wuhan strain of SARS-CoV-2.

Following the discharge of these early patients from hospital, some of the continuing problems (shortness of breath, muscle weakness, depression and a spectrum of other problems) that doctors saw were already well known under the PICS rubric, the Post Intensive Care Syndrome. In some cases, there was an obvious reason, like evidence of lung fibrosis, that explained continuing clinical compromise. Otherwise, though, there could be a lack of correlation between the severity of the symptoms that patients had experienced in hospital and the extent of chronic debility. Similar observations have also been made in other early COVID-19 clinical series.

The term 'Long COVID' was yet to be coined in the first half of 2020; and it was, in fact, people suffering from this condition who first brought it to the fore. Then the medical ‘heavy brigade’ became involved, with the US NIH (National Institute of Health) changing the name to 'PASC' (Post-Acute Sequelae of SARS-CoV-2 infection) in January 2021 while, in October 2021, the WHO officially recognised Long COVID but called it 'Post Covid'. The patient groups would have none of it, and it remains Long COVID. And that’s the term used by the authors of the Wuhan study, who point to their series as the longest running Long COVID study. What did they report?

The situation two years later was that most (89%) had been able to return to their original work, though 55% of them were still reporting at least one ‘sequelae symptom”, with the most common being fatigue and muscle weakness. That’s only a 13% fall-off from the figure of 68% reported at six months, so could this be a measure of permanent damage that is unlikely to resolve? Indeed, there was physiological evidence of continuing lung function impairment for many of those who had required respiratory support while hospitalised. The other prominent feature was increased anxiety and depression.

But as we know, this ‘post hospitalization syndrome’, – we can’t invent a PHS acronym as that’s already taken across the word for ‘Public Health Service’ – is only one form of Long COVID. Though not invariably, it’s generally older people who are very sick during the initial phase of COVID-19 and, even if they don’t quite go back to their earlier health status, they will obviously be grateful to just be out of hospital. But what is more difficult, especially for a young, fit person to deal with, is to have a mild or even inapparent initial infection, perhaps feel better, then suddenly start to decline with brain fog, muscle weakness, pain, depression, even paranoia, and a spectrum of other possible symptoms that just won’t go away.

This spectrum of clinical presentation, along with the fact that most of the data presented in various studies is self-reported, may be one of the reasons that it can be hard to come to any solid conclusion about the protective effect of vaccination beyond stopping the infection in the first place. And that, of course, varies with how well the sequentially emerging variants are matched to the Wuhan ‘spike’ protein that is the ‘target’ of the vaccines available to date. The most divergent are, of course, the various Omicron sub-strains.

However, one point that does come through clearly is that having been vaccinated before an initial SARS-CoV-2 infection does not increase the likelihood of developing Long COVID. In fact, most of the published evidence suggests that there is some protective effect. We’ll try to unpick that next week.