Case of the Month #24: Long Covid by Dr Angeline Lee

What is long Covid?
‘Post-Covid-19 syndrome’, or ‘long Covid’ as it is colloquially known, is defined by the
National Institute of Health and Care Excellence (NICE) as a group of signs and symptoms
that develop during or after an infection consistent with Covid-19, continue for more than
12 weeks and are not explained by an alternative diagnosis. [1] In December 2020, the United Kingdom Office of National Statistics (ONS) estimated that prevalence of long Covid was 10%. [2] Since the advent of vaccination, an updated May 2022 ONS estimate is that 4-5% of triple vaccinated adults report long Covid symptoms 12 to 16 weeks after Covid-19 infection. [3] 

What are the long Covid pathways to care?
The National Institute for Health Research has highlighted the diversity of patient
experience of Covid-19 and called for urgent prioritisation on establishing new care models
for long Covid [3], and rapid guidelines have been published in December 2020 by the
National Institute of Health and Care Excellence on supporting, diagnosing, and setting up
services to treat long Covid based primarily on expert panel advice. [1] Since then, outside of self-management, systematic review evidence has recommended that most long Covid-related healthcare should be in primary care, with referral pathways to specialised long Covid outpatient assessment clinics for patients with complex symptoms. Patients with one dominant symptom should be directed to the respective specialist for a second assessment. [1,4] It is likely that pain clinicians will meet patients from this latter group. 

What are the symptoms of long Covid?
Systematic review evidence from 27 articles describes a constellation of long Covid symptoms affecting all body systems. [5] The ten most prevalent reported symptoms (percentage prevalence and 95% confidence intervals (CI)) were:[5] 

1)    Fatigue 47% (95% CI 31–63)
2)    Dyspnoea (shortness of breath) 32% (95% CI 18–47)
3)    Myalgia (muscle pain) 25% (95% CI 13–37)
4)    Joint pain 20% (95% CI 13–27)
5)    Headache 18% (95% CI 9–27)
6)    Cough 18% (95% CI 12–25)
7)    Chest pain 15% (95% CI 9–20)
8)    Altered smell 14% (95% CI 11–18)
9)    Altered taste 7% (95% CI 4–10)
10)    Diarrhoea 6% (95% CI 4–9)

Four out of ten of these symptoms are pain related and other symptoms such as fatigue and dyspnoea may impact on pain experience and influence patients’ ability to engage with therapies and management. Evidence suggests that people with long Covid experience significant reductions in quality of life. [6]

Why is this happening?
The molecular mechanisms involved in the pathogenesis of long Covid are complex and not fully understood. A systematic review of the pathophysiology of long Covid suggests that Covid-19 infection leads to systematic and local inflammation in the muscle/joints with increased production of muscle-derived cytokines and therefore increased downstream production of IL-6 and other pro-inflammatory factors. Muscle biopsy analyses have noted generalised atrophy of muscle fibres with sporadic necrosis and focal infiltrations of immune cells into muscle fibres; derangement of the arrangement of myofibrils and disc Z flows and neuronal demyelination.[7] 

It is thought that SARS-CoV-2 virus itself can directly invade neurones and survive in neural tissue.[7] Human ACE-2 receptors (hACE-R), widely thought to be the receptor that binds to the spike protein of the virus and providing a route of entry of the virus into the body, is abundant in the central and peripheral nervous system.[7] Preclinical studies in rats have demonstrated the viral-hACE-R complex in cerebrospinal fluid and crossing the blood brain barrier to infect many different regions of the brain.[7]

Pain from long Covid could therefore arise from a proinflammatory state in muscles and peripheral nerves, or a nociplastic mechanism from viral infiltration into the central nervous system. 

Long Covid and people with existing chronic pain

Long Covid appeared to affect people with existing chronic pain in several ways: [8]
1)    Increased physical and mental health burden, particularly in some subsets
2)    Increased pain due to a combination of factors such as social isolation, lack of psychological support and disabled employment status
3)    Telemedicine in most developed countries has supported delivery of chronic pain care but has delayed access to many types of interventional treatments in other settings. [9]
4)    Steroid exposure may reduce the efficacy of Covid-19 vaccines (data is insufficient to make a definitive conclusion). It is best to consider avoiding steroid injections 2 weeks prior to and 1 week following the vaccine.
5)    Steroid exposure does not seem to affect the Covid-19 infection rate.
6)    Exposure to chronic opioids might be a risk factor for increased Covid-19 infection severity.

Investigations for long Covid
There is no objective test to confirm a diagnosis of long Covid, although investigations such as magnetic resonance imaging of the brain, heart and lungs; and biochemical investigations have demonstrated objective, quantifiable changes in the physiology of patients with long Covid. [5] 

NICE recommend tailoring investigations to individual patients’ signs and symptoms to rule out acute or life-threatening complications and find out if symptoms are most likely to be caused by long Covid or ongoing symptomatic Covid-19 or a new unrelated diagnosis. [1]