2020 will be remembered as the year that the global healthcare system had to deal one of the greatest challenges in living memory. Since the initial outbreak in December 2019 coronavirus disease 2019 (COVID-19) has become the one of the most rapidly spreading infections in terms of a global pandemic. The sudden onset left even the most efficient healthcare services struggling to cope.
Even now the treatment needs of COVID-19 are not fully understood because what was initially thought to be a respiratory disease has expanded to affects a variety of systems. The nervous system and the pain pathways have been influenced as much as any other system and for pain physicians it will pose long term management issues that we must accommodate. Dr. Dominic Hegarty, (Pain Consultant and Clinical Director of Pain Relief Ireland) examines the challenges that lie ahead for pain management in those suffer COVID-19 infection.
Acute challenges with long-term impact
Although the acute challenges of managing COVID-19 have been very evident and highly significant, it may be the long-term effects, including pain, that will have the greatest impact on survivors and society. The treatment needs of COVID-19 survivors are not yet fully appreciated therefore the impact may not have even begun. As we move forward, new challenges resulting from the impact of this must be faced.
COVID impacts on the pain pathway
We are beginning to see that the treatment needs of COVID-19 survivors are more complex than first appreciated. Although initially assumed to be a respiratory disease, multi-organ failure can occur, with reports of cardiac, renal, haematological, and neurological effects in the acute stages. It is likely, therefore, that these survivors will have significant multi-domain impairment requiring ongoing support. There has been a recent ‘call to action’ amongst the rehabilitation community to act quickly to ensure adequate resources provide early phase, multidisciplinary interventions to provide the car that will be needed.
What is the cause of pain in COVID-19?
There appears to be a number of key features in those who report pain following COVID-19 illness. These include:
a) Muscle pain and weakness in COVID-19
Muscle weakness is a well-recognised in high risk of associated ICU-acquired weakness (ICUAW). Although the focus of ICUAW is often the motor component, there is growing evidence for sensory disruption and associated pain. Weakness can lead to rapid deconditioning, joint-related pain, and contractures and, although mechanisms remain unclear, shoulder pain in particular has been highlighted as a significant problem in the population.
b) Neuropathic pain
These neuropathic symptoms including numbness, paraesthesia, and pain are well documented after critical illness; abnormalities in nerve conduction studies can be demonstrated up to 5 years after the initial event. Even in the absence of electrophysiological abnormalities, small nerve fibre impairment associated with neuropathic symptoms can persist for several months. Reports of neurological sequelae of COVID-19 infection are emerging, indicating both central and peripheral nervous system involvement; symptoms such as confusion, headache and dizziness, anosmia and nerve pain are now described in retrospective cohorts and case reports.
They appears to be a role for angiotensin-converting enzyme 2 (ACE2) receptor, the functional receptor for SARS-CoV-2. Both muscle and neural tissue express this receptor which might explain the cross-over of symptoms. This is important because it is related to the SARS-CoV virus and also associated with neural injury, including axonopathic polyneuropathy. It has also been detected in both the CSF and brain tissue. Efforts to determine which human cells are susceptible to SRARS-CoV-2 infection but direct neural invasion has not been demonstrated yet.
Regardless of direct neural entry, SARS-CoV-2 appears to have the capacity to induce painful para-infectious neurological disease as shown by a number of case reports of Guilline-Barre syndrome and polyneuritis.
d) Vascular implications
Thrombotic, hypotensive, and hypoxaemic consequences of infection can also contribute to longstanding, potentially painful neurological sequelae such as stroke. Renal dysfunction is also common and may be associated with a peripheral neuropathy, particularly if renal impairment persists after the acute injury. Dr. Hegarty suggests that “prolonged periods of microvascular insufficiency may result in injury to the small nerves tissue and drive persistent pain such as we see in other neuropathies”.
e) Drug-induce pain
A further aspect to consider is neuropathic pain as a side-effect of putative therapeutic agents currently under investigation for modifying disease severity, such as lopinavir/ ritonavir and hydroxychloroquine. This need to be considered when appropriate.
What is clear is that COVID-19 itself is associated with painful symptoms, including myalgia, arthralgia, abdominal pain, headache, and chest pain, and even those not admitted to critical care environments may have pain requiring opioids for symptoms management.
|Table 1: Pathophysiology of pain in COVID-19|
|a) Muscle pain and weakness in COVID|
|b) Neuropathic pain|
|c) Angiotensin-converting enzyme 2 (ACE2) receptor|
|d) Vascular Implications|
|e) Drug-induce pain|
The psychological impact of COVID-19, with the unique social restrictions likely to create an additional burden. Pain is thought to have a bidirectional relationship with such psychological factors: in the acute phase it may be a risk factor contributing to the development of mental health co-morbidities, with chronic pain being a well recognised co-morbidity.
Even baseline patient characteristics, identified as factors associated with the development of severe COVID-19, overlap with those associated with chronic pain after critical illness, including multi-morbidity and increasing age. It is also likely that those with pre-existing multi-morbidity were at higher risk of chronic pain before infection, which may predispose them to exacerbation of current or development of new pain condition.
Emerging reports from Wuhan, which is now operating several rehabilitation institutions for COVID-19 survivors, and from Italy indicate that COVID-19 survivors report significant issues including anxiety, sleep disorders, fatigue, limited exercise tolerance, and memory and executive function impairment. Dr. Hegarty says “These features are all well recognised in chronic pain patients worldwide so we should not be surprised if the numbers seeking assistance from the pain services increase in the months and years ahead”.
Such symptoms are likely to be exacerbated or even attributed to pain, although this is yet to be explored. What remains unclear is the level of rehabilitation that will be possible for different countries in the early phase of recovery. Early intervention including adequate pain management, combined psychological and physical therapy, has the potential to reduce the risk of long-term COVID-19 pain. Currently resources are focused on frontline services and the risk of resurgence or second wave. This will may leave limited support for such an unprecedented cohort of patients.
Without doubt, we must creatively develop and consider innovative ways to deliver therapy that is accessible to those who need it.
Firstly, the use of telemedicine and the promotion of self-management programmes. Need to be explored for this cohort. This may be part of the ‘new normal’ for delivery of this type of service to this group. Yet for some vulnerable patient groups (e.g. older, cognitively impaired, high deprivation), access may be problematic.
Secondly the traditional way of stratifying patients to high-intensity or speciality-specific rehabilitation through a stepped care model is difficult to envision given the lack of specific COVID-19 research and experience.
Historically, rehabilitation has been disease specific. For example, cardiac patients may get streamed to a cardiac rehabilitation pathway; those with chronic respiratory disease to pulmonary rehabilitation; those with a stroke to post-stroke resources.
However, this model is problematic for two reasons: firstly, these classes and pathways were not designed to address the additional burden of sudden increase in COVID-19 symptoms in addition to the patients with another underlying condition; Secondly, there was a large proportion of patients that did not fall into these categories, and may have ‘slipped through the net’, and will receive sub-optimal care. We will miss many COVID-19 sufferers who were infected but did not require acute admission to the hospital. The impact of the illness on these individuals has yet to appear. The true actual numbers many be much higher than we think.
For now Dr. Hegarty believes that we will need to extrapolate best practice from across healthcare. Pain physicians may be uniquely positioned to assist in this process. Pain services are traditionally multidisciplinary, incorporating physical and psychological expertise with the goal of improving function and quality of life, and could therefore have a great deal to offer overwhelmed critical care services.
By integrating follow-up pathways it would provide us with an opportunity to develop embedded research and registries to learn more about the features, aetiology, risk factors, and therapeutic interventions for chronic pain after critical illness, an as yet neglected area of critical care survivorship.
In the rapidly changing clinical environment, flexibility and changes to health and social care delivery are required.
Whilst the trajectory of this pandemic has not given us the luxury of developing a high-quality evidence base on which to base our management decisions, it is beholden on us to critically assess what we are doing. We need to work collaboratively to assess interventions used in rehabilitation of post-COVID-19 patients. As an academic community and responsible clinicians, understanding post-COVID-19 effects and ensuring a strong evidence base for how to manage these is vital for patients, health and social care systems, and for policy makers to ensure we are “bullet-proof” for the next pandemic when it arrives.
If you suffered from COVID-19 related illness and have any of the signs and symptoms noted in this article please discuss them with your doctor or arrange an appointment with Pain Relief Ireland so that we can assist your recovery as soon as possible.
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