Pain Management in The Post-COVID Era—An Update: A Narrative Review Part 1

ABSTRACT

An extensive computer search (from January 2020 to January 2023) was conducted including literature from PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. According to preset criteria, a total of 58 articles were included in this review article. Generally, any patient who becomes infected with COVID-19 can develop post-COVID-19 conditions. The course of COVID-19 is divided into three main stages: acute COVID-19 (up to 4 weeks), post-acute COVID-19 (from 4 to 12 weeks), and post-COVID (from 12 weeks to 6 months). If a more protracted course of COVID-19 (over 6 months) is demonstrated, the term "long-COVID" is used. Although the acute stage of COVID-19 infection most commonly manifests with acute respiratory symptoms, one very common symptom of the disease is pain, while the most common symptoms of post-COVID syndrome are shortness of breath, dry cough, fatigue, loss of olfactory and gustatory function, tightness and chest pain, sleep and mood disturbances, body aches, muscle and joint pain, sore throat, fever, and persistent headaches. All observations demonstrated a high incidence of chronic pain syndromes of various localization in the postand long-COVID period. Post-COVID chronic pain might include a newly developed chronic pain as a part of post-viral syndrome; worsening of preexisting chronic pain due to the associated changes in the medical services, or a de novo chronic pain in healthy individuals who are not infected with COVID. Chronic pain during and post-COVID-19 pandemic is an important health issue due to the significant impacts of pain on patients, healthcare systems, and society. Therefore, patients with chronic pain must receive effective treatment according to their specific needs. Accordingly, the main goal of this review article is to provide a broad description of post-COVID pain explore the impact of long-term COVID-19 on chronic pain patients, and also give brief reports about the prevalence, risk factors, possible mechanisms, different presentations, and the management tools through a systematic approach.

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Keywords: COVID-19; Long COVID; PostCOVID pain; Post-COVID pain syndromes; Post-COVID chronic pain; Post-COVID neuropathic pain; Post-COVID musculoskeletal  pain; Post-COVID headache; Telemedicine

Key Summary Points

Why carry out this study?

Post-COVID-19 pain is prevalent and can develop into more challenging and persistent pain. Accordingly, the main  objectives of this review are:

To give a brief report about the challenges facing chronic pain management during post-COVID-19.

To describe the prevalence, risk factors,  and possible mechanisms of chronic pain conditions associated with long COVID- 19.

To focus on the strategies to overcome the limitations in healthcare delivery and provide the appropriate management for chronic pain patients.

To explore the practical tips for the management of post-COVID chronic pain.

What was learned from the study?

The post-COVID era represents a great challenge to healthcare services and has changed our approaches to medicine.

All observations demonstrated a high incidence of chronic pain syndromes of various localization in the post- and long-COVID periods.

COVID-19 is having a profound effect on patients with pain. Delaying, or stopping, treatment will have negative consequences on chronic pain patients.

Evidence is promising that new tools such as telemedicine and mobile opioid treatment programs can help to provide ongoing services to chronic pain patients.

INTRODUCTION

Healthcare systems worldwide have been facing extraordinary challenges since the COVID-19  pandemic. Globally, with the end of 2022 and the beginning of a new year, the COVID-19 epidemiological update showed that there have been 657,977,736 confirmed cases of COVID-19, including 6,681,433 deaths globally. This number should be taken with caution, as many countries have changed the practice of routine COVID-19 testing, resulting in underestimations of the actual numbers [1].

The COVID-19 pandemic has changed our approaches to medicine and created a whole new generation of people who have chronic pain. Many pending answers on COVID-19 and its sequelae remain unclear and will remain a challenge for the foreseeable future [2, 3]. The COVID-19 pandemic has drawn attention to the weaknesses of health systems around the world [4].

A significant proportion of patients with COVID-19 experienced long-term and persistent symptoms. Published reports indicate that approximately 10–20% of COVID-19 patients experience persistent long COVID symptoms from a few weeks to a few months following acute infection [5]. This syndrome is characterized by a wide range of health problems including "brain fog" with cognitive disturbances, fatigue, dyspnea, myalgia and muscle weakness, depression, and persistent headaches [6]. Furthermore, a recent comprehensive systematic review and meta-analysis estimated the prevalence of long-term COVID-19 and showed that 45% of COVID-19 survivors were experiencing a wide range of unresolved symptoms for at least 4 months after a confirmed COVID-19 infection [7].

Chronic pain is an important health issue and is the most common reason to seek medical care. It ranks among the ten most prevalent diseases worldwide and years lost to disability. For this reason, chronic pain should be properly managed to avoid further complications [8]. COVID-19 is having a profound effect on patients with chronic pain. Delaying or stopping treatment for chronic pain patients will have negative consequences, including increases in pain, disability, and depression. The management of chronic pain during the COVID-19 pandemic is a challenging process,  especially with growing evidence that COVID-19 infection is associated with persistent myalgias, referred pain, and widespread hyperalgesia [9].

METHODS

An extensive computer search was conducted including literature from PubMed, Scopus, MEDLINE, Web of Science, and EMBASE databases. Manual screening of references was also conducted, and additional references were added from sites for pain organizations, e.g., the International Association for the Study of Pain (IASP) and the World Health Organization (WHO). Relevant guidelines from the American Society of Anesthesiologists (ASA), American Society of Regional Anesthesia (ASRA), American Society of Interventional Pain Physicians, and American Academy of Physical Medicine and Rehabilitation, European Pain Federations, and The WHO database on COVID-19 were screened for relevant publications. The search strategy was restricted to articles that were published between January 2020 and January 2023. The following related keywords were used for the search ("COVID-19", "coronavirus and SARS-CoV-2", "post-COVID pain", "post-COVID pain syndromes", "post-COVID headache", "post-COVID chronic pain" "post-COVID neuropathic pain" and "post-COVID musculoskeletal pain"). Articles that met the inclusion criteria, such as articles relevant to the condition and presented information on post-COVID pain conditions, and articles published in the English language and involving adult humans were included. The search included observational study, cross-sectional study, cohort study, case–control study, longitudinal study,  systematic reviews, and meta-analysis. The exclusion criteria included non-English-language articles, failure to get the full articles, post-COVID pain in children, case reports, editorials, or expert opinions. The selected articles for inclusion were screened by two independent reviewers using the same method of evaluation. The final reviewing strategy of the literature search results in a total of 58 articles in this review (Fig. 1) [10]. This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

DEFINITIONS

Various definitions have been developed to define different stages of COVID-19 based on the durations and clinical presentations. Standardized definitions are important for the proper diagnosis and management of those patients. The following definitions can be used to differentiate different stages of both ongoing or post-COVID-19 signs and symptoms [1, 11, 12].

– Acute COVID-19 infection: Signs and symptoms of COVID-19 for up to 4 weeks [1]. 

– Ongoing symptomatic COVID-19: Signs and symptoms of COVID-19 from 4 weeks up to 12 weeks [1]. 

– Post-COVID-19 syndrome: Signs and symptoms that develop during or after an infection consistent with COVID-19, continue for more than 12 weeks to 6 months, and are not explained by an alternative diagnosis. It usually presents with clusters of symptoms, often overlapping, which can fluctuate and change over time and can affect any system in the body. Post-COVID-19 syndrome may be considered before 12 weeks while the possibility of an alternative underlying disease is also being assessed [1, 11]. 

– Long COVID: there are different definitions with more or less similar meanings.

o According to the National Institute for Health and Care Excellence (NICE)  guidelines, long COVID is commonly used to describe signs and symptoms that continue or develop after acute infection consistent with COVID-19 and persist longer than 4 weeks. It includes both ongoing symptomatic COVID-19 (from 4 to 12 weeks) and post-COVID-19 syndrome (12 weeks or more). If a more protracted course of COVID-19 (over 6 months) is discussed, the term "long COVID" is used [11, 12]. 

o Centers for Disease Control and Prevention (CDC, 2021): "Wide range of new,  returning, or ongoing health problems people can experience 4 or more weeks after first being infected with the virus that causes COVID-19" [13]. 

o World Health Organization (WHO, 2021): "Illness that occurs in people who have a history of probable or confirmed SARS-CoV-2 infection, usually within 3 months from the onset of COVID-19, with symptoms and effect that last for at least 2 months, that cannot be explained by an alternative diagnosis" [1]. 

o National Health Service (NHS, 2021): "Symptoms lasting weeks or months after the infection has gone [11, 14].

– Post-COVID-19 condition is defined as the illness that occurs in individuals with a history of probable or confirmed SARS CoV- 2 infections, usually 3 months from the onset of COVID-19 with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include fatigue, shortness of breath, cognitive dysfunction, but also others, and generally have an impact on everyday functioning. Symptoms may be new-onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms may also fluctuate or relapse over time [13].

– Post-COVID headache: The International Classification of Headache Disorders uses a headache duration of more than 3 months after the acute infection for the diagnosis of "Chronic headache attributed to systemic viral infection" [15].

– Chronic pain: chronic pain is defined by the International Association for the Study of Pain (IASP) as persistent or recurrent pain lasting more than 3 months or beyond normal tissue healing [16].

– Nociplastic pain: the IASP defines neoplastic pain that 'arises from altered nociception despite no clear evidence of actual or threatened tissue damage causing the activation of peripheral nociceptors or evidence for disease or lesion of the somatosensory system causing the pain' [17]. 

– Musculoskeletal pain: The Pain Task Force (IASP), defines Chronic Primary Musculoskeletal Pain (CPMP) as "chronic pain in the muscles, bones, joints, or tendons that are characterized by significant emotional distress (i.e., anxiety, anger, frustration, and depressed mood) or functional disability" [9, 18].

Challenges Facing Post-COVID-19 Chronic Pain Management

Chronic pain patients may experience an additional potential risk of functional and emotional deterioration during a pandemic, which can increase the long-term health burden [19, 20].

The ongoing and long COVID-19 pandemic is associated with new problems affecting chronic pain management. Difficult access to healthcare facilities, a lack of resources, burdened healthcare services, mental health problems, and a patient's associated comorbidities may add more burden to chronic pain patients [9, 21]. All of these factors contribute to making the delivery of effective pain management more challenging.

– Problems related to the pandemic: [19, 20, 22].

o Lockdown, travel restrictions, social and physical distances, and isolation. 

o Fear of infection or the health care facilities get infected.

o Decrease the risk of exposure of the health care workers to severe infection overtly burdened health care system. 

o All elective consultations and interventions are canceled or postponed. 

o Interrupted care due to isolations and closing of many services such as physiotherapy & supportive services.

- Problems related to the overstretched health care systems: [9, 23]

o Increased demand on the health care systems, health care workers, and facilities. 

o The overuse of imaging as a result of the pandemic and its sequel. Around 69% of general practitioners would refer patients for radiography at first presentation, despite routine use being discouraged due to a poor relationship between imaging findings with symptoms. 

o The rate of some surgical procedures, e.g., orthopedic and spine surgeries, has increased markedly in recent years.

– Problems related to the rehabilitation programs: [9, 20].

o Lack of physical activities, impacting patients who relied on physical therapy or exercise programs as part of their pain management regimen. 

o Closure or overloaded rehabilitation services due to the pandemic.

– Patient-related factors: [18, 24, 25]

o Failure to provide education or advice. 

o Limited access to the health care facilities. 

o Difficulty in getting a refill of pain medications, especially for controlled medications and opioids. 

A significant number of patients are elderly with many comorbidities and multiple medications. 

o They are more susceptible to morbidity and mortality from COVID-19. 

o Possible immune suppression, fatigue,  weakness, and associated comorbidities.

– Mental health problems: [24, 25].

o Onset of new or exacerbation of mental health concerns, including anxiety, stress, depression, and post-traumatic stress disorder, have become significant concerns. 

o Less access to treatment facilities due to isolation, social distancing, and fear of infection, lifting opioid-tolerant patients struggling with addiction. 

o This interruption has had serious consequences, as it has led to an increase in chronic pain, psychological worsening,  and a decrease in the quality of life.

– Interaction between treatment of chronic  pain and COVID-19 pandemic: [16, 26]

o Painkillers such as NSAIDs and paracetamol may mask the symptoms of COVID-19 infection, e.g., fever and myalgias. 

o Pain medications may interact with the immune system or mask the signs or symptoms of COVID-19 infection. 

o Chronic opioid therapy with high doses may induce immunosuppression. 

o Oral or injectable steroids (e.g., used for interventional pain procedures) are immunosuppressive. 

o Steroid injections for pain management may affect the efficacy of COVID-19 vaccines.

PREVALENCE OF POST-COVID-19 PAIN

Approximately 10–20% of acute infection with COVID-19 patients go on to develop prolonged symptoms that may be post-COVID-19 conditions [1]. In the United States, there are more than 80 million patients and survivors of COVID-19, which is the highest number in the world [27]. A recent comprehensive systematic review and meta-analysis estimated the prevalence of long-term COVID-19, regardless of hospitalization status. A total of 194 studies including 735,006 participants worldwide were included in the analysis. Results showed that 45% of COVID-19 survivors experienced a wide range of unresolved symptoms for at least 4 months after COVID-19 infection [7].

Pain can be an early symptom of acute COVID-19 infection, including sore throat, myalgias, back pain, and headache [28]. It seems that no relationship exists between the initial severity of COVID-19 infection and the likelihood of developing post-COVID-19 conditions(5). Chronic pain might affect up to 50% of the general population, while the prevalence of post-COVID-19 chronic pain was estimated to be 63.3% [29].

Patients with chronic pain infected with COVID-19 are at higher risk for exacerbation of their symptoms, and this is attributed to many factors including social threats, discontinuation of therapy, reduced access to treatments, or associated mental health problems and concerns about health outcomes [25, 30, 31]. COVID-19 may exacerbate preexisting pain or be associated with the appearance of new pain. Another study compared two groups of patients, one group was admitted to the hospital due to COVID-19 infection, and the other group was admitted due to other causes. Results showed that COVID-19 infection was associated with a significantly higher prevalence of de novo chronic pain, chronic daily headache, and new-onset pain in general, which was associated with persistent anosmia [32].

Chronic pain has a positive relationship to viral infection, psychological stress, and the consequences of admission to the hospital or intensive care unit (ICU). Post-COVID-19 chronic pain may include either regional or widespread pain [33, 34]. It often causes peripheral or central neurological complications, either through direct invasion of the nervous system or through immune reactions (35, 36).

– Prevalence of chronic pain according to the demographics: A cross-sectional study showed that more than three out of five COVID-19 survivors experience chronic pain. Increasing age and female sex correlated with the presence of chronic pain in this population [37].

– Prevalence of chronic pain according to the site of pain: COVID-19 pain was more frequently located in the head/neck and lower limbs (p\0.05), followed by joint pain. New-onset fatigue was more common in COVID-19 survivors necessitating inpatient hospital care. The presence of insomnia in COVID-19 patients correlates with the presence of more new-onset pain (83.3%) compared to those who did not (48.0%, p = 0.024) [32, 38].

Prevalence of chronic pain according to the pathophysiological type of pain: Post-COVID chronic pain exhibits both musculoskeletal and neuropathic pain features. The discrimination between nociceptive, neuropathic, and neoplastic pain represents a current challenge for clinicians [9]. The prevalence of neuropathic pain was estimated to be 24.4% [29]. Preliminary evidence suggests the presence of neuropathic pain in individuals exhibiting post-COVID pain. The neuropathic pain symptoms were positively associated with the duration of post-COVID pain, anxiety levels, and kinesiophobia levels. It was found that almost 25% of previously hospitalized COVID-19  survivors with "de novo" post-COVID pain reported a neuropathic pain component [30, 31]. 

– Prevalence in non-hospitalized patients: Few reports that included long-term follow-up in non-admitted patients suggest that (31–53%) still have one or several persistent painful symptoms 1 year after COVID-19 infection, which would translate to a significant number of people worldwide [21, 39, 40]. A recent meta-analysis has revealed that more than 60% of patients exhibited at least one post-COVID-19 symptom. The most prevalent post-COVID-19 symptoms experienced by both hospitalized and non-hospitalized patients were fatigue and dyspnea. The other symptoms including headache, anosmia, chest pain, or joint pain are lower and more variable [41]. In non-hospitalized patients, the most frequent symptoms were fatigue (34.8), breathlessness (20.4%), muscle pain/myalgia (17.0%), impaired sleep (15.3%), and loss of sense of smell (12.7%) [7]. 

– Prevalence in hospitalized patients: The reported prevalence of musculoskeletal pain post-COVID-19 in previously hospitalized patients ranged from (11–45%) at 6 months or more after discharge [42]. Patients with post-COVID musculoskeletal pain showed a greater number of COVID-19 symptoms at hospital admission, with a greater prevalence of myalgia and headache, longer stay of hospitalization, and higher incidence of ICU admission than those not reporting long-term musculoskeletal post-COVID pain [43]. In hospitalized patients, the five most prevalent symptoms reported were fatigue (28.4%), pain/discomfort (27.9%), impaired sleep (23.5%), breathlessness (22.6%), and impaired usual activity (22.3%) [7].

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