Pain Management Recommendations During the Progression of SARS-CoV-2 Infection

Abstract

COVID-19, an infection caused by SARS-CoV-2, had a devastating impact on people’s lives. The pandemic placed a heavy burden on healthcare systems and impacted the care of patients, including those with pain. This narrative review aims to highlight the challenges in managing pain and fever resulting from COVID-19 and pre-existing conditions, and to discuss the role of over the counter analgesics as a key part of the COVID-19 treatment regimen. As most patients with COVID-19 are being managed in the outpatient setting, lifestyle interventions and over the counter analgesics are readily available options to effectively treat pain and fever, which can help to decrease the burden on the healthcare system during the COVID-19 pandemic.

Plain language summary

COVID-19 is an infection caused by SARS-CoV-2. The COVID-19 pandemic not only affects patient lives, but also heavily impacts healthcare systems. This review aims to discuss the available literature on how to manage pain from COVID-19 and encourage a consensus meeting for recommendations. As most patients with COVID-19 are being managed in the outpatient setting, lifestyle interventions and over the counter analgesics are readily available options to effectively treat pain and fever, which can help to decrease the demand on the healthcare system during the COVID-19 pandemic.

Keywords::

• analgesics
• COVID-19
• fever
• OTC
• pain
• pain management
• SARS-CoV-2

Practice points

• Due to the risk of COVID-19 exposure, healthcare practices should be able to provide convenient and accessible telehealth options for patients.

• Healthcare practitioners should provide patients with treatment options that are readily accessible such as over-the-counter analgesics to manage acute and chronic pain related to COVID-19.

• Educational tools and resources regarding over-the-counter analgesics should be increased as more patients seek self-care options for pain management.

• Perception of pain is subjective and dependent on factors beyond the physical state, and includes physiological and emotional states.

• Lifestyle modifications should always be emphasized for patients general well-being such as daily exercise, balanced meals and improved sleep hygiene.

Over the past 2 years, more than 570 million confirmed cases of COVID-19 have been reported globally [1]. COVID-19 is caused by the SARS-CoV-2 and is associated with a wide array of symptoms and adverse outcomes [2]. Although the underlying mechanism is complex, imbalances in angiotensin-converting enzyme-2 and induction of an inflammatory immune response lead to conditions such as interstitial fibrosis, myocardial hypertrophy, endothelial fibrosis and increased inflammation in patients with COVID-19 [2]. Furthermore, SARS-CoV-2 stimulates multiple inflammatory pathways, producing high levels of proinflammatory cytokines, resulting in a cytokine storm. Cytokine storm correlates with COVID-19 severity and is life-threatening [3]. A common mechanism that may be responsible for inducing pain from an infectious stimulus is the arachidonic pathway. Prostaglandins such as PGE2 and PGD2 are derived from this pathway and are known to mediate inflammatory pain in patients; increased levels of these prostaglandins have been found in patients with COVID-19 [4].

The COVID-19 global pandemic had a devastating impact on people’s lives, and it consumed significant time and resources of healthcare authorities and regulatory bodies worldwide. Consequently, the care of patients with non-COVID-19 pre-existing conditions (including pain flares) has been substantially impacted from a clinical and organizational perspective, as well as the management of pain and other symptoms resulting from COVID-19 [5].

The complex and dynamic pathophysiology of pain mandates a multimodal approach involving a combination of nonpharmacologic and pharmacologic treatments for effective management [6]. However, despite a substantial impact on physical, psychological and social components, a cross-sectional international survey conducted prior to the outbreak of COVID-19 revealed that 65% of respondents delayed treatment and 14% entirely avoided pain management [7]. Furthermore, treatment of pain has been severely affected by the ongoing COVID-19 pandemic owing to cancellation, postponement or reductions in elective surgical procedures, outpatient procedures and patient visits. The goal has been to limit contact between patients and healthcare workers, so clinicians can focus their attention on patients who require urgent interventions, particularly those with suspected COVID-19 [8]. As healthcare systems worldwide have struggled to control coronavirus infection, most pain treatment services have been deemed non urgent [9], leading to further delay or even discontinuation of treatment of patients suffering with pain [10]. Shutdown of pain services and government mandated home lockdowns are associated with severe negative consequences for patients, including increases in pain, disability and depression, which in turn can lead to worsening mental health, addiction disorders and financial burden [9–11]. This review aims to highlight the challenges faced by patients in managing pain and fever resulting from the COVID-19 pandemic, as well as managing pain flares in patients with existing chronic conditions that have been exacerbated by the pandemic.

Pain associated with COVID-19

Symptoms of acute SARS-CoV-2 infection

Although patients with COVID-19 exhibit a broad range of symptoms, respiratory symptoms remain a consistent presentation. SARS-CoV-2 infection is responsible for SARS, which involves pulmonary manifestations of dyspnea with or without chronic oxygen dependence, difficult ventilator weaning and fibrotic lung damage [12]. A large cohort of patients (n = 1487) with confirmed SARS-CoV-2 infection, per the WHO definition, who were managed in outpatient settings reported their symptoms. The most frequently reported symptoms included fever and cough (n = 1351; 91%), body aches/myalgia (n = 845; 57%), headache (n = 824; 55%), asthenia (n = 886; 60%); ear–nose–throat symptoms such as anosmia (n = 415; 28%), ageusia (n = 422; 28%), ageusia + anosmia (n = 335; 23%), shortness of breath (n = 479; 32%), chest pain (n = 320; 22%) and hemoptysis (n = 41; 3%) [13]. Furthermore, increasing evidence suggests that subacute (symptoms present from 4–12 weeks beyond acute COVID-19) and long COVID-19 (symptoms present >12 weeks from the onset of acute COVID-19 and not attributable to alternative diagnoses) can affect multiple organ systems, including cardiac, pulmonary and neurologic (Figure 1) [12–14].

Figure 1. Timeline of post acute COVID-19.

Acute COVID-19 generally lasts 4 weeks from the onset of symptoms, after which the virus can no longer be detected via PCR. Subacute and chronic COVID-19 is characterized by persistent symptoms occurring later than 5–12 weeks after onset and/or delayed or long-term complications occurring more than 12 weeks after onset. Common acute, subacute and chronic COVID-19 symptoms are summarized.

Pain as a symptom of acute SARS-CoV-2 infection

As with most viral infections, pain is a common symptom in patients with COVID-19 [15]. In a multicenter prospective study, 73/169 (43.2%) patients with severe active COVID-19 also reported varying pain symptoms, the most common types being headache (n = 22; 30.1%), chest pain (n = 17; 23.3%), spinal pain (n = 18; 24.7%), myalgia (n = 13; 17.8%), abdominal or pelvic pain (n = 13; 17.8%), arthralgia (n = 11; 15.1%) and generalized pain (n = 9; 12.3%) [16]. The median age of the 65 patients with active pain was 56.0 years and 28 (43.1%) were women. Another eight patients with pain consults had a median age of 32.5 years; four (50.0%) were women. Only nine patients (12.3%) reported their primary pain symptom to be an exacerbation of a pre-existing pain condition [16]. In children, COVID-19 related multisystem inflammatory syndrome is associated with pain, particularly abdominal pain [17]. The most commonly reported pain symptoms of COVID-19 in children included sore throat, headache, myalgia and abdominal pain [18].

In a retrospective study of patients diagnosed with COVID-19 who were admitted to a hospital, pain intensity was assessed in 192 patients by the visual analog scale. Of these patients, 133 (69.3%) reported pain, which started on average 2.2 days before admission to the hospital. On a scale from 0 to 10, with higher scores indicating greater pain intensity, the mean visual analog scale score among patients with pain complaints was 4.8 [19].

There is strong evidence that patients with SARS-CoV-2 infections are at risk of developing widespread and regional chronic pain, and persistent pain symptoms have been reported by patients in the acute and chronic SARS-CoV-2 infection stages [20,21]. A systematic review and meta-analysis found that an estimated 80% of patients with a confirmed COVID-19 diagnosis continue to have at least one overall effect beyond 2 weeks following acute infection [22]. In an Italian study, after a mean of 60 days post-symptom onset, only 18/143 patients (12.6%) were free of all COVID-19 related symptoms [23]. The persisting pain conditions caused by COVID-19 included joint pain in 27.3% and chest pain in 21.7% of the patients. Other pain conditions reported post acute COVID-19 including migraine-like headaches and late-onset headaches attributed to high cytokine levels [12]. In a prospective study of 130 COVID-19 patients, 97 patients (74.6%) had headaches; of those, 24 patients (24.7%) had migraine-like headaches while in the emergency room. After 6 weeks of follow-up, 28 of 74 patients (37.8%) had ongoing headaches [24].

Additionally, critically ill patients usually experience pain post-discharge resulting from several painful invasive procedures performed while in the intensive care unit, including endotracheal tube suctioning, turning, arterial/intravenous line insertion, peripheral blood draw and chest tube removal [20,25].

Pain as a symptom of long COVID 19

Some patients with the SARS-CoV-2 infection reported symptoms for months, a condition that has been termed ‘long COVID’ [26]. This condition is similar to myalgic encephalomyelitis/chronic fatigue syndrome, wherein patients experience extreme fatigue, worsening of symptoms following physical/mental exertion, nonrestorative sleep, impaired function and orthostatic intolerance [26]. A recent review based on more than 1000 entries from selected database searches and two independent researchers identified fatigue, shortness of breath, muscle pain, joint pain, headache, cough, chest pain, altered smell, altered taste and diarrhea as the ten most commonly reported symptoms of long COVID [14]. The pain symptoms reported in these studies are supported by neurobiological evidence, which has identified pain as an important symptom in the acute phase and long COVID owing to the interaction of COVID-19 with the peripheral nervous system [27]. In addition to the aforementioned symptoms, fibromyalgia, a neurologic disorder characterized by abnormal pain sensitivity, has been reported to be a common symptom of long COVID. Among 616 Italian patients who completed an online survey an average of 6 months after their COVID-19 diagnosis, 189 patients (30.7%) met the fibromyalgia classification based on American College of Rheumatology modified 2010 criteria [28].

Secondary complications of the COVID-19 pandemic

The pandemic has also severely impacted healthcare workers who may be at increased risk for development of chronic pain. In a study involving nursing staff at an Israeli medical center, 20 (9.7%) of a cohort of 206 nurses fulfilled criteria for fibromyalgia (10.9% in females; 3.1% in males). The symptoms strongly correlated with post-traumatic stress disorder, related symptoms and stress arising from management-, patient- and workload-related issues [29]. These findings suggest that the prevalence of fibromyalgia among healthcare staff could increase due to the additional stress resulting from the COVID-19 pandemic.

Challenges associated with treating pain resulting from COVID-19

Patients seeking management of pain arising from COVID-19 face numerous challenges. Patients with COVID-19 without any contraindications requiring non lifesaving symptomatic control may not receive adequate care, as healthcare systems, particularly intensive care units, were pushed past their limits [20]. Consequently, immediate healthcare concerns have been directed toward containment and acute care for critically ill patients [30]. If patients do not have regular access to their usual primary care physician or pain specialist, their only recourse may be to receive care via the emergency/urgent care setting or through remote prescribing with a practitioner not familiar with their condition. This could result in an increase in chronic opioid or oral or injectable steroid use to manage pain rather than nonpharmacologic, psychological and interdisciplinary treatment approaches [10]. Although this may be considered a requirement during the pandemic owing to an increase in the prevalence of pain conditions, an assessment of risks and benefits as well as monitoring of opioid use will be challenging due to the lack of access to pain care facilities [10].

Pain associated with other conditions during the pandemic

The COVID-19 pandemic has posed critical challenges for individuals with pre-existing health issues, including those with chronic conditions involving flares or recurrent pain, particularly those with advanced osteoarthritis [31] and low back pain [32]. A European survey revealed that approximately 42% of respondents with pre-existing pain conditions reported worsening pain intensity during the COVID-19 pandemic [33]. An online Spanish survey conducted in 502 patients with chronic pain also revealed worsening of pain intensity and frequency and pain related interference and distress during the COVID-19 lockdown. Among approximately 80% of the respondents, worsening pain mainly affected distress, sleep and interference of pain in physical activities [34]. A Canadian survey among people living with pain reported that the worsening pain during the COVID-19 pandemic was associated with psychological distress and detrimental consequences on mental well-being [35]. Another survey conducted in the Philippines in 512 patients with rheumatoid arthritis or systemic lupus erythematosus reported pain flares, with increases in muscle and joint pain during the pandemic owing to disruption in the supply of medications, particularly, hydroxychloroquine or methotrexate [36].

Challenges associated with treating pain flares from pre-existing conditions during the COVID-19 pandemic

A myriad of persistent challenges posed by the COVID-19 pandemic may cause pain flares, even in the absence of viral illness. First, exacerbations of pain conditions during the pandemic were reported because of disruption in the supply of medications to patients and reduced prescribing [36]. Second, a lack of clinical encounters with interdisciplinary healthcare team members comprising physiotherapists, psychologists and self-help groups may be a threat to the health and well-being of patients with pain. Third, the lack of access to healthcare has disproportionally affected people with lower socioeconomic status, the uninsured, migrants and minorities [37,38]. Fourth, patients who require regular physical therapy or those planning elective orthopedic surgery for pain management have witnessed a reduction in activity due to stay-at-home orders and deferment of elective procedures [8]. Postponement of these procedures can impact physiological variables such as muscle mass deterioration, which can delay long-term improvements in pain and function. Moreover, patients also may be reluctant to travel for treatment for fear of exposure to infection.

Female sex, depression, reduced physical activity and mobility, stress and employment status are known risk factors for exacerbating pain conditions [39,40]. The psychological distress of COVID-19 that results in pain flare-ups is considerably exacerbated by social isolation, breakdown of social networks and fear of mortality [20]. Limited social support is known to impact psychological health. Semi structured interviews of 117 Turkish females revealed a strong association between perceived social support and depression, anxiety, burnout and severity of pain in patients with fibromyalgia [41]. Moreover, loneliness from social isolation owing to social distancing and lockdown norms may have potentially serious mental and physical health consequences [42]. An online survey conducted in Japan in 25,482 participants reported that the prevalence/incidence of pain and pain intensity were positively correlated with loneliness or the severity of perceived social isolation [43]. The authors noted that the increase in pain and pain intensity may be a result of psychological stress or enhanced perception of the pain [43]. These factors of psychological stress, increased pain perception and isolation [41–43] could contribute to risk for overdose.

Another complication is that geographic and related socioeconomic factors may influence pain burden. This is illustrated by an online survey involving 2124 and 2110 adult respondents from the USA and Canada, respectively, which found a 45% greater incidence rate of pain in southern and Appalachian states of Arkansas, Tennessee, Mississippi, Alabama, Kentucky, Georgia and Kansas and the western states of Oregon and Nevada compared with other areas in the USA and Canada. About 33% of the increased pain incidence rate could be attributed to economic factors, leaving the source of the remaining difference unknown [44]. Additionally, groups reporting serious financial hardship associated with COVID-19 coincided with those reporting the highest average pain scores in the USA and Canada [44].

Recommendations for treating pain resulting from COVID-19 & other pre-existing conditions

Change in the logistical approach to pain management during the pandemic

This pandemic has mandated the re-examination of the traditional face-to-face patient-physician care system globally. In response to physical distancing regulations, telemedicine is recommended as the first line of care for patients with chronic pain [45–47]. Telemedicine facilitates consultations and interactions with healthcare professionals while remote, are improving the provision of health services and supporting the ability of the educated patient to manage their care without the need to visit a healthcare facility [48]. During these visits, a thorough examination of the patient should be considered, including pain assessments. A search of the literature revealed few recommendations focusing on the clinical management of pain during the COVID-19 pandemic.

Shanthanna and colleagues [45] assembled an expert panel of pain physicians, psychologists and researchers from North America and Europe to formulate recommendations to assist healthcare professionals managing patients with chronic pain. The expert panel recommended the use of telemedicine, maintaining a biopsychosocial management approach, evaluating urgent and semi urgent procedures to avoid morbidity and modifying ongoing therapies to reduce risk of infection.

Cohen and colleagues [46] assembled an expert panel comprising a team of US pain management experts from the military (Army, Navy and Air Force), Veterans Health Administration and academia. The recommendations focus on risk mitigation, patient flow issues and staffing plans, telemedicine options, triage best practices, mental health considerations to reduce psychological impact on healthcare providers and resource utilization to guide healthcare providers to all available resources related to managing the pandemic.

A joint statement was issued by the American Society of Regional Anesthesia and Pain Medicine and European Society of Regional Anesthesia and Pain Therapy [47] in 2020 to provide recommendations for managing chronic pain. Briefly, the guidelines recommend considering telemedicine whenever possible.

Reprioritization of treatment options to focus on avoidance of healthcare settings

While new models of care utilizing digital technology have been rapidly implemented, there is a need for national and international professional bodies to establish robust pharmacological recommendations for pain management that can be universally implemented in the absence of face-to-face contact. In such situations, clinicians and caregivers should provide patients with treatment options that are readily available, easily fit the remote model and effectively control pain and related symptoms such as over the counter (OTC) analgesics that can be used to support self-care. Guidelines should also focus on improving implementation of pain management options that can be effective alternatives to hands-on components of healthcare delivery. This is particularly important for managing treatments that require close monitoring, such as opioids, during the COVID-19 pandemic.

Self-care is also supported by access to effective OTC medications. Approximately 80% of patients with COVID-19 are receiving outpatient treatment and may depend more on selfcare options such as the use of OTC medications [13]. In a retrospective cohort study of 403 confirmed cases of COVID-19, more than 50% of patients reported using paracetamol or ibuprofen [49]. Clinicians should consider treating patients with OTC analgesics such as paracetamol and NSAIDs to manage pain flares exacerbated during the pandemic in patients with pre-existing conditions. Patients should consult with their primary care physicians regarding appropriate use of OTC analgesics and should have access to a pharmacist to provide recommendations and to address any queries regarding their medication. However, access may be a challenge in some areas due to OTC stockpiling [50].

Paracetamol and NSAIDs are known to be effective in the management of mild-to-moderate pain including headache and migraine; toothache; muscle and joint, menstrual, visceral and postoperative pain [51]. Additionally, these medications can be used to control symptoms of SARS-CoV-2 infection, such as fever, as most of these medications have analgesic and antipyretic properties [52]. The CDC COVID-19 guidelines state, “Get rest and stay hydrated. Take OTC medicines, such as paracetamol, to help you feel better” [53]. A retrospective observational study in 90 patients with mild COVID-19 reported complete remission, defined as resolution of major symptoms, following initiation of treatment with NSAIDs at home within a median of 2 days of symptom onset [54]. A prospective multicenter cohort study involving 78,674 patients with a confirmed or highly suspected SARS-CoV-2 infection across 255 healthcare facilities in England, Scotland and Wales did not observe any increase in in-hospital mortality, critical care admission, requirement for invasive and noninvasive ventilation or oxygen or occurrence of acute kidney injury with NSAID use [55]. A number of observational and retrospective studies in smaller population-based cohorts have consistently reported a lack of association between ongoing NSAID therapy and increased mortality or worsening of clinical outcomes in patients with COVID-19 [49,56–59]. Therefore, international guidelines and policymakers should provide updates and guidance on the use of these medications in the management of pain specifically during the COVID-19 pandemic.

The joint statement issued by the American Society of Regional Anesthesia and Pain Medicine and European Society of Regional Anesthesia and Pain Therapy advises caution regarding immunosuppression associated with chronic opioid therapy and steroids [47]. The guidelines also recommend that patients prescribed or using NSAIDs on a regular basis should continue using them; however, patients are advised to promptly report mild fever or new myalgia while on anti-inflammatory treatment.

A systematic review provides strategies for the management of pain due to COVID-19 in the pediatric population [18]. Paracetamol and ibuprofen are effective and well-tolerated agents to treat an array of pain symptoms associated with COVID-19, including sore throat, headache, myalgia and abdominal pain. While both agents are options for pain management, treatment selection should be tailored to each child. If the child complains of a headache, paracetamol is the preferred agent. If the child experiences abdominal pain and is taking ibuprofen for pain, switching treatment to paracetamol is reasonable [18].

Conclusion

The COVID-19 pandemic had a devastating impact on people’s lives, especially those requiring access to healthcare resources, such as those suffering with pain. COVID-19 can induce pain and pain flares in patients with pre-existing chronic conditions involving pain. Pain resulting from COVID and pain from other pre-existing conditions are exacerbated owing to numerous conditions arising due to the pandemic. They include lack of management of pain in the outpatient space following an inpatient procedure, lack of adherence to preventative activities and other management tools while in COVID-19 isolation, and lack of access to clinicians and prescription medications. Furthermore, seeking help as needed for pain in the emergency setting where opioid prescribing is higher, and other disruptions to normal routine leading to delays in receiving treatment are additional challenges in managing pain. Delaying treatment of pain can lead to worsening of the pain condition, disability and increases in psychological stressors, which are further exacerbated by isolation and social distancing norms. This review provides available data on pain management during the COVID-19 crisis so that clinicians and patients may make informed decisions and calls on the need for a consensus meeting for grades of recommendations.

Telemedicine is being recommended as the first line of care for patients with pain to provide them with necessary medical services. Clinicians should encourage their patients to seek specialized care during their treatment and access local health authority online resources focusing on pain education and provide online training programs on pain self-care, as the majority of patients with COVID-19, particularly during the Omicron wave, relied on outpatient or self-care treatment options during the pandemic. Some helpful resources may be found on health authority websites such as the CDC website: www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/index.html; or the WHO website: www.who.int/emergencies/diseases/novel-coronavirus-2019/advice-for-public. Lifestyle interventions, such as incorporating daily exercise, balanced meals and improved sleep hygiene and OTC analgesics employing different mechanisms of action for improved analgesia can be used to combat pain and lower fevers. Self-management interventions such as OTC analgesics for pain and fever can be undertaken conveniently without having to leave the home, consequently avoiding increased burden on the healthcare system during the COVID-19 pandemic.

Future perspective

With the emergence of COVID-19, telehealth and self-care has been at the forefront of healthcare by expanding access to care for patients. While telehealth was a means to reduce disease exposure for both patients and healthcare professionals, it is now a resource for future medicinal practices. Self-care also provides a method for reducing exposure and could grow in the future. With the growth of telemedicine and self-care, the number of readily accessible OTC pain management options may grow along with related educational self-care resources and guidelines.

Author contributions

Collection and assembly of data: all authors. Data analysis: all authors. Data interpretation: all authors. Manuscript preparation: all authors. Manuscript review and revisions: all authors. Final approval of manuscript: all authors.

Financial & competing interests disclosure

P Kachroo, A Dhar and R Petruschke are employees of Haleon (formerly GSK Consumer Healthcare). M Herve was a GSK employee at the time of the study and now is a Sanofi employee. Funding was provided by Haleon (GSK Consumer Healthcare). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Medical writing support was provided by Peloton Advantage, LLC, an OPEN Health company, NJ, USA and was funded by Haleon (formerly GSK Consumer Healthcare).

Additional information

Funding

P Kachroo, A Dhar and R Petruschke are employees of Haleon (formerly GSK Consumer Healthcare). M Herve was a GSK employee at the time of the study and now is a Sanofi employee. Funding was provided by Haleon (GSK Consumer Healthcare). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Medical writing support was provided by Peloton Advantage, LLC, an OPEN Health company, NJ, USA and was funded by Haleon (formerly GSK Consumer Healthcare)