EFIC COVID-19 Task Force

The EFIC COVID-19 Task Force was created after realizing the need for news related to COVID-19 being distributed and shared with our community which is looking for advice with regards to pain treatment of their patients. The intended outcome is to distribute relevant news on our website and other communication channels. Our goal here is to put forward what is being said in an objective manner and provide a neutral overview on current research. The information will of course be updated as more research becomes available.

Click here to view the most recent research on COVID-19 and pain.

Task Force Members

Arun Bhaskar
Silviu Brill
Anne Estrup Olesen
Luis Garcia Larrea
Roger Knaggs (Task Force Leader)
Bart Morlion
Gisèle Pickering
Michael Schäfer
Hilde Verbeke
Phil Wiffen

Watch the video below with Prof. Roger Knaggs to find out more about the EFIC COVID-19 Task Force.

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Recent Research on COVID-19 and Pain

Reviewed by EFIC on May 28, 2020

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) for people with or at risk of COVID-19 (National Institute for Health and Care Excellence, May 2020)

Read the full article here

Management of osteoarthritis during COVID-19 pandemic (American Society for Clinical Pharmacology and Therapeutics, 21 May 2020)

Type of study: Review

Level of evidence: 3A (less systematic review of a variety of study designs, including in-vitro, in-vivo, animal and human-studies.)

Population: People with osteoarthritis

Results: NSAIDs: No evidence for discontinuation

Corticosteroids: No evidence for discontinuation of systemic treatment

Opioids: No evidence for discontinuation – the authors recommend weak opioids with no immunosuppressive activity

Monoclonal Antibodies (mAbs): No evidence for experimental use of mAbs in OA and COVID-19 patients except compassionate use or within clinical trials

Commentary: This paper does not add new findings to the existing literature but offers a good one-stop review for the specific care of patients with osteoarthritis. Overall, therapies for osteoarthritis appear to be safe and there is not any clear indication to avoid prescription or suggest discontinuation of existing pharmacological therapies due to COVID-19 infection or its complications.

The authors preference for weak opioids without immunosuppressive activity is subjective opinion and may be dose related. High dose weak opioid may have similar effects as low dose strong opioids. Although different opioids vary in their effects on the immune system, any clinical relevance is still uncertain.

The authors acknowledge that decisions need to be scrutinized in the high inflammatory stage of COVID-19 infection.

Read the full article here

COVID-19 pandemic and therapy with ibuprofen or renin-angiotensin system blockers: no need for interruptions or changes in ongoing chronic treatments (Naunyn-Schmiedeberg's Archives of Pharmacology, 15 May 2020)

Type of study: Review

Level of evidence: 5 (Expert opinion without critical opinion or based on physiology bench research or first principles)

Results: There remains no scientific evidence establishing a clear link between renin-angiotensin system (RAS) blockers (including angiotensin receptor blockers (ARBs), angiotensin converting enzyme inhibitors ACE-I), or non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and the worsening of COVID-19. In contrast, experimental data support the idea that ACE-2 not only serves as an entry receptor for SARS-CoV-2 but also protects the lungs from acute injury, and hence may therefore be beneficial in COVID-19 infection.

Implications: The authors propose that effective treatment with RAS blockers should not be discontinued or switched. There is insufficient evidence to recommend patients who take ibuprofen for medically indicated reasons to change their anti-inflammatory medicine in light of the COVID-19 pandemic. The choice of drug to treat COVID-19-associated fever or pain should be based on a benefit-risk assessment considering known side effects (e.g. kidney damage, gastrointestinal ulceration).

Commentary: The hypothetical risk of worsening COVID-19 does not justify discontinuing or switching RAS blockers or ibuprofen. Changes to treatment should be made in the light of benefit-risk assessment of these drugs for individuals.

Read the full article here

Reviewed by EFIC on May 22, 2020

Radiotherapy for pain relief from bone metastases during Coronavirus (COVID-19) pandemic (European Journal of Pain, 16 May 2020)

Type of article: Letter to the Editor

Population: Patients with cancer pain from bone metastases

Intervention: Radiotherapy for painful bone metastases

Results: Bone metastases are a common complication of advanced cancer that cause spinal cord compression, life-threatening electrolyte imbalances, pathologic fracture and severe pain. Stepwise treatments are opioids/NSAIDs, bisphosphonates, chemo & hormone-therapy, radiation and surgery. Palliative radiotherapy for painful uncomplicated bone metastases yields significant palliation for approximately 70% of people and complete pain relief for 10-35%. In previous RCTs, both single fraction and multiple fraction radiation therapy were efficacious for pain in bone metastases, multiple fraction are better only for patients with complicated metastases, neuropathic pain or cord compression.

In the context of the current COVID-19 epidemic, this choice must be weighted with the infection risks cancer patients due to a compromised immune system. In patients with cord compression and poor survival prognosis, a single fraction of 8 Gy was found as effective as multifractionated regimens while minimizing multiple treatment visits.

Implications: In order to minimize the exposure of people with bone metastases to COVID-19 without compromising oncological outcome, the choice of a palliative radiotherapy with 8 Gy in one single fraction may be the most reasonable, with good efficacy and reduced length of patients’ exposure to hospital environment and contagion.

Commentary: The National Institute for Health and Care Excellence (NICE) in the UK recommended using radiotherapy “only if unavoidable” (Mahase E BMJ. 2020 Apr 1;369:m1338.). In the light of literature, this report recommends the use of single fraction 8 Gy radiotherapy instead of longer schedules as a safer and reasonable procedure for painful bone metastases refractory to pain medication or with spinal cord compression, during the COVID-19 epidemic.

Of particular note, the risks and benefits of radiotherapy should always be discussed with patients and staff, and adequate preventive and protective measures provided to patients and radiotherapy technicians. Radiation treatment room and nearby areas should be sanitized during treatment intervals, and the time patients spend in the waiting room minimised. A dedicated path for cancer patients separated from other hospital patients should be assured.

Read the full article here

Managing chronic pain patients at the time of COVID-19 pandemic (Minerva Anestesiologica, 12 May 2020)

Coluzzi F, Marinangeli F, Pergolizzi J. Minerva Anestesiol. 2020 May 12. doi: 10.23736/S0375-9393.20.14666-2. [Epub ahead of print] PubMed PMID: 32400999.

Read the full article here

Pain: A Potential New Label of COVID-19 (Science Direct, 7 May 2020)

Type of study: Letter to editor

Level of evidence: 5 (Expert opinion without critical opinion or based on physiology bench research or first principles)

Results: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as the pathogen of COVID-19. The spike protein on this virus binds the angiotensin-converting enzyme 2 (ACE2) receptor, mediating entry into human cells. Studies have also detected SARS-CoV-2 in the cerebrospinal fluid of infected patients. Although the expression of ACE2 receptor in the human nervous system has not been fully identified, ACE2 has been detected in neurons and microglia in the spinal dorsal horn of mice.

The study suggests that SARS-CoV-2 might infect ACE2-positive cells in human spinal dorsal horn and decrease functional ACE2 activity resulting in the accumulation of angiotensin-II and decrease of angiotensin (1-7). Consequently, SARS-CoV-2 infection in the spinal cord may induce pain.

Implications: The potential burden of pain induced by COVID-19 cannot be ignored. However, the role of the ACE2 receptor in pain transmission and pain management for people infected with SARS-CoV-2 needs further scientific and clinical studies, in order to guide treatment and public health policy.

Commentary: There is no definitive evidence yet on the importance of this mechanism in humans, but a scientifically sound hypothesis is proposed. Yet, we should be cautious when drawing conclusions from mechanistic or theoretical pharmacology, especially from rodents, as a number of examples show that such evidence can later be refuted by clinical data.

Read the full article here

Availability of Internationally Controlled Essential Medicines in the COVID-19 Pandemic (Journal of Pain and Symptom Management, 30 April 2020)

Pettus K, Cleary JF, de Lima L, Ahmed E, Radbruch L. J Pain Symptom Manage. 2020; S0885-3924(20):30375-4. doi:10.1016/j.jpainsymman.2020.04.153

Read the full article here

Reviewed by EFIC on May 14, 2020

Managing patients with chronic pain during the COVID-19 outbreak: considerations for the rapid introduction of remotely supported (eHealth) pain management services (PAIN, May 2020)

Eccleston C, Blyth FM, Dear BF, Fisher EA, Keefe FJ, Lynch ME, Palermo TM, Reid MC, Williams ACC. PAIN. 2020 May;161(5):889-893. doi:10.1097/j.pain.0000000000001885.

Read the full article here

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Identifying rheumatic disease patients at high risk and requiring shielding during the COVID-19 pandemic (Clinical Medicine, May 2020)

Price E, MacPhie E, Kay L, Lanyon P, Griffiths B, Holroyd C, Abhishek A, Youngstein T, Bailey K, Clinch J, Shaikh M, Rivett A. Clinical Medicine (Lond). 2020 May 1. pii: clinmed.2020-0160. doi: 10.7861/clinmed.2020-0160.

Read the full article here

EMA advice on the use of NSAIDs for Covid-19 (Drug and Therapeutics Bulletin, March 2020)

Drug Ther Bull. 2020 May;58(5):69. doi: 10.1136/dtb.2020.000021. Epub 2020 Mar 31.

Read the full article here

Reviewed by EFIC on May 8, 2020

Pain Management During the COVID-19 Pandemic in China: Lessons Learned (Pain Medicine, 22 April 2020)

Type of article: Case reports from physicians about managing pain during the COVID-19 pandemic

Level of evidence: 5 (Expert opinion without critical appraisal or based on physiology bench research or first principles

Results: Most medical services In Wuhan not directly involved in intensive care, including pain management services, were partially or completely shut down. This posed challenges for clinicians and people with chronic pain. The pain medicine department found that widespread pain can be an early symptom of COVID-19 infection.

On the other hand, an increasing concern is that the concern of missing other urgent medical conditions or diagnoses when focusing on assessing for COVID-19 infection. A case of thoracic spinal neuratoma left undiagnosed due to similarities in presentation to COVID-19 infection is reported. The pandemic provided clinicians an opportunity to incorporate telemedicine into pain management for the first time due to the urgent need to provide healthcare services remotely. Clinicians need to consider strategies to encourage people with health issues needing management to seek outpatient care as many are still understandably wary of seeking in-person health care. We may prepare ourselves to see more patients who previously had COVID-19 infection visiting pain clinic as the epidemic slows.

Commentary: As well as clinical research, personal experiences in the pandemic are be important to share too. The included case reports illustrate how the combination of chronic pain and COVID-19 infection can challenge diagnosis and treatment.

Beneficial strategies for managing pain during the COVID-19 pandemic are reported and recommendations based on lessons learned in the pain medicine departments of Wuhan and Shenzhen hospitals are discussed.

Read the full article here

Reviewed by EFIC on April 30, 2020

Headache medication and the COVID-19 pandemic (Journal of Headache Pain, 25 April 2020)

Type of article: Commentary, brief literature analysis

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)

Population: Patients suffering chronic headache and treated with ACE inhibitors (ACE-I), angiotensin II receptor blockers (ARB) or ibuprofen

Results: Concern has arisen in view of a putative link between the use of inhibitors of the renin-angiotensin system (ACE-I, ARB) and ibuprofen and an increased risk for COVID-19 infection. The authors discuss this concern in relation to headache treatment and conclude that, based on current evidence, there is no reason to abandon treatment with ACEI, ARB or ibuprofen in people with headache. There is no convincing evidence in medical / research literature that either renin-angiotensin system blockers or ibuprofen worsen SARS-CoV-2 infection in any type of patient, including headache patients.

Implications: The authors, in agreement with the advice of international cardiovascular societies, see no rationale to alter the prescription of these drugs that have an important role in the treatment of headache.

Commentary: There is no reason, empirical or scientific, to discontinue a treatment with ACE-I/ARB or ibuprofen in patients with COVID-19 infection. Discussion on mechanisms is short but sensible and rich. Conclusions are in line with recent results from Zhang et al (Circ. Res 2020, doi: 10.1161/CIRCRESAHA.120.317134.), that shows absence of complications and even better outcome in hypertensive patients with Covid19 treated with ACE-I/ARB.

Read the full article here.

Caring for patients with pain during the COVID‐19 pandemic: consensus recommendations from an international expert panel (Anesthesia, 7 April 2020)

Type of study: Practice recommendations to help with the care of chronic pain patients during the COVID-19 pandemic.

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles).

Results: Consensus recommendations on a range of topics including:

  • face to face consultations (not recommended)
  • telemedicine (recommended providing fits with legislative regulations)
  • biopsychosocial management (recommended if social distancing can be maintained or using remote consultations)
  • maintain regular review of patients prescribed opioids and that all patients receive their prescription of opioids to avoid withdrawal; and
  • patients may continue prescribed NSAIDs for pain relief.

Commentary: The paper gives an overview of the expert opinion of a panel. However, the size of panel not stated. While the quality low, evidence in the paper may provide a benchmark for comparison to any local practice.

Read the full article here.

Characteristics, symptom management and outcomes of 101 patients with COVID-19 referred for hospital palliative care (Journal of Pain and Symptom Management, April 2020)

Type of study: retrospective analysis of 101 medical and nursing case notes by clinician-researchers

Level of evidence: Level 4 (case series)

Results: Of the 101 patients with COVID-19 infection referred for end-of-life palliative care 64 were males and 37 females with a median age of 82 [72-89]. The most prevalent symptoms were in descendent order breathlessness, agitation, drowsiness, pain, and delirium. Apart from non-pharmacological treatment, patients received mainly symptom-relieving drugs with a median final dose of 10 mg/24 h morphine and 10 mg/24 h midazolam. Patients spent a median of 2 [1–4] days under the palliative care team and received 3 [2–5] contacts. 75 patients died, 13 were discharged and 13 remained under palliative inpatient care.

Implications: This retrospective analysis of a case series of COVID-19 patients receiving end-of-life palliative care instead of a referral to an intensive care ward gives some interesting insights into the course of the disease, the main symptoms under which the patients suffer, the required treatment measures, and their effectiveness.

Commentary: Intriguing is the information on end-of-life palliative care patients with COVID-19 infection in comparison to the intensive care patients that receive much more media attention. However, it provides little new information for the commonly known palliative care. The therapies that were initiated belong to the standard of care.

Read the full article here.

Pain Management Best Practices from Multispecialty Organizations during the COVID-19 Pandemic and Public Health Crises (Pain Medicine, 7 April 2020)

Type of study: Narrative review

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)

Results: This consensus provides a good overview on safety precautions to reduce risks of infection with SARS-CoV-2 for clinicians working in pain management and the patients they treat. Other issues considered include patient flow issues and staffing plans, telemedicine options, triaging recommendations and resource utilization, and impacts on mental health of both patients and healthcare workers. Guidance on the prescription of opioids and use of steroids for interventions is provided

Commentary: The paper summarises the opinions of an expert panel that included pain management experts from the military, Veterans Health Administration, and academia in the US. Hence, the recommendations reflect current practices in the US and may not be directly applicable in other settings.

Read the full article here.

Reviewed by EFIC on April 24, 2020

Acute use of non-steroidal anti-inflammatory drugs (NSAIDs) for people with or at risk of COVID-19 (RPS NHS, 14 April 2020)

Type of study: Systematic review

Results: A systematic literature search identified 156 references but found no studies that determined whether acute use of non-steroidal anti-inflammatory drugs (NSAIDs) is related to increased risk of developing COVID-19 or increased risk of a more severe illness. Although NSAIDs may reduce acute symptoms of acute respiratory tract infection (such as fever), they may either have no effect on or worsen, long-term outcomes.

Implications: When people are starting treatment for fever and/or pain with confirmed or suspected COVID-19, all treatment options, including paracetamol and NSAIDs, should be considered and selected based on the greatest benefit compared to potential harms using each medicine.

Commentary: NSAIDs are common treatments for pain, fever, and inflammation. On 14th March 2020 possible concerns about their use in people with COVID-19 were raised due to an apparent observed worsening in the severity of symptoms in people taking anti-inflammatory medicines. There is currently no evidence that the acute use of NSAIDs causes an increased risk of developing COVID-19 or of developing a more severe COVID-19 disease.

The full article can be found here.

The role and response of palliative care and hospice services in epidemics and pandemics: a rapid review to inform practice during the COVID-19 pandemic (Journal of Pain and Symptom Management, 8 April 2020)

Type of study: A rapid systematic literature review of published case studies, cross-sectional studies, cohort studies, and intervention studies

Level of evidence: Level 3A (Systematic review of case-control studies)

Results: Out of 2207 identified studies, 36 underwent full-text review, and 10 studies were finally selected for analysis.

To guide hospices and palliative care teams they should focus on:

  • maintaining the ability to respond rapidly and flexibly;
  • ensuring protocols for symptom management and psychological support, and non-specialists are trained in their use;
  • being involved in triage;
  • considering shifting resources from inpatient to community settings;
  • considering redeploying volunteers to provide psychosocial care;
  • facilitating camaraderie among staff and adopting measures to deal with stress;
  • using technology to communicate with patients and carers; and
  • adopting standardised data collection systems to inform operational changes and improve care.

Implications: Palliative care teams need to be flexible and rapidly redeploy resources in the face of changing needs during a pandemic, such as COVID-19. Particular attention should be to the triage of patients, palliative care expertise staff, workload and stress, anticipatory allocation of space and equipment, and standardised documentation of data.

Commentary: This rapid review provides guidance for hospices and palliative care teams to ensure that they do not become overwhelmed by rapid developments of a pandemic. There was limited detail about how studies were selected for undergoing full-text review. In addition, there was only limited evidence and a lack of quantitative data, no assessment of quality of studies, and no grading of recommendations. The use of a developed palliative care surge plan might have been used as a filter for the selection of studies. Despite these limitations, this paper gives a valuable review of literature relevant for palliative care and provides important guidance.

Read the full text here.

Cannabidiol as prophylaxis for SARS-CoV-2 and COVID-19? Unfounded claims versus potential risks of medications during the pandemic (RSAP, 31 March 2020)

Type of study: Letter to the Editor

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)

Results: During the COVID-19 pandemic, many patients may look for natural remedies to protect themselves. Use of products containing cannabinoids have proliferated amidst claims of health benefits including immune “support” or “boosting”. Cannabidiol (CBD) and tetrahydrocannabinol (THC) have complex pharmacological properties, including anti-inflammatory effects, that may be useful in certain conditions (including autoimmune and neurodegeneration diseases). However, they suppress cytokines, chemokines, effector T-cells, and microglial cells, reducing the host response to pathogens including viruses like SARS-CoV-2.

Implications: Current pharmacological and clinical evidence suggest CBD and THC decrease the body’s ability to fight infections, in particular viral and respiratory infections. In a clinical trial of cannabidiol for epilepsy, respiratory infections (pneumonia) were over 30% more common in those receiving CBD versus placebo. The author recommends avoiding the use of cannabinoids during this pandemic unless medically supported for recognised indications (e.g. seizures, cancer, chronic pain), and highlights false marketing claims of medical benefit including “immune system boosting” or antiviral effects, that should be reported to regulatory bodies.

Commentary: A very concise yet well-documented summary of the potentially serious problems of health-marketing as applied to cannabis. The analysis is USA-centred, where the direct advertisement and marketing of medicines is greater than in Europe.

Read the full article here.

Safety of ibuprofen in patients with COVID-19: causal or confounded? (CHEST, 31 March 2020)

Type of article: Commentary

Level of evidence: 5 (Expert opinion without explicit critical appraisal or based on physiology bench research or first principles)

Results: This commentary retraces the origins of the worldwide alarm towards the use of ibuprofen, starting with a tweet from the French Health Minister who, after 4 young people reportedly developed serious COVID-19 disease after taking NSAIDs, advised that ibuprofen could aggravate the infection. The report, although unpublished, was reported in The BMJ and endorsed by specialists from France and UK, and by the WHO.

The authors criticise the low level of evidence of these reports, as well as the notion, published in The Lancet, that ibuprofen could enhance coronavirus infectivity by increasing the bioavailability of angiotensin converter enzyme (ACE), to which the virus binds. They argue that drawing conclusions from theoretical pharmacology is dangerous and can lead to erroneous results, such as the hypothesis that co-administration of ibuprofen and aspirin could counteract antiplatelet effectiveness, which was based on pharmacological thromboxane levels but then refuted in a randomized controlled trial.

Implications: Rather than concluding that ibuprofen is safe for COVID-19 related fever, the authors observe that current epidemiologic evidence “is not strong enough to infer a causal link of a harmful effect of ibuprofen in COVID-19”. They advise, however, that patients with COVID-19 take acetaminophen monotherapy for fever reduction.

Commentary: A very interesting critique of the multiple biases and insufficiencies that have polluted medical literature on this topic. It is, however, amusing that after such a clear analysis the authors end up recommending the same approach –paracetamol (acetaminophen) – as the French Minister in his initial tweet.

Read the article in full here.

Associations between immune-suppressive and stimulating drugs and novel COVID-19 (eCancer, 27 March 2020)

Type of study: Review

Level of evidence: 3A (systematic review of a variety of study types including in-vitro-, case-, in-vivo, animal- and human studies).

Results:

NSAIDs: The search did not identify any strong evidence for or against the use of ibuprofen for treatment of COVID-19 specifically.

Corticosteroids: Some evidence that corticosteroids may be beneficial in the treatment of SARS-CoV. However, this is not specific to COVID-19.

Commentary: There is no definitive evidence that NSAIDs or corticosteroids are contraindicated in COVID-19.

Read the full article here.

Latest EMA advice on the use of non- steroidal anti-inflammatories for COVID-19 (DTB, March 2020)

The European Medicine Agency has issued advice on the use of ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) in people who are infected with the Coronavirus disease (COVID-19).

The published article states that there is currently no scientific evidence establishing a link between ibuprofen and the worsening of COVID-19. It advises that when treating fever or pain in people with covid19, patients and healthcare professionals should take into account the harms and benefits of all available treatment options including paracetamol and NSAIDs.

People who have been advised to use ibuprofen by a healthcare professional should therefore not stop taking it. EMA is monitoring the situation closely and will review any new information that becomes available on this issue in the context of the pandemic and EFIC will make sure to keep everyone updated by making the news available on our website.

Read and download the full article here.