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.

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 webinar

On July 8, the task force held a webinar on “Pain Management during COVID-19”. Feel free to watch it below:

Due to technical difficulties, two sessions were uploaded separately. Watch them here:

Recent Research on COVID-19 and Pain

Commentary on articles

Adverse outcomes and mortality in users of non-steroidal anti-inflammatory drugs who tested positive for SARS-CoV-2: A Danish nationwide cohort study (Plos Medicine, 8 September 2020)

Type of study: Cohort study

Level of evidence: 2B (individual cohort study)

Population: All Danish residents who tested positive for the infectious agent of COVID-19. A total of 9,236 SARS-CoV-2 PCR-positive individuals were eligible for inclusion.

Intervention: Users of NSAIDs (248 (2.7%) had filled a prescription for NSAIDs)

Comparison: Non-users of NSAIDs

Results: Treatment with NSAIDs was not associated with 30-day mortality, risk of hospitalization, ICU admission, mechanical ventilation or renal replacement therapy.

Implications: Use of Danish registries allowed for identification of all individuals who had been tested for SARS-CoV-2 in Denmark and allowed for obtaining data on prescription drug use, medical history, migration, hospital admissions, and death through individual-level linkage between health and administrative registries. The main limitations of the study are possible exposure misclassification, as not all individuals who fill an NSAID prescription use the drug continuously, and possible residual confounding by indication, as NSAIDs may generally be prescribed to healthier individuals due to their side effects, but on the other hand may also be prescribed for early symptoms of severe COVID-19.

Considering the available evidence, there is no reason to withdraw well-indicated use of NSAIDs during the SARS-CoV-2 pandemic. However, the well-established adverse effects of NSAIDs, particularly their renal, gastrointestinal, and cardiovascular effects, should always be considered, and NSAIDs should be used in the lowest possible dose for the shortest possible duration for all patients.

Commentary: This is a large cohort study demonstrating that NSAIDs do not lead to more severe coronavirus disease. This is an important finding as different theories on the use of NSAIDs were proposed during the early phases of the COVID-19 pandemic where concerns were raised that NSAIDs may lead to a more severe course of coronavirus disease.

Reviewed by EFIC on September 21, 2020 – Read the full article here

Telehealth for musculoskeletal physiotherapy (Musculoskeletal Science and Practice, August 2020)

Type of study: Masterclass / non-systematic overview

Level of evidence: 5 (Expert opinion)

Results: Telehealth is defined as the ‘delivery of healthcare at a distance using information and communication technology’. Published systematic reviews shows that delivering interventions via telehealth methods yield similar effects on pain and disability as face to face interventions in patients with low back pain and hip/knee osteoarthritis. This is based on low certainty evidence and higher-quality trials are required.

A systematic review [Mani S et al. J Telemed Telecare 2017; 23(3): 379–391] found that telehealth assessments have good concurrent validity for pain, swelling, range of motion, muscle strength, balance, gait and functional assessment. However, only low to moderate concurrent validity was demonstrated for special orthopaedic tests, neurodynamic tests, and lumbar posture.

There is high satisfaction with telehealth interventions among individuals with musculoskeletal conditions. Patient barriers to engaging with telehealth include computer literacy, older age, lower education levels, and lack of trust in the clinician. Physiotherapist barriers to engaging with telehealth include unwillingness to change current clinical practice, low confidence with technology, and concerns over safety and patient privacy.

When choosing a telehealth platform, physiotherapists should consider components needed for their assessment (e.g. range of motion features), national privacy and security regulation for the transfer and storage of patient information, usability for the patient, cost, functionality (can be used across different browsers and has multiple features including appointment scheduling).

Implications: Telehealth seems a useful alternative to face to face consultations and interventions in terms of effectiveness for treating musculoskeletal pain conditions.

Commentary: This paper provides a useful overview of the current evidence base for the effectiveness of telehealth interventions for the treatment of pain and disability among patients with musculoskeletal conditions. The paper highlights the results of published systematic reviews showing that telehealth interventions provide similar effects to face to face rehabilitation.

The authors specifically mention the limitations in the evidence base and call for the conduct of high-quality trials before any definitive conclusions can be drawn. The paper outlines very practical tips for picking a telehealth platform and implementing telehealth in physiotherapy practice.

Reviewed by EFIC on August 11, 2020 – Read the full article here

Home-based management of knee osteoarthritis during COVID-19 pandemic: literature review and evidence-based recommendations (Journal of Experimental Orthopaedics, 19 July 2020)

Type of study: Review article

Level of evidence: 5 (Narrative systematic review)

Results: Management strategies identified include exercise, proper nutrition, physical therapy, and use of corrective and assistive orthotics.

Telehealth methods may be considered to deliver self-management advice to patients with knee osteoarthritis who had their surgery deferred. Home exercise programmes consisting of a combination of aerobic, resistance, and flexibility work should be considered.

Where patients with knee osteoarthritis have co-morbid obesity, a combined exercise, and diet approach to encourage weight loss can be considered.

The role of knee braces, sleeves, foot orthoses, footwear, walking aids and heat is uncertain in terms of pain, disability, and quality of life.

Commentary: This review article provides an overview of the non-pharmacological options for the home management of knee osteoarthritis. Exercise and virtual education appear to be the most promising interventions with the strongest supporting evidence. However, the review article lacks a risk of bias assessment and pooled analyses and so the true effectiveness of any of the proposed strategies remains uncertain.

Reviewed by EFIC on August 11, 2020 – Read the full article here

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings (Brain, 8 July 2020)

Type of study: Case series

Level of evidence: 4 (Case series)

Population: Patients with COVID-19 presenting with neurological syndromes

Results: Clinical and paraclinical data collected from 43 consecutive cases with COVID-19 confirmed through RNA PCR, or with probable/possible disease according to World Health Organization criteria, and presenting with neurological symptoms. Five major categories are described:

  • (i) encephalopathies (n= 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, with 9 patients making a full or partial recovery with supportive care only;
  • (ii) inflammatory CNS syndromes (n= 12) including encephalitis, acute disseminated encephalomyelitis, and isolated myelitis. Of these, 10 were treated with corticosteroids, and one patient died;
  • (iii) ischaemic strokes (n= 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died;
  • (iv) peripheral neurological disorders (n= 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six making an ongoing recovery; and
  • (v) miscellaneous central disorders (n=5) who did not fit the categories above.

Implications: Such syndromes have similarities to those described in the other coronavirus epidemics (severe acute respiratory syndrome (SARS) in 2003, and Middle East acute respiratory syndrome (MERS) in 2012). However, overall numbers of infected individuals were much smaller, and neurological presentations were few in comparison with those being recognized in the current pandemic.

Commentary: This is probably the most detailed clinical report on the nature of neurological syndromes associated with COVID-19. To be contrasted with the previous report from the Strasbourg group (Helms et al NEJM 2020) who described essentially encephalopathy with agitation, confusion and corticospinal tract signs in 64 patients, as well other less comprehensive reports (Guan et al. NEJM 2020; Mao et al. JAMA Neurol 2020; Varatharaj et al., Lancet Psych 2020).

Reviewed by EFIC on August 11, 2020 – Read the full article here

The Effect of the COVID-19 Pandemic on Electively Scheduled Hip and Knee Arthroplasty Patients in the United States (The Journal of Arthroplasty, 22 April 2020)

Type of study: Survey

Level of evidence: 2C (Ecological study)

Population: Patients awaiting elective hip and knee arthroplasty

Intervention: A survey (electronically or over the phone) to patients awaiting hip or knee replacement to assess pain, anxiety, physical function and economic capacity to undergo a delayed surgery.

Results: Hospitals in the United States – similar to hospitals in many other countries– stopped performing elective procedures when COVID-19 was declared a pandemic. This led to the deferral of a large number of hip and knee arthroplasties between March and July 2020 and increasing waiting times. Six institutions distributed the survey and 360 patients responded.

Most patients were anxious about the uncertainty of when their deferred surgery would take place. While 85% of the sample agreed with the surgery deferral in line with public health advice, 90% planned to reschedule their surgery as soon as possible. Patients in North East States were most concerned with contracting COVID-19 during their hospital admission. Younger patients were more anxious about the financial situation and job security and its impact on being able to afford the cost of the future surgery.

Implications: The COVID-19 pandemic has a significant impact on patients with hip and knee osteoarthritis who have to wait in uncertainty until their surgery is rescheduled. Supporting individuals during this time with managing pain is very important in terms of both physical and emotional wellbeing.

Commentary: This small survey offers an insight into the impact that COVID-19 is having on patients with knee and hip osteoarthritis who require surgery. The result that 90% of the sample will reschedule their surgery as soon as possible is interesting in light of debate on social media that COVID-19 might lead to a reduction in the number of musculoskeletal pain procedures. A limitation of this study is that it does not reveal how many individuals received the survey, so we are unable to assess the response rate.

Reviewed by EFIC on August 11, 2020 – Read the full article here

Novel Coronavirus (COVID-19) - Associated Guillain–Barré Syndrome: Case Report (Journal of Clinical Neuromuscular Disease, June 2020) + Guillain–Barré syndrome associated with leptomeningeal enhancement following SARS-CoV-2 infection (Clinical Medicine Journal, 9 June 2020)

Type of study: Clinical case reports

Level of evidence: Level 4 (Case series)

Case history: Commonly middle aged patients with positive RT-PCR tests for COVID-19. Typical COVID-19 symptoms like chills, fever, dry cough, shortness of breath can be pronounced or only mild.

Neurological symptoms usually started within 4-10 days after the onset of the first clinical symptoms and included slowly progressing motor weakness of the lower and/or upper limbs, occasionally with involvement of the facial and/or oropharyngeal nerves or paraesthesias in the lower and/or upper limbs, and at times difficulty in voiding urine. However, neurological symptoms can show great variability.

Following lumbar puncture, the cerebrospinal fluid was often negative for COVID-19 with a normal protein concentration and only few leukocytes. Electrophysiological findings have usually indicated a demyelinating polyneuropathy, particularly of motor neurons.

Intervention: Intravenous immunoglobulin (400 mg/kg daily over 5 to 7 days) has been used after which the clinical symptoms quickly improve.

Commentary: The most important finding in these case reports is to consider the possibility of neurological complications in people with COVID-19, which are usually respiratory symptoms. Moreover, shortness of breath does not exclusively be related to COVID-19 -induced pneumonia but may also – in rare cases – be caused by motor neuron pathology.

Reviewed by EFIC on July 2, 2020 – Read the full first article here and the second here

Perspectives of patients with rheumatic diseases in the early phase of COVID-19 (Arthritis Care & Research, 11 June 2020)

Type of study: Online survey of rheumatology patients

Level of evidence: Level 4 (Case series or poor quality cohort or case-control study)

Population: Rheumatological patients at a large tertiary hospital in Australia

Methodological approach: People were invited to complete a survey that assessed their concerns regarding risks conferred by their rheumatological condition or medications, impact of receiving information about on the likelihood of continuing medication during the COVID-19 pandemic, and acceptance of telehealth.

Results: The response rate was 21% (550/2630 people). Most people (63.8%) were prescribed more than one conventional synthetic disease-modifying antirheumatic drug and 17.8% were prescribed a biologic or targeted synthetic anti-rheumatic drug. Prednisolone and non-steroidal anti-inflammatory drugs (NSAIDs) use was reported by 26.7% and 22.4% of people, respectively.

41% of people were concerned that their rheumatological disease increased their risk of COVID-19 infection and severity of infection (52.3%). More people were concerned that their medications increased their risk of COVID-19 infection (55.7%), while 76.1% were concerned that medications increased the severity of infection.

Most people (61%) had been provided with information about the impact of COVID-19 on rheumatological conditions. Telehealth was considered appropriate to almost all people (98.4%) during the pandemic.

Commentary: This article exemplifies concerns that either rheumatological conditions and/or their medication might increase the risk for COVID-19 and its severity. Understandably some people may consider stopping their medicines and run the risk of subsequent complications or worsening of their underlying disease.

Reviewed by EFIC on June 12, 2020 – Read the full article here

Coronavirus disease 2019 (COVID-19) and ischemic colitis: An under-recognized complication (The American Journal of Emergency Medicine, 26 May 2020)

Type of study: Case reports

Level of evidence: 4 (Case studies)

Population: Two people with COVID-19 presenting with abdominal pain

Case 1:

  • Male, 73 years old, hypertension, end-stage renal disease and haemodialysis

  • Presented with fever, cough, dyspnoea, bleeding diarrhoea

  • Developed acute left lower quadrant abdominal pain with red bright rectal bleeding

  • PCR positive for SARS-CoV-2

  • Anaemia, leucopoenia, lymphopenia

  • D-dimer level 4226.0 ng/ml; increased ferritin CRP, procalcitonin

  • Thoracic X-rays demonstrated bilateral opacities and abdominal CT-scan suggested ischaemic colitis. Anticoagulant prescribed

  • Stable for 5 days, then cardiac arrest and death

Case 2:

  • Female, 61 years old, with a history of type II diabetes mellitus

  • Three-day history of dry cough and non-radiating abdominal pain for one day

  • Sharp, severe, periumbilical pain which began acutely that morning

  • Positive for SARS-CoV-2

  • Pulmonary angiography CT-scan showed thromboembolism in thoracic + abdominal aorta. D-dimer 8264 ng/ml (>16 times normal)

  • Clinically significant venous and arterial that required tissue plasminogen activator

Implications: COVID-19 associated coagulopathy can include thromboembolism and may present with abdominal pain or pulmonary embolism. In patients with alerting symptoms, increased D-dimer levels should prompt appropriate investigation to detect thrombosis.

Commentary: These are examples of COVID-19 presenting with abdominal pain as presenting symptom. COVID-19 associated coagulopathy can worsen prognosis, because of undetected intestinal ischaemia. D-Dimer is an important investigation if suspect coagulopathy in these patients.

Other cases of COVID-19 related acute-pseudo-surgical abdomen have been reported including;
Ahmed AOE, Badawi M, Ahmed K, Mohamed MFH. COVID-19 Masquerading as an Acute Surgical Abdomen. Am J Trop Med Hyg. 2020 Jun 9.

doi: 10.4269/ajtmh.20-0559. [Epub ahead of print]

Reviewed by EFIC on June 5, 2020 – Read the full article here

Management of osteoarthritis during COVID-19 pandemic (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.

Reviewed by EFIC on May 20, 2020 – Read the full article here

Model based approach for estimating the dosage regimen of indomethacin a potential antiviral treatment of patients infected with SARS CoV-2 (Journal of Pharmacokinetics and Pharmacodynamics, 20 May 2020)

Type of study: Mini-review and theoretical model of optimal dosage

Population: in vitro studies; in vivo animal studies

Results: Indometacin, an anti-inflammatory drug, has been used as symptomatic treatment to improve oxygenation in patients with acute respiratory distress [Hanly et al Lancet 1987; Steinberg et al Circ Shock 1990] and to reduce proinflammatory interleukin-6 levels [Sacerdote et al Inflamm Res 1995]. In addition, indometacin has been shown to have potent in-vitro antiviral properties against human SARS-CoV-1, canine CCoV, and more recently on human SARS CoV-2 [Amici et al Antivir Ther. 2006, Xu et al Front Med J. 2020].

In this paper the authors propose indometacin as a promising candidate for the treatment of SARS-CoV-2 and try to provide criteria for comparing benefits of alternative dosage regimens using a model-based approach. They characterize % of recovery and viral load in CCoV-infected dogs, to estimate the PK of indometacin in dog and human using published data after administration of immediate (IR) and sustained-release (SR) formulations, and to estimate the expected antiviral activity as a function of different assumptions on the effective exposure in human.

Implications: Should indometacin prove active against SARS CoV-2 in humans, the best theoretical dosing regimens modelled were 50 mg three-times-a-day for the IR formulation, and 75 mg twice-a-day for the SR formulation.

Commentary: The main interest of this paper is in the reference list, which provides published data on the efficacy of Indometacin on various coronaviruses including COVID-1 and COVID-2, in vitro, in dogs, and potentially in humans. Should current clinical trial using indometacin (that started April 2020) be positive, this study provides a PK/PD basis to determine best therapeutic regimens. Of particular note, indomethacin has a higher toxicity index than other NSAIDs, including ibuprofen (especially GI related) and the recommended dosing is relatively high. So, a gastroprotective drug should be indicated also.

Reviewed by EFIC on May 28, 2020 – read the full article here

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.

Reviewed by EFIC on May 20, 2020 – read the full article here

COVID-19 is a Real Headache! (Headache Journal, 15 May 2020)

Type of study: Views and perspectives

Level of evidence: 2A (systematic review of cohort studies)

Results: Initial reported symptoms of SARS‐CoV‐2 infection were mainly respiratory, and were characterised by fever, sore throat, cough, and dyspnoea. Other symptoms, including headache, abdominal pain, diarrhoea, loss of taste and smell, have been added as possible symptoms of COVID-19 over time. Reports of neurological symptoms are increasing rapidly, and headache appears to be most common. Headache has been reported in 11%-34% of hospitalized COVID-19 patients, however clinical features of these headaches are not reported. The authors experience suggest significant features of headache presentation in symptomatic COVID-19 patients were new-onset, moderate-severe, bilateral headache with pulsating or pressing quality in the temporoparietal, forehead or periorbital region. The most striking features of the headache were variable onset and poor response to common analgesics, or high relapse rate, that was limited to the active phase of the COVID-19.

Implications: As a common non-respiratory symptom of COVID-19, headache should not be overlooked, and its characteristics should be recorded with scrutiny. If headache is ignored as a symptom of COVID-19, there may be delay in diagnosis, leading to further infection cases in the community.

Commentary: Clinical features of headache related have to COVID-19 have not been well documented. A case vignette is described and several possible pathophysiological mechanisms are proposed from theoretical considerations.

Reviewed by EFIC on May 20, 2020 – 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.

Reviewed by EFIC on May 20, 2020 – Read the full article here

Pain: A Potential New Label of COVID-19 (Brain, Behavior, Immunity, 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.

Reviewed by EFIC on May 15, 2020 – read the full article here

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.

Reviewed by EFIC on May 15, 2020 – read the full article here.

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.

Reviewed by EFIC on May 8, 2020 – read the full article here.

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

Reviewed by EFIC on April 30, 2020 – 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.

Reviewed by EFIC on April 30, 2020 – read the full text 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.

Reviewed by EFIC on April 30, 2020 – 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.

Reviewed by EFIC on April 30, 2020 – 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.

Reviewed by EFIC on April 30, 2020 – read the full article 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.

Reviewed by EFIC on April 23, 2020 – 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.

Reviewed by EFIC on April 23, 2020 – 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.

Reviewed by EFIC on April 23, 2020 – 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.

Reviewed by EFIC on April 23, 2020 – read and download the full article here.

Highlighted articles

Optimizing telehealth pain care after COVID-19, (Pain, 20 August 2020)


The COVID-19 pandemic has presented major challenges to pain care, as pain clinicians face severe restrictions in their ability to provide usual in-person assessments and treatments. COVID-19 has also exposed pre-pandemic problems in providing comprehensive pain care. Yet despite this crisis, there have been encouraging developments for long-term delivery of pain services, most notably the explosive growth in the adoption of telehealth technology and clinical resourcefulness in its applications. Further, the size and urgency of the COVID-19 pandemic has seen many cumbersome local, regional, and national health policy rules regarding the access, delivery and reimbursement of telehealth temporarily waived. These changes have afforded an opportunity to develop new ways of operating and a glimpse of how life could be for pain services under a “new normal”[82]. Importantly, telehealth has the potential to transform pain management, particularly for those with complex pain care needs living remotely from pain facilities or in low resource settings, removing barriers to multidisciplinary pain management delivered in a collaborative, interdisciplinary way – the optimal treatment approach for chronic pain [21]. Pain researchers have provided timely reports of the available evidence for treatment modalities capable of being delivered remotely [25,82]. However, the provision of pain services at local, regional, and national levels entails more than a consideration of evidence for individual service components. A broader framework is needed. This topical review considers the valuecase for telehealth-based multidisciplinary pain management approaches, reviews available evidence, delineates obstacles and proposes solutions across the domains of health systems, public health, and reimbursement policies. We should not turn back; rather, we should advance the potential gains of telehealth pain services. At the same time, it is imperative that we implement a research agenda evaluating outcomes, costs, and acceptability alongside these new clinical developments.


Tauben, David J. MD, FACP; Langford, Dale J. PhD; Sturgeon, John A. PhD; Rundell, Sean D. PT, DPT, PhD; Towle, Cara RN, MSN MA; Bockman, Christina PharmD; Nicholas, Michael PhDdoi: 10.1097/j.pain.0000000000002048

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The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings (Brain, 8 July 2020)


Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms, which will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.


Paterson RW, Brown RL, Benjamin L, Nortley R, Wiethoff S, Bharucha T, Jayaseelan DL, Kumar G, Raftopoulos RE, Zambreanu L, Vivekanandam V, Khoo A, Geraldes R, Chinthapalli K, Boyd E, Tuzlali H, Price G, Christofi G, Morrow J, McNamara P, McLoughlin B, Lim ST, Mehta PR, Levee V, Keddie S, Yong W, Trip SA, Foulkes AJM, Hotton G, Miller TD, Everitt AD, Carswell C, Davies NWS, Yoong M, Attwell D, Sreedharan J, Silber E, Schott JM, Chandratheva A, Perry RJ, Simister R, Checkley A, Longley N, Farmer SF, Carletti F, Houlihan C, Thom M, Lunn MP, Spillane J, Howard R, Vincent A, Werring DJ, Hoskote C, Jäger HR, Manji H, Zandi MS; UCL Queen Square National Hospital for Neurology and Neurosurgery COVID-19 Study Group. Brain. 2020 Jul 8. pii: awaa240. doi: 10.1093/brain/awaa240. [Epub ahead of print]. PMID: 32637987 [PubMed – as supplied by publisher]

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COVID-19 gastrointestinal symptoms mimicking surgical presentations (Annals of Medicine & Surgery, 24 June 2020)

Ashcroft J, Hudson VE, Davies RJ. Ann Med Surg (Lond). 2020 Jun 24;56:108-109. doi: 10.1016/j.amsu.2020.06.025. eCollection 2020 Aug. No abstract available. PMID: 32632349 [PubMed]

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Involvement of digestive system in COVID-19: manifestations, pathology, management and challenges (Therapeutic Advances in Gastroenterology, 18 June 2020


The pandemic of novel coronavirus disease (COVID-19) has developed as a tremendous threat to global health. Although most COVID-19 patients present with respiratory symptoms, some present with gastrointestinal (GI) symptoms like diarrhoea, loss of appetite, nausea/vomiting and abdominal pain as the major complaints. These features may be attributable to the following facts: (a) COVID-19 is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its receptor angiotensin converting enzyme 2 (ACE2) was found to be highly expressed in GI epithelial cells, providing a prerequisite for SARS-CoV-2 infection; (b) SARS-CoV-2 viral RNA has been found in stool specimens of infected patients, and 20% of patients showed prolonged presence of SARS-CoV-2 RNA in faecal samples after the virus converting to negative in the respiratory system. These findings suggest that SARS-CoV-2 may be able to actively infect and replicate in the GI tract. Moreover, GI infection could be the first manifestation antedating respiratory symptoms; patients suffering only digestive symptoms but no respiratory symptoms as clinical manifestation have also been reported. Thus, the implications of digestive symptoms in patients with COVID-19 is of great importance. In this review, we summarise recent findings on the epidemiology of GI tract involvement, potential mechanisms of faecal–oral transmission, GI and liver manifestation, pathological/histological features in patients with COVID-19 and the diagnosis, management of patients with pre-existing GI and liver diseases as well as precautions for preventing SARS-CoV-2 infection during GI endoscopy procedures.

Su S, Shen J, Zhu L, Qiu Y, He JS, Tan JY, Iacucci M, Ng SC, Ghosh S, Mao R, Liang J. Therap Adv Gastroenterol. 2020 Jun 18;13:1756284820934626. doi: 10.1177/1756284820934626. eCollection 2020. Review. PMID: 32595762 [PubMed] Free PMC Article

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COVID-19 presenting as severe, persistent abdominal pain and causing late respiratory compromise in a 33-year-old man (BMJ Case Reports, 16 June 2020)


A 33-year-old man presented repeatedly with severe abdominal pain and diarrhoea. Renal colic was suspected, and he was admitted for pain management. Questioning elicited an additional history of sore throat and mild, dry cough. Inflammatory markers were mildly raised (C reactive protein (CRP) 40 mg/L). Initial nasopharyngeal swabs were negative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by PCR. CT of the kidneys, ureters and bladder (CT KUB) was normal; however, CT of the thorax showed multifocal bilateral peripheral areas of consolidation consistent with COVID-19 infection. He developed respiratory compromise and was transferred to the intensive care unit (ICU). Sputum was positive for SARS-CoV-2 by PCR, and culture grew Yersinia enterocolitica. He recovered following supportive management and treatment with piperacillin-tazobactam.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

Walpole SC, McHugh R, Samuel J, Schmid ML. BMJ Case Rep. 2020 Jun 16;13(6). pii: e236030. doi: 10.1136/bcr-2020-236030.
PMID: 32546557 [PubMed – in process]

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COVID-19 presenting as severe, persistent abdominal pain and causing late respiratory compromise in a 33-year-old man (BMJ Case Reports, 16 June 2020)


A 33-year-old man presented repeatedly with severe abdominal pain and diarrhoea. Renal colic was suspected, and he was admitted for pain management. Questioning elicited an additional history of sore throat and mild, dry cough. Inflammatory markers were mildly raised (C reactive protein (CRP) 40 mg/L). Initial nasopharyngeal swabs were negative for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by PCR. CT of the kidneys, ureters and bladder (CT KUB) was normal; however, CT of the thorax showed multifocal bilateral peripheral areas of consolidation consistent with COVID-19 infection. He developed respiratory compromise and was transferred to the intensive care unit (ICU). Sputum was positive for SARS-CoV-2 by PCR, and culture grew Yersinia enterocolitica. He recovered following supportive management and treatment with piperacillin-tazobactam.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

Walpole SC, McHugh R, Samuel J, Schmid ML. BMJ Case Rep. 2020 Jun 16;13(6). pii: e236030. doi: 10.1136/bcr-2020-236030.
PMID: 32546557 [PubMed – in process]

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Does Ibuprofen Worsen COVID-19? (Drug Safety, 11 June 2020)


Moore N, Carleton B, Blin P, Bosco-Levy P, Droz C. Drug Saf. 2020 Jul;43(7):611-614. doi: 10.1007/s40264-020-00953-0. No abstract available.PMID: 32529474 [PubMed – indexed for MEDLINE] Free PMC Article

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No current evidence supporting risk of using Ibuprofen in patients with COVID‐19 (The International Journal of Clinical Practice, 7 June 2020)


SARS‐CoV‐2 is a novel RNA virus that infects cells expressing the angiotensin‐converting enzyme (ACE2) receptor and is associated with an acute respiratory disease named COVID‐19. It has been hypothesized that ACE2 expression can be increased by Ibuprofen leading to a higher risk for severe COVID‐19 (1). Despite the reasonable mechanistic background and results from studies suggesting that Ibuprofen may be associated with complications of community‐acquired pneumonia in children (2,3), there is no current evidence that this NSAID aggravates a SARS‐CoV‐2 infection in any age group.

Martins-Filho PR, do Nascimento-Júnior EM, Santana Santos V. Int J Clin Pract. 2020 Jun 7:e13576. doi: 10.1111/ijcp.13576. [Epub ahead of print]. PMID: 32506743 [PubMed – as supplied by publisher]

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Gastrointestinal involvement in COVID-19: a systematic review and meta-analysis (Annals of Gastroenterology, 6 June 2020)



Patients with COVID-19 usually manifest fever and respiratory symptoms. However, some patients also experience gastrointestinal (GI) symptoms such as diarrhea, vomiting and abdominal pain. In addition, SARS-CoV-2 RNA has been detected in feces of infected patients. Currently there is huge evolving research interest in this potentially lethal disease. We systematically reviewed and meta-analyzed the evidence suggesting involvement of the digestive system in COVID-19.



PubMed, Medline and Embase databases were searched up to 10 April 2020, using suitable keywords. Individual and pooled prevalence rates with 95% confidence intervals (CI) were calculated using the fixed- or random-effects model as appropriate. Heterogeneity between studies was calculated employing the Cochran Q test and I2 values, whereas the possibility of publication bias was examined by constructing funnel plots. Additionally, subgroup and sensitivity analyses were performed.



In adult COVID-19 patients, the prevalence rates (95%CI) for all GI symptoms, and separately for diarrhea, nausea/vomiting, and abdominal discomfort/pain were 9.8% (6.4-14.7), 10.4% (95%CI 7.7-13.9), 7.7% (95%CI 4.8-12.1), and 6.9% (95%CI 3.9-11.9) respectively. The prevalence rates for children were 9.6% (95%CI 6.3-14.3) for all symptoms, 9.6% (95%CI 6.3-14.3) for diarrhea, and 6.8% (95% CI 4.2-11) for nausea/vomiting. In 30.3% (95%CI 10.5-61.6) of the patients SARS-CoV-2 RNA was detected in feces.



A percentage of patients with COVID-19 will manifest symptoms from the digestive system. The GI tract may be a target organ and potential transmission route of SARS-CoV-2, with important implications for disease management and transmission.

Rokkas T. Ann Gastroenterol. 2020 Jul-Aug;33(4):355-365. doi: 10.20524/aog.2020.0506. Epub 2020 Jun 6. PMID: 32624655 [PubMed]

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Considering the potential for an increase in chronic pain following the COVID-19 pandemic (Pain, 3 June 2020)


Clauw DJ, Häuser W, Cohen SP, Fitzcharles MA. Considering the potential for an increase in chronic pain following the COVID-19 pandemic [published online ahead of print, 2020 Jun 3]. Pain. 2020;10.1097/j.pain.0000000000001950. doi:10.1097/j.pain.0000000000001950

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The Stanford Hall consensus statement for post-COVID-19 rehabilitation (British Journal of Sports Medicine, 31 May 2020)


The highly infectious and pathogenic novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2, has emerged causing a global pandemic. Although COVID-19 predominantly affects the respiratory system, evidence indicates a multisystem disease which is frequently severe and often results in death. Long-term sequelae of COVID-19 are unknown, but evidence from previous CoV outbreaks demonstrates impaired pulmonary and physical function, reduced quality of life and emotional distress. Many COVID-19 survivors who require critical care may develop psychological, physical and cognitive impairments. There is a clear need for guidance on the rehabilitation of COVID-19 survivors. This consensus statement was developed by an expert panel in the fields of rehabilitation, sport and exercise medicine (SEM), rheumatology, psychiatry, general practice, psychology and specialist pain, working at the Defence Medical Rehabilitation Centre, Stanford Hall, UK. Seven teams appraised evidence for the following domains relating to COVID-19 rehabilitation requirements: pulmonary, cardiac, SEM, psychological, musculoskeletal, neurorehabilitation and general medical. A chair combined recommendations generated within teams. A writing committee prepared the consensus statement in accordance with the appraisal of guidelines research and evaluation criteria, grading all recommendations with levels of evidence. Authors scored their level of agreement with each recommendation on a scale of 0–10. Substantial agreement (range 7.5–10) was reached for 36 recommendations following a chaired agreement meeting that was attended by all authors. This consensus statement provides an overarching framework assimilating evidence and likely requirements of multidisciplinary rehabilitation post-COVID-19 illness, for a target population of active individuals, including military personnel and athletes.

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download, and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

Barker-Davies RM, O’Sullivan O, Senaratne KPP, Baker P, Cranley M, Dharm-Datta S, Ellis H, Goodall D, Gough M, Lewis S, Norman J, Papadopoulou T, Roscoe D, Sherwood D, Turner P, Walker T, Mistlin A, Phillip R, Nicol AM, Bennett AN, Bahadur S. Br J Sports Med. 2020 May 31. pii: bjsports-2020-102596. doi: 10.1136/bjsports-2020-102596. [Epub ahead of print]. PMID: 32475821 [PubMed – as supplied by publisher]

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Neuropathogenesis and Neurologic Manifestations of the Coronaviruses in the Age of Coronavirus Disease 2019 (JAMA Neurology, 29 May 2020)


Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in December 2019, causing human coronavirus disease 2019 (COVID-19), which has now spread into a worldwide pandemic. The pulmonary manifestations of COVID-19 have been well described in the literature. Two similar human coronaviruses that cause Middle East respiratory syndrome (MERS-CoV) and severe acute respiratory syndrome (SARS-CoV-1) are known to cause disease in the central and peripheral nervous systems. Emerging evidence suggests COVID-19 has neurologic consequences as well.

Zubair AS, McAlpine LS, Gardin T, Farhadian S, Kuruvilla DE, Spudich S. A Review. JAMA Neurol. 2020 May 29. doi: 10.1001/jamaneurol.2020.2065. [Epub ahead of print]. PMID: 32469387 [PubMed – as supplied by publisher]

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Daring discourse: are we ready to recommend neuraxial anesthesia and peripheral nerve blocks during the COVID-19 pandemic? A pro-con (Regional Anesthesia & Pain Medicine, 23 May 2020)


The recent joint statement from the American Society of Regional Anesthesia and Pain Medicine (ASRA) and the European Society of Regional Anesthesia and Pain Therapy (ESRA)recommends neuraxial and peripheral nerve blocks for patients with coronavirus disease 2019 (COVID-2019) illness. The benefits of regional anesthetic and analgesic techniques on patient outcomes and healthcare systems are evident. Regional techniques are now additionally promoted as a mechanism to reduce aerosolizing procedures. However, caring for patients with COVID-19 illness requires rapid redefinition of risks and benefits—both for patients and practitioners. These should be fully considered within the context of available evidence and expert opinion. In this Daring Discourse, we present two opposing perspectives on adopting the ASRA/ESRA recommendation. Areas of controversy in the literature and opportunities for research to address knowledge gaps are highlighted. We hope this will stimulate dialogue and research into the optimal techniques to improve patient outcomes and ensure practitioner safety during the pandemic

Singleton MN, Soffin EM. Reg Anesth Pain Med. 2020 May 23. pii: rapm-2020-101653. doi: 10.1136/rapm-2020-101653. [Epub ahead of print]. PMID: 32447292 [PubMed – as supplied by publisher]

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Medications in COVID-19 patients: summarizing the current literature from an orthopaedic perspective (Int Orthopedics, 22 May 2020)


Purpose: The review aims to provide a summary of the current literature regarding common medications prescribed in orthopedic surgery and their potential implications in COVID-19 patients.

Methods: A systematic review was performed using the PRISMA guidelines. All clinical studies, reviews, consensus, and guidelines related to the above medications and COVID-19 were included.

Results: A total of 18 articles were included. The use of analgesia, anti-inflammatories, steroids, anticoagulants, antibiotics, vitamin B, vitamin C, and vitamin D and their potential impact on COVID-19 patients were reported.

Conclusion: Eight main recommendations were derived from the review. Firstly, paracetamol remains the first line of analgesia and antipyretic. Secondly, there is no need to avoid NSAIDs for COVID-19 patients. Thirdly, opioids have the potential for immunosuppression in addition to respiratory depression and, therefore, should be prescribed with care in COVID-19 patients. Fourthly, patients with conditions where steroids are proven to be efficacious can continue to receive their steroids; otherwise, systemic steroids are not recommended for COVID-19 patients. Fifthly, orthopedic surgeons following up on COVID-19 patients who are using steroids should continue to follow them up for possible avascular necrosis. Sixthly, whenever possible, oral anticoagulation should be converted to parental heparin. Seventhly, common orthopedic antibiotics including penicillin and clindamycin are safe to continue for COVID-19 patients. However, for COVID-19 patients, the antibiotics can potentially be switched to macrolides and tetracyclines if the organisms are sensitive. Lastly, prescription for vitamins B, C, and D should continue as per usual clinical practice.

Tan SHS, Hong CC, Saha S, Murphy D, Hui JH. Int Orthop. 2020 May 22. doi: 10.1007/s00264-020-04643-5. [Epub ahead of print] Review. PMID: 32445030 [PubMed – as supplied by publisher]

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Emergence from the COVID-19 Pandemic and the Care of Chronic Pain: Guidance for the Interventionalist (Anesthesia & Analgesia, 21 May 2020)


Introduction: The current coronavirus disease (COVID-19) pandemic led to a significant disruption in the care of pain from chronic and subacute conditions. The impact of this cessation of pain treatment may have unintended consequences of increased pain, reduced function, increased reliance on opioid medications, and potential increased morbidity, due to the systemic impact of untreated disease burden. This may include decreased mobility, reduction in overall health status, and increase of opioid use with the associated risks.

Methods: The article is the work of the American Society of Pain and Neuroscience (ASPN) COVID-19 Task Force to evaluate the policies set forth by federal, state, and local agencies to reduce or eliminate elective procedures for those patients with pain from spine, nerve and joint disease. The impact of these decisions, which were needed to reduce the spread of the pandemic, led to a delay in care for many patients. We hence review an emergence plan to reinitiate this pain-related care. The goal is to outline a path to work with federal, state, and local authorities to combat the spread of the pandemic and minimize the deleterious impact of pain and suffering on our chronic pain patients.

Result: The paper sets forth a strategy for the interventional pain centers to reemerge from the current pandemic and to set a course for future events.

Deer T, Sayed D, Pope J, Chakravarthy K, Petersen E, Moeschler SM, Abd-Elsayed A, Amirdelfan K, Mekhail N; ASPN COVID Workgroup. Anesth Analg. 2020 May 21. doi: 10.1213/ANE.0000000000005000. [Epub ahead of print]. PMID: 32452905 [PubMed – as supplied by publisher]

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Managing patients with rheumatic diseases during the COVID-19 pandemic: The French Society of Rheumatology answers to most frequently asked questions up to May 2020 (Joint Bone Spine, 19 May 2020)


Background: Rheumatologists must contend with COVID-19 pandemic in the management of their patients and many questions have been raised on the use of both anti-inflammatory drugs and disease-modifying anti-rheumatic drugs (DMARD). The French Society of Rheumatology (SFR) selected the most critical ones to the daily practice of a rheumatologist and a group of 10 experts from SFR and Club Rheumatism and Inflammation (CRI) boards proposed responses based on the current knowledge of May 2020.

Basic procedure: Following the availability of the first 18 questions and statements, 1400 individuals consulted the frequently asked questions between the March 31, 2020 and April 12, 2020. As a result, 16 additional questions were forwarded to the SFR, and answered by the board. An additional round of review by email and video conference was organized, which included updates of the previous statements. The scientific relevance of 5 of the questions led to their inclusion in this document. Each response received a final assessment on a scale of 0–10 with 0 meaning no agreement whatsoever and 10 being in complete agreement. The mean values of these votes for each question are presented as the levels of agreement (LoA) at the end of each response. This document was last updated on April 17, 2020.

Main findings: Based on current scientific literature already published, in most circumstances, there is no contraindication to the initiation or continuation of anti-inflammatory drugs as well as DMARDs. If signs suggestive of infection (coronavirus or other) occurs, treatments should be discontinued and resumed, if necessary, after 2 weeks without any symptoms. Only, some signals suggest that people taking an immunosuppressive dose of corticosteroid therapy are at greater risk of developing severe COVID-19. Intra-articular injections of glucocorticoids are allowed when there is no reasonable therapeutic alternative, and providing that precautions to protect the patient and the practitioner from viral contamination are adopted, included appropriate information to the patient.

Principal conclusions: Currently available data on managing patients with rheumatic diseases during the COVID-19 pandemic are reassuring and support continuing or initiating symptomatic as well as specific treatments of these diseases, the main target of their management remaining their appropriate control, even during this pandemic.

Keywords: COVID-19 inflammatory rheumatic diseases; treatment; health system

Richez C, Flipo RM, Berenbaum F, Cantagrel A, Claudepierre P, Debiais F, Dieudé P, Goupille P, Roux C, Schaeverbeke T, Wendling D, Pham T, Thomas T. Joint Bone Spine. 2020 May 27. pii: S1297-319X(20)30092-0. doi: 10.1016/j.jbspin.2020.05.006. [Epub ahead of print]. PMID: 32473418 [PubMed – as supplied by publisher]C Article

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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.

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How psychosocial and economic impacts of COVID-19 pandemic can interfere on bruxism and temporomandibular disorders? (Journal of Aplied Oral Science, 11 May 2020)

Almeida-Leite CM, Stuginski-Barbosa J, Conti PCR. J Appl Oral Sci. 2020;28:e20200263. Epub 2020 May 11. No abstract available. PMID: 32401942 [PubMed – indexed for MEDLINE] Free PMC Article

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


Rheumatology teams care for patients with diverse, systemic autoimmune diseases who are often immunosuppressed and at high risk of infections. The current COVID-19 pandemic has presented particular challenges in caring for and managing this patient group. The office of the chief medical officer (CMO) for England contacted the rheumatology community to provide expert advice on the identification of extremely vulnerable patients at very high risk during the COVID-19 pandemic who should be ‘shielded’. This involves the patients being asked to strictly self-isolate for at least 12 weeks with additional funded support provided for them to remain at home. A group of rheumatologists (the authors) have devised a pragmatic guide to identifying the very highest risk group using a rapidly developed scoring system which went live simultaneous with the Government announcement on shielding and was cascaded to all rheumatologists working in England.

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.

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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)

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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.

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


Section 2 of the 2019 World Health Organization Model List of Essential Medicines includes opioid analgesics formulations commonly used for the control of pain and respiratory distress, as well as sedative and anxiolytic substances such as midazolam and diazepam. These medicines, essential to palliative care, are regulated under the international drug control conventions overseen by United Nations specialized agencies and treaty bodies and under national drug control laws. Those national laws and regulations directly affect bedside availability of Internationally Controlled Essential Medicines (ICEMs). The complex interaction between national regulatory systems and global supply chains (now impacted by COVID-19 pandemic) directly affects bedside availability of ICEMs and patient care. Despite decades of global civil society advocacy in the United Nations system, ICEMs have remained chronically unavailable, inaccessible, and unaffordable in low- andmiddle-income countries, and there are recent reports of shortages in high-income countries as well. The most prevalent symptoms in COVID-19 are breathlessness, cough, drowsiness, anxiety, agitation, and delirium. Frequently used medicines include opioids such as morphine or fentanyl and midazolam, all of them listed as ICEMs. This paper describes the issues related to the lack of availability and limited access to ICEMs during the COVID-19 pandemic in both intensive and palliative care patients in countries of all income levels and makes recommendations for improving access

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

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NSAIDs in patients with viral infections, including Covid-19: Victims or perpetrators? (Italian Society of Pharmacology, 29 April 2020)


Taking anti-inflammatory drugs, including non-steroidal (NSAIDs), during Covid-19 infection, how much is risky? The French Minister of Health, who has raised an alarm on a possible risk deriving from the use of ibuprofen for the control of fever and other symptoms during the disease, opened the debate a few days ago.

In this paper we examine available evidence from preclinical and clinical studies that had analysed the role of COX in the inflammatory process and the effects of NSAIDs in patients with infections. Most of the published studies that suggested not protective effects of NSAIDs were mainly performed in vitro or on animals. Therefore, their meaning in humans is to be considered with great caution. Based also on data suggesting protective effects of NSAIDs, we concluded that currently there is no evidence suggesting a correlation between NSAIDs and a worsening of infections. Further studies will be certainly needed to better define the role of NSAIDs and particularly COX2 inhibitors in patients with infections. In the meantime, we must wait for results of the revision started by the PRAC on May 2019 on the association ibuprofen/ketoprofen​​​​​​ and worsening of infections. Since nowadays no scientific evidence establishes a correlation between NSAIDS and worsening of COVID-19, patients should be advice against any NSAIDs self-medication when COVID-19 like symptoms are present.

Capuano A, Scavone C, Racagni G, Scaglione F; Italian Society of Pharmacology. Pharmacol Res. 2020 Jul;157:104849. doi: 10.1016/j.phrs.2020.104849. Epub 2020 Apr 29. PMID: 32360482 [PubMed – indexed for MEDLINE] Free PMC Article

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EMA advice on the use of NSAIDs for Covid-19 (Drug and Therapeutics Bulletin, 31 March 2020)

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

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