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Warning Against the Use of Anti-Inflammatory Medicines to Cure COVID-19: Building Castles in the Air

  • Paolo Procacci Foundation


COVID-19 is developing rapidly and invading the whole world in a real pandemic. There is much discussion (appropriate or less appropriate,) on this hot topic. Recent declarations have focused attention on the risk of interactions between NSAIDs and COVID-19. There are also theories on the potential interactions between the use of ACE inhibitors, the use of ibuprofen and the increased risk of infection. At the moment, there are no data in the literature showing that this would be the case. Pain patients may be reassured by their physicians on the safety of using ACE inhibitors and NSAIDs (especially ibuprofen), because there is nothing to show the potential for an increased risk of viral infection, and especially of COVID-19.
Warning Against the Use of Anti-Inflammatory
Medicines to Cure COVID-19: Building Castles
in the Air
Giustino Varrassi
Received: March 23, 2020
The Author(s) 2020
Keywords: Anti-inflammatory medicines;
Key Summary Points
COVID-19 is developing rapidly and
invading the whole world in a real
There is much discussion, appropriate or
less appropriate, of this hot topic.
Recent declarations have focused
attention on the risk of interactions
between NSAIDs and COVID-19.
There are also theories on the potential
interactions between the use of ACE
inhibitors, the use of ibuprofen and the
increased risk of infection.
At the moment, there are no data in the
literature showing that this would be the
Pain patients may be reassured by their
physicians on the safety of using ACE
inhibitors and NSAIDs (especially
ibuprofen), because there is nothing to
show the potential for an increased risk
of viral infection, and especially of
A recent article in Le Figaro has focused atten-
tion on the use of anti-inflammatory medicines
because they could be responsible for an
increased incidence of infections due to
COVID-19 [1]. This article reports and empha-
sizes the opinion of politicians expressed via
social media suggesting the use of one medicine
instead of others, but not referencing opinions
based on scientific data.
A recent article focused its attention on the
supposed relationship between chronic
pathologies (hypertension and diabetes melli-
tus) and COVID-19 infection and their phar-
macological treatment [2]. The initial
assumption is based on two recent papers
reporting the clinical experience in China,
during the dramatic epidemic now becoming a
pandemic [3,4]. Both articles suggest that
patients affected by COVID-19 frequently had
concomitant chronic pathologies, especially
hypertension and diabetes mellitus, pathologies
that might be treated with angiotensin-con-
verting-enzyme (ACE) inhibitors. Fang et al. [2]
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00193 Rome, Italy
Adv Ther
based their intriguing theory, of an increased
risk of COVID-19 infection on patients treated
with ACE inhibitors, on the relationship
between the ACE system, which can be influ-
enced by anti-inflammatory medicines, and the
lung epithelial cells. Following this theory, their
conclusion was the most obvious: ‘‘patients
treated with ACE2-increasing drugs are at
higher risk for severe COVID-19 infection’’ .
None of the quoted articles reporting the clini-
cal experience in China has assessed the previ-
ous pharmacological therapy of the patients
infected by COVID-19 [3,4].
In the last part of this recent article, the
authors suggest that, based on a search on
PubMed made on February 28, 2020, there are
no reports on the potential influence of calcium
channel blockers on ACE2 activity [2]. There-
fore, these drugs could be used as an ‘‘alterna-
tive treatment in these patients’’. Actually,
nobody knows what the pharmacological ther-
apy of the Chinese patients was. Maybe some of
them were already using calcium antagonists.
Hence, it seems that Fang et al.’s [2] theory is
not related to what is reported in the two Chi-
nese papers.
Recently (March 9, 2020), I carried out a very
thorough literature search for all the published
material on COVID-19. None of the articles
found on PubMed reports data connecting the
use of ACE-inhibitors or NSAIDs to an increased
incidence or risk of COVID-19 infection. I am
not excluding that it might be shown in the
future, when the literature will have more clear
and valid scientific information, but at the
moment it seems very premature. I think that,
especially in a dramatic moment like the one we
are living in, it would be more prudent to pre-
vent the temptation to build castles in the air.
Funding. This article has been possible
thanks to the unconditional support of the
Paolo Procacci Foundation. No Rapid Service
Fee was received by the journal for the publi-
cation of this article.
Authorship. The named author meets the
International Committee of Medical Journal
Editors (ICMJE) criteria for authorship for this
article, takes responsibility for the integrity of
the work as a whole, and has given approval for
this version to be published.
Disclosures. Giustino Varrassi is a section
editor of this journal.
Compliance with Ethics Guidelines. The
article is based on previously conducted studies
and publications, and does not contain any
studies with human participants or animals
performed by the author.
Data Availability. Data sharing is not
applicable to this article as no datasets were
generated or analyzed during the current study.
Open Access. This article is licensed under a
Creative Commons Attribution-NonCommer-
cial 4.0 International License, which permits
any non-commercial use, sharing, adaptation,
distribution and reproduction in any medium
or format, as long as you give appropriate credit
to the original author(s) and the source, provide
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Accessed 15 Mar 2020.
2 Fang L, Karakiulakis G, Roth M. Are patients with
hypertension and diabetes mellitus at increased risk
Adv Ther
for COVID-19 infection? Lancet Respir Med. 2020. (published on line March
3 Yang X, Yu Y, Xu J, et al. Clinical course and outcomes
of critically ill patients with SARS-CoV-2 pneumonia
in Wuhan, China: a single-centered, retrospective,
observational study. Lancet Respir Med. 2020. https:// (published
online Feb 24).
4 Guan W, Ni Z, Hu Y, et al. Clinical characteristics of
coronavirus disease 2019 in China. N Engl J Med.
2020. (pub-
lished online Feb 28).
Adv Ther
... Early in the pandemic, the unfounded speculation that taking nonsteroidal anti-inflammatory drugs could be linked to severe forms of COVID-19 in young and healthy subjects might had a significant impact on pain management [23]. Luckily, it was immediately and successfully opposed by the healthcare community [24,25]. Other misinformation included the suggestion to avoid ACE2-increasing drugs for patients with cardiac diseases, hypertension, or diabetes [26]. ...
... Other misinformation included the suggestion to avoid ACE2-increasing drugs for patients with cardiac diseases, hypertension, or diabetes [26]. This also created a tsunami of responses by the health community [24,[27][28][29] and forced the initial authors to review and eventually withdraw their overinterpreted hypothesis [30]. ...
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Palliative medicine is an important topic, especially during the COVID pandemia. The authors present a review of many of the critical aspects and challenges. They conclude that at the moment, due to the general situation of the global health care systems, palliative medicine would deserve an increasing attention and a more scientific approach. They also suggest to postpone the deadline of this special issue on palliative medicine, in order to offer the possibility of more manuscripts to be submitted bu many researchers around the world.
... Third, a lot of 'fake news' circulated on social networks and in the media during the beginning of the pandemic [33]. For instance, the NSAID COVID-19 hoax phenomenon, which was immediately criticized [34], directly impacted prescription patterns in chronic pain patients. Unverified information on NSAIDs as a factor worsening the course of SARS-CoV-2 infection, published by Le Figaro (the oldest national newspaper), was taken seriously by many physicians [35]. ...
Aims: The authors evaluated the impact of the first coronavirus disease 2019 pandemic wave on French chronic pain structures (CPSs). Methods: An online survey assessed CPS resource allocation, workflow and perceived impact on patient care. Results: All CPS workflow was severely impacted by the reallocation of 42% of specialists. In-person appointments were cancelled by 72% of participants. Follow-up was maintained in 91% of participants (telemedicine). Skills in end-of-life decision-making/counseling were rarely solicited. The perceived impact of the crisis on the experience of patients was high (eight out of ten), with a significant increase in access-to-care delay. Conclusion: CPSs maintained patient follow-up. Special features of CPS specialists were rarely solicited by coronavirus disease 2019 teams experiencing a high workload. Recommendations on optimal CPS resource reallocations have to be standardized in crisis conditions.
... Nonsteroidal anti-inflammatory drugs (NSAIDs) may be appropriate for pain control in certain patients, but there remain some unknowns in their use with COVID-19 patients [48]. At first, there was controversy about the use of ibuprofen, often chosen for its antipyretic properties, but these concerns were shown to be unfounded [49]. It was further speculated that NSAIDs may be safe but could potentially mask symptoms of the infection that would be better to recognize early. ...
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Vaccinations and therapeutics have been developed for COVID-19, but vaccine uptake varies markedly among countries. Public health responses have also varied, in particular, with lockdown efforts and school closing. All over the world, the pandemic exposed healthcare and economic weaknesses. COVID-19 exacerbated mental health issues by exposing the population to prolonged periods of fear, anxiety, financial stress, psychological uncertainties, and sometimes isolation from even family and friends. Chronic pain patients have been disproportionately affected. The pandemic-associated stresses may have exacerbated their already painful symptoms while at the same time interrupting their access to care. The ramifications of the COVID-19 post-viral syndrome ("long COVID-19") are not yet known. COVID-19 viral infection has been associated with neuropathic pain symptoms. Tele-triage and telehealth applications can help manage chronic pain patients in the COVID-19 era, but many interventional procedures, injections, or other treatments have been delayed. The role of palliative care for patients with terminal cases of infection must be reexamined. Palliative care is a relatively new medical specialty and allows terminally ill patients to die in as much comfort and peace as can be afforded to them. More training in palliative care for all clinicians is urgently needed. COVID-19 exposed much that is wrong or weak or inadequate in our healthcare systems, but it also allowed us to embrace new technologies and develop better systems to manage the challenge of a pandemic.
... Many scientists produced important publications on the abovementioned assertion by resorting to incredible and convoluted scientific justifications [13]. One of those articles was immediately criticized for its inconsistency [14][15][16][17]. The authors were obliged to completely revise their opinion in a subsequent article, but the effort was futile [18]. ...
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It opens the discussion on the relationship between analgesic drugs and COVID-19
... This advice, which was not based on any scientific evidence [27], was quickly retracted, but this one remark was sufficient to confuse clinicians, patients, and ordinary citizens not just in France but around the world [28]. There is no evidence that ibuprofen exacerbates COVID-19 and there is no immediately evident mechanism by which it could do so [29,30]. On March 18, 2020, the European Medicines Agency stated there was no scientific evidence that ibuprofen exacerbated COVID symptoms [31]. ...
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... The scientific article presented an interesting theory on the necessity to change therapy to patients in treatment with ACEinhibitors and/or ibuprofen [11]. Immediately after, it has been criticized because of its scientific inconsistency [12]. Actually, ...
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Ibuprofen is a long lasting non-steroidal anti-inflammatory drugs (NSAIDs) and still represents one of the most diffused analgesics around the world. It has an interesting story started over 50 years ago. In this short comment to an already published paper, the authors try to focus some specific important point. On top, they illustrate the recent, confusing and fake assertion on the potentially dangerous influence that ibuprofen could have, increasing the risk of Coronavirus infection. This is also better illustrated in a previously published paper, where the readers could find more clear responses to eventual doubts.
... It should be noted that the use of non-steroidal anti-inflammatory drugs (NSAIDs), ibuprofen in particular, has been cautioned due to the potential interaction with the angiotensin converting enzyme 2 (ACE 2) receptor [35]. ACE 2 has been previously described as the cellular binding site of the spiked proteins on the SARS CoV-2 surface [36]. ...
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... The hasty response against specific drugs in the setting of COVID-19 has been effectively challenged as being speculative rather than evidence based. 7 Results from several Chinese reports are summarized in Table 1. None of these studies described drug regimens of these patients. ...
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... As stated by both European Medicine Agency (EMA) and Food and Drug Administration (FDA), there is currently no scientific evidence establishing a link between ibuprofen and COVID-19. Pending further research, people taking NSAIDs for other reasons should not stop doing so for fear of increasing their COVID-19 risk[16,[30][31][32]. ...
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Coronavirus Disease 2019 (COVID-19) is spreading rapidly around the world with devastating consequences on patients, healthcare workers, health systems as well as economies. While, health-care systems are globally operating at maximum capacity, healthcare workers and especially anesthesia providers are facing extreme pressures, something that is also leading to declining availability and increasing stress. In this regard, it is extremely concerning the fact that some regions worldwide have reported up to 20% of their cases to be health care workers. When considering that the global case fatality rate may be as much as 5.4%, these numbers are concerning and unacceptable. As this pandemic accelerates, access to personal protective equipment for health workers is a key concern since at present, health-care workers are every country’s most valuable resource in the fight against COVID-19. Governments and heath organizations should take care of their staff and support them in any way possible. This review aims to describe the current situation anesthesia providers are facing in the setting of COVID-19 and provide solutions and evidence on important concerns including which guidance to follow, the level of equipment that is adequate and level of protection they need for every patient being administered an anesthetic.
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Background: Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods: We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results: The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions: During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.).
Background Small airway dysfunction is a common but neglected respiratory abnormality. Little is known about its prevalence, risk factors, and prognostic factors in China or anywhere else in the world. We aimed to estimate the prevalence of small airway dysfunction using spirometry before and after bronchodilation, both overall and in specific population subgroups; assess its association with a range of lifestyle and environmental factors (particularly smoking); and estimate the burden of small airway dysfunction in China. Methods From June, 2012, to May, 2015, the nationally representative China Pulmonary Health study invited 57 779 adults to participate using a multistage stratified sampling method from ten provinces (or equivalent), and 50 479 patients with valid lung function testing results were included in the analysis. We diagnosed small airway dysfunction on the basis of at least two of the following three indicators of lung function being less than 65% of predicted: maximal mid-expiratory flow, forced expiratory flow (FEF) 50%, and FEF 75%. Small airway dysfunction was further categorised into pre-small airway dysfunction (defined as having normal FEV1 and FEV1/forced vital capacity [FVC] ratio before bronchodilator inhalation), and post-small airway dysfunction (defined as having normal FEV1 and FEV1/FVC ratio both before and after bronchodilator inhalation). Logistic regression yielded adjusted odds ratios (ORs) for small airway dysfunction associated with smoking and other lifestyle and environmental factors. We further estimated the total number of cases of small airway dysfunction in China by applying present study findings to national census data. Findings Overall the prevalence of small airway dysfunction was 43·5% (95% CI 40·7–46·3), pre-small airway dysfunction was 25·5% (23·6–27·5), and post-small airway dysfunction was 11·3% (10·3–12·5). After multifactor regression analysis, the risk of small airway dysfunction was significantly associated with age, gender, urbanisation, education level, cigarette smoking, passive smoking, biomass use, exposure to high particulate matter with a diameter less than 2·5 μm (PM2·5) concentrations, history of chronic cough during childhood, history of childhood pneumonia or bronchitis, parental history of respiratory diseases, and increase of body-mass index (BMI) by 5 kg/m². The ORs for small airway dysfunction and pre-small airway dysfunction were similar, whereas larger effect sizes were generally seen for post-small airway dysfunction than for either small airway dysfunction or pre-small airway dysfunction. For post-small airway dysfunction, cigarette smoking, exposure to PM2·5, and increase of BMI by 5 kg/m² were significantly associated with increased risk, among preventable risk factors. There was also a dose-response association between cigarette smoking and post-small airway dysfunction among men, but not among women. We estimate that, in 2015, 426 (95% CI 411–468) million adults had small airway dysfunction, 253 (238–278) million had pre-small airway dysfunction, and 111 (104–126) million had post-small airway dysfunction in China. Interpretation In China, spirometry-defined small airway dysfunction is highly prevalent, with cigarette smoking being a major modifiable risk factor, along with PM2·5 exposure and increase of BMI by 5 kg/m². Our findings emphasise the urgent need to develop and implement effective primary and secondary prevention strategies to reduce the burden of this condition in the general population. Funding Ministry of Science and Technology of China; National Natural Science Foundation of China; National Health Commission of China.
Background: An ongoing outbreak of pneumonia associated with the severe acute respiratory coronavirus 2 (SARS-CoV-2) started in December, 2019, in Wuhan, China. Information about critically ill patients with SARS-CoV-2 infection is scarce. We aimed to describe the clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia. Methods: In this single-centered, retrospective, observational study, we enrolled 52 critically ill adult patients with SARS-CoV-2 pneumonia who were admitted to the intensive care unit (ICU) of Wuhan Jin Yin-tan hospital (Wuhan, China) between late December, 2019, and Jan 26, 2020. Demographic data, symptoms, laboratory values, comorbidities, treatments, and clinical outcomes were all collected. Data were compared between survivors and non-survivors. The primary outcome was 28-day mortality, as of Feb 9, 2020. Secondary outcomes included incidence of SARS-CoV-2-related acute respiratory distress syndrome (ARDS) and the proportion of patients requiring mechanical ventilation. Findings: Of 710 patients with SARS-CoV-2 pneumonia, 52 critically ill adult patients were included. The mean age of the 52 patients was 59·7 (SD 13·3) years, 35 (67%) were men, 21 (40%) had chronic illness, 51 (98%) had fever. 32 (61·5%) patients had died at 28 days, and the median duration from admission to the intensive care unit (ICU) to death was 7 (IQR 3-11) days for non-survivors. Compared with survivors, non-survivors were older (64·6 years [11·2] vs 51·9 years [12·9]), more likely to develop ARDS (26 [81%] patients vs 9 [45%] patients), and more likely to receive mechanical ventilation (30 [94%] patients vs 7 [35%] patients), either invasively or non-invasively. Most patients had organ function damage, including 35 (67%) with ARDS, 15 (29%) with acute kidney injury, 12 (23%) with cardiac injury, 15 (29%) with liver dysfunction, and one (2%) with pneumothorax. 37 (71%) patients required mechanical ventilation. Hospital-acquired infection occurred in seven (13·5%) patients. Interpretation: The mortality of critically ill patients with SARS-CoV-2 pneumonia is considerable. The survival time of the non-survivors is likely to be within 1-2 weeks after ICU admission. Older patients (>65 years) with comorbidities and ARDS are at increased risk of death. The severity of SARS-CoV-2 pneumonia poses great strain on critical care resources in hospitals, especially if they are not adequately staffed or resourced. Funding: None.