Can ibuprofen worsen COVID-19 symptoms. How does fever reduction affect viral illness duration. Why might ibuprofen’s superior antipyretic effect be concerning in COVID-19 cases. What are the potential benefits of allowing a natural fever response.

The Controversy Surrounding Ibuprofen Use in COVID-19 Patients

The use of ibuprofen in COVID-19 patients has sparked debate within the medical community. Initial concerns arose from anecdotal reports in France, where four young, previously healthy individuals experienced worsening symptoms after taking ibuprofen early in their illness. This led to temporary caution from health organizations regarding nonsteroidal anti-inflammatory drugs (NSAIDs) for COVID-19 symptoms.

However, due to a lack of clinical or population data, both the European Medicines Agency and the World Health Organization have since revised their stance. They no longer recommend avoiding NSAIDs when clinically indicated for COVID-19 patients. Despite this, questions remain about the potential indirect effects of ibuprofen use, particularly its role in fever reduction.

The Role of Fever in Viral Infections

Fever is a common symptom in COVID-19 cases, observed in up to 99% of patients. Many individuals may instinctively reach for over-the-counter medications like ibuprofen or acetaminophen to alleviate discomfort. However, this action may inadvertently interfere with the body’s natural defense mechanisms.

Benefits of Fever in Fighting Viral Illnesses

• Reduction in viral illness duration
• Potential decrease in associated mortality
• Activation of the immune system
• Increased lymphocyte activity
• Enhanced oxygenation of organ tissues

Research has shown that fever plays a crucial role in the body’s response to viral infections. It acts as a systemic alert system, activating various immune responses to combat invading pathogens. Suppressing this natural fever response may have unintended consequences on the healing process.

Ibuprofen’s Superior Antipyretic Effect: A Double-Edged Sword?

Studies have consistently demonstrated that ibuprofen is more effective than acetaminophen in reducing fever. This superior antipyretic effect has been observed in both children and adults. While this might seem beneficial for patient comfort, it raises concerns about potentially hindering the body’s natural defense mechanisms against COVID-19.

Comparative Efficacy of Ibuprofen and Acetaminophen

1. Larger temperature decrease with ibuprofen
2. Longer duration of antipyretic response
3. More effective fever reduction in children and adults

The enhanced fever-reducing capabilities of ibuprofen may inadvertently suppress the beneficial effects of fever in fighting viral infections, including COVID-19. This raises questions about whether the use of such potent antipyretics early in the course of the illness could potentially lead to worse outcomes.

The Physiological Impact of Fever Suppression in COVID-19

Understanding the complex interplay between fever and the body’s response to COVID-19 is crucial. Recent research has revealed that certain COVID-19 proteins interact with hemoglobin, potentially impairing oxygen transport and leading to hypoxemia. In this context, the role of fever becomes even more significant.

Fever’s Effect on Oxygen Delivery

A key physiological fact is that increased body temperature facilitates the unloading of oxygen from hemoglobin to tissues in need. By suppressing fever, we may inadvertently hinder this crucial process, potentially exacerbating the hypoxic conditions observed in severe COVID-19 cases.

Balancing Patient Comfort and Therapeutic Benefit

The use of antipyretics in viral illnesses, including COVID-19, presents a challenging balance between alleviating patient discomfort and preserving the body’s natural defense mechanisms. While reducing fever may provide temporary relief, there is little evidence to support that it leads to better overall outcomes in otherwise healthy patients.

Considerations for Antipyretic Use

• Patient’s overall health status
• Severity of symptoms
• Stage of illness
• Potential risks vs. benefits of fever reduction

Healthcare providers and patients must weigh these factors carefully when deciding whether to use antipyretics like ibuprofen in the early stages of COVID-19. The potential benefits of allowing a natural fever response should be considered against the immediate comfort provided by fever reduction.

Implications for COVID-19 Treatment Protocols

The hypothesis that ibuprofen’s potent antipyretic effect may indirectly lead to worse outcomes in COVID-19 cases warrants further investigation. This concept challenges current practices and raises important questions about the routine use of over-the-counter antipyretics in the early stages of viral illnesses.

Potential Areas for Future Research

1. Comparative studies of outcomes in COVID-19 patients using different antipyretics
2. Investigation of the optimal fever threshold for intervention in viral illnesses
3. Exploration of alternative methods for managing patient discomfort without suppressing fever
4. Analysis of the impact of fever reduction on viral shedding and disease transmission

These research directions could provide valuable insights into optimizing treatment protocols for COVID-19 and other viral infections, potentially leading to improved patient outcomes.

The Broader Implications of Fever Management in Infectious Diseases

The discussion surrounding ibuprofen use in COVID-19 patients opens up a broader conversation about fever management in infectious diseases. It challenges long-held assumptions about the necessity of fever reduction and prompts a reevaluation of our approach to symptomatic treatment in viral illnesses.

Rethinking Fever Reduction Strategies

• Tailoring antipyretic use to individual patient needs
• Exploring non-pharmacological methods of comfort management
• Educating patients about the potential benefits of fever
• Developing guidelines for appropriate fever management in different clinical scenarios

This shift in perspective could lead to more nuanced and potentially more effective approaches to managing infectious diseases, not just COVID-19. It emphasizes the importance of supporting the body’s natural defense mechanisms while still prioritizing patient comfort and safety.

Navigating Patient Care in the Face of Uncertainty

The ongoing debate about ibuprofen use in COVID-19 patients highlights the challenges healthcare providers face when making treatment decisions in the midst of a rapidly evolving pandemic. It underscores the importance of continual reassessment of medical practices in light of new evidence and emerging hypotheses.

Key Considerations for Healthcare Providers

1. Staying informed about the latest research and guidelines
2. Communicating uncertainty and evolving recommendations to patients
3. Individualizing treatment approaches based on patient-specific factors
4. Monitoring patients closely for any signs of symptom progression
5. Being prepared to adjust treatment strategies as new information becomes available

By adopting a flexible and patient-centered approach, healthcare providers can navigate the complexities of treating COVID-19 while minimizing potential risks associated with antipyretic use.

The Role of Public Health Education in Fever Management

As the scientific community continues to explore the potential implications of antipyretic use in COVID-19, there is a growing need for public health education on fever management. Many individuals may instinctively reach for over-the-counter medications at the first sign of fever, unaware of the potential benefits of allowing a natural fever response.

Key Messages for Public Health Education

• Understanding the purpose and potential benefits of fever
• Recognizing when fever reduction is necessary versus when it can be safely tolerated
• Awareness of different antipyretic options and their varying efficacy
• Importance of consulting healthcare providers before self-medicating, especially in suspected COVID-19 cases
• Non-pharmacological methods for managing discomfort associated with fever

By empowering the public with this knowledge, we can promote more informed decision-making about fever management and potentially improve outcomes in viral illnesses, including COVID-19.

Integrating Traditional Wisdom with Modern Medical Practice

The hypothesis that allowing fever to run its course may be beneficial in viral illnesses aligns with some traditional medical practices that have long recognized the healing power of fever. This presents an opportunity to bridge traditional wisdom with modern medical understanding, potentially leading to more holistic approaches to disease management.

Exploring Complementary Approaches

1. Investigating traditional remedies that support the body during fever
2. Studying the impact of stress reduction techniques on immune function
3. Examining the role of nutrition in supporting natural fever responses
4. Evaluating the potential of hydrotherapy and other non-pharmacological interventions

By integrating these approaches with evidence-based medicine, we may develop more comprehensive strategies for managing viral illnesses that support the body’s natural healing processes while ensuring patient safety and comfort.

Ethical Considerations in Fever Management Research

As the medical community explores the potential risks and benefits of fever reduction in COVID-19, ethical considerations come to the forefront. Conducting research on fever management in the context of a potentially life-threatening illness raises important ethical questions that must be carefully addressed.

Key Ethical Considerations

• Balancing the potential benefits of research against risks to participants
• Ensuring informed consent in studies involving fever management
• Addressing equity in access to experimental treatments or approaches
• Managing conflicts of interest in research funded by pharmaceutical companies
• Communicating evolving research findings responsibly to avoid public confusion

Navigating these ethical challenges will be crucial in advancing our understanding of optimal fever management strategies in COVID-19 and other viral illnesses while protecting patient rights and safety.

The Future of Personalized Fever Management

As our understanding of the complex interplay between fever, immune response, and viral infections deepens, we may be moving towards more personalized approaches to fever management. The future could see tailored strategies based on individual patient characteristics, specific pathogens, and stage of illness.

Potential Developments in Personalized Fever Management

1. Genetic testing to identify individuals who may benefit from or be at risk from fever reduction
2. Real-time monitoring of immune markers to guide antipyretic use
3. AI-assisted decision support tools for optimizing fever management
4. Development of targeted antipyretics that preserve beneficial aspects of the fever response
5. Integration of wearable technology for continuous temperature and symptom monitoring

These advancements could revolutionize our approach to fever management, allowing for more precise and effective interventions that balance the benefits of fever with patient comfort and safety.

Global Perspectives on Fever Management in COVID-19

The debate surrounding ibuprofen use in COVID-19 patients has highlighted variations in fever management practices across different countries and cultures. These diverse approaches offer valuable insights and opportunities for cross-cultural learning in the global fight against the pandemic.

Comparing International Approaches

• Differences in antipyretic preferences across regions
• Cultural attitudes towards fever and its management
• Variations in healthcare system responses to fever in COVID-19 cases
• Impact of local regulations on access to and use of antipyretics
• Traditional medicine practices for fever management in different cultures

By examining these global perspectives, we can identify best practices, challenge assumptions, and develop more comprehensive, culturally sensitive approaches to fever management in COVID-19 and other infectious diseases.

The Economic Impact of Fever Management Strategies

The approach to fever management in COVID-19 has potential economic implications that extend beyond individual patient care. Understanding these economic factors is crucial for developing sustainable and effective public health strategies.

Economic Considerations in Fever Management

1. Cost-effectiveness of different antipyretic strategies
2. Economic impact of potential increases in hospitalization due to fever suppression
3. Market dynamics of over-the-counter antipyretics during pandemics
4. Healthcare resource allocation for fever management in COVID-19
5. Long-term economic effects of different fever management approaches on population health

Analyzing these economic aspects can help policymakers and healthcare systems make informed decisions about fever management strategies that balance clinical efficacy, patient outcomes, and economic sustainability.

Leveraging Technology in Fever Research and Management

Advancements in technology offer new opportunities for studying and managing fever in the context of COVID-19 and other viral illnesses. These innovations have the potential to revolutionize our understanding of fever’s role in disease progression and inform more precise management strategies.

Technological Innovations in Fever Research

• Big data analysis of fever patterns in large patient populations
• Machine learning algorithms for predicting fever outcomes
• Telemedicine platforms for remote fever monitoring and management
• Advanced imaging techniques for visualizing fever’s effects on the body
• Development of smart antipyretics with targeted release mechanisms

By harnessing these technological advancements, researchers and clinicians can gain deeper insights into the complex dynamics of fever in viral infections, potentially leading to more effective and personalized management approaches.

The Psychological Aspects of Fever Management in COVID-19

The decision to use antipyretics like ibuprofen in COVID-19 cases involves not only physiological considerations but also psychological factors. Understanding and addressing these psychological aspects is crucial for comprehensive patient care and effective public health strategies.

Psychological Factors in Fever Management

1. Anxiety and fear associated with fever during a pandemic
2. Cultural beliefs and misconceptions about fever
3. Impact of fever on mental well-being and cognitive function
4. Patient preferences and tolerance for fever-related discomfort
5. Psychological effects of different fever management approaches on caregivers

Addressing these psychological aspects can lead to more patient-centered approaches to fever management, potentially improving adherence to treatment recommendations and overall patient satisfaction.

The use of ibuprofen to treat fever in COVID-19: A possible indirect association with worse outcome?

Med Hypotheses. 2020 Nov; 144: 109880.

Published online 2020 May 25. doi: 10.1016/j.mehy.2020.109880

^a,b,⁎ and ^c

Author information Article notes Copyright and License information Disclaimer

Supplementary Materials

Fever has been reported as a common symptom occurring in COVID-19 illness. Over the counter antipyretics such as ibuprofen and acetaminophen are often taken by individuals to reduce the discomfort of fever. Recently, the safety of ibuprofen in COVID-19 patients has been questioned due to anecdotal reports of worsening symptoms in previously healthy young adults. Studies show that ibuprofen demonstrates superior efficacy in fever reduction compared to acetaminophen. As fever may have benefit in shortening the duration of viral illness, it is plausible to hypothesize that the antipyretic efficacy of ibuprofen may be hindering the benefits of a fever response when taken during the early stages of COVID-19 illness.

Recently, controversy concerning use of ibuprofen in patients with COVID-19 has arisen. The concern was initially expressed after an anecdotal report of 4 cases of worsening symptoms of COVID-19 in France that occurred after early treatment with ibuprofen in young people with no underlying health problems [1]. As a result, the WHO initially cautioned against the use of ibuprofen for symptoms of COVID-19. This initial recommendation was revised and now the European Medicines Agency and the WHO, citing the absence of clinical or population data, do not recommend nonsteroidal anti-inflammatory drugs (NSAIDs) be avoided when clinically indicated [2].

The concern related to ibuprofen use has centered on the pharmacological property of the drug and whether inhibition of the release of prostaglandins will interfere with the adaptive immune system [3]. However, aside from the direct anti-inflammatory effects of NSAIDS, there are also indirect confounding factors when ibuprofen is used to reduce fever. In the situation of early viral illness, the use of ibuprofen and acetaminophen in the home environment is often as an antipyretic. Since fever has been observed in up to 99% of COVID-19 cases [4], many patients may self treat their discomfort of an elevated temperature with over the counter agents such as ibuprofen or acetaminophen thereby unwittingly interfere with the benefits of fever in the natural course of the disease.

There are important factors which may be confounders in assessing causality of ibuprofen with possibly worse COVID-19 illness. First, fever has been shown to be beneficial toward a reduction in the duration of viral illness and the mortality associated with illness [5]. Outside of reducing patient discomfort, there is little evidence to support administration of antipyretics to reduce fever results in better overall outcomes in previously healthy patients [6]. To the contrary, in several studies, the use of antipyretics has been associated with an increase in mortality and morbidity [7]. It is therefore a concern of whether these agents may suppress the natural mechanism of the body to fight infection.

Secondly, there is evidence to support that ibuprofen is superior to acetaminophen in reducing fever. In a randomized controlled trial in children comparing ibuprofen and acetaminophen at equipotent doses, ibuprofen provided a larger temperature decrease and a longer duration of response [8]. Meta analyses have also shown that ibuprofen has a larger temperature reduction effect compared to acetaminophen in children [9] and in adults [10]. Thus, a superior antipyretic effect may be related to ibuprofen more effectively hindering the beneficial effect of fever in COVID-19 viral illness.

To the extent a direct relationship between the fever response and a number of consequential impacts on healing processes in progress exists, these findings suggest allowing the natural response to occur is essential. Febrile temperatures have been shown to work as a systemic alert system activating the immune system during a challenge by invading pathogens [11]. Suppressing the fever response also blunts the associated hyperemic response, increased lymphocyte activity, and related oxygenation of organ tissues which leads to multiple organ failure in the COVID-19 patient. A recent study shows that COVID-19 proteins ORF8 and surface glycoproteins bind with the heme component of hemoglobin rendering it incapable of oxygen and CO2 transport resulting in hypoxemia [12]. A physiologic fact is also that oxygen is more easily unloaded from hemoglobin to deliver it to tissues in need when temperature is increased [13].

In conclusion, it is plausible to hypothesize that the antipyretic efficacy of ibuprofen may be hindering the benefits of a fever response. The difference in perceived safety of these agents in COVID-19 illness could be related to the more potent efficacy to reduce fever with ibuprofen compared to acetaminophen. Compelling data on the benefit of fever warrant further research and review to determine when to treat or withhold ibuprofen for early stage fever for COVID-19 and other related viral illnesses.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

^{Appendix A}Supplementary data to this article can be found online at https://doi.org/10.1016/j.mehy.2020.109880.

The following are the Supplementary data to this article:

Supplementary data 1:

Click here to view.^{(213 bytes, xml)}

1. Day M. Covid-19: ibuprofen should not be used for managing symptoms, say doctors and scientists. BMJ. 2020;368 [PubMed] [Google Scholar]

2. Weikle B. WHO clarifies guidance on ibuprofen, says there’s no evidence it can worsen COVID-19. CBC website. https://www.cbc.ca/news/health/ibuprofen-covid-19-novel-coronavirus-1.5501496. Accessed April 19 2020.

3. Crosby J.C., Heimann M.A., Burleson S.L., Anzalone B.C., Swanson J.F., Wallace D.W. COVID-19: a review of therapeutics under investigation. JACEP Open. 2020:1–7. [PMC free article] [PubMed] [Google Scholar]

4. Wang D., Hu B., Hu C., Zhu F., Liu X., Zhang J. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China. Jama. 2020;2020(323):1061–1069. [PMC free article] [PubMed] [Google Scholar]

5. Carey J.V. Literature review: should antipyretic therapies routinely be administered to patient fever? J Clin Nurs. 2010;19:2377–2393. [PubMed] [Google Scholar]

6. Mackowiak P.A. Physiological rationale for suppression of fever. Clin Infect Dis. 2000;31:S185–S189. [PubMed] [Google Scholar]

7. Ludwig J., McWhinnie H. Antipyretic drugs in patients with fever and infection: literature review. British J Nurs. 2019;28:610–618. [PubMed] [Google Scholar]

8. Kauffman R.E., Sawyer L.A., Scheinbaum M.L. Antipyretic efficacy of ibuprofen vs acetaminophen. Am J Dis Child. 1992;146:622–625. [PubMed] [Google Scholar]

9. Perrott D.A., Piira T., Goodenough B., Champion G.D. Efficacy and safety of acetaminophen vs ibuprofen for treating children’s pain or fever: a meta-analysis. Arch Pediatr Adolesc Med. 2004;158:521–526. [PubMed] [Google Scholar]

10. Pierce C.A., Voss B. Efficacy and safety of ibuprofen and acetaminophen in children and adults: a meta-analysis and qualitative review. Ann Pharmacother. 2010;44:489–506. [PubMed] [Google Scholar]

11. Evans S.S., Repasky E.A., Fisher D.T. Fever and the thermal regulation of immunity: the immune system feels the heat. Nat Rev Immunol. 2015;15:335–349. [PMC free article] [PubMed] [Google Scholar]

12. Wenzhong L., Hualan L. COVID-19: attacks the 1-beta chain of hemoglobin and captures the porphyrin to inhibit human heme metabolism. ChemRxiv. 2020;6 doi: 10.26434/chemrxiv. [CrossRef] [Google Scholar]

13. Patel S., Mohiuddin S.S. In StatPearls Publishing; Treasure Island, FL: 2020. Physiology, oxygen transport and carbon dioxide dissociation curve. [Google Scholar]

Acetaminophen vs. Ibuprofen: What to Take When

Most of us manage common aches and pains, fevers and other minor health concerns by reaching for acetaminophen or ibuprofen. You may also think of it as Tylenol vs. Advil. But, what’s the difference between the two? Jordan Reeder, ARNP, UnityPoint Health, helps you decide which over-the-counter pain reliever is best for your situation.

What is Acetaminophen?

It’s easy to confuse acetaminophen as an anti-inflammatory drug, but Reeder says it actually isn’t meant for that purpose.

“Acetaminophen is a pain reliever and fever reducer,” Reeder says. “Tylenol is the brand usually associated with over-the-counter acetaminophen.”

While Tylenol’s only active ingredient is acetaminophen, there are hundreds of other medications that include acetaminophen. It’s a good idea to check the labels of all medications, both prescription and over-the-counter, to prevent overdosing.

What is Ibuprofen?

Unlike acetaminophen, ibuprofen acts as an anti-inflammatory drug, which means it reduces inflammation and swelling. However, it also offers other benefits.

“Ibuprofen is a non-steroid, anti-inflammatory. In other words, it reduces inflammation and pain in the body, and it can also be used as a fever reducer,” Reeder says.

Types of Painkillers

• Acetaminophen – brand names include Tylenol. Acetaminophen is also included in hundreds of medications including Excedrin, Nyquil, Sudafed, Mucinex and Theraflu. 
• Ibuprofen – brand names include Advil and Motrin.
• Naproxen – brand names include Aleve
• Aspirin – brand names include Bayer and Ecotrin

Make sure to check the label before taking over-the-counter painkillers. Midol uses ibuprofen, naproxen and acetaminophen in its products. Pamprin uses acetaminophen and asprin in its products.

Should I Take Acetaminophen or Ibuprofen?

Reeder says determining which pain reliever to take is a matter of finding what works best for you. However, here are soft recommendations for common health ailments:

• Headache, common cold or fever.  This is a personal preference. Some feel acetaminophen works better for them, whereas others find ibuprofen better relieves a headache.
• Muscle ache or pulled/strained muscle. Ibuprofen typically works better for this kind of pain relief, due to the anti-inflammatory effects.

Naproxen and aspirin are two other common over-the-counter pain relievers. Reeder describes the uses, benefits and potential problems with these as well:

• Naproxen. Another anti-inflammatory drug, which works much like ibuprofen. Some studies show this may be a better choice than ibuprofen for people at risk for heart disease.
• Aspirin. This also belongs to the non-steroid, anti-inflammatory medication class. It works similarly to ibuprofen but slows the clotting ability in the bloodstream. Because of this, it’s often given to reduce someone’s risk for heart attack and stroke. Aspirin isn’t recommended for children; it is linked to Reye’s syndrome, a childhood illness affecting the brain and liver.

Reeder says if you’re looking for advice about whether to take acetaminophen or ibuprofen for COVID-19, here are some thoughts from a UnityPoint Health infectious disease expert. Read more about COVID-19. 

Health Risks of Acetaminophen vs. Ibuprofen

While most people have no issue taking the appropriate doses of acetaminophen or ibuprofen, Reeder says there are situations where you should be extremely cautious.

“Acetaminophen should be used carefully in those with liver problems, but it is safe for pregnant women. Ibuprofen, on the other hand, should be used cautiously by individuals with heart disease, high blood pressure, clotting disorders, kidney problems and the elderly. If you are pregnant or trying to conceive, you should not use ibuprofen,” Reeder says.

Children specifically can only take pain relievers based on their age and weight.

“Children 6-months-old and under can only take acetaminophen for fever. Ibuprofen may be used once children are over 6 months of age. The difference between adult versions of these medications and children versions is the dosing is adjusted based on the weight of the child,” Reeder says.

Regardless of age, taking too much acetaminophen or ibuprofen can lead to health concerns in the future.

“Too much ibuprofen can cause long-term kidney complications and potentially liver complications, too. It can also cause painful and bleeding ulcers in the stomach. Acetaminophen can be hard on the liver and may also cause kidney problems with long-term, chronic use,” Reeder says.

Reeder stresses how taking more than the recommended amount of any medication is dangerous. She says to talk to your UnityPoint Health provider before taking either acetaminophen or ibuprofen regularly.

Is Ibuprofen best for COVID-19?

Related Content

Article

Injuries & Pain: When to Use Ice or Heat

Article

Which Type Of Allergy Medication Is Right For You

Article

How Do Vaccines Work?

Fever with acute respiratory infections – why the temperature rises with coronavirus and how ibuprofen works / NV

1

Why does body temperature rise?

The reason that the body temperature rises, as a rule, are substances called pyrogens. These are fragments of the cell wall, that is, small particles of the shell of microorganisms, their metabolic products, or toxins.

Pyrogens can be formed due to damage to body tissues: during mechanical damage, such as shock, physical, or under the influence of high or low temperature, and also due to tissue death during myocardial infarction or aseptic inflammation. When pyrogens enter the body, they cause fever. Fever, as a rule, has three stages: in fact, an increase in temperature, its retention at a high level, and a decrease to a normal state.

Depending on the maximum temperature rises to during the second stage, the fever is divided into several types.

Subfebrile fever – one in which the body temperature is not higher than 38 ℃, mild fever – when the mark on the thermometer does not exceed 38.5 ℃, febrile, it is also moderate – up to 39 ℃, pyretic, or high – up to 41 ℃. Hyperpyretic fever, in which the temperature can be above 41 ℃, is the most life-threatening, especially when it comes to a child.

2

Fever in ARVI: what happens in the body?

Symptoms of the disease, as a rule, depend on what kind of infection we are dealing with. For example, in most acute respiratory infections (ARVI), subfebrile temperature is observed. But during the flu, the thermometer mark can reach up to 39 ℃ and above.

High fever helps the body fight infection. Therefore, hyperthermia or elevated body temperature in an infectious disease is usually a good sign. Under such conditions, harmful microorganisms die or slow down reproduction in the human body, the immune system begins to work more actively, produces antibodies to the pathogen and other substances. Metabolic processes are accelerated, and the liver helps to cleanse the body of toxins.

However, fever can be harmful, especially in hyperpyrexia, which is the most dangerous for children.

3

What body temperature should be brought down in case of SARS and why?

It is necessary to lower the temperature if the mark of 38-38. 5 ℃ does not decrease within three to five days. Also if a person has concomitant diagnoses or complications, such as cardiovascular disease, seizures and other conditions that worsen the general condition. It is recommended to bring down the temperature even if this condition is difficult to tolerate in principle.

Otherwise, body temperature below 38℃ is considered acceptable. This is a reaction that says: the body fights the infection on its own.

Fever is usually brought down by antipyretics, among which paracetamol and ibuprofen are first-line drugs for fever. To reduce intoxication, it is recommended to drink a lot. Herbal teas are well suited for this, you can add ginger, lemon, honey, homemade raspberry jam, viburnum and the like. At the same time, drinks should not be hot. Ideally, if your tea is warm, or at room temperature.

4

What drugs are used to lower body temperature?

Antipyretics are a group of medicines that include antipyretic analgesics, such as paracetamol, and non-steroidal anti-inflammatory drugs (NSAIDs), such as acetylsalicylic acid, ibuprofen, naproxen, etc. Antipyretic analgesics have antipyretic and analgesic effects, then as for NSAIDs, in addition, they also act as anti-inflammatory.

One of the common types of NSAIDs are salicylates, that is, derivatives of salicylic acid. They are part of acetylsalicylic acid, which is known to many as the basis of aspirin. Salicylates in a small amount are also found in raspberries, and also in willow bark. That is why raspberry jam and tea with its addition are useful to drink during a fever.

Propionic acid derivatives include, for example, ibuprofen, one of the leading drugs for the treatment of fever.

Antipyretic drugs should not be taken “for prophylaxis”, but only according to indications, according to the instructions and prescribed by the doctor, in strictly defined doses and with the appropriate multiplicity. If the temperature does not decrease even after taking medication, you should immediately consult a doctor.

5

What is ibuprofen?

Ibuprofen is a non-steroidal drug that has analgesic, anti-inflammatory and antipyretic effects. This drug was invented and patented by Dr. Adams in 1962. In the late 70s, an oral formulation containing ibuprofen at a dose of 200 mg received a prescription drug license in the UK, and in 1983, after five years of clinical trials, the drug received OTC status; it was released without a prescription. Since then, ibuprofen has been widely used in most countries of the world and is one of the most common means of combating fever symptoms.

6

How does ibuprofen work?

Ibuprofen directly affects those peptides and proteins that trigger and generate inflammatory processes in the body. The action of this drug interrupts the chain of development of inflammatory processes, and therefore eliminates fever, headache, inflammation in the throat and improves general well-being in case of a cold.

7

Is ibuprofen safe?

Numerous clinical studies have been carried out since the initial registration of the drug with ibuprofen, confirming the effectiveness and safety of this drug. Thus, its antipyretic, analgesic and anti-inflammatory effects have been proven. Subsequently, ibuprofen became widely used to combat the symptoms of SARS in children and adults.

In addition to relieving symptoms of colds and flu, treating headaches, medicines containing ibuprofen are used to treat toothache, menstrual pain, neuralgia, as well as pain in the back, joints, muscles, and rheumatic pain.

8

Can ibuprofen be used on children?

For fever caused by SARS, WHO recommends the use of ibuprofen and paracetamol. They are one of the most widely used dosage forms in children. Pharmacies offer a wide range of children’s uniforms ibuprofen: suspensions, suppositories, tablets, capsules and others. Consult your doctor before using these drugs, read and follow the medical instructions carefully.

9

Why is it sometimes not possible to lower the temperature with antipyretics?

Antipyretic drugs may not help if the dose is not calculated correctly. Also, the medicinal product loses its quality if the storage conditions indicated on the packaging and in the instructions for medical use are violated: the integrity of the primary packaging (oral forms) is violated, the drug was kept open for a long time and could deteriorate under the influence of moisture, light or air. Drugs of dubious quality may also not work. It is difficult to achieve a result in lowering body temperature and if you do not adhere to the temperature regime in the room, dress too warmly, drink not enough liquid.

If the temperature cannot be brought down by antipyretics, this is not a reason to start taking antibiotics on your own. Be sure to check with your doctor for each step.

10

Can I take ibuprofen with COVID-19?

There are currently no drugs specifically designed to treat COVID-19.

Ibuprofen and paracetamol are used as one of the ways to reduce high fever in coronavirus infection. Despite recent discussions, there is no scientific evidence to establish a link between ibuprofen and worsening of COVID-19. This is evidenced by statements from the WHO, the European Medicines Agency (EMA), the US Food and Drug Administration (FDA) and other global health authorities. That is, ibuprofen may be prescribed by a doctor for the symptomatic treatment and management of fever in patients with COVID-19.

Radio NV

The relevance of the use of NSAIDs in the treatment of fever in children | Mubarakshina O.A.

Fever is the leading symptom in infectious, and primarily in respiratory viral diseases in children. The starting point of its development is the impact of exogenous pyrogens of a viral or bacterial nature. They stimulate the secretion of endogenous pyrogens (interleukins, tumor necrosis factor, interferons).

The main trigger for fever is interleukin-1 (IL-1). Through intermediate links in the hypothalamus, it contributes to excessive heat generation, delayed heat transfer and the occurrence of hyperthermia. Under normal conditions, IL-1 does not cross the blood-brain barrier. However, in the presence of inflammation, IL-1 reaches the preoptic region of the anterior part of the hypothalamus and interacts with neuronal receptors of the thermoregulation center. This activates the enzyme cyclooxygenase (COX), which leads to an increase in the synthesis of prostaglandins and an increase in the intracellular level of cyclic adenosine-3,5-monophosphate (cAMP).
An increase in the concentration of cAMP contributes to the accumulation of calcium ions inside the cells and the restructuring of the activity of the centers of heat production and heat transfer. As a result, a new level of temperature homeostasis is established at a higher point: heat production increases and heat transfer decreases. In addition, prostaglandins formed in the affected tissues are important mediators of the inflammatory response and are involved in the pathogenesis of all signs of inflammation (pain, swelling and heat).
The mechanisms of the development of fever determine the fact that over the past years, non-steroidal anti-inflammatory drugs (NSAIDs) have been the drugs of choice for fever and other signs of inflammation (pain syndrome, etc. ). By blocking COX, they inhibit the biosynthesis of prostaglandins, which, along with thromboxane and leukotrienes, are part of the group of oxygenation products of polyunsaturated long-chain fatty acids known as eicosanoids.
NSAIDs used in pediatric practice should have the most favorable efficacy/safety ratio. Moreover, not all drugs popular in our country today meet modern requirements.
In the past, salicylic acid preparations and pyrazolone derivatives have been used for a long time. However, at present, the Russian National Pharmacological Committee and the Russian Union of Pediatricians do not recommend the use of some previously widely used drugs in pediatric practice. Thus, the use of acetylsalicylic acid for the treatment of fever, especially viral etiology, in children under 15 years of age is not recommended.
This prohibition is associated with pronounced toxic effects of acetylsalicylic acid and the possibility of developing Reye’s syndrome, characterized by toxic encephalopathy and fatty degeneration of internal organs, mainly the liver and brain. The widespread use of metamizole sodium is also limited due to the high frequency of side effects.
The main drugs that meet the criteria for efficacy and safety are acetaminophen (paracetamol) and ibuprofen (Nurofen for children). It is these drugs that should be the means of choice for fever in children in accordance with official WHO recommendations and national pediatric programs.
Ibuprofen is a derivative of propionic acid. It was developed in 1962 and registered in England in 1968 as a prescription anti-inflammatory drug for the treatment of rheumatoid arthritis. And only then did ibuprofen begin to be used as an over-the-counter pain reliever and antipyretic drug.
The experience of using ibuprofen showed high efficiency, good tolerability and caused less pronounced side effects from the gastrointestinal tract than acetylsalicylic acid. Further clinical studies have confirmed these properties. It was found that the pharmacological effects of ibuprofen are primarily due to its antiprostaglandin action due to non-selective blockade of COX-1 and COX-2.
In the 1980s, ibuprofen was introduced into pediatric practice in a number of countries, including the United States and Great Britain. Currently, the drug is registered and used in many countries under the patented name “Nurofen”. In children, ibuprofen suspension (20 mg / ml) is used – “Nurofen for Children”, which does not contain sugar, is approved for over-the-counter use in children from the age of 3 months.
Pharmacokinetics. When taken orally, ibuprofen is well absorbed from the gastrointestinal tract, being partially absorbed in the stomach, and completely in the small intestine. The time to reach maximum plasma concentration (Tmax) when taken orally with ibuprofen tablets or ibuprofen pediatric suspension is on an empty stomach from 45 minutes to 1 hour, when taken after a meal – from 1.5 to 2.5 hours. Infants aged 6-18 months have been reported to have a higher Tmax (3 hours). In human plasma, ibuprofen is more than 90% bound to protein. Although ibuprofen actively binds to albumin, this does not affect drug interactions.
Ibuprofen is extensively metabolized in the liver, rapidly eliminated from plasma, and has a relatively short half-life (about 2 hours). The CYP2C9 isoenzyme takes part in the metabolism of the drug. It is excreted by the kidneys and, to a lesser extent, with bile. Urinary excretion of metabolites is usually completed within 24 hours of the last dose. The total excretion of ibuprofen and its metabolites in the urine is linearly dependent on the dose of the drug.
Antipyretic effect. Ibuprofen has a dual anti-inflammatory and antipyretic action – central and peripheral. The central antipyretic effect of ibuprofen occurs due to the suppression of the synthesis and release of prostaglandins in the central nervous system. This leads to a normalization of the level of thermoregulation in the hypothalamus, and thus helps to reduce fever.
The peripheral antipyretic effect of ibuprofen is due to the inhibition of prostaglandin synthesis in damaged tissues, which reduces the activity of inflammation and the production of endogenous pyrogens, in particular IL-1.
Ibuprofen causes a rapid and effective reduction in high body temperature. The therapeutic effect of the drug begins with a dose of ibuprofen equal to 5 mg / kg. However, the greatest clinical effect is caused by a dose of 7 to 10 mg per 1 kg of body weight; moreover, ibuprofen at a dose of 7–7.5 mg/kg has an antipyretic effect similar to paracetamol at a dose of 10 mg/kg.
The antipyretic effect when taking ibuprofen begins as quickly as when using paracetamol, that is, within 30-40 minutes from the moment of administration. However, in some patients, body temperature decreases after 15–20 minutes.
Comparison of the effectiveness of paracetamol and ibuprofen showed that both drugs are effective in febrile conditions, but ibuprofen acts more powerfully and for a longer time.
This observation is confirmed by the results of a large, randomized, double-blind, parallel-group, repeated-dose study comparing the effects of ibuprofen at doses of 7 and 10 mg/kg with those of paracetamol at a dose of 10 mg/kg [1]. In patients treated with ibuprofen, the mean body temperature was lower than in patients treated with paracetamol.
Ibuprofen has also been found to be more effective than paracetamol in reducing very high body temperature (above 39.2°C) in children. This action has also been demonstrated in a double-blind study [2]. The effect of single doses of ibuprofen 5 mg/kg and 10 mg/kg, paracetamol 10 mg/kg and placebo was studied. Ibuprofen at a dose of 10 mg/kg was more effective in lowering body temperature than paracetamol at a dose of 10 mg/kg in both the subgroup of children with very high fever and in the children of the entire group as a whole.
Thus, ibuprofen in children provides:
• rapid decrease in high body temperature during fever;
• long antipyretic effect, lasting up to 8 hours;
• decrease in body temperature during fever for a longer period of time than when taking a suspension of paracetamol.
This allows us to recommend ibuprofen as the optimal antipyretic drug both for fever of infectious origin and for the relief of post-vaccination reactions.
Pain-relieving and anti-inflammatory effects. When choosing NSAIDs, one should also take into account the fact that fever in acute respiratory viral infections, tonsillitis, otitis media is often accompanied by the development of inflammation and pain of various localization: in the throat, ear, head.
The inflammatory reaction in the upper respiratory tract occurs as a result of damage by viruses and bacteria to the epithelium of the respiratory tract and the presentation of their antigens by macrophages and other cells of the immune system. In this regard, it is desirable that the antipyretic drug also reduces the inflammatory response and alleviates pain.
Ibuprofen relieves pain by inhibiting cyclooxygenase enzymes, which prevents the conversion of arachidonic acid to prostaglandins at the site of inflammation. This reduces the action of prostaglandins on pain receptors, reducing the inflammatory response and resulting tissue damage.
Peripheral action is considered the main mechanism by which ibuprofen relieves pain. This drug is especially effective in clinical conditions associated with inflammation, which are accompanied by increased prostaglandin synthesis. Moreover, it must be taken into account that paracetamol has no peripheral anti-inflammatory effect.
Given this fact, a number of national pediatric societies recommend the use of ibuprofen as an antipyretic for infections with a pronounced inflammatory component; as well as in cases where the temperature in children is accompanied by pain reactions.
Various studies also show that ibuprofen is an effective treatment for mild to moderate pain in children. In particular, the drug is effective for toothache, acute sore throat with tonsillitis and pharyngitis.
A randomized, double-blind, multicenter study of the efficacy of ibuprofen (10 mg/kg), paracetamol (10 mg/kg), or placebo was conducted in children with tonsillitis and pharyngitis [3]. Patients received drugs daily 3 times a day for 7 days along with antibiotics.
After treatment for 48 hours, 80% of children treated with ibuprofen did not complain of any pain. In the group of patients treated with paracetamol, the pain disappeared in 70% of children, and in the placebo group, this figure was 55%. A similar trend was observed in relation to the disappearance of pain when swallowing: 76%, 64% and 43%, respectively.
The effectiveness of ibuprofen in reducing ear pain in acute otitis media was studied in a multicentre, double-blind and controlled study in children [4]. Its results noted that ibuprofen at a dose of 10 mg/kg was effective in reducing pain in otitis media. It was significantly superior to placebo, with no significant differences in tolerability between paracetamol and placebo.
Thus, ibuprofen is an effective tool for the short-term treatment of pain associated with acute otitis media, tonsillitis and pharyngitis.
Safety in children. Short-term treatment with ibuprofen for fever and pain is well tolerated in children. For safety in children, ibuprofen is considered one of the best non-steroidal anti-inflammatory drugs. These are the data of a study that included 84,192 children aged 6 months to 12 years [5]. The study assessed the increased risk of hospitalization in children treated with ibuprofen at a dose of 5 or 10 mg/kg for fever compared with children treated with paracetamol at a dose of 12 mg/kg.
The results indicate that the risk of serious side effects with ibuprofen is no higher than with paracetamol.
Serious adverse events from the gastrointestinal tract occurred very rarely. Ibuprofen, compared with paracetamol, did not increase the risk of hospitalization associated with one of the 4 serious treatment outcomes, such as gastrointestinal bleeding, development of renal failure, anaphylaxis, or Reye’s syndrome. There were also no cases of death associated with the side effects of drugs.
Other gastrointestinal adverse events included dyspepsia, abdominal pain, nausea and vomiting. The number of outpatient visits to the doctor for these complaints also did not differ in the comparison groups [5].
A detailed analysis of other adverse events from various organs and systems when using ibuprofen showed the following:
– differences in the frequency of adverse events by age or gender were not noted;
– adverse reactions in all cases were minor and stopped when treatment was discontinued;
– The risk of visiting outpatient medical facilities for asthma was significantly lower in the ibuprofen group. Thus, this study demonstrated that ibuprofen is at least as safe as paracetamol in children with asthma.
Data on good tolerability of paracetamol and ibuprofen were also confirmed in other multicenter studies [6-11]. Among all antipyretic analgesics, ibuprofen and paracetamol have been shown to be the safest drugs. Even with their long-term use, the frequency of adverse events was comparable and amounted to approximately 8-9% for both ibuprofen and paracetamol.
It should also be noted that, compared with paracetamol and acetylsalicylic acid, ibuprofen has less toxicity in case of overdose and a high safety threshold. Unlike paracetamol, ibuprofen does not form toxic metabolites. Ibuprofen has a relatively large therapeutic index, which is about 4 times higher than that of paracetamol.
Symptoms of an ibuprofen overdose may include nausea, vomiting, abdominal pain, headache, hypotension, dizziness, drowsiness, nystagmus, blurred vision, and tinnitus. Rarely, metabolic acidosis, renal failure, and loss of consciousness occur. There is no clear correlation between the doses taken and the clinical effect. Therefore, patients are treated symptomatically. You can use activated charcoal within an hour after taking a high dose or gastric lavage.
Ibuprofen in combination therapy. The combined use of two drugs from the NSAID group is usually not considered rational, since adverse reactions from the gastrointestinal tract are possible. An exception is the combination of paracetamol with other NSAIDs, when the side effects do not increase with the summation of the analgesic effect.
The possibility of combined use of ibuprofen and paracetamol in pediatric practice was evaluated in a randomized trial in 146 children aged 6 months to 6 years [12]. In order to reduce the temperature, children were prescribed ibuprofen at a dose of 10 mg/kg, paracetamol at a dose of 15 mg/kg, or both drugs.
The results indicate that in the first 4 hours after taking the drug, the duration of febrile illness decreased by 55 minutes with combination therapy compared with paracetamol. Ibuprofen was comparable to combination therapy in this respect.
Overall, over 24 hours, the combination of ibuprofen and paracetamol reduced the duration of febrile illness by 4.4 hours compared with paracetamol and by 2.5 hours compared with ibuprofen. Side effects were not significantly different for all treatment options.
Thus, the treatment of fever in children is recommended to begin with ibuprofen. Moreover, it is possible to add paracetamol to the therapy regimen on the first day of treatment of febrile syndrome.

Literature
1. Sidler J. et al. A double-blind comparison of ibuprofen and paracetamol in juvenile pyrexia. Br. J.Clin. Pract. 1–990; 44(Suppl. 70): 22–25.
2 Walson P.D. et al. Ibuprofen, acetaminophen, and placebo treatment of febrile children. Clin Pharmacol Ther 1989; 46:9–17.
3. Bertin L. et al. Randomised, double-blind, multicenter, controlled trial of ibuprofen versus acetaminophen (paracetamol) and placebo for treatment of symptoms of tonsillitis and pharyngitis in children. Journal of Pediatrics 1991; 119(5): 811–4.
4. Bertin L. et al. A randomised, double-blind, multicentre controlled trial of ibuprofen versus acetaminophen and placebo for symptoms of acute otitis media in children. Fundam Clin Pharmacol 1996; 10:387–92.
5. Lesko S.M. The safety of acetaminophen and ibuprofen among children less than two years old. Pediatrics 1999; 104(4) 1–5.
6. Lesko S.M., Louic C., Vezina R., Mitchell A.A. Asthma morbidity after he short-term use of ibuprofen in children. Pediatrics 2002; 109(2) 1–4.
7. Kauffmann R.E., Sawyer L.A., Scheinbaum M.L. Antipyretic Efficacy of Ibuprofen vs Acetaminophen.