Indomethacin: Can It Counteract Bradykinin Effects in COVID-19 Patients?

Alkotaji, Myasar; Al-Zidan, Radhwan Nidal

doi:10.1007/s40495-021-00257-6

Cited by 18 publications

(14 citation statements)

References 46 publications

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“…Alkotaji et al 29 had hypothesised the importance of indomethacin in reducing cough and myalgia through its inhibitive action on bradykinin, and the mechanism and ill-effects of bradykinin are well documented. The theory proposed in this study explains the difference in symptomatic relief between the two groups.…”

Section: Discussionmentioning

confidence: 99%

An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients

Rajan

Mohan²,

Sukumaran³

et al. 2022

Sci Rep

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Indomethacin, a non-steroidal anti-inflammatory drug (NSAID), has been presented as a broad-spectrum antiviral agent. This randomised clinical trial in a hospital setting evaluated the efficacy and safety of this drug in RT-PCR-positive coronavirus disease 2019 (COVID-19) patients. A total of 210 RT-PCR-positive COVID-19 patients who provided consent were allotted to the control or case arm, based on block randomisation. The control arm received standard of care comprising paracetamol, ivermectin, and other adjuvant therapies. The patients in the case arm received indomethacin instead of paracetamol, with other medications retained. The primary endpoint was the development of hypoxia/desaturation with SpO2 ≤ 93, while time to become afebrile and time for cough and myalgia resolution were the secondary endpoints. The results of 210 patients were available, with 103 and 107 patients in the indomethacin and paracetamol arms, respectively. We monitored patient profiles along with everyday clinical parameters. In addition, blood chemistry at the time of admission and discharge was assessed. As no one in either of the arms required high-flow oxygen, desaturation with a SpO2 level of 93 and below was the vital goal. In the indomethacin group, none of the 103 patients developed desaturation. On the other hand, 20 of the 107 patients in the paracetamol arm developed desaturation. Patients who received indomethacin also experienced more rapid symptomatic relief than those in the paracetamol arm, with most symptoms disappearing in half the time. In addition, 56 out of 107 in the paracetamol arm had fever on the seventh day, while no patient in the indomethacin group had fever. Neither arm reported any adverse event. The fourteenth-day follow-up revealed that the paracetamol arm patients had faced several discomforts; indomethacin arm patients mostly complained only of tiredness. Indomethacin is a safe and effective drug for treating patients with mild and moderate covid-19.

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Section: Discussionmentioning

confidence: 99%

An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients

Rajan

Mohan²,

Sukumaran³

et al. 2022

Sci Rep

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“…The importance of indomethacin in reducing cough and myalgia through its inhibitive action of bradykinin has been hypothesised by Alkotaji et.al [28] and the mechanism and the ill-effects of bradykinin are well documented. The theory proposed in this reference explains the difference in symptomatic relief between the two groups.…”

Section: Discussionmentioning

confidence: 99%

Indomethacin Use for Mild & Moderate hospitalised Covid-19 patients: An open label randomized clinical trial

Rajan

Surapaneni²,

Sukumaran³

et al. 2021

Preprint

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Background Indomethacin has shown to be a broad spectrum anti-viral agent apart from it being a non-steroidal anti-inflammatory drug (NSAID). This randomized clinical trial in a hospital setting is to evaluate the efficacy and safety of this drug in RT-PCR positive Covid patients. Materials and Methods RT-PCR positive Covid-19 patients, who gave the consent for the trial, were allotted to a control, or case, arm based on block randomization procedure. The control arm received the standard care consisting of paracetamol, ivermectin and other adjuvant therapy. The case arm had indomethacin instead of paracetamol, retaining the other medications. The endpoint was the development of hypoxia/desaturation. Secondary endpoints were time to become afebrile and time to resolution of cough and myalgia. The results of 210 patients were available at this point, with 102 patients in the indomethacin arm and 108 in the paracetamol arm. The complete patient profile along with everyday clinical parameters were monitored. Blood chemistry at the time of admission and discharge were also carried out. Results As no one required high-flow oxygen, desaturation with an SpO2 level of 93 and below was considered an important goal. In the indomethacin group, no one out of the 102 patients developed desaturation. On the other hand, 20 of the 108 patients in the paracetamol arm developed desaturation. Patients who received indomethacin also experienced more rapid symptomatic relief compared to those in the paracetamol arm, with most symptoms disappearing in half the time. A total of 56 patients out of 108 in the paracetamol arm had fever on the seventh day, while no one recorded fever in the indomethacin arm. No adverse event was reported in either arms. A fourteenth day follow up revealed that the paracetamol arm patients had several discomforts including myalgia, joint pain and tiredness while the indomethacin arm patients complained only of tiredness. Conclusion Indomethacin is a safe and effective drug for the treatment of mild and moderate Covid-19 patients.

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“…Although no conclusive evidence is available for or against the use of NSAIDs, observational studies suggest that the use of selective COX-2 inhibitors, together with other drugs, can reduce the frequency of hospitalization, although it does not reduce the duration of symptoms [ 3 ]. In particular, indomethacin is an old and inexpensive anti-inflammatory drug used for headache and arthritis [ 77 , 78 ], and it can combat cough [ 79 , 80 ], which is a major cause of the spread of infection.…”

Section: Indomethacin As a Promising Nsaidmentioning

confidence: 99%

“…A recent network pharmacology approach identified 3 target proteins associated with the renin-angiotensin system imbalance caused by SARS-CoV-2 (MAPK8, MAPK10, and BAD) and showed that indomethacin can reduce excessive inflammation by inactivating target proteins [ 22 ]. It has also been hypothesized that indomethacin can counteract the proinflammatory effects of bradykinin, thus reducing the COVID-19-induced symptoms induced by bradykinin network activation, such as dry cough and musculoskeletal pains [ 80 ]. It has also been shown that indomethacin together with resveratrol can improve the disease [ 81 ].…”

Section: Indomethacin As a Promising Nsaidmentioning

confidence: 99%

“…Finally, another peculiar aspect of the action of indomethacin is that it reduces bradykinin, which is linked to RAS imbalance and is responsible for important symptoms such as generalized pain, myalgia, and dry cough [ 80 ]. The specific involvement of bradykinin metabolism in the disease also depends on the fact that the enzyme ACE2 is involved in the degradation of bradykinin [ 92 , 93 ], and the acute phases of the inflammatory process in COVID-19 has been also defined as “bradykinin storm” [ 71 – 73 , 94 ].…”

Section: Indomethacin As a Promising Nsaidmentioning

confidence: 99%

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A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19

2022

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In the past 2 years, the coronavirus disease 2019 (COVID-19) pandemic has driven investigational studies and controlled clinical trials on antiviral treatments and vaccines that have undergone regulatory approval. Now that the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants may become endemic over time, there remains a need to identify drugs that treat the symptoms of COVID-19 and prevent progression toward severe cases, hospitalization, and death. Understanding the molecular mechanisms of SARS-CoV-2 infection is extremely important for the development of effective therapies against COVID-19. This review outlines the key pathways involved in the host response to SARS-CoV-2 infection and discusses the potential role of antioxidant and anti-inflammatory pharmacological approaches for the management of early mild-to-moderate COVID-19, using the examples of combined indomethacin, low-dose aspirin, omeprazole, hesperidin, quercetin, and vitamin C. The pharmacological targets of these substances are described here for their possible synergism in counteracting SARS-CoV-2 replication and progression of the infection from the upper respiratory airways to the blood, avoiding vascular complications and cytokine and bradykinin storms.

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Indomethacin: Can It Counteract Bradykinin Effects in COVID-19 Patients?

Cited by 18 publications

References 46 publications

An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients

An open label randomized clinical trial of Indomethacin for mild and moderate hospitalised Covid-19 patients

Indomethacin Use for Mild & Moderate hospitalised Covid-19 patients: An open label randomized clinical trial

A Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Management of Mild-to-Moderate Symptomatic COVID-19

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