14/01/2022.Naproxen in the treatment of COVID-19: a case report

Krystyna Knypl

The treatment of COVID-19 is a huge challenge for every physician and every health care system around the world. Various methods of prevention and treatment of this disease are being sought, but their effectiveness is not satisfactory both individually and globally. The January 13, 2022 issue of "Gazeta dla Lekarzy" summarizes a theoretical report on the use of naproxen as an antiviral drug

https://gazeta-dla-lekarzy.com/index.php/wazniejsze-nowosci/1681-naproksen-w-leczeniu-covid-19

The information above is a summary of a report by O.Terrier et al. "Antiviral properties of the NSAID drug naproxen targeting the nucleoprotein of SARS-CoV-2 coronavirus" https://www.mdpi.com/1420-3049/26/9/2593

The study by fluorescence spectroscopy, fluorescence anisotropy, and dynamic light scattering assays demonstrated sustained binding of naproxen to protein N, the nucleoprotein of SARS-Co-V-2 coronavirus. This resulted in a blockade of the function of protein N, resulting in a large reduction in viral replication and anti-inflammatory activity through inhibition of the cyclooxygenase cascade.

Naproxen

https://de.wikipedia.org/wiki/Naproxen

In addition to the above theoretical report, there is an ongoing clinical study "Efficacy of addition of naproxen in the treatment of critically III patients hospitalized for COVID-19 infection (ENACOVID)" , in whose description we find the following rationale for the administration of naproxen:

Coronavirus Disease 2019 (COVID-19) is due to SARS-CoV-2 infection. (1,2) The exacerbated inflammatory response in COVID-19 infected critically ill patients calls for appropriate anti inflammatory therapeutics combined with antiviral effects. Thus, drugs combining anti-inflammatory and antiviral effects may reduce the symptoms of respiratory distress caused by COVID-19. This dual effect may simultaneously protect severely ill patients and reduce the viral load, therefore limiting virus dissemination. Naproxen, an approved anti-inflammatory drug, is an inhibitor of both cyclo oxygenase (COX-2) and of Influenza A virus nucleoprotein (NP). The NP of Coronavirus (CoV), positive-sense single-stranded viruses, share with negative-sense single-stranded viruses as Influenza the ability to bind to- and protect genomic RNA by forming self-associated oligomers in a helical structure with RNA. Naproxen was shown to bind the Influenza A virus NP making electrostatic and hydrophobic interactions with conserved residues of the RNA binding groove and C terminal domain. (3) Consequently, naproxen binding competed with NP association with viral RNA and impeded the NP self-association process which strongly reduced viral transcription/replication. This drug may have the potential to present antiviral properties against SARS-CoV-2 suggested by modelling work based on the structures of CoV NP. The high sequence conservation within the coronavirus family, including severe acute respiratory syndrome (SARS-CoV) and the present SARSCoV-2 coronavirus allows to perform this comparison. (4) A recent clinical trial shown that the combination of clarithromycin, naproxen and oseltamivir reduced mortality of patients hospitalized for H3N2 Influenza infection. (5). Inappropriate inflammatory response in CODIV-19 patients was demonstrated in a recent study where Intensive Care Unit (ICU) patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNF? compared with non-ICU patients.(2) We suggest that naproxen could combine a broad-spectrum antiviral activity with its well-known anti inflammatory action that could help reducing severe respiratory mortality associated with COVID-19.

 

https://clinicaltrials.gov/ct2/show/NCT04325633

The study is performed in France, the sponsor of the study is Assistance Publique - Hôpitaux de Paris (https://www.aphp.fr/hopitaux). The study involves 30 patients, the principal investigator is Professor Frédéric Adnet, head of the intensive care unit of L'hôpital Avicenne et du Samu de la Seine-Saint-Denis in Bobigny, France.

https://www.univ-paris13.fr/entretien-frederic-adnet-professeur-de-medecine-durgence-chef-service-urgences-de-lhopital-avicenne/

Case report

A 53-year-old female pediatric primary care physician seeing patients with upper respiratory tract infections of which 2-3 per day tested positive for Covid-19 Group A Rh(+).

Height: 164 cm, weight 108 kg. Dg. Hypertension Io treated with bisocard 5mg/day for this reason. RR 135/95. T68/min (history of ventricular bigeminy), without arrhythmia since bisocard was started. Degenerative changes in all parts of the spine, more severe in the lumbar region, giving periodic intense pain. A history of melanoma removal from the intercostal region 11 years ago.

Vaccinated with three doses of Comirnaty vaccine https://www.pfizerpro.com.pl/product/comirnaty/szczepionka-mrna-przeciw-covid-19/ulotka-chpl-comirnaty anti SARS-CoV-2 antibody titer 3000 units.

8 /01/ 2022: Complaints of headache in the sinus area and rib pain, feeling of nasal congestion, runny nose. Temperature 36.9 Tachycardia 120 / min. Performed by the patient at home positive antigen test.

9/01/ 2022. - continued headache and rib pain, runny nose, the patient performed an antigen test, which gave a positive result. In the afternoon hours, she independently drove by car (10 km) to the laboratory, where an RT-PCR test was performed. The RT-PCR test received in the evening was positive.

Telephone consultation with an internal medicine physician who suggested taking naproxen. The patient had naproxen 220 mg at home and therefore started taking the drug in a dose of 2 x440 mg. She took the first dose of naproxen in the evening. She filled out an application at IKP for an RT-PCR test. Around 10 pm, she received a positive RT- PCR result.

10 /01/ 2022: the aforementioned complaints were accompanied by a feeling of significant weakness. She could walk a few meters to the bathroom, but climbing 12 steps on the stairs to her room on the second floor was a big challenge, at the limit of her abilities.

11 /01/ 2022: After 2 days of taking naproxen, she felt much better - runny nose reduced, headaches subsided, and she was able to perform minor housekeeping tasks around the house.

13 /01/ 2022: the fifth day of taking naproxen, reduced dose to 2x220 mg due to observed prolonged bleeding after a skin scratch near the knee. History of bleeding tendency, multiple tests ( platelets, coagulogram) normal.

14 /01/ 2022: feels well, can perform household activities requiring moderate physical effort, has no pains or shortness of breath. The complaints of musculoskeletal pains have decreased.

The continuation of the course of infection of the patient presented above will be completed after receiving a control RT-PCR test, which will be performed in the next few days.

This case report is also available on www.sermo.com , a global/american portal for physicians, which can be accessed at https://app.sermo.com/post/888866 (for registered physicians only). This case report has received a lot of interest from medical colleagues around the world.

References

1.Antiviral properties of the NSAID drug naproxen targeting the nucleoprotein of SARS-CoV-2 coronawirus" https://www.mdpi.com/1420-3049/26/9/2593

2. Effcacy of Addition of naproxen in the treatment of Critlically ill patients hospitalized for COVI-19 infection (ENACOVID)

https://clinicaltrials.gov/ct2/show/NCT04325633

3.Naproksen w ciągu godziny obniża o 82% ilość wirusów w płucach - badanie naukowe. Oprac. Ewa Bzymek

https://psnlin.pl/artykuly,naproksen-w-ciagu-godziny-obniza-o-82-ilosc-wirusow-w-plucach-badanie-naukowe,21,140.html

 Krystyna Knypl

GdL 1 / 2022