The symptoms of respiratory distress caused by COVID-19 may be reduced by drugs combining anti-inflammatory and antiviral effects. This dual effect may simultaneously protect severely-ill patients and reduce the viral load, therefore limiting virus dissemination We want to demonstrate the superiority of naproxen (anti-inflamatory drug) treatment addition to standard of care compared to standard of care in term of 30-day mortality.
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.
Drug: 1: Naproxen
Description : Administration of naproxen 250 mg twice and lansoprazole 30 mg daily for prevention of gastropathy induced by stress or a nonsteroidal anti-inflammatory drug (NSAID) in addition to standard of care (SOC)
Drug: 2: Standard of care
Standard of care
Inclusion Criteria:
- COVID-19 infected patient
- Age 18 years or older
- Presence of pneumonia
- PaO2/FiO2 < 300 mm Hg or SpO2 < 93% in air ambient or need to supplementary oxygen
administration in order to maintain SpO2 range in [94-98%] or lung infiltrates > 50%
- Medical insurance
Exclusion Criteria:
- Presence of do-not-resuscitate order
- Pregnancy
- Prisoners
- Known Naproxen allergy or intolerance
- Severe renal failure
Réanimation médico-chirurgicale, Avicenne Hospital
Bobigny, France
Urgences, Avicenne Hospital
Bobigny, France
Frédéric ADNET, MD, PhD, Principal Investigator
Assistance Publique - Hôpitaux de Paris