COVID-19 Early Treatment with Non-Steroidal AntiInflammatory Drugs Reduces Hospitalizations andSymptom Duration

At the beginning of the SARS-CoV-2 pandemic we stated that,
given the new virus and the little-known disease it caused, in the
absence of Evidence-Based Medicine indications, patients should
have been treated with drugs already available, useful to counteract
the pathophysiology of the COVID-19 [1]. Recent literature has
confirmed that this could be a successful approach, demonstrating
that an early treatment with nonsteroidal anti-inflammatory drugs
(NSAIDs), in patients with mild-to-moderate COVID-19, produces
significant reduction of hospitalizations and disease duration [2-4].
The NSAIDs have indication in the COVID-19 not only for their antiinflammatory actions but also, some molecules, for their antiviral
properties [2,3,5].

Aim and Scope
The aim of this study was to verify whether a prompt home
treatment with NSAIDs could reduce hospital admissions and
disease duration in patients with mild-to-moderate COVID-19.
This multicenter retrospective observational study was
performed by analyzing the data of 966 Italian unvaccinated
patients (age≥18 years) with mild-to-moderate confirmed
COVID-19. The data were collected from February to December
2021 by some physicians, members of the “terapia domiciliare
COVID-19” (an Italian group founded by lawyer Erich Grimaldi to
assist people with COVID-19). The protocol was approved by the
ethical committee of the ASL Napoli 2 and all the patients provided
written informed consent. According to a previous observation [2],
the 966 patients (539 females), mean age±SD 45±14, were divided
into two groups: Group 1 consisted of 561 patients who started the
therapy within the first 72 hours from onset of symptoms, Group 2
included 405 patients, who, were referred later and started therapy
after 72 hours. All patients had an initial treatment with a NSAID
(Ibuprofen 40%, Aspirin 26%, Indomethacin 18%, Nimesulide
11%, Ketoprofen 5%). When appropriate, for those whose clinical
condition worsened, cortisone was added, and/or a prophylactic

dose of low molecular weight heparin and/or antibiotics. From the
whole group, a subgroup of 339 over-50-year-old patients (over-
50) with a mean age±SD of 60±9 years (183 females) was selected.
It was divided in: Subgroup 1 of 190 patients who started the
therapy within the first 72 hours and Subgroup 2 of 149 pts who
started later.
Descriptive statistics (mean values and standard deviation)
were used to measure the central tendency and dispersion of the
data. The dataset was analyzed by considering all the subjects
recruited and the subgroup over-50, according to the time of
starting the therapy: within or after 72 hours, respectively, named
as “early treatment” and “late treatment”. To compare the difference
between the subgroups for anthropometric parameters and
comorbidities, the non-parametric Mann-Whitney U test was used,
assuming a significance level of p = 0.05. The chi-square test was
adopted to compare the differences between hospitalizations. Stat
view software was used to perform statistical analysis.

We analyzed the data from the whole group of 966 pts and
the subgroup of 339 over-50. The data analysis showed that the
two groups and the two over-50 subgroups were not significantly
different for age, sex distribution, BMI and comorbidities. The results
show a significant reduction in the number of hospitalizations in
Group 1 as compared to Group 2 (13 vs 41, p<0.0001) and between
the two over-50 subgroups (9 vs 24, p<0.001), showing a reduction
of hospital admissions of 68 and 63 %, respectively (Figure 1).
Furthermore, there was a reduction of disease symptom duration
from 15 to 11 days and from 16 to 11 days, respectively (Figure 1).
Early treatment with indomethacin and nimesulide produced zero
hospitalizations. A total of 6 hospitalized patients died: 5 in the
Group 2 and only one in the Group 1, all among the over-50

This study clearly shows that a prompt therapy with NSAIDs,
started within 72 hours of the onset of symptoms, reduces the
number of hospitalizations and the disease symptoms duration
in patients with mild-to-moderate COVID-19. Although it is an
observational retrospective study, these results confirm, in a
larger population, the ones reported by a previous study [2], and,
importantly, the reductions of hospitalizations and symptom
duration were also confirmed in the over-50 subgroup.

In most western countries, at the beginning of the SARS-CoV-2
pandemic, a “watchful waiting” attitude and/or a symptomatic
treatment were indicated for patients with mild-to-moderate
COVID-19: this approach might have resulted in the largest number
of hospitalizations. Further prospective controlled studies are
needed to confirm these findings and to verify whether, among the
different NSAIDs, there is one that could give better outcome