Abstract: Letter to the Editor
doi: 10.1111/joim.13121
Treatment with proton pump inhibitors increases the risk of
secondary infections and ARDS in hospitalized patients with
COVID-19: coincidence or underestimated risk factor?
Dear Sir,
In December 2019, several cases of pneumonia of
unknown origin have been reported in China, and
later, SARS-CoV2 was identified as the causative
pathogen for coronavirus disease 2019 (COVID-19)
[1]. In some cases of COVID-19, the clinical
courses are more severe and may be aggravated
by secondary infections and the development of an
acute respiratory distress syndrome (ARDS) with a
high morbidity and mortality [1]. However, risk
factors for severe clinical courses including
patients’ medication are poorly described. Proton
pump inhibitors (PPI) play an important role in the
treatment of acid-related disorders. As a result of
their high efficacy, PPIs have become one of the
most commonly prescribed agents. However, PPIs
may trigger the development of pneumonia [2] due
to the reduced gastric acid production with subsequent bacterial overgrowth in the upper gastrointestinal tract and microaspiration with following
colonization of the pneumonia [2]. Therefore, we
hypothesized that PPI treatment may also be a
potential risk factor for the development of secondary infections and of ARDS in hospitalized
patients with COVID-19.
In total, 152 patients with confirmed SARS-Cov-2
infection were included in the analysis (Figure S1).
Baseline characteristics are summarized in
Table 1. Sixty-two patients (40.8%) received regular treatment with PPI. Importantly, in 30 patients
(48.4%), no clear reason for the PPI intake was
detectable in the medical records of the patients
and during assessment of patients’ medical history. Forty-eight patients (31.6%) presented with a
secondary infection during hospitalization. In
patients with PPI treatment, 30 of 62 patients
(48.4%) presented with secondary infection compared to 11 of 90 patients (20.0%) without PPI
treatment (P < 0.001, Table 1) indicating that PPI
treatment is a significant risk factor for the
[Correction added on 23 July 2020, after first online publication: The
percentage, (48.4%)“ has been corrected to (27.4%)” in the preceding
sentence.]
development of secondary infections in patients
with SARS-CoV-2 infection. After adjusting for
other risk factors, especially for other predisposing
comorbidities, PPI treatment remained a significant predictive factor for development of secondary
infection (OR 2.37 [01.08–5.22], P = 0.032,
Table S2). Moreover, gastroesophageal reflux disease also emerged as a significant independent
predictive factor of secondary infection (OR 6.40
[1.50–35.51]; P = 0.034) underlining the role of
microaspiration in the pathogenesis of secondary
infection in these patients.
Further, PPI-treated patients developed ARDS in
17 of 62 patients (27.4%) compared to 11 of 90
patients (12.2%) without PPI treatment (P = 0.020,
Table 1). However, development of ARDS was
strongly associated with the presence of a secondary infection as only two patients (1.9%) without a secondary infection developed ARDS
compared to 26 patients (54.2%) with confirmed
secondary infection (P < 0.001). In summary, PPIs
have an indirect effect on ARDS development by
triggering secondary infection. In accordance with
the increased risk of a secondary infection and
consecutive development of ARDS, PPI-treated
patients showed a significantly higher index mortality (19.4% vs. 5.6%, P =..
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