PPI and COVID-19
PPIs are medicines that are primarily used to suppress gastric acid
production. Examples of PPIs include dexlansoprazole, esomeprazole,
lansoprazole, omeprazole, pantoprazole, and rabeprazole. PPIs can be
very useful in treating acid-related symptoms such as acid reflux,
heartburn, and dyspepsia, and to treat and protect from acid-related
complications such as reflux oesophagitis and peptic ulcers.
Stomach acid helps to keep the digestive system free of infections by
killing swallowed viruses and bacteria that might be in saliva or in
food (2). Many viruses are sensitive to low gastric pH, and hence
theoretically, hypochlorhydria induced by PPI agents can increase the
risk of viral infections (15). It has already been established that PPIs
can increase the risk for enteric diseases such as food poisoning,
traveller’s diarrhoea and Clostridium diffcile infections (4, 5).
Similarly, PPIs may also increase the risk of community-acquired
pneumonia (16-18).
Earlier studies have shown that stomach acid can kill coronaviruses
(19). Coronaviruses shed into saliva. SARS-CoV-2 uses the
angiotensin-converting enzyme–2 receptor to invade enterocytes (10).
Therefore, the virus can rapidly invade and replicate within cells
lining the intestinal tract (10, 20). As stomach acid can be protective
against the acquisition of coronavirus, PPIs induced hypochlorhydria may
facilitate an environment in which coronavirus may thrive. As a result
of the use of PPIs, the stomach pH will increase above 3. This rise in
the gastric pH might allow the virus to enter the GI tract more
efficiently, leading to enteritis, colitis, and systemic spread to other
organs, including the lungs. Therefore, there is a theoretical concern
that the use of PPIs could diminish or abolish the neutralising effects
of gastric acid on SARS-CoV-2, which could potentially increase the risk
of GI manifestations and severity in COVID-19.
In a recently published extensive, nationwide survey of over 53,000
Americans, PPI use was independently associated with increased odds for
COVID-19, compared to those not using PPIs (11). Moreover, there was a
dose-response relationship between PPI use and the risk of COVID-19.
After adjusting for confounding factors (age, sex, race/ethnicity,
education, marital status, household income, body mass index, smoking,
alcohol consumption, US region, insurance status, and the GI diseases,
diabetes, and HIV/AIDS), the highest risk was seen among those taking
PPIs twice a day. This group had almost 4-times the odds of being
positive for COVID-19 when compared to people not using PPIs [odds
ratio (OR) 3.67; 95% CI, 2.93 – 4.60]. Those taking PPIs up to once
a day were twice as likely to have had a positive COVID-19 test result
than those who did not take the drugs (OR 2.15; 95% CI, 1.90 – 2.44).
The risk of PPIs remained significant regardless of the duration of use,
including those who had been on PPIs for six months or greater, before
the start of the pandemic (11).
In contrast, the use of the less powerful H2RAs was not associated with
an increased risk for COVID-19. The use of lower-dose H2RAs was
associated with 15% decreased odds of reporting a positive test, while
no association was seen for the higher dose of H2RAs.
Importantly, this study was not a randomised, controlled trial; it does
not definitively prove that PPIs increase the risk for COVID-19. Future
research is needed to confirm the findings in this new study.
Contrarily to the findings of the above study by Almario et al., a
recent survey of a Korean nationwide cohort with propensity score
matching, revealed PPI usage, including current and past use, did not
increase susceptibility to SARS-CoV-2 infection (12). However, current
PPI usage was associated with worse outcomes of COVID-19. The ongoing
short-term use of PPIs (<1 month) conferred a 90% increased
risk of worse clinical outcomes of COVID-19. These findings continue to
highlight the potential risk of continued PPI use in the setting of
COVID-19 infection.