Reduced gastric acidity, proton pump inhibitors and increased severity of COVID-19 infections
Critical Care volume 25, Article number: 73 (2021)
There are now articles linking the use of proton pump inhibitors (PPIs) to an increased risk of more severe COVID-19 infections [1, 2]. As discussed in our research letter , this is not surprising because these viruses can be swallowed and may spread via the gastrointestinal tract as well as the respiratory tract. Gastric acid is a partial barrier which restricts the entry of SARS-CoV-2 viruses into the rest of the gastrointestinal tract. This acid barrier is removed by a single dose of a PPI, as it raises the gastric pH from its usual level of 1.5 -3.5 to over 6.0. At this less acid pH, these viruses are not inactivated [3, 4]. This may be part of the reason young people and children rarely get a severe COVID-19 illness, as this age group usually has good gastric acidity.
For ventilated patients, as well as the PPI risk, continuous nasogastric feeding regimes may present a risk of a more severe COVID-19 illness. For patients on these continuous regimes, the gastric pH will be around 4.0 or 5.0. At this pH, SARS-CoV-2 viruses will not be inactivated [3, 4]. In contrast, intermittent nasogastric feeding will allow the gastric pH to fall to < 2.0 between periods of feeding. At this more acid pH level, the viruses could be inactivated.
During the present pandemic, it would be useful if a risk–benefit assessment could be carried out for patients on PPIs. A histamine-2 receptor antagonist (sometimes specified as famotidine) has been mentioned as a possible alternative but further review is needed [2, 5]. In addition, maintaining gastric acidity in ventilated COVID-19 patients by intermittent nasogastric feeding, could be considered where possible.
Availability of data and materials
Lee SW, Ha EK, Yeniova AO, et al. Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching. Gut. 2020. https://doi.org/10.1136/gutjnl-2020-32224.
Hariyanto TI, Prasetya IB, Kurniawan A. Proton pump inhibitor use is associated with increased risk of severity and mortality from coronavirus disease 2019 (COVID-19) infection. Dig Liver Dis. 2020;S1590–8658(20):30930. https://doi.org/10.1016/j.dld.2020.10.001.
Price E. Could the severity of COVID-19 be increased by low acidity? Critical Care. 2020;24:456. https://doi.org/10.1186/s13054-020-03182-0.
Chan KH, Sridhar S, Zhang RR, Chu H, Fung AY, Chan G, et al. Factors affecting stability and infectivity of SARS-CoV-2. J Hosp Infect. 2020;106(2):226–31. https://doi.org/10.1016/j.jhin.2020.07.009.
Freedberg DE, Conigliaro J, Wang TC, Tracey KJ, Callahan MV, Abrams JA, et al. Famotidine use is associated with improved clinical outcomes in hospitalized COVID-19 patients: a propensity score matched retrospective cohort study. Gastroenterology. 2020;159(3):1129-1131.e3. https://doi.org/10.1053/j.gastro.2020.05.053.
We acknowledge the advice of the following: Dr Richard Cunningham MB FRCPath, Professor John Walker-Smith MD FRCP FRACP FRCHCH
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Price, E., Treacher, D.F. Reduced gastric acidity, proton pump inhibitors and increased severity of COVID-19 infections. Crit Care 25, 73 (2021). https://doi.org/10.1186/s13054-021-03497-6