低胃酸会增加 COVID-19 的严重程度吗？,Critical Care

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低胃酸会增加 COVID-19 的严重程度吗？
Critical Care ( IF 8.8 ) Pub Date : 2020-07-22 , DOI: 10.1186/s13054-020-03182-0
Elizabeth Price ₁

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低胃酸会增加患严重 COVID-19 疾病的风险吗？尽管它主要是呼吸道感染，但据报道，SARS-CoV-2（COVID-19 [1, 2] 的病毒）以及 SARS-CoV-1 [3] 和 MERS-CoV 会导致吞咽冠状病毒引起胃肠道感染病毒[4]。胃肠道可能是扩散到肺部和身体其他部位的次要途径。一个可能的假设可能是，上呼吸道受到吸入和咳出痰中的病毒的攻击，而下呼吸道也受到类似的感染，但同时也受到血源性病毒的攻击（从重要的病毒易位后）胃肠道负荷）。前者可能只会导致轻度或中度疾病。后者可能导致更严重的疾病，因为肺部同时受到来自两条途径的病毒的攻击。虽然它可能会暂时升高，但正常胃酸的 pH 值通常在 1.5 到 3.5 之间。SARS-CoV-1 病毒在 pH < 3.0 和 > 12.0 时失活 [5]。假设这些灭活水平与 SARS-CoV-2 相似，胃酸不会抑制胃中的所有病毒（有些病毒会隐藏在食物中）。然而，确实发生的抑制作用可能足以减少进入小肠的病毒载量。在许多老年人中，胃酸 pH 值高于正常值，要么是因为萎缩性胃炎，要么是因为服用了抗酸剂和减酸药物。口服一剂质子泵抑制剂可使胃酸 pH 从 2.0 升高至 6.0 以上，但不会抑制病毒 [6]。（对于 MERS-CoV，在动物模型中使用质子泵抑制剂治疗导致小肠感染加重 [4]。）在一项对 204 名 COVID-19 患者的研究中，普遍存在发烧或呼吸道症状，但 50% 还报告了消化系统症状，尤其是食欲丢失和腹泻[1]。在文献检索中，腹痛与严重疾病的几率增加近四倍有关，这可能是因为高病毒载量、肠道中的病毒复制和病毒血症 [2]。儿童很少患有 COVID19 的严重疾病。除了与免疫因素相关的保护作用以及肺部 ACE2 受体浓度可能存在的差异外，儿童（婴儿除外）通常具有良好的胃酸水平。这可能会提供一些防止吞食病毒的保护，尽管年幼的孩子通常会吞下痰而不是吐出来。为了确定胃酸是否对 COVID-19 有一定的保护作用，可以将严重感染患者使用的抗酸剂和减酸药物的用量与轻度或无疾病患者的用量进行比较。不应忽视的是，这些药物中的许多可能是非处方药，并且只是偶尔因胃肠道症状服用，而不是由医生开处方。因此，它们可能不会出现在患者常用药物的列表中。可以考虑服用这些药物与临床过程是否有任何关系。入院期间服用的药物也应记录下来，因为医院可能会继续在家服用药物。此外，许多插管患者接受了降酸药物，胃肠道喂养可能是连续的而不是间歇的。这些因素可能导致胃 pH 值约为 4.0 或 5.0。这不会使这些病毒失活，然后这些病毒可能会进入相关 ACE2 受体丰富的小肠。如果有证据表明胃酸有一定的保护作用，可以考虑停用抗酸剂和降酸药物，尤其是在患者风险增加的时候。

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Could the severity of COVID-19 be increased by low gastric acidity?

Could low gastric acidity increase the risk of a severe COVID-19 illness? Although it is primarily a respiratory infection, gastrointestinal involvement from swallowed coronaviruses is reported for SARS-CoV-2 (the virus of COVID-19 [1, 2]), as well as SARS-CoV-1 [3] and MERS-CoV viruses [4]. The gastrointestinal tract may be a secondary route for spread to the lungs and other parts of the body. A possible hypothesis might be that the upper respiratory tract is attacked by viruses which are breathed in and coughed up in sputum while the lower respiratory tract is similarly infected, but is also attacked at the same time by bloodborne viruses (following translocation from a significant viral load in the gastrointestinal tract). The former might result in mild or moderate illnesses only. The latter may cause a more severe illness, as the lungs are being attacked by viruses coming from two routes simultaneously. Although it can be transiently higher, the pH of normal gastric acid is generally between 1.5 and 3.5. The SARS-CoV-1 virus is inactivated at a pH < 3.0 and > 12.0 [5]. Assuming these inactivation levels are similar for SARS-CoV-2, gastric acid will not inhibit all the viruses in the stomach (and some viruses will be hidden in food boluses). However, the inhibition that does occur may be enough to decrease the viral load entering the small intestine. In many older adults, the gastric acid pH is higher than normal, either because of atrophic gastritis or because of antacid and acid-reducing medications. One oral dose of a proton pump inhibitor raises the gastric acid pH from 2.0 to over 6.0, which will not inhibit the virus [6]. (For MERS-CoV, treatment with a proton pump inhibitor in an animal model resulted in exaggerated infection in the small intestine [4].) In a study of 204 COVID-19 patients, fever or respiratory symptoms were generally present but 50% also reported digestive symptoms, particularly appetite loss and diarrhoea [1]. In a literature search, abdominal pain was associated with a near fourfold increased odds of severe disease, possibly because of a high viral load, viral replication in the gut and viremia [2]. Children rarely suffer from severe illnesses with COVID19. As well as protection related to immunological factors and possible differences in the ACE2 receptor concentrations in their lungs, children (other than infants) generally have good levels of gastric acid. This may provide some protection from swallowed viruses, even though young children usually swallow their sputum rather than spit it out. To determine whether gastric acid gives some protection from COVID-19, the amount of antacids and acid-reducing drugs used by patients with severe infections could be compared with the amount used by patients with mild or no disease. It should not be overlooked that many of these medications may be purchased over-the-counter and be taken only occasionally for gastrointestinal symptoms, rather than being prescribed by a medical practitioner. Therefore, they may not appear on a list of a patient’s usual medications. Whether there is any relation between taking these drugs and the clinical course could be considered. Drugs taken during hospital admissions should also be recorded, as hospitals may continue medications taken at home. In addition, many intubated patients are given acidreducing drugs and gastrointestinal feeding may be continuous rather than intermittent. Such factors could result in a gastric pH of around 4.0 or 5.0. This would not inactivate these viruses, which might then pass into the small intestine where the relevant ACE2 receptors are abundant. If there is evidence for some protection by gastric acidity, stopping antacids and acid-reducing medications could be considered, particularly at times when patients are at increased risk.

更新日期：2020-07-22

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