In a new study by researchers from the University of Ferrara-Italy and the University Hospital of Ferrara Arcispedale Sant’Anna-Italy, it was found that bowel or intestinal ischemia and, in some cases, gastrointestinal issues were an onset of COVID-19 in otherwise asymptomatic patients with persistently negative swab.
Then there are also studies and autopsies that have demonstrated viral persistence not only in those that were symptomatic but also in the asymptomatic.
The study findings were published in the peer reviewed Journal of Internal Medicine. https://onlinelibrary.wiley.com/doi/10.1111/joim.13385
It is estimated that around 80% of persons infected with the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus have no symptoms or very mild symptoms [1].
Since the literature data on CoronaVirus Disease 2019 (COVID-19) are mainly based on the evaluation of hospitalized patients, including those requiring intensive care [1-3], few data are available on the clinical course of COVID-19 in asymptomatic cases.
The endothelium of large or small, arterial or venous, blood vessels seems to be a target for SARS-CoV-2 infection [4-6].
Furthermore, SARS-CoV-2 infection often induces an unexplained hypercoagulable state, leading to severe and potentially fatal vascular events, as venous thromboembolism [4-13] of cerebral and lower limb arteries [14, 15].
Literature data support the implication of SARS-CoV-2 infection in the manifestation of major adverse cardiovascular events, symptomatic venous thromboembolism and major arterial or venous thromboembolism in patients with COVID-19, especially in the intensive care setting, despite the use of thromboprophylaxis [16, 17].
On the contrary, no data are available on patients with acute abdominal symptoms and oro/nasopharyngeal samples test negative for SARS-CoV-2.
In this report, we analyzed resected specimens from three consecutive patients with acute abdominal symptoms and no signs of interstitial pneumonia and oro/nasopharyngeal swabs persistently negative for SARS-CoV-2.
Discussion
The results reported in this research suggest that some patients, characterized by abdomen leading to intestinal infarction and necrosis, even in the absence of the usual (respiratory or otherwise) symptoms and signs of COVID-19, and negative oro/nasopharyngeal samples, might present SARS-CoV-2 infection in the resected tissues.
The thrombosis, endothelitis and neo-angiogenesis that we observed in the small blood vessels of intestinal submucosa (Fig. 2) were closely similar to those described in the lungs of COVID-19 patients [4], supporting the correlation between SARS-CoV-2 infection and gastrointestinal symptoms.
To our knowledge, this acute and severe intestinal onset has never been reported, even if intestinal infarction was reported as a complication of interstitial pneumonia in patients testing positive for SARS-CoV-2 [19-25] and in patients with COVID-19-like pneumonia, but a SARS-CoV-2 negative swab [26].
As a confirmation of the possible involvement of the gastrointestinal tract in COVID-19 patients, literature data report nausea/vomiting symptoms in 5.0% and diarrhea in 3.8% of COVID-19 patients [3]. However, SARS-CoV-2 presence was not previously reported in the gastrointestinal samples [20, 21, 26].
It seems unlikely that a virus that gains entry to the body via the respiratory tract and whose typical manifestations are mainly respiratory, should primarily infect the gut. However, in COVID-19 patients whose respiratory symptoms have subsided, the virus may persist in the intestines for an extended period.
In a meta-analysis, viral RNA was found in the feces of 48% (95% CI, 38.3–57.9) of COVID-19 patients, even if the 70.3% (95% CI, 49.6–85.1) was SARS-CoV-2 negative in oro/nasopharyngeal samples [27, 28].
We can hypothesize that these three patients were infected with SARS-CoV-2, which remained asymptomatic at the respiratory level, but evolved in gastrointestinal pathogenesis. The negative results of the oro/nasopharyngeal samples might be due to the limit of detection of the test, especially in late infections [29].
The presence of the virus in the gastrointestinal tissues suggests the transmission of the infection from the respiratory tract to the gastrointestinal compartment via intestinal blood vessels, perhaps in relation to declining levels of neutralizing antibodies, particularly Immunoglobulin A (IgA).
IgA is principally expressed in the body’s mucous membranes, particularly in the respiratory and gastrointestinal tracts where IgA is involved in the control of viral infections [30] as the earliest neutralizing antibody response to SARS-CoV-2 infection [31]. These three cases might be representative of an acute gastrointestinal infection/re-infection with SARS-CoV-2, that developed in severe gastrointestinal symptoms without affecting the respiratory tract.
These data suggest the fecal-oral infection/re-infection as a possible alternative way of SARS-CoV-2 spreading, which deserves further investigation. In fact, even more, evidence suggests that, like other related viruses, SARS-CoV-2 may also be an enteric virus that can infect via the fecal-oral route, possibly via angiotensin-converting enzyme 2 expression in the gut [32].
Such a hypothesis, together with the presence of SARS-CoV-2 RNA in the feces of COVID-19 patients, underlines the possible presence of potentially infectious materials [33], such as stools or baby diapers, that might increase the viral persistence in the environment.
