Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause a wide range of symptoms, some of which include headache, anosmia, vomiting and nausea. To date, there are still limited data on the effect of coronavirus disease 2019 (COVID-19) on the gastrointestinal tract (GI).
In a recent With study, researchers are investigating how the presence of SARS-CoV-2 ribonucleic acid (RNA) in feces may be associated with the presentation of GI symptoms.
Examination: Gastrointestinal symptoms and fecal secretion of SARS-CoV-2 RNA suggest long-term gastrointestinal infection. Image credit: PopTika / Shutterstock.com
About the study
A total of 120 people suffering from mild to moderate COVID-19 between 25 April 2020 and 17 July 2020 were enrolled in the Peginterferon Lambda-1a (IFN-gamma) trial. Of these, 113 participants collected at least one stool sample at one of the predefined times, which included three, 14, 28, 120, 210, and 300 days after enrollment. 86 of these 113 participants provided samples at least three times.
Oropharyngeal (OP) inoculations were taken daily in the initial phase of the study and then again on days 120, 210 and 300, while blood samples were taken on days zero, five, 14, 28, 120, 210 and 300. Clinical samples were also paired with self-reported symptom data collected through questionnaires.
The median age of participants was 36 years, and the study population was mostly male (59%) and Hispanic (65%). The analyzes focused on the overall cohort and two subgroups consisting of those who reported GI symptoms and those who did not.
Those who report GI symptoms are more likely to experience several other symptoms, including myalgia, chills, decreased sense of smell, headaches, and joint pain. There were also significant differences between the two subgroups in terms of age, gender, ethnicity, and several different clinical factors.
RNA was extracted from fecal samples and analyzed for four target genes in the genomic SARS-CoV-2 RNA (gRNA) including the sheath (E), nucleocapsid (N1 and N2) and RNA-dependent RNA polymerase (RdRp). In addition, 278 of the RNA samples collected from the first month of the study were also analyzed for the E and N genes by reverse transcription polymerase chain reaction (RT-PCR) assays for confirmation.
A logistic regression model that averaged RT-PCR-derived viral concentrations with fixed effects to correct for systematic differences was applied to the results using a generalized estimation equation approach.
Stool samples were positive for SARS-CoV-2 RNA the first point on day three, where the number of participants with fecal excretion gradually decreased over time to 40% on day 14 and 11% on day 28. Compared with OP samples from 6 p.m. the same individuals, 12.7% of the participants who provided paired samples, tested negative for OP samples but positive from stool samples. None of the samples collected after 300 days were positive for SARS-CoV-2.
The absolute concentrations of RNA in the samples were subsequently calculated, with samples collected around day three showing viral secretion in between 54-77% of the participants, depending on the gene of interest. For the N1 gene, most fecal samples had between 0.32 and 3.97 logs10 copies of viral RNA / microliter (µl).
To better understand the temporal dynamics of outcomes, the time since admission to the study was treated as a continuous variable. A decrease in fecal genomic RNA (gRNA) during the first month was generally observed, with a few selected individuals exhibiting secretion for a longer period of time; however, this can also be a sign of re-infection.
When the study participants were part of a trial with Peginterferon, the researchers investigated whether the drug could affect fecal RNA clearance. For this purpose, no significant difference was observed until the analyzes were adjusted for age, sex, and target gene. These adjusted analyzes revealed that intervention with the drug was associated with lower amounts of RNA in the stool.
Longitudinal symptom data were collected from study participants and compared with absolute fecal RNA concentrations. These studies revealed that participants currently secreting viral RNA were more likely to report nausea, vomiting, and abdominal painsas well as some respiratory symptoms and head / body pain.
After examining the two subsets of data and participants whose OP inoculations were collected within three days of the stool sample, those who did not secrete RNA from the oropharynx generally reported significantly lower frequency of symptoms.
The study results provide a greater understanding of the pathophysiology of GI SARS-CoV-2 infection over significant periods of time. To this end, the current study shows that fecal secretion can continue past the point where viral RNA can be detected in OP inoculations and is associated with many different GI symptoms.
Together, these findings may help healthcare professionals treating SARS-CoV-2 patients who complain of GI problems that no longer test positive for the disease.
- Natarajan, A., Zlitni, S., Brooks, EF, et al. (2022). Gastrointestinal symptoms and fecal secretion of SARS-CoV-2 RNA suggest long-term gastrointestinal infection. With. doi: 10.1016 / j.medj.2022.04.001.