How does COVID-19 influence your gut microbiota?

By Vijay Kumar MalesuAug 23 2023Reviewed by Sophia Coveney

In a recent study published in the BMC Infectious Diseases, a group of researchers analyzed the fecal microbiota composition in Coronavirus disease 2019 (COVID-19) patients in comparison to non-COVID-19 controls.

They assessed its correlation with disease severity and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) excretion in the gastrointestinal tract.

Background

The SARS-CoV-2 virus, which surfaced in Wuhan in December 2019, was initially thought to affect only the respiratory system. However, it soon became evident that COVID-19 could affect multiple organs, including the gastrointestinal tract. Although primarily a respiratory infection, the gut plays a pivotal role in the disease progression and immune response.

The gut's significance is further underscored by the high COVID-19 positivity rate of stool samples, even when respiratory indications diminished. The gut's molecular involvement is attributed to angiotensin-converting enzyme 2 (ACE2) expression, the primary receptor for the virus.

The human gut microbiota, dominated by three main bacterial phyla, impacts host health and possibly the body's immune response to respiratory diseases like COVID-19.

Few studies have delved into the gut microbiota dynamics in COVID-19 patients. However, their findings highlight a reduction in beneficial bacteria and an increase in opportunistic pathogens among COVID-19 patients. This highlights the need for further detailed studies to explore the gut microbiota in critical COVID-19 patients.

About the study

The present study was conducted on adult patients admitted with confirmed SARS-CoV-2 from March to December 2020. The criteria for inclusion comprised patients aged over 18 years, exhibiting COVID-19 symptoms, with a positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, and consent.

Pregnant or lactating women, those with certain bowel conditions, or those unable to give consent were excluded, and non-COVID critically ill patients were used as controls.

Every day, a list of PCR-positive SARS-CoV-2 patients was updated and reviewed by infectious disease doctors. Stool samples were taken at various intervals after the SARS-CoV-2 diagnosis. The hospital's electronic health record (EHR) system provided a plethora of patient information, including clinical, radiological, and laboratory data.

For control intensive care unit (ICU) patients, stool samples were collected within a specified timeframe post-intubation. The frequency and method of sample collection varied depending on circumstances such as suspected infection or ICU discharge.

Data, including clinical, laboratory, and radiological details, were sourced from the EHR and recorded in an electronic clinical report form using the research electronic data capture (REDCap) platform. Statistical analyses were executed with the R software. Different diagnostic methods were employed to detect SARS-CoV-2 in stool samples. Furthermore, 16S ribosomal ribonucleic acid (rRNA) metagenomic sequencing was carried out to study bacterial communities in the samples.

This study was conducted ethically, following the Declaration of Helsinki, Good Clinical Practice, and the Swiss Human Research Act. The Ethics Committee of Canton Vaud approved the study, and the data were anonymized for analysis.

Study results

During the investigation, 57 individuals diagnosed with SARS-CoV-2 infection were studied. Their median age stood at 68 years, with the majority falling within the 60-79 age range. Notably, about 23% of the participants were over 80 years old. A minority (8.8%) belonged to the 18-49 age bracket.

The median body mass index (BMI) was measured at 25.6, and a significant proportion, 54.4%, were overweight or obese, while 56.2% had hypertension. The median Charlson Comorbidity Index (CCI) was 5.0. Of the total, 40.4% were on angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors (ACEI).

Upon comparison between ventilated (24.5% of total) and non-ventilated patients, those with ventilation showed a higher incidence of renal insufficiency and elevated C-reactive protein levels.

The median period before hospital admission post-symptoms was roughly 6 days. Common symptoms included fatigue (80.7%), cough (73.7%), dyspnea (64.9%), and fever (59.6%). By the study's end, over a quarter of patients were either hospitalized or in rehab, while 61.4% returned home. Regrettably, 10.5% succumbed during their hospital stay, with hypertension being a significant mortality indicator.

Nineteen individuals served as the control set, split between those intubated but infection-free (5 patients) and those with pulmonary infections (14 patients). The median age for the control group was 62.4 years, with males comprising 57.9%. The baseline characteristics of ventilated SARS-CoV-2 patients and the control group appeared consistent in terms of age and gender.

Researchers sought to discern if there was a fecal microbiota distinction between COVID-19 patients and non-COVID-19 ICU patients. Initial observations showed no significant differences.

However, by the seventh day, variations in the microbiota composition became apparent. Notably, the COVID-19 cluster showed unique microbial attributes distinct from both the pneumonia and control groups. Intriguingly, only the COVID-19 condition exhibited a profound influence on the bacterial composition.

To comprehend microbial variances amid ventilated and non-ventilated patients, bacterial genera diversities were noted with time-adjusted sampling. For those on ventilation, some bacterial genera showed an increased presence, while others diminished.

In assessing variables impacting the microbiota, only ventilation displayed a considerable influence on microbial composition. As the study progressed, ventilated patients manifested rapid microbiota shifts, suggesting a dynamic change in their gut bacterial makeup.

Evaluating SARS-CoV-2 particle excretion in the gastrointestinal tract showed a comparable proportion of quantitative polymerase chain reaction (qPCR)-positive patients between ventilated and non-ventilated groups. However, ventilated patients demonstrated a notably higher viral load. There seemed to be a divergence between viral load, disease severity, and inflammation levels.