Temporal changes in fecal microbiota of patients infected with COVID-19: a longitudinal cohort.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a multifaceted disease potentially responsible for various clinical manifestations including gastro-intestinal symptoms. Several evidences suggest that the intestine is a critical site of immune cell development, gut microbiota could therefore play a key role in lung immune response. We designed a monocentric longitudinal observational study to describe the gut microbiota profile in COVID-19 patients and compare it to a pre-existing cohort of ventilated non-COVID-19 patients. METHODS: From March to December 2020, we included patients admitted for COVID-19 in medicine (43 not ventilated) or intensive care unit (ICU) (14 ventilated) with a positive SARS-CoV-2 RT-PCR assay in a respiratory tract sample. 16S metagenomics was performed on rectal swabs from these 57 COVID-19 patients, 35 with one and 22 with multiple stool collections. Nineteen non-COVID-19 ICU controls were also enrolled, among which 14 developed ventilator-associated pneumonia (pneumonia group) and five remained without infection (control group). SARS-CoV-2 viral loads in fecal samples were measured by qPCR. RESULTS: Although similar at inclusion, Shannon alpha diversity appeared significantly lower in COVID-19 and pneumonia groups than in the control group at day 7. Furthermore, the microbiota composition became distinct between COVID-19 and non-COVID-19 groups. The fecal microbiota of COVID-19 patients was characterized by increased Bacteroides and the pneumonia group by Prevotella. In a distance-based redundancy analysis, only COVID-19 presented significant effects on the microbiota composition. Moreover, patients in ICU harbored increased Campylobacter and decreased butyrate-producing bacteria, such as Lachnospiraceae, Roseburia and Faecalibacterium as compared to patients in medicine. Both the stay in ICU and patient were significant factors affecting the microbiota composition. SARS-CoV-2 viral loads were higher in ICU than in non-ICU patients. CONCLUSIONS: Overall, we identified distinct characteristics of the gut microbiota in COVID-19 patients compared to control groups. COVID-19 patients were primarily characterized by increased Bacteroides and decreased Prevotella. Moreover, disease severity showed a negative correlation with butyrate-producing bacteria. These features could offer valuable insights into potential targets for modulating the host response through the microbiota and contribute to a better understanding of the disease's pathophysiology. TRIAL REGISTRATION: CER-VD 2020-00755 (05.05.2020) & 2017-01820 (08.06.2018).

Detection of SARS-CoV-2 infection clusters: The useful combination of spatiotemporal clustering and genomic analyses.

Background: The need for effective public health surveillance systems to track virus spread for targeted interventions was highlighted during the COVID-19 pandemic. It spurred an interest in the use of spatiotemporal clustering and genomic analyses to identify high-risk areas and track the spread of the SARS-CoV-2 virus. However, these two approaches are rarely combined in surveillance systems to complement each one's limitations; spatiotemporal clustering approaches usually consider only one source of virus transmission (i.e., the residential setting) to detect case clusters, while genomic studies require significant resources and processing time that can delay decision-making. Here, we clarify the differences and possible synergies of these two approaches in the context of infectious disease surveillance systems by investigating to what extent geographically-defined clusters are confirmed as transmission clusters based on genome sequences, and how genomic-based analyses can improve the epidemiological investigations associated with spatiotemporal cluster detection. Methods: For this purpose, we sequenced the SARS-CoV-2 genomes of 172 cases that were part of a collection of spatiotemporal clusters found in a Swiss state (Vaud) during the first epidemic wave. We subsequently examined intra-cluster genetic similarities and spatiotemporal distributions across virus genotypes. Results: Our results suggest that the congruence between the two approaches might depend on geographic features of the area (rural/urban) and epidemic context (e.g., lockdown). We also identified two potential superspreading events that started from cases in the main urban area of the state, leading to smaller spreading events in neighboring regions, as well as a large spreading in a geographically-isolated area. These superspreading events were characterized by specific mutations assumed to originate from Mulhouse and Milan, respectively. Our analyses propose synergistic benefits of using two complementary approaches in public health surveillance, saving resources and improving surveillance efficiency.