Detection of Intestinal Dysbiosis in Post-COVID-19 Patients One to Eight Months after Acute Disease Resolution

Abstract

The intestinal microbiota plays an important role in the immune response against viral infections, modulating both innate and adaptive immune responses. The cytokine storm is associated with COVID-19 severity, and the patient’s immune status is influenced by the intestinal microbiota in a gut-lung bidirectional interaction. In this study, we evaluate the intestinal microbiota of Brazilian patients in different post-COVID-19 periods, and correlate this with clinical data and the antibiotic therapy used during the acute phase. DNA extracted from stool samples was sequenced and total anti-SARS-CoV-2 antibodies and C-reactive protein were quantified. Compared with controls, there were significant differences in the microbiota diversity in post-COVID-19 patients, suggesting an intestinal dysbiosis even several months after acute disease resolution. Additionally, we detected some genera possibly associated with the post-COVID-19 dysbiosis, including Desulfovibrio, Haemophillus, Dialister, and Prevotella, in addition to decreased beneficial microbes, associated with antibiotic-induced dysbiosis, such as Bifidobacterium and Akkermansia. Therefore, our hypothesis is that dysbiosis and the indiscriminate use of antibiotics during the pandemic may be associated with post-COVID-19 clinical manifestations. In our study, 39% (n = 58) of patients reported symptoms, including fatigue, dyspnea, myalgia, alopecia, anxiety, memory loss, and depression. These data suggest that microbiota modulation may represent a target for recovery from acute COVID-19 and a therapeutic approach for post-COVID-19 sequelae.

Gut Microbiota Composition Can Predict Colonization by Multidrug-Resistant Bacteria in SARS-CoV-2 Patients in Intensive Care Unit: A Pilot Study

“…On the contrary, in colonized patients Dialister propionicifaciens could be crucial in MDRB colonization. As mentioned above, this bacterium is recognized as an opportunistic pathogen [ 53 ] and, moreover, it has been positively correlated with SARS-CoV-2 infection [ 54 , 55 ]. However, its impact on MDRB colonization in these patients remains unknown.…”

Pentosan Polysulfate Affords Pleotropic Protection to Multiple Cells and Tissues

“…The depletion of microbiota with immunomodulatory properties may prolong physiological effects on lung injury through the gut–lung axis [ 21 ]. Any delay in the re-establishment of these health-promoting gut symbionts may contribute to lingering effects induced by systemic inflammation [ 21 , 22 , 23 ].…”

Folgen nach SARS-CoV-2-Infektion einschließlich Post-COVID-Syndrom

“…Im Gegensatz zu der zuvor beschrieben Resilienz des Mikrobioms nach Genesung von einer SARS-CoV-2-Infektion, gibt es auch Belege, dass bei Patient:innen mit Post-COVID-Syndrom, persistierende Veränderung des Mikrobioms im Vergleich zu gesunden Kontrollen vorliegen. So fand sich neben Unterschieden im Tryptophan- und Serotoninmetabolismus des Mikrobioms bei Post-COVID-Patient:innen [ 19 ] auch eine Zunahme von Desulfovibrio, Haemophilus, Dialister sowie Prevotella , während potenziell „protektive“ Spezies wie Bifidobacterium und Akkermansia reduziert sind [ 15 ]. Wie auch bei den anderen diskutierten pathophysiologischen Mechanismen können diese Veränderungen nicht bei allen Patient:innen beobachtet werden.…”

“…Während das akute Krankheitsbild COVID-19 mittlerweile gut verstanden wird, sind die genauen pathophysiologischen Mechanismen und Langzeitfolgen, die zur Entstehung von Post-COVID-Syndromen führen, zurzeit noch unzureichend verstanden. Aktuell diskutierte Mechanismen beinhalten unter anderem eine Viruspersistenz, eine andauernde (systemische) Inflammation [11], die Entwicklung von agonistischen Autoantikörpern gegen G-Proteingekoppelte Rezeptoren [12], eine Veränderung in regulatorischen T-Zellen [13], mikrovaskuläre Veränderungen im Sinne einer "Endotheliitis" [14] und eine intestinale Dysbiose [15]. Dabei ist zu beachten, dass es zu keinem der diskutierten pathophysiologischen Mechanismen eindeutige Beweise gibt und auch eine multifaktorielle Genese aktuell nicht auszuschließen ist.…”