Gut Microbiota Dysbiosis Correlates with Abnormal Immune Response in Moderate COVID-19 Patients with Fever

Abstract

Background Most COVID-19 patients are moderate, and fever is the most common clinical manifestation and associated with poorer prognosis. Gut microbiota may also play important roles in COVID-19 pathogenesis. However, the association between gut microbiota and fever in individuals with moderate COVID-19 remains unclear. Methods We compared the clinical features and laboratory results of 187 moderate COVID-19 patients with fever and without fever and identified several inflammatory markers in patients with fever. Then, we performed gut metagenome-wide association study for 31 individuals to identify the microbes and their epitopes which have potential role in fever and hyperinflammation. Results Among 187 moderate COVID-19 patients, 127 (67.9%) patients presented with fever. Lymphocytes, CD3+ T cells, CD4+ T cells and the ratio of CD4+ T cells to CD8+ T cells were significantly reduced, while AST, LDH, CRP, IL-6 and IL-10 were significantly elevated in patients with fever. Gut microbiome composition was significantly altered in patients with fever compared with those with non-fever. Opportunistic pathogens such as Enterococcus faecalis and Saccharomyces cerevisiae were enriched in patients with fever. E. faecalis was positively correlated with LDH and D-dimer and negatively correlated with CD8+T cells and IL-4, while S. cerevisiae was positively correlated with diarrhea symptom. Furthermore, several species with anti-inflammatory and protective effects, such as Bacteroides fragilis and Eubacterium ramulus , were enriched in patients with non-fever. B. fragilis was positively correlated with lymphocytes, and E. ramulus was negatively correlated with LDH, AST and IL-6. Finally, we found that several bacterial epitopes of GroEL, a homolog of human HSP60, were enriched in patients with fever and positively correlated with IL-6, IL-10, WBC, neutrophils, D-dimer, LDH, CRP, and E. faecalis . Conclusion Gut microbiota dysbiosis correlates with abnormal immune response in moderate COVID-19 patients with fever.

Gut Microbiota Disruption in COVID-19 or Post-COVID Illness Association with severity biomarkers: A Possible Role of Pre / Pro-biotics in manipulating microflora

“…Furthermore, dysbiosis due to declined Bacteroides spp. the population was positively correlated with D-dimer, neutrophils, IL-6, CRP, and LDH in acute and long-term COVID infection [ 127 ].…”

Blowing Hot and Cold: Body Temperature and the Microbiome

“…However, the impact of acute fever responses on the mammalian microbiota is relatively unknown. A recent study found that patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-Cov2) show fever-dependent shifts in the gut microbiota, including an increase in bacterial heat shock proteins, suggesting that fever temperatures do impact the human microbiome ( 58 ).…”

Cross-talk between immune system and microbiota in COVID-19

“…Patients with fever had a significant different gut microbiota composition than those who did not have a fever. Patients with fever had higher opportunistic infections, including Enterococcus faecalis and Saccharomyces cerevisiae [ 139 ]. In the cross-sectional study conducted by Gu et al ., it was discovered that the microbiological profile of COVID-19 patients differed from that of patients with influenza A and healthy controls.…”