SARS-CoV-2-specific IgA and limited inflammatory cytokines are present in the stool of select patients with acute COVID-19

Abstract

Background and aims: Immune dysregulation caused by SARS-CoV-2 infection is thought to play a pathogenic role in COVID-19. SARS-CoV-2 can infect a variety of host cells, including intestinal epithelial cells. We sought to characterize the role of the gastrointestinal immune system in the pathogenesis of the inflammatory response associated with COVID-19. Methods: We measured cytokines, inflammatory markers, viral RNA, microbiome composition and antibody responses in stool and serum samples from a prospectively enrolled cohort of 44 hospitalized COVID-19 patients. Results: SARS-CoV-2 RNA was detected in stool of 41% of patients and was found more frequently in patients with diarrhea than those without (16[44%] vs 5[19%], p=0.06). Patients who survived had lower median viral genome copies than those who did not (p=0.021). Compared to uninfected controls, COVID-19 patients had higher median fecal levels of IL-8 (166.5 vs 286.5 pg/mg; p=0.05) and lower levels of fecal IL-10 (678 vs 194 pg/mg; p<0.001) compared to uninfected controls. Stool IL-23 was higher in patients with more severe COVID-19 disease (223.8 vs 86.6 pg/mg; p=0.03) and we find evidence of intestinal virus-specific IgA responses, which was associated with more severe disease. Fecal cytokines and calprotectin levels were not correlated with gastrointestinal symptoms or with the level of virus detected. Conclusions: Although SARS-CoV-2 RNA was detectable in the stools of COVID-19 patients and select individuals had evidence for a specific mucosal IgA response, intestinal inflammation was limited, even in patients presenting with gastrointestinal symptoms.

Is Gut Microbiota Dysbiosis a Predictor of Increased Susceptibility to Poor Outcome of COVID-19 Patients? An Update

“…This study raises the premise that the cytokine storm observed in COVID-19 cases might be correlated with disease severity, as IL-2, IL-7, IL-10, G-CSF, MCP-1, IP-10, TNF-α, and MIP-1α levels were higher in ICU patients compared with non-ICU ones [ 63 ]. Moreover, a study evaluating a cohort of 44 hospitalized COVID-19 patients reported the existence of higher median fecal levels of IL-8 and lower levels of fecal IL-10 in COVID-19 patients compared with control individuals [ 65 ]. Furthermore, IL-23 fecal levels were increased in severe patients, suggesting the involvement of the GI tract in the SARS-CoV-2 infection in an immunological manner [ 65 ].…”

“…Moreover, a study evaluating a cohort of 44 hospitalized COVID-19 patients reported the existence of higher median fecal levels of IL-8 and lower levels of fecal IL-10 in COVID-19 patients compared with control individuals [ 65 ]. Furthermore, IL-23 fecal levels were increased in severe patients, suggesting the involvement of the GI tract in the SARS-CoV-2 infection in an immunological manner [ 65 ]. More severe cases were also associated with higher serum levels of IL-6, IL-8, tumor necrosis factor α (TNF-α), C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, ferritin, and procalcitonin [ 65 ].…”

“…Furthermore, IL-23 fecal levels were increased in severe patients, suggesting the involvement of the GI tract in the SARS-CoV-2 infection in an immunological manner [ 65 ]. More severe cases were also associated with higher serum levels of IL-6, IL-8, tumor necrosis factor α (TNF-α), C-reactive protein (CRP), lactate dehydrogenase (LDH), D-dimer, ferritin, and procalcitonin [ 65 ]. Furthermore, a study performed by Li et al allowed to observe that the lower the counts on admission of total T cell, CD4+ T cell, and CD8+ T cell, the more serious the disease and the worse the prognosis of the patients [ 66 ].…”

“…Another study has reported that abundant bacteria in COVID-19 patients, including Rothia, Streptococcus, Veilonella, and Actinomyces, are positively correlated with high levels of CRP and D-dimer, once more evidencing the influence of gut microbiota composition in the host’s inflammatory profile [ 31 ]. However, no significant alterations were observed in gut microbiota composition between patients with different disease severity stages [ 65 ]. These results suggest that, in this complex scenario of interactions between different systems (namely intestinal microbiota–immune system–inflammatory response), there may be additional factors playing a relevant role for disease severity.…”

“…These results suggest that, in this complex scenario of interactions between different systems (namely intestinal microbiota–immune system–inflammatory response), there may be additional factors playing a relevant role for disease severity. On the other hand, it also suggests that other elements able to shape microbiota should be carefully considered, including age; comorbidities; and especially the impact of drugs, particularly antibiotics, as highlighted in the study of Britton et al [ 65 ].…”