Table 1.
Key gut immunologic barrier parameters that serve as prognostic markers for severity of SARS-CoV-2 infection and poor prognosis.
| Parameter studied | Endpoints of the study | Results of the study | Refs. |
|---|---|---|---|
| Serum calprotectin | Identification of the association between serum calprotectin, neutrophil secretory proteins, and other inflammatory mediators with COVID-19 severity and outcome. | Correlation between serum calprotectin levels and disease severity. Significant increase in serum calprotectin along with worsening of clinical symptoms of the disease. |
(31) |
| Fecal calprotectin | Identification of an association between fecal calprotectin and the severity of pulmonary manifestations caused by COVID-19. | Significant association between COVID-19 pneumonia and high levels of fecal calprotectin. Higher calprotectin levels in women compared with men, suggesting that men with high calprotectin have a worse prognosis. |
(26) |
| sMAdCAM | Cross-sectional and longitudinal study of sMAdCAM at different stages of disease progression after SARS-CoV-2 infection. | sMAdCAM is considered a possible integrated marker of inflammation and homeostatic immune migration. Association of sMAdCAM with COVID-19 disease progression and generation of potentially neutralizing antibody responses against SARS-CoV-2. |
(68) |
| Autoantibodies to type I IFNs | Evaluation of immunological and clinical characteristics of APS-1 patients during the course of SARS-CoV-2 infection. | Pre-existing neutralizing autoantibodies to type I IFNs pose an increased risk of life-threatening COVID-19 pneumonia at any age. | (51) |
| High-throughput autoantibody screening for autoantibodies against 2,770 extracellular and secreted proteins in SARS-CoV-2- infected individuals. | Pathologic role of exoproteome-targeted autoantibodies in SARS-CoV-2 infection and differential impact on immune function and clinical course. | (54) | |
| Evaluation of the prevalence of IFN I autoantibodies and their association with clinical disease progression. | In the presence of IFN-I autoantibodies, there is an increased risk of developing severe COVID-19. | (57) | |
| Type I IFN variants | Assessment of the role of monogenic inborn errors in the development of life-threatening COVID-19. | Inborn errors of IRF7- and TLR3-dependent type I IFN immunity cause life-threatening COVID-19 pneumonia in patients without prior severe infection. | (59) |
| Cytokines in stool samples | Evaluation of cytokines, inflammatory markers, viral RNA, microbiome composition, and antibody responses in stool samples from hospitalized COVID-19 patients. | Increased fecal levels of IL-8 and lower fecal levels of IL-10 in COVID-19 hospitalized patients. Fecal IL-23 is higher in more severe COVID-19. Intestinal virus-specific IgA responses are associated with more severe disease. |
(63) |
| Secretory IgA antibodies | Characterization of IgA response to SARS-CoV-2 after COVID-19 diagnosis. | Responses against dimeric IgA may be a valuable tool for protection against SARS-CoV-2 and for vaccine efficacy. | (79) |
| Gut microbiota | Association of intestinal microflora alterations with COVID-19 and its severity. | Poor prognosis is associated with: ↑Bacteroides, ↑Parabacteroides, ↑Clostridium, ↑Bifidobacterium, ↑Ruminococcus, ↑Campylobacter, ↑Rothia, ↑Enterococcus, and ↑Aspergillus spp. ↓Roseburia, ↓Eubacterium, ↓Lachnospira, ↓Faecalibacterium, and ↓Firmicutes/Bacteroidetes ratio. |
(11) |
I-FABP, intestinal fatty-acid binding protein; sMAdCAM, soluble mucosal addressin cell adhesion molecule; IFN, interferon; APS-1, autoimmune polyendocrine syndrome type 1; IRF7, IFN regulatory factor 7, toll-like receptor 3, TLR3; IgA, immunoglobulin A. Upward arrows are used to indicate an increase, and downward arrows indicate a decrease.