Case report: hepatitis in a child infected with SARS-CoV-2 presenting toll-like receptor 7 Gln11Leu single nucleotide polymorphism

Abstract

Background Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2′-5′-oligoadenylate synthase-3, oas-3). Case presentation We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein–Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out. Conclusion To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications.

The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development—A Systematic Review

“…When some polymorphisms (NSP1 K194R and NSP13 A335V) present in MHV-JHM.SD were introduced into an MHV-JHM.WU-like virus, the viral replication in the liver was diminished, but there is no data on the brain viral titers or overall lethality and weight loss that mice experienced [ 97 ]. Such results are difficult to extrapolate to SARS-CoV-2, which seems not to be as neurovirulent [ 148 ] and does not readily replicate in the liver in most individuals [ 149 ]. In fact, SARS-CoV-2, SARS-CoV MA15 and Urbani and MERS-CoV are primarily respiratory viruses, but MHV-A59 and MHV-JHM have a broader tropism and replicate effectively in the brain, spleen and liver [ 149 ].…”

“…Such results are difficult to extrapolate to SARS-CoV-2, which seems not to be as neurovirulent [ 148 ] and does not readily replicate in the liver in most individuals [ 149 ]. In fact, SARS-CoV-2, SARS-CoV MA15 and Urbani and MERS-CoV are primarily respiratory viruses, but MHV-A59 and MHV-JHM have a broader tropism and replicate effectively in the brain, spleen and liver [ 149 ]. The scale of attenuation used in this work reflects this issues.…”

An Overview of Recent Insights into the Response of TLR to SARS-CoV-2 Infection and the Potential of TLR Agonists as SARS-CoV-2 Vaccine Adjuvants

“…Infrared light therapy has been shown to decrease TLR4-dependent induction of IL-6, IL-8, TNF-α, INF-α, and INF-β in COVID-19 hyperinflammation [61]. It was observed that a child with hepatitis after SARS-CoV-2 infection had a polymorphism, Gln11Leu (rs179008), in TLR7 [62], which could impair an efficient initial immune response. Elevated cytokine levels have been linked to SARS-CoV-2 infection in adults (median age, 51 years) [63].…”

Emerging cases of acute hepatitis of unknown origin in children amid the ongoing COVID-19 pandemic: Needs attention – Correspondence

“…The patients (n = 8) with MIS having a high level of inflammatory markers which required admission to critical care, and three patients had an adverse outcome [ 13 ]. Pessoa and his coworkers have reported the first case of hepatitis in a male child infected with SARS-CoV-2 that has the Toll-like receptor 7 (TLR-7) Gln11Leu single nucleotide polymorphism, which could impair an efficient initial immune response [ 14 ]. Furthermore, Antala and coworkers have reported severe hepatitis in four previously healthy children as the primary manifestation of SARS-CoV-2 infection without respiratory symptoms, out of which two patients had acute liver failure [ 15 ].…”