Abstract: “SARS-CoV-2 infection intrigued medicine with diverse outcomes ranging from asymptomatic to severe acute respiratory syndrome (SARS) and death. After more than two years of pandemic, reports of reinfection concern researchers and physicists. Here, we will discuss potential mechanisms that can explain reinfections, including the aggravated ones. The major topics of this hypothesis paper are the disbalance between interferon and antibodies responses, HLA heterogeneity among the affected population, and increased proportion of cytotoxic CD4+ T cells polarization in relation to T follicular cells (Tfh) subtypes. These features affect antibody levels and hamper the humoral immunity necessary to prevent or minimize the viral burden in the case of reinfections.“
Costa Silva RCM, Bandeira-Melo C, Paula Neto HA, Vale AM, Travassos LH. COVID-19 diverse outcomes: Aggravated reinfection, type I interferons and antibodies. Med Hypotheses. 2022 Oct;167:110943. doi: 10.1016/j.mehy.2022.110943. Epub 2022 Sep 9. PMID: 36105250; PMCID: PMC9461281.
https://pubmed.ncbi.nlm.nih.gov/36105250/
See also:
Robertson SJ, Bedard O, McNally KL, Lewis M, Clancy C, Shaia C, Broeckel RM, Chiramel AI, Sturdevant GL, Forte E, Preuss C, Baker CN, Harder J, Brunton C, Munger S, Sturdevant DE, Martens C, Holland SM, Rosenthal NA, Best SM. Genetically diverse mouse models of SARS-CoV-2 infection reproduce clinical variation and cytokine responses in COVID-19. bioRxiv [Preprint]. 2022 Feb 24:2021.09.17.460664. doi: 10.1101/2021.09.17.460664. PMID: 35233576; PMCID: PMC8887079.
Abstract: Inflammation in response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection drives severity of coronavirus disease 2019 (COVID-19), with effective versus dysregulated responses influenced by host genetics. To understand mechanisms of inflammation, animal models that reflect genetic diversity and clinical outcomes observed in humans are needed. We report a mouse panel comprising the diverse genetic backgrounds of the Collaborative Cross founder strains crossed to K18-hACE2 transgenic mice that confers high susceptibility to SARS-CoV-2. Infection of CC x K18-hACE2 F1 progeny resulted in a spectrum of weight loss, survival, viral replication kinetics, histopathology, and cytokine profiles, some of which were sex-specific. Importantly, survival was associated with early type I interferon (IFN) expression and a phased proinflammatory response distinct from mice with severe disease. Thus, dynamics of inflammatory responses observed in COVID-19 can be modeled in diverse mouse strains that provide a genetically tractable platform for understanding antiviral immunity and evaluating countermeasures.
https://pubmed.ncbi.nlm.nih.gov/35233576
and
Bastard P, Rosen LB, … Casanova JL.: Autoantibodies against type I IFNs in patients with life threatening COVID-19. Science. 2020 Oct 23;370(6515):eabd4585. doi: 10.1126/science.abd4585. Epub 2020 Sep 24. PMID: 32972996; PMCID: PMC7857397.
Abstract: Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-ω (IFN-ω) (13 patients), against the 13 types of IFN-α (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men.
