- A distinct innate immune signature marks progression from mild to severe COVID-19
Coronavirus disease 2019 (COVID-19) manifests with a range of severities, but immune signatures of mild and severe disease are still not fully understood. Mass cytometry and targeted proteomics were used to profile the innate immune response of patients with mild or severe COVID-19 and of healthy individuals. Sampling at different stages allows reconstruction of a pseudo-temporal trajectory of the innate response. A surge of CD169+ monocytes associated with an IFNγ+MCP-2+ signature rapidly follows symptom onset. At later stages, a persistent inflammatory phenotype is observed in patients with severe disease, dominated by high CCL3 and CCL4 abundance correlating with the re- appearance of CD16+ monocytes, whereas the response of mild COVID-19 patients normalizes. The data provide insights into the dynamic nature of inflammatory responses in COVID-19 patients and identify sustained innate immune responses as a likely mechanism in severe patients, thus supporting investigation of targeted interventions in severe COVID-19.
- Induction of alarmin S100A8/A9 mediates activation of aberrant neutrophils in the pathogenesis of COVID-19
Evidence suggests that SARS-CoV-2 infection causes dysregulation of the immune system. However, the unique signature of early immune responses remains elusive. The transcriptome of rhesus macaques and mice infected with SARS-CoV-2 was characterized. Alarmin S100A8 was robustly induced in SARS-CoV-2 infected animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could rescue pneumonia with a substantial reduction of viral loads in SARS-CoV-2 infected mice. Remarkably, Paquinimod treatment resulted in almost 100% survival in a lethal model of mouse coronavirus infection using mouse hepatitis virus (MHV). A group of neutrophils that contributes to the uncontrolled pathological damage and onset of COVID-19 were dramatically induced by coronavirus infection. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and aberrant neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention.
- Discordant neutralizing antibody and T cell responses in asymptomatic and mild SARS-CoV-2 infection
Authors analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. These findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.
- How CDC Is Making COVID-19 Vaccine Recommendations
Vaccination in the initial phase of the COVID-19 vaccination program (Phase 1a) should be offered to both 1) healthcare personnel and 2) residents of long-term care facilities. Healthcare personnel are defined as paid and unpaid people serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care facility residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care, to persons who are unable to live independently.
- The Advisory Committee on Immunization Practices’ Updated Interim Recommendation for Allocation of COVID-19 Vaccine — United States, December 2020
On December 20, ACIP updated interim vaccine allocation recommendations. In Phase 1b, COVID-19 vaccine should be offered to persons aged ≥75 years and non–health care frontline essential workers, and in Phase 1c, to persons aged 65–74 years, persons aged 16–64 years with high-risk medical conditions, and essential workers not included in Phase 1b. In Phase 1c, vaccine should be offered to persons aged 65–74 years, persons aged 16–64 years with medical conditions that increase the risk for severe COVID-19, and essential workers not previously included in Phase 1a or 1b. Phase 2 includes all other persons aged ≥16 years not already recommended for vaccination in Phases 1a, 1b, or 1c. Currently, in accordance with recommended age and conditions of use, any authorized COVID-19 vaccine may be used.