Definition of the Immune Parameters Related to COVID-19 Severity

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Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of individuals and also killed millions worldwide. SARS-CoV-2 infection causes coronavirus disease 2019 (COVID-19), ranging from asymptomatic to fatal.

Although about 80% of Covid-19 patients display a benign clinical phenotype, up to 20% of the patients can develop rapidly progressing respiratory failure. While several clinical and epidemiological factors have been associated with poor outcomes, which include the presence of co-morbidities, such as cardiovascular, metabolic and pulmonary comorbidities, and older age, the specific immunologic aspects featuring the worst clinical outcome are still elusive.

In any viral infection, a multi-layered immune response is necessary to effectively clear the virus and form an immune memory that protects against re-infections or disease. Several studies have already shown that a multi-layered defense forms in patients that recovered from both acute and mild COVID-19, even though with differences in immunophenotype and functionality. An effective multi-layered immune response includes RBD-specific Abs, RBD-specific memory B cells, and spike-specific CD4 T- and CD8+ T cells. Furthermore, peripheral blood monocytes can be infected by SARS-COV-2, in turn migrating to tissues as tissue-resident macrophages. Both circulating and tissue-residents monocyte/macrophage produce a large amount of pro-inflammatory chemokines and cytokines, therefore contributing to an exaggerated pro-inflammatory milieu known as “cytokine storm”.

Those patients that showed an overactivation of the immune response, i.e. cytokine storm, and higher levels of local tissue inflammation are more likely to develop COVID-19-related complications such as acute respiratory distress syndrome (ARDS), and are more likely to die. This suggests that a dysfunctional immune response and its dysregulation has a pivotal role in severity manifestation.

There is a strong need for the identification of immune pathways/mechanisms underlying an altered immune response to SARS-CoV-2 infection that are associated and possibly also prognostic of a worse prognosis, to be further translated in clinical settings to better direct management and treatment strategies. Such biomarkers could potentially modify and optimize the therapeutic approach, thus improving the prognosis of COVID-19 patients.

Although the variety of the symptoms is well recognized, the factors that dictate whether or not a patient will develop an asymptomatic infection or will manifest with severe disease, and whether this is linked to long-term impairments development, are not clear. In this Research Topic, we aim to get a better understanding of those aspects of SARS-CoV-2 immune response that may contribute to protection against disease in the asymptomatically infected patients, allowing the identification of immune correlates of protection playing a key role in preventing end-organ disease.

This approach will shed light on the pathogenesis of COVID-19 and will help guide future therapeutic and immunization approaches. The Research Topic will also try to investigate possible correlates of COVID-19 in adults vis-a-vis infants, who are known to generally develop less severe outcomes, as well as particular population groups such as the elderly, immune depressed, and co-morbid patients.

We welcome the submission of Original Research, Reviews, and Mini-Reviews, as well as Opinion, Theory, Hypothesis and Perspective, Clinical Trial and Case Report articles evaluating the parameters which cause differences in the mechanistic immune pathways and/or factors that have a clinically relevant impact on the SARS-CoV-2 immune response to infection and COVID-19 severity:

1. Aspects that differentiate RBD-specific Abs, RBD-specific memory B cells, and spike-specific CD4 T- and CD8-T cells in asymptomatically infected individuals compared to symptomatic individuals, i.e. quality of the immune response;

2. Functional changes (activation and exhaustion) of T and B cell repertoire in relation to the severe outcome of COVID-19;

3. Monocyte and macrophage responses in COVID-19 patients with different degree of disease severity;

4. Local tissue Inflammation as correlates of COVID-19 disease severity;

5. Viral and host genetic factors which alter the immune response;

6. SARS-COV-2 Viral load ab initium;

7. Elderly as opposed to children, patients with co-morbidities with special focus on HIV co-infection and primary immune deficiencies

Keywords: Biomarkers, immune correlates of infection and protection, symptoms, host factors, SARS-COV-2 viral factors, severe, mild, asymptomatic COVID-19

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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