Immunology of COVID-19: Current State of the Science

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide, igniting an unprecedented effort from the scientific community to understand the biological underpinning of COVID19 pathophysiology. In this Review, we summarize the current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death. We also discuss the rationale and clinical outcome of current therapeutic strategies as well as prospective clinical trials to prevent or treat SARS-CoV-2 infection.

Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence

“…A dysregulated immune response, as observed in COVID-19, especially in the late stages of the disease, plays a decisive role in endothelial dysfunction and thrombosis [190,191], and microvascular permeability is crucial in viral infections [192]. Indeed, pulmonary endothelium represent a fundamental barrier between the blood and interstitium and have vital regulatory functions; specifically, endothelial cells represent one-third of the cell population of the lung [193], and pulmonary endothelial damage is considered the hallmark of acute respiratory distress syndrome (ARDS) [194].…”

Androgen Regulates SARS-CoV-2 Receptor Levels and Is Associated with Severe COVID-19 Symptoms in Men

“…It has been well documented that organ involvement and disease manifestation are correlated with the expression of SARS-CoV receptor and co-receptors on the membrane of target cells 4 . The spike (S) protein, which is responsible for the characteristic crown-like shape of coronaviruses, facilitates the binding of the virus to its receptors on the cell membrane 5,6 . ACE2 has been identified as the main receptor utilized by SARS-CoV-2 and SARS-CoV-1 to enter cells 7 .…”

Blocking inflammation on the way: Rationale for CXCR2 antagonists for the treatment of COVID-19

“…Several clinical studies using the IL-6 receptor-blocking antibodies tocilizumab, sarilumab, or the IL-6-blocking antibody siltuximab are ongoing. IL-6 receptor inhibition is effectively used to relieve CAR-T cell therapy-induced cytokine storm, and the first anecdotal reports in COVID-19 treatment raise hope (Vabret et al, 2020). The list of therapeutic interventions targeting the overactive innate immune system is growing, with several studies investigating the IL-1 receptor antagonist anakinra or Targeting tissue migration of inflammatory myeloid cells…”

“…In a recent Perspective, Barnes et al (2020) suggest that aberrant NET formation may contribute to organ damage, thrombosis, and cytokine secretion and discuss NETs as a potential drug target. Further evidence for neutrophil involvement is given by the fact that neutrophil counts are increased in severe versus mild cases and the neutrophil-to-lymphocyte ratio is a predictive marker of mortality (Vabret et al, 2020).…”

“…While the viral load decreases in later stages of COVID-19, symptoms frequently do not resolve concomitantly. It is widely appreciated that an overreactive immune system with infiltration of inflammatory monocytes and neutrophils to the site of infection alongside an exaggerated release of proinflammatory cytokines is an important driver of severe lung damage in COVID-19 (Vabret et al, 2020). In some cases, this leads to acute respiratory distress syndrome (ARDS) which may extend to fatal acute lung injury-similar to the courses observed for the earlier coronavirus outbreaks caused by SARS-CoV-1 and by Middle East respiratory syndrome (MERS) coronavirus.…”