Pulmonary immune responses against SARS-CoV-2 infection: harmful or not?
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UNDERSTANDING THE DISEASE
Pulmonary immune responses against SARS‑CoV‑2 infection: harmful or not? A. Guillon1,2,3* , P. S. Hiemstra4 and M. Si‑Tahar2,3 © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
Although our knowledge of the pulmonary immune response in patients with SARS-CoV-2 infection is still limited, intensivists will be offered to prescribe immunomodulatory interventions in patients with severe COVID-19 disease admitted to the ICU. Controlling the lung inflammatory response may be as important as targeting the virus, but the optimal timing and immune targets have not been clearly defined. Here, we summarize and discuss current knowledge on pulmonary immune responses against SARS-CoV-2 infection and its implication for decision-making processes at the ICU.
The SARS‑CoV‑2 virus replicates in human airways but evades lung innate immune response COVID-19 autopsied lung studies (n = 4 patients) showed that ciliated cells of the proximal airway epithelium and alveolar cells (type I and II pneumocytes) were infected, but not goblet cells and submucosal glands [1]. The isolation of SARS-CoV-2 virus enabled experimental infections of human lung tissue, showing that SARS-CoV-2 replicates better than other coronaviruses, with a peak of viral replication reached in 48–72 h [2, 3]. Viral entry and cell infection trigger the host’s immune response. However, immune evasion strategies are suspected by SARSCoV-2 to alter host mucosal defenses. SARS-CoV-2 was capable of replicating in the human lungs while activating low levels of antiviral IFN (type I and III) and pro-inflammatory cytokines [2, 3]. How SARS-CoV-2 virus subverts the first line of lung innate immunity is still an unanswered question, but coronaviruses are known for their ability to subvert innate immune response, including *Correspondence: antoine.guillon@univ‑tours.fr 1 Intensive Care Unit, Tours University Hospital, 2 Bd Tonnellé, 37044 Tours Cedex 9, France Full author information is available at the end of the article
viral RNA sensing and signaling pathways involved in IFN secretion (reviewed in [4]). The limited activation of the innate immune response during the early phases of SARS-CoV-2 infection may facilitate its replication, but also explain the delayed clinical symptoms observed in most COVID-19 patients. This early, delayed immune activation may be followed in patients with severe disease by an imbalanced and overwhelming inflammatory response causing tissue injury and respiratory dysfunction (Fig. 1).
The inflammatory response is mostly compartmentalized into the lung tissues (and is not a systemic cytokine storm) Immune responses with high levels of pro-inflammatory cytokines were described in the plasma of these patients, some of these cytokines being associated with the disease severity and progression [5]. This systemic inflammatory response was described as a “cytokine storm”, but it is questionable whether this term is appropriate for the COVID-19 as mean circulating IL-6 levels often not exceeding 30 pg/mL [5–7]. I
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