The COVID-19 pandemic caused by the SARS-CoV-2 infection has caused more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is one of the main causes of disease severity and death in infected patients. Macrophages are a population of innate immune cells that detect and respond to microbial threats by producing inflammatory molecules that kill pathogens and promote tissue repair.
However, a dysregulated macrophage response can be detrimental to the host, as seen in macrophage activation syndrome induced by severe infections, including infections with the related SARS-CoV virus. Here we describe the potentially pathological functions of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in COVID-19 patients.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel enveloped RNA betacoronavirus that emerged in December 2019 in Wuhan, China, and is the cause of coronavirus disease 2019 (COVID-19). The most common clinical presentation of severe COVID-19 is pneumonia with fever, cough, and dyspnea.
The Chinese Center for Disease Control and Prevention reported that out of 44,500 confirmed infections, the majority of infected patients (80%) experienced mild illness (no or only mild pneumonia), 14% developed severe illness (with dyspnea, hypoxia, or more than 50% lung involvement on imaging tests) and 5% developed critical illness (characterized by respiratory failure, systemic shock, or multiple organ failure) 1. Approximately 20-30% of patients who have been hospitalized with pneumonia associated with COVID-19 have required intensive care for respiratory support2,3.
Acute respiratory distress syndrome (ARDS) is a common complication of severe viral pneumonia, including pneumonia caused by highly pathogenic coronaviruses such as SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) 4. In one group Of 1,099 hospitalized patients with COVID-19, ARDS was reported to occur in 15.6% of patients with severe pneumonia5.
A recent study of the New York area, which has emerged as the epicenter of the pandemic in the United States, reported that of 2,634 patients who were hospitalized with confirmed COVID-19 between March 1 and April 4, 2020, 14.2% of the patients were treated. In the intensive care units (ICU), 12.2% of the patients required invasive mechanical ventilation and 21% of the patients died. The mortality of those who required mechanical ventilation was 88.1% 6.
The factors that trigger severe disease in people infected with SARS-CoV-2 are not fully understood and the development of severe disease does not appear to be related solely to viral load and could imply a defective response to interferon7. Excessive inflammatory response to SARS-CoV-2 is believed to be a major cause of illness severity and death in COVID-19 patients (ref. 8) and is associated with high levels of circulating cytokines, profound lymphopenia, and substantial infiltration. of mononuclear cells. in the lungs, heart9, spleen, lymph nodes, and kidney10,11, as observed in the post-mortem analysis.
Since the morbidity and mortality observed in COVID-19 are associated with excessive inflammation, a better understanding of the immunological underpinnings of the differential responses observed in patients infected with SARS-CoV-2 is necessary to better identify therapeutic targets. Dozens of immunomodulatory agents are rapidly entering clinical trials and are already routinely used in the clinic on an unauthorized basis.
Without a thorough understanding of which inflammatory pathways and particular cell types represent the best targets, some of these strategies could have detrimental effects in certain patients and/or at different stages of COVID-19 disease. In this Progress article, we discuss the nature of the inflammatory responses that have been detected so far in COVID-19 patients; In particular, we highlight the emerging roles of monocytes and macrophages in COVID-19 pathology.