ABSTRACT
Macrophages are key cellular contributors to the pathogenesis of COVID-19, the disease caused by the virus SARS-CoV-2. The SARS-CoV-2 entry receptor ACE2 is present only on a subset of macrophages at sites of SARS-CoV-2 infection in humans. Here, we investigated whether SARS-CoV-2 can enter macrophages, replicate, and release new viral progeny; whether macrophages need to sense a replicating virus to drive cytokine release; and, if so, whether ACE2 is involved in these mechanisms. We found that SARS-CoV-2 could enter, but did not replicate within, ACE2-deficient human primary macrophages and did not induce proinflammatory cytokine expression. By contrast, ACE2 overexpression in human THP-1-derived macrophages permitted SARS-CoV-2 entry, processing and replication, and virion release. ACE2-overexpressing THP-1 macrophages sensed active viral replication and triggered proinflammatory, antiviral programs mediated by the kinase TBK-1 that limited prolonged viral replication and release. These findings help elucidate the role of ACE2 and its absence in macrophage responses to SARS-CoV-2 infection.
Subject(s)
COVID-19 , SARS-CoV-2 , Humans , SARS-CoV-2/physiology , Angiotensin-Converting Enzyme 2/genetics , Cytokines , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/metabolism , Macrophages/metabolism , Virion/metabolismSubject(s)
Betacoronavirus , Coronavirus Infections , Noninvasive Ventilation , Pandemics , Pneumonia, Viral , COVID-19 , Head Protective Devices , Humans , SARS-CoV-2ABSTRACT
Mechanical ventilation as a resource is limited and may lead to poor outcomes in at-risk populations. Critical care supports may not be preferred by those at risk of deterioration in the COVID-19 setting. Patient-centred communication and shared decision-making should continue to remain central to clinical practice.
Subject(s)
Communication , Coronavirus Infections/psychology , Coronavirus Infections/therapy , Decision Making, Shared , Health Care Rationing/statistics & numerical data , Patient-Centered Care/methods , Physician-Patient Relations , Pneumonia, Viral/psychology , Pneumonia, Viral/therapy , Ventilators, Mechanical/supply & distribution , COVID-19 , Coronavirus Infections/epidemiology , Humans , Pandemics , Patient Education as Topic , Pneumonia, Viral/epidemiology , Practice Guidelines as TopicABSTRACT
The SARS-CoV-2 pandemic is unprecedented in our professional lives and much effort and resources will be devoted to care of patients (and HCW) affected by this illness. We must also continue to aim for the same standard of care for our non-COVID respiratory patients, while minimizing risks of infection transmission to our colleagues. This commentary addresses the key paired issues of minimizing performance of diagnostic/staging bronchoscopy in patients with suspected/known lung cancer while maximizing the safety of the procedure with respect to HCW transmission of COVID-19.
Subject(s)
Bronchoscopy/methods , Coronavirus Infections/epidemiology , Disease Transmission, Infectious/prevention & control , Endosonography/methods , Lung Neoplasms , Pneumonia, Viral/epidemiology , Safety Management/trends , Betacoronavirus/isolation & purification , COVID-19 , Comorbidity , Humans , Infection Control/methods , Infection Control/organization & administration , Lung Neoplasms/diagnosis , Lung Neoplasms/epidemiology , Pandemics , SARS-CoV-2ABSTRACT
These recommendations for physicians who perform bronchoscopy will help to protect those patients (un)-affected by the current COVID-19 pandemic, minimize the risk of transmission, and maintain clinical care for all patients.