Macrophage ACE2 is necessary for SARS-CoV-2 replication and subsequent cytokine responses that restrict continued virion release.

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.

Telemedicine in rheumatology care: A systematic review.

OBJECTIVE: The COVID-19 pandemic led to a sudden uptake of telemedicine in rheumatology. We analyzed the recent published literature on telemedicine for the diagnosis and management of inflammatory, non-inflammatory and/or autoimmune rheumatic diseases. METHODS: We performed a registered systematic search (CRD42020202063) for interventional or observational studies published between August 2015 and January 2022. We included studies of telemedicine that reported outcomes (e.g., satisfaction, disease activity, quality of life) in ten or more people with rheumatic disease. Reviewers screened manuscripts, extracted data, and assessed bias. RESULTS: Of the 2,988 potentially eligible studies, 36 reports were included: 27 observational studies, 7 randomized clinical trials, and 2 controlled clinical trials. Studies focused on general rheumatology (n = 18), rheumatoid arthritis (n = 9), gout (n = 3), osteoarthritis (n = 2), unspecified inflammatory arthritis (n = 1), osteoporosis (n = 2), and systemic lupus erythematosus (n = 1). Patient satisfaction with telemedicine was the most common reported outcome (n = 23) with majority of studies demonstrating high levels of satisfaction. Among interventional studies, the effect of telemedicine on the primary outcomes varied, with most finding that telemedicine was as good as usual / in-person care for disease activity control, patient satisfaction, total societal costs, and other patient reported outcomes. Effectiveness and feasibility were high across studies, though most demonstrated a high risk of bias. Meta-analysis was not feasible given the heterogeneity of interventions and outcome instruments utilized. CONCLUSION: Although the number of studies to date is low, telemedicine may be an effective mode to deliver care for people with rheumatic diseases. Most studies demonstrated limitations due to study design and risk of bias. Randomized clinical studies are needed to determine best uses of telemedicine for the diagnosis and management of rheumatic conditions.