COVID-19: immunopathology and its implications for therapy
Severe coronavirus disease 2019 (COVID-19) is characterized by pneumonia, lymphopenia, exhausted lymphocytes and a cytokine storm. Significant antibody production is observed; however, whether this is protective or pathogenic remains to be determined. Defining the immunopathological changes in patients with COVID-19 provides potential targets for drug discovery and is important for clinical management.
Nat Rev Immunol.2020 Apr 9. doi: 10.1038/s41577-020-0308-3.
SARS-CoV-2 Vaccines: Status Report
Fatima Amanat1,2 and Florian Krammer2
SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and causedmore than 43,000 deaths globally. Here,we discuss therapeutic and prophylactic interventions for SARS-CoV-2 with a focus on vaccine development and its challenges. Vaccines are being rapidly developed but will likely come too late to affect the first wave of a potential pandemic. Nevertheless, critical lessons can be learned for the development of vaccines against rapidly emerging viruses. Importantly, SARS-CoV-2 vaccines will be essential to reducing morbidity and mortality if the virus establishes itself in the population.
Immunity. 2020 Apr 14;52(4):583-589. doi: 10.1016/j.immuni.2020.03.007.
Dysregulation of lung myeloid cells in COVID-19
Acute respiratory distress syndrome (ARDS) and robust cytokine storm are the hallmark of severe COVID-19 cases. Using single-cell RNA sequencing of bronchoalveolar lavage fluid, this preprint study from Liao et al. found that the depletion of tissue-resident alveolar macrophages and the accumulation of monocyte- derived inflammatory macrophages associate with disease severity. Inflammatory macrophages adopted interferon- signalling and monocyte-recruiting chemokine programmes that may drive ARDS. Increased clonal expansion of CD8+ T cells was found in mild cases; this may reflect viral clearance due to the induction of virus- specific cytotoxic T cells, as is seen in influenza virus infection. Overall, these data support therapeutic strategies that target the myeloid cell compartment, such as IL-6 inhibitors, to treat COVID-19- associated inflammation.
Nat Rev Immunol. 2020 Apr 6. doi: 10.1038/s41577-020-0303-8.
Neutralizing Antibodies against SARS-CoV-2 and Other Human Coronaviruses
Shibo Jiang,1,2 Christopher Hillyer,1 and Lanying Du1
Coronavirus (CoV) disease 2019 (COVID-19) caused by severe acute respiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) is threatening global public health, social stability, and economic development. To meet this challenge, this article discusses advances in the research and development of neutralizing antibodies (nAbs) for the prevention and treatment of infection by SARS-CoV-2 and other human CoVs.
Trends Immunol. 2020 Apr 2. pii: S1471-4906(20)30057-0. doi: 10.1016/j.it.2020.03.007.
In the eye of the COVID-19 cytokine storm
Not all patients with COVID-19 develop the same symptoms, but the immunological determinants of a poor prognosis are unknown. In this preprint article, Yang, Y et al. followed a cohort of 53 clinically moderate and severe patients; they conducted a multiplex screen for 48 cytokines and correlated these results with lab tests, clinical characteristics and viral loads. They found a marked increase of 14 cytokines in patients with COVID-19 compared with healthy controls. Continuously high levels of three of these cytokines (CXCL10, CCL7 and IL-1 receptor antagonist) were associated with increased viral load, loss of lung function, lung injury and a fatal outcome. These observations offer key insights into the immunopathology of COVID-19 and provide new avenues for prognosis and therapy.
Nat Rev Immunol. 2020 Apr 6. doi: 10.1038/s41577-020-0305-6.