COVID-19: immunopathology and itsimplications for therapy

Xuetao Cao1,2

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.2020Apr 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 robustcytokine storm are the hallmark of severe COVID-19 cases.Using single-cell RNA sequencing of bronchoalveolarlavage fluid, this preprint study from Liao et al. found thatthe depletion of tissue-resident alveolar macrophages and theaccumulation of monocyte- derived inflammatory macrophagesassociate with disease severity. Inflammatory macrophagesadopted interferon- signalling and monocyte-recruitingchemokine programmes that may drive ARDS. Increased clonalexpansion of CD8+ T cells was found in mild cases; this mayreflect viral clearance due to the induction of virus- specificcytotoxic T cells, as is seen in influenza virus infection. Overall,these data support therapeutic strategies that target themyeloid cell compartment, such as IL-6 inhibitors, to treatCOVID-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,1,2Christopher Hillyer,1 andLanying Du1

Coronavirus (CoV) disease 2019(COVID-19) caused by severe acuterespiratory syndrome (SARS)-CoV-2 (also known as 2019-nCoV) isthreatening global public health,social stability, and economic development.To meet this challenge,this article discusses advances inthe research and development ofneutralizing antibodies (nAbs) forthe prevention and treatment ofinfection by SARS-CoV-2 and otherhuman 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 prognosisare unknown. In this preprint article, Yang, Y et al. followeda cohort of 53 clinically moderate and severe patients; theyconducted a multiplex screen for 48 cytokines and correlatedthese results with lab tests, clinical characteristics and viralloads. They found a marked increase of 14 cytokines in patientswith COVID-19 compared with healthy controls. Continuouslyhigh levels of three of these cytokines (CXCL10, CCL7 and IL-1receptor antagonist) were associated with increased viral load,loss of lung function, lung injury and a fatal outcome. Theseobservations offer key insights into the immunopathology ofCOVID-19 and provide new avenues for prognosis and therapy.

Nat Rev Immunol.2020 Apr 6. doi: 10.1038/s41577-020-0305-6.