Anti-spike IgG causes severe acute lung injury by skewing macrophage responses during acute SARS-CoV infection.

By Li Liu, Q. Wei, Q. Lin, Jun Fang, Haibo Wang, H. Kwok, Hangying Tang, K. Nishiura, Jie Peng, Z. Tan and 9 more. JCI Insight, 2019

825 citations recorded by the source corpus.

Newly emerging viruses, such as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle Eastern respiratory syndrome CoVs (MERS-CoV), and H7N9, cause fatal acute lung injury (ALI) by driving hypercytokinemia and aggressive inflammation through mechanisms that remain elusive. In SARS-CoV/macaque models, we determined that anti-spike IgG (S-IgG), in productively infected lungs, causes severe ALI by skewing inflammation-resolving response. Alveolar macrophages underwent functional polarization in acutely infected macaques, demonstrating simultaneously both proinflammatory and wound-healing characteristics. The presence of S-IgG prior to viral clearance, however, abrogated wound-healing responses and promoted MCP1 and IL-8 production and proinflammatory monocyte/macrophage recruitment and accumulation. Critically, patients who eventually died of SARS (hereafter referred to as deceased patients) displayed similarly accumulated pulmonary proinflammatory, absence of wound-healing macrophages, and faster neutralizing antibody responses. Their sera enhanced SARS-CoV-induced MCP1 and IL-8 production by human monocyte-derived wound-healing macrophages, whereas blockade of FcγR reduced such effects. Our findings reveal a mechanism responsible for virus-mediated ALI, define a pathological consequence of viral specific antibody response, and provide a potential target for treatment of SARS-CoV or other virus-mediated lung injury.

Subfields: Infectious Diseases, Neurology

View Paper: https://www.semanticscholar.org/paper/0f482c7be4ef40cc6b0bd10d1b03d496eca1db91

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Infectious Diseases

1. Kwok-Yung Yuen
2. J. Chan
3. K. To
4. V. Cheng
5. Kwok-Hung Chan
6. Shuofeng Yuan
7. Andrew G. Harrison
8. Tao Lin

In Neurology

1. Andrew G. Harrison
2. Tao Lin
3. Penghua Wang

Citations in the corpus

• A Thermostable mRNA Vaccine against COVID-19 (2020, positive): “d Development of LNP-encapsulated mRNA vaccine (ARCoV) targeting the RBD of SARS-CoV-2 d ARCoV induces neutralizing antibodies and T cell immunity in mice and NHPs d ARCoV vaccination confers full protection against SARS- CoV-2 challenge in mice d ARCoV is a thermostable vaccine candidate for phase ”
• Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment (2020, background): “Recently, iron-mediated cell death, known as ferroptosis, was reported to play a role in pathogenesis miscellaneous diseases [35, 36].”
• Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools (2020, background): “…it has been found that S-IgG present in infected lungs can facilitate severe lung injury; in these SARS-CoV S proteinvaccinated Chinese macaques, acute lung injury was more pronounced than in unvaccinated control animals that showed only minor to moderate lung inflammation (Liu et al. 2019).”
• Host-Viral Infection Maps Reveal Signatures of Severe COVID-19 Patients (2020, neutral): “We expect that as the pandemic keeps spreading and global research efforts grow, additional scRNA-seq samples from COVID-19 patients will be generated, including patients treated with emerging immunotherapies (Liu et al., 2019).”
• Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2. (2020, neutral): “5) 17 (34) 13 (29) 5 (38) Otherh 6 (10) 2 (9) 3 (10) 3 (10) 1 (8) 5 (11) 1 (14) 5 (10) 0 6 (12) 3 (7) 3 (23) Clinical features at presentationi Abdominal pain 31 (53) 13 (57) 18 (62) 13 (45) 2 (15) 29 (64) 1 (14) 30 (59) 2 (33) 29 (58) 24 (55) 7 (50) Diarrhea 30 (52) 10 (44) 19 (66) 11 (38) 7 (54) 2”
• Mechanisms of SARS-CoV-2 Transmission and Pathogenesis (2020, positive): “Accordingly, reports of antibody-dependent enhancement, as well as of non-neutralizing humoral responses to the conserved regions of SARS-CoV-2, raise concerns on our future ability to effectively administer an immunogen without inducing immunopathology [129,130].”
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