key: cord-0995888-ggw3epq9
authors: García-Nicolás, O; V’kovski, P; Zettl, F; Zimmer, G; Thiel, V; Summerfield, A
title: No evidence for human monocyte-derived macrophage infection and antibody-mediated enhancement of SARS-CoV-2 infection
date: 2020-12-23
journal: bioRxiv
DOI: 10.1101/2020.12.22.423940
sha: f573f3af5f89ee5a624aa73cfc515604912666b9
doc_id: 995888
cord_uid: ggw3epq9

Vaccines are essential to control the spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and to protect the vulnerable population. However, one safety concern of vaccination is the possible development of antibody-dependent enhancement (ADE) of SARS-CoV-2 infection. The potential infection of Fc receptor bearing cells such as macrophages, would support continued virus replication and inflammatory responses, and thereby potentially worsen the clinical outcome of COVID-19. Here we demonstrate that SARS-CoV-2 and SARS-CoV-1 neither infect human monocyte-derived macrophages nor induce inflammatory cytokines in these cells, in sharp contrast to Middle East respiratory syndrome (MERS) coronavirus and the common cold human coronavirus 229E. Furthermore, serum from convalescent COVID-19 patients neither induced enhancement of SARS-CoV-2 infection nor innate immune response in human macrophages. These results support the view that ADE may not be involved in the immunopathological processes associated with COVID-19, however, more studies are necessary to understand the potential contribution of antibodies-virus complexes with other cells expressing FcR receptors.

Since the emergence of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 29 December 2019 in the Chinese city of Wuhan, the virus has spread globally causing the 30 coronavirus disease 2019 (COVID- 19) pandemic. The high morbidity and severity of COVID- 31 19 in some of the affected patients have jeopardized the public health system of affected 32 countries. In addition, the public health measures that have been implemented to control the 33 pandemic have affected the life and economy of millions of people around the world. 34 In the current situation, there is no preexisting immunity to SARS-CoV-2, which allows the 35 virus to spread rapidly in the human population. A global vaccination campaign may have the 36 potential to finally control the pandemic and vaccination programs have started recently. 37 However, a concern is the possibility that vaccination could promote antibody-dependent Buffy coats from anonymous healthy blood donors were obtained from the regional transfusion 57 blood service of the Swiss Red Cross (SRC) (Bern, Switzerland). The use of buffy coats was 58 approved by the SRC review board. All serum samples employed in this study were collected 59 following the guidance of the Act on Medical Devices (MPG guideline 98/79/EC) for the 60 collection of human residual material to evaluate suitability of an in vitro diagnostic medical 61 device ( §24). For this study an informed consent and ethical approval was not needed because 62 only leftovers of serum samples for diagnostic laboratory procedures were used. (Table 1) . (Table 2) . 180 Using the same approach, a larger collection of sera from COVID-19 convalescent patients with 181 neutralization titers ranging from <10 to 1:2560 was incubated at different concentrations with 182 SARS-CoV and SARS-CoV-2 and added to hMDM. Importantly, with none of the tested serum 183 dilutions which went up to1:10'000 infection of hMDM was observed. Moreover, hMDM 184 exposed to virus-antibodies complexes did not secrete any detectable pro-inflammatory 185 cytokines (Table 2 ). These results indicate that the potential uptake of SARS-CoV-1 and SARS- Our results are also in line with a previous report demonstrating that following infection with 207 HCoV-229E human macrophages strongly secrete TNF, but also produce IL-6 and some IFN- We would like to thank all members of the IVI and for their support and helpful discussions. 248 We are grateful Daniela Niemeyer, Marcel Müller, and Christian Drosten (Charité, Berlin, 249 Germany) for providing the viruses and to the Swiss Transfusion SRC (Swiss Red Cross) Inc. 250 (Regional transfusion blood service, Bern, Switzerland) for providing human buffy coats. 

The convalescent sera option for containing COVID-265

Isolation and characterization of current human coronavirus 268 strains in primary human epithelial cell cultures reveal differences in target cell 269 tropism

Infection of human alveolar macrophages by human coronavirus strain 229E

Development of an 274 inactivated vaccine candidate for SARS-CoV-2

Early safety indicators of COVID-19 convalescent plasma in 278 5000 patients

Antibody-dependent 280 enhancement and SARS-CoV-2 vaccines and therapies

Preexisting and de novo humoral immunity to SARS-CoV-2 in humans

Macrophages: a Trojan horse in COVID-19?

Monocyte DPP4 Expression in Human Atherosclerosis Is Associated With Obesity 289 and Dyslipidemia

Oxidized LDL upregulates macrophage DPP4 expression via TLR4/TRIF/CD36 292 pathways

Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from 295 disease in a small animal model

Little to no 298 expression of angiotensin-converting enzyme-2 (ACE2) on most human peripheral 299 blood immune cells but highly expressed on tissue macrophages

SARS-CoV-2 entry factors are highly expressed in nasal epithelial 303 cells together with innate immune genes

Fc 306 receptors in antibody-dependent enhancement of viral infections

Infectious RNA transcribed in vitro 309 from a cDNA copy of the human coronavirus genome cloned in vaccinia virus

Mechanisms and enzymes involved in SARS coronavirus genome expression

Genomic characterization of a newly discovered coronavirus 316 associated with acute respiratory distress syndrome in humans

Structure of 319 MERS-CoV spike receptor-binding domain complexed with human receptor DPP4

Human aminopeptidase N is a receptor for human 323 coronavirus 229E

DNA vaccine protection against SARS-CoV-2 in rhesus 326 macaques

Rapid Quantification of SARS-CoV-2-Neutralizing Antibodies Using 329 Propagation-Defective Vesicular Stomatitis Virus Pseudotypes. Vaccines (Basel)

CoV-2-induced immune activation and death of monocyte-derived human 333 macrophages and dendritic cells

A potential role for dendritic cell/macrophage-expressing DPP4 in obesity-336 induced visceral inflammation

Active replication of Middle East respiratory syndrome coronavirus and aberrant 339 induction of inflammatory cytokines and chemokines in human macrophages: 340 implications for pathogenesis