Distinct Immune Response in Two MERS-CoV-Infected Patients: Can We Go from Bench to Bedside?

Abstract

One year after the occurrence of the first case of infection by the Middle East Respiratory Syndrome coronavirus (MERS-CoV) there is no clear consensus on the best treatment to propose. The World Health Organization, as well as several other national agencies, are still working on different clinical approaches to implement the most relevant treatment in MERS-CoV infection. We compared innate and adaptive immune responses of two patients infected with MERS-CoV to understand the underlying mechanisms involved in the response and propose potential therapeutic approaches. Broncho-alveolar lavage (BAL) of the first week and sera of the first month from the two patients were used in this study. Quantitative polymerase chain reaction (qRTPCR) was performed after extraction of RNA from BAL cells of MERS-CoV infected patients and control patients. BAL supernatants and sera were used to assess cytokines and chemokines secretion by enzyme-linked immunosorbent assay. The first patient died rapidly after 3 weeks in the intensive care unit, the second patient still recovers from infection. The patient with a poor outcome (patient 1), compared to patient 2, did not promote type-1 Interferon (IFN), and particularly IFNα, in response to double stranded RNA (dsRNA) from MERS-CoV. The absence of IFNα, known to promote antigen presentation in response to viruses, impairs the development of a robust antiviral adaptive Th-1 immune response. This response is mediated by IL-12 and IFNγ that decreases viral clearance; levels of both of these mediators were decreased in patient 1. Finally, we confirm previous in vitro findings that MERS-CoV can drive IL-17 production in humans. Host recognition of viral dsRNA determines outcome in the early stage of MERS-CoV infection. We highlight the critical role of IFNα in this initial stage to orchestrate a robust immune response and bring substantial arguments for the indication of early IFNα treatment during MERS-CoV infection.

Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

“…In view of the high amount of cytokines induced by SARS-CoV, 22,24 MERS-CoV, 25,26 and 2019-nCoV infections, corticosteroids were used frequently for treatment of patients with severe illness, for possible benefit by reducing inflammatory-induced lung injury. However, current evidence in patients with SARS and MERS suggests that receiving corticosteroids did not have an effect on mortality, but rather delayed viral clearance.…”

Characteristics of Traveler with Middle East Respiratory Syndrome, China, 2015

“…However, a previous study also showed increased levels of interferon-α in a patient who survived MERS-CoV infection but not in a person who died of MERS ( 7 ). Although MERS-CoV evades induction of innate immune responses by cell types, the virus elicits interferon responses in plasmacytoid dendritic cells in vitro ( 8 ).…”

Middle East respiratory syndrome: An emerging coronavirus infection tracked by the crowd

“…Also, infection triggered significantly higher levels of IP-1o and RANTES than the equivalent dose of SARS-CoV (Zhou et al, 2014). In clinical practice, two MERS patients in France were found to differ in their IFN␣ responses (Faure et al, 2014). Patient 1, who died, did not mount a robust type I IFN response while Patient 2, who survived, did mount a response; particularly notable in Patient 1 was the absence of IFN␣ and comparatively little RIG-I, MDA5, IRF3, IRF7, IL-12 and IFN␥ (Faure et al, 2014).…”

“…MERS-CoV viral RNA detection in serum has proven a useful retrospective source of PCR template when respiratory samples were not available (Hijawi et al, 2013). RNAaemia may also correlate with disease severity; signs of virus cleared from serum in one recovered human case while lingering until the death of another (Faure et al, 2014).…”