Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans, South Korea

Park, Wan Beom; Perera, Ranawaka A.P.M.; Choe, Pyoeng Gyun; Lau, Eric H. Y.; Choi, Seong Jin; Chun, June Young; Oh, Hong Sang; Song, Kyoung Ho; Bang, Ji Hwan; Kim, Eu Suk; Kim, Hong Bin; Park, Sang Won; Kim, Nam Joong; Poon, Leo L. M.; Peiris, Malik; Oh, Myoung Don

doi:10.3201/eid2112.151421

Cited by 145 publications

(166 citation statements)

References 8 publications

(10 reference statements)

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“…Our current diagnostic algorithm for identification of MERS‐CoV‐specific serum antibodies in patients with a suspected history of MERS‐CoV infection includes initial screenings by indirect ELISA using MERS‐CoV nucleocapsid (N) protein, and then confirmation with immunofluorescent staining of MERS‐infected cells, and microneutralization titration (MNt) assays . Other international groups are primarily using a combination of indirect ELISA against the spike (S) protein with confirmatory neutralization assays . S1 ELISAS have been found to correlate well with neutralizing antibodies .…”

Section: Introductionmentioning

confidence: 99%

Inclusion of MERS‐spike protein ELISA in algorithm to determine serologic evidence of MERS‐CoV infection

Trivedi

Miao

Alabdallat

et al. 2017

Journal of Medical Virology

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The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS-CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or micro-neutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS-CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus.

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Section: Introductionmentioning

confidence: 99%

Inclusion of MERS‐spike protein ELISA in algorithm to determine serologic evidence of MERS‐CoV infection

Trivedi

Miao

Alabdallat

et al. 2017

Journal of Medical Virology

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“…The patients were categorized into a group with severe disease (severe group) or a group with mild disease (mild group), depending on whether oxygen supplementation was used during the hospital stay. 3 Chest radiographs were scored as described previously (higher scores indicate greater involvement; see the Supplementary Appendix, available with the full text of this letter at NEJM.org). 4 Quantitative real-time reversetranscriptase polymerase chain reaction (rRT-PCR) for the envelope gene (upE) was performed with the PowerChek MERS Real-time PCR kit (Kogenebiotech).…”

Section: Viral Load Kinetics Of Mers Coronavirus Infectionmentioning

confidence: 99%

Viral Load Kinetics of MERS Coronavirus Infection

Oh¹,

Park²,

Choe³

et al. 2016

N Engl J Med

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200

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No potential conflict of interest relevant to this letter was reported. The authors reply: Campochiaro and Caruso are correct that mention of cardiovascular associations with ankylosing spondylitis and axial spondyloarthritis, including specific conductionsystem lesions and aortic-root lesions, was largely absent from our review of spondyloarthritis. These specific lesions are uncommon and tend to occur late in the disease course, as does the other more common but less specific cardiovascular illness mentioned in their letter. The focus of our article was on early diagnosis and clinical management of the axial disease, and this priority, along with space and citation limitations, precluded our describing specific cardiovascular manifestations. Rudwaleit M, van derRudwaleit and colleagues make the important point that diagnosis in clinical practice cannot be based solely on fulfillment of classification criteria. We tried to make this point in the article, but perhaps our wording conveyed some unintended ambiguity. In order to introduce the new concept of axial spondyloarthritis, we described the classification criteria for this entity proposed by the ASAS in 2009. In discussing this concept, including the critical role of MRI, we referred to this entity as a diagnosis, in the sense of its being a defined medical condition. We did not intend by this to imply that one can rely strictly on these criteria to establish a diagnosis in clinical practice. In fact, we stated explicitly, "These classification criteria have limited use outside the arena of clinical research," to introduce the algorithm (in Fig. 2 of our article) for use in clinical practice.The algorithm itself is a modification of one published by the correspondents and their colleagues, 1 but it was modified specifically to further emphasize the importance of weighing clinical data and post-test probabilities 2 and of applying clinical judgment to the diagnostic process. Moreover, the discussion of MRI findings includes mention of lesions that are not part of the classification criteria but that can be helpful in supporting a diagnosis in clinical practice. Finally, the Summary section in our article reemphasizes the potential difficulty in accurately establishing or ruling out a diagnosis of axial spondyloarthritis, with no mention of criteria. Viral Load Kinetics of MERS Coronavirus InfectionTo the Editor: The outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection in South Korea involved 186 patients and resulted in 38 deaths, with four large hospital outbreaks accounting for 82% of the total cases. 1,2 Here, we report changes in viral load over time in patients with MERS.We included all patients who were admitted to three Seoul National University-affiliated hospitals; the institutional review boards of these hospitals approved this study and waived the need for written informed consent on public health grounds. The patients were categorized into a group with severe disease (severe group) or a group with mild disease (mild grou...

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“…Thus, the pool of healthy subjects with sufficient neutralizing antibody titer in convalescent plasma might be very limited. Finally, the hyperimmune plasma used in this study had a high neutralizing antibody titer of 3840, whereas at best human convalescent plasma has neutralizing antibody titers of 320e800 (Park et al, 2015;Arabi et al, 2016) (these studies use different methods to measure neutralizing antibodies). It is unclear whether convalescent plasma with lower neutralizing titers would have a similar effect on disease progression, as lower neutralizing antibody titers in the circulation will likely be reached.…”

Section: Discussionmentioning

confidence: 96%

“…treatment for MERS-CoV would be the use of neutralizing antibodies, either via convalescent plasma or monoclonal antibodies. Severity of disease has been associated with a delayed adaptive immune response (Park et al, 2015), and thus antibody-based therapy might be beneficial. Administration of neutralizing antibodies early in disease onset when patients were infected with respiratory pathogens such as SARS-CoV and influenza A virus was reported to be beneficial (Mair-Jenkins et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…A recent study suggests that the availability of donors with sufficiently high MERS-CoV antibody titers might be limited; only 12 out of 443 tested sera obtained from patients, healthcare workers and household contacts were positive on ELISA (Arabi et al, 2016). Furthermore, it has been suggested that severity of disease is linked to serological response; in patients who developed severe disease upon infection with MERS-CoV higher neutralizing antibody levels were detected, whereas in patients with mild or subclinical disease lower and potentially short-lived neutralizing antibody levels were detected (Drosten et al, 2014;Park et al, 2015). It has been well-established that severity of disease is linked to the prevalence of comorbidities (Badawi and Ryoo, 2016), the existence of which might contradict the collection of convalescent serum.…”

Section: Discussionmentioning

confidence: 99%

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Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets

et al. 2017

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Cases of Middle East respiratory syndrome coronavirus (MERS-CoV) continue to be identified and with a lack of effective clinical treatment and no preventative strategies, treatment using convalescent plasma or monoclonal antibodies (mAbs) is a potential quick route to an intervention. Passive immunotherapy via either convalescent plasma or mAbs has proven to be effective for other infectious agents. Following infection with MERS-CoV, common marmosets were treated with high titer hyperimmune plasma or the mAb m336, at 6 and 48 h post inoculation. Both treatments reduced signs of clinical disease, but reduction in viral loads in the respiratory tract were only found in the hyperimmune plasma group. A decrease in gross pathology was found only in the mAb-treated group, but no histological differences were observed between treated and control animals. While both hyperimmune plasma and the m336 treatments reduced the severity of disease in the common marmoset, neither treatment resulted in full protection against disease.

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Kinetics of Serologic Responses to MERS Coronavirus Infection in Humans, South Korea

Cited by 145 publications

References 8 publications

Inclusion of MERS‐spike protein ELISA in algorithm to determine serologic evidence of MERS‐CoV infection

Inclusion of MERS‐spike protein ELISA in algorithm to determine serologic evidence of MERS‐CoV infection

Viral Load Kinetics of MERS Coronavirus Infection

Efficacy of antibody-based therapies against Middle East respiratory syndrome coronavirus (MERS-CoV) in common marmosets

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