Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19

Authors: MartinDugasa1TanjaGrote-Westrickb1UtaMerledMichaelaFontenaylmAndreas E.KremerhFrankHansesijRichardVollenbergcEvaLorentzenbShilpaTiwari-BecklerdJérômeDucheminlSyrineEllouzelMarcelVetterhJuliaFürsthPhilippSchusterkTobiasBrixaClaudia M.DenkingerfgCarstenMüller-TidoweHartmutSchmidtcJoachimKühnb1

Highlights

Does prior infection with seasonal human coronavirus OC43 protect against critical COVID-19?•

Findings: In an international multi-center study inpatients without anti-HCoV OC43 NP antibodies had an increased risk of critical disease.•

Meaning: Prior infections with seasonal HCoV OC43 have a protective effect against critical COVID-19.

Abstract

Background

The vast majority of COVID-19 patients experience a mild disease. However, a minority suffers from critical disease with substantial morbidity and mortality.

Objectives

To identify individuals at risk of critical COVID-19, the relevance of a seroreactivity against seasonal human coronaviruses was analyzed.

Methods

We conducted a multi-center non-interventional study comprising 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France. The ICU group comprised more males, whereas the outpatient group contained a higher percentage of females. For each patient, the serum or plasma sample obtained closest after symptom onset was examined by immunoblot regarding IgG antibodies against the nucleocapsid protein (NP) of HCoV 229E, NL63, OC43 and HKU1.

Results

Median age was 60 years (range 18-96). Patients with critical disease (n=106) had significantly lower levels of anti-HCoV OC43 nucleocapsid protein (NP)-specific antibodies compared to other COVID-19 inpatients (p=0.007). In multivariate analysis (adjusted for age, sex and BMI), OC43 negative inpatients had an increased risk of critical disease (adjusted odds ratio (AOR) 2.68 [95% CI 1.09 – 7.05]), higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis.

Conclusions

Our results suggest that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Therefore, anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment for each patient. Hence, we expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination against SARS-CoV-2, especially with other risk factors prevailing.

For More Information: https://www.sciencedirect.com/science/article/pii/S1386653221001141

What is OC43?

Authors: By Benedette Cuffari, M.Sc.Reviewed by Emily Henderson, B.Sc.

In an effort to further understand and predict the health effects that can arise following infection by SARS-CoV-2, which is the infection that causes the disease COVID-19, many researchers have reevaluated the pathogenesis associated with coronaviruses that have already been identified. One type of coronavirus that has infected individuals around the world is HCoV-OC43.

A history of coronaviruses

In 1965, the first human coronavirus (HCoV) strain, which was eventually named B814, was identified from a patient’s nasal discharge. Since then, over 30 different HCoV strains have been isolated, the most notable of which include HCoV-229E, HCoV-NL63, HCoV-HLU1, and HCoV-0C43.

In addition to the aforementioned human-infecting coronavirus strains, several highly pathogenic zoonotic strains such as the severe acute respiratory syndrome coronavirus (SARS-CoV) of 2002, the Middle East respiratory syndrome coronavirus (MERS-CoV) of 2011 and the novel coronavirus COVID-19 that has, as of June 18, 2020, infected 8.24 million people and claimed the lives of over 446,000 thousand individuals around the world.

Classification of HCoV-OC43

Within the virus order of Nidiovirules is the suborder of Cornidovirineae. Within Cornidovirineae are two subfamilies known as Letovirinae and Orthocoronairinae.

All coronaviruses are within the subfamily of Orthocornavirinae; however, specific coronavirus strains can be further classified into one of four genera including Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Whereas HCoV and HCoV-NL63 are found in the Alphacoronavirus genus, HCoV-OC43, as well as HCoV-HKU1, MERS-CoV, SARS-CoV and SARS-CoV-2 are all classified within the Betacoronavirus genus.

How does HCoV-OC43 enter cells?

The entry of HCoV-OC43 into human cells is largely achieved through the caveolin-1-dependent pathway of endocytosis; however, virus-containing vesicles at the cell surface can also undergo scission to also penetrate human cells.

Notably, while host factors like interferon-inducible transmembrane proteins (IFITMs) often prevent the entry of coronaviruses like HCoV-229E, -NL63, SARS-CoV and MERS-CoV from entering cells through its various antiviral functions, IFITM2 and IFITM3 promote the entry and subsequent infection of HCoV-OC43 into human cells.

For More Information: https://www.news-medical.net/health/What-is-OC43.aspx

Lack of antibodies against seasonal coronavirus OC43 nucleocapsid protein identifies patients at risk of critical COVID-19

Authors: Martin Dugas 1Tanja Grote-Westrick 2Uta Merle 3Michaela Fontenay 4Andreas E Kremer 5Frank Hanses 6Richard Vollenberg 7Eva Lorentzen 8Shilpa Tiwari-Heckler 9Jérôme Duchemin 10Syrine Ellouze 11Marcel Vetter 12Julia Fürst 13Philipp Schuster 14Tobias Brix 15Claudia M Denkinger 16Carsten Müller-Tidow 17Hartmut Schmidt 18Phil-Robin Tepasse 19Joachim Kühn 20

Abstract

Background: The vast majority of COVID-19 patients experience a mild disease. However, a minority suffers from critical disease with substantial morbidity and mortality.

Objectives: To identify individuals at risk of critical COVID-19, the relevance of a seroreactivity against seasonal human coronaviruses was analyzed.

Methods: We conducted a multi-center non-interventional study comprising 296 patients with confirmed SARS-CoV-2 infections from four tertiary care referral centers in Germany and France. The ICU group comprised more males, whereas the outpatient group contained a higher percentage of females. For each patient, the serum or plasma sample obtained closest after symptom onset was examined by immunoblot regarding IgG antibodies against the nucleocapsid protein (NP) of HCoV 229E, NL63, OC43 and HKU1.

Results: Median age was 60 years (range 18-96). Patients with critical disease (n=106) had significantly lower levels of anti-HCoV OC43 nucleocapsid protein (NP)-specific antibodies compared to other COVID-19 inpatients (p=0.007). In multivariate analysis (adjusted for age, sex and BMI), OC43 negative inpatients had an increased risk of critical disease (adjusted odds ratio (AOR) 2.68 [95% CI 1.09 – 7.05]), higher than the risk by increased age or BMI, and lower than the risk by male sex. A risk stratification based on sex and OC43 serostatus was derived from this analysis.

Conclusions: Our results suggest that prior infections with seasonal human coronaviruses can protect against a severe course of COVID-19. Therefore, anti-OC43 antibodies should be measured for COVID-19 inpatients and considered as part of the risk assessment for each patient. Hence, we expect individuals tested negative for anti-OC43 antibodies to particularly benefit from vaccination against SARS-CoV-2, especially with other risk factors prevailing.

For More Information: https://pubmed.ncbi.nlm.nih.gov/33965698/

PubChem

OC43

Non-structural protein 2a

NCBI ProteinQ80872
TaxonomyHuman coronavirus OC43
DatesModify2021-08-11Create2017-04-15
UniProt

1Names and Identifiers

1.1Synonyms

Non-structural protein 2a

ns2a

32 kDa accessory protein

32 kDa non-structural protein

ns2UniProt

1.2Other Identifiers

1.2.1UniProt ID

Q80872UniProt

2Sequence

>sp|Q80872|NS2A_CVHOC Non-structural protein 2a (Run BLAST)

MAVAYADKPNHFINFPLTHFQGFVLNYKGLQFQILDEGVDCKIQTAPHISLTMLDIQPEDYKSVDVAIQEVIDDMHWGDGFQIKFENPHILGRCIVLDVKGVEELHDDLVNYIRDKGCVADQSRKWIGHCTIAQLTDAALSIKENVDFINSMQFNYKITINPSSPARLEIVKLGAEKKDGFYETIVSHWMGIRFEYTSPTDKLAMIMGYCCLDVVRKELEEGDLPENDDDAWFKLSYHYENNSWFFRHVYRKSFHFRKACQNLDCNCLGFYESPVEEDNCBI Protein

For More Information: https://pubchem.ncbi.nlm.nih.gov/protein/Q80872

The OC43 human coronavirus envelope protein is critical for infectious virus production and propagation in neuronal cells and is a determinant of neurovirulence and CNS pathology

Authors:Jenny K.Stodola1GuillaumeDubois1AlainLe CoupanecMarcDesforgesPierre J.Talbot

Highlights

Coronavirus structural envelope (E) protein specific motifs involved in protein-protein interaction or in homo-oligomeric ion channel formation are needed for optimal production of recombinant infectious virus.•

Fully functional E protein of HCoV-OC43 is crucial for viral propagation in the CNS and neurovirulence.•

Fully functional E protein of HCoV-OC43 is crucial for efficient viral propagation in the central nervous system and thereby for neurovirulence.

Abstract

The OC43 strain of human coronavirus (HCoV-OC43) is an ubiquitous respiratory tract pathogen possessing neurotropic capacities. Coronavirus structural envelope (E) protein possesses specific motifs involved in protein-protein interaction or in homo-oligomeric ion channel formation, which are known to play various roles including in virion morphology/assembly and in cell response to infection and/or virulence. Making use of recombinant viruses either devoid of the E protein or harboring mutations either in putative transmembrane domain or PDZ-binding motif, we demonstrated that a fully functional HCoV-OC43 E protein is first needed for optimal production of recombinant infectious viruses. Furthermore, HCoV-OC43 infection of human epithelial and neuronal cell lines, of mixed murine primary cultures from the central nervous system and of mouse central nervous system showed that the E protein is critical for efficient and optimal virus replication and propagation, and thereby for neurovirulence.

For More Information: https://www.sciencedirect.com/science/article/pii/S0042682217304361

OC43 Membrane Protein Science

UniProtKB – Q01455 (VME1_CVHOC)


TopBLASTAlignFormatAdd to basketHistory

Membrane protein

Gene

M

OrganismHuman coronavirus OC43 (HCoV-OC43)StatusReviewed-Annotation score:-Experimental evidence at protein leveli

Functioni

Component of the viral envelope that plays a central role in virus morphogenesis and assembly via its interactions with other viral proteins.UniRule annotation

GO – Molecular functioni

Complete GO annotation on QuickGO …

GO – Biological processi

Complete GO annotation on QuickGO …

Keywordsi

Biological processHost-virus interactionViral immunoevasion

Names & Taxonomyi

Protein namesiRecommended name:Membrane proteinUniRule annotationShort name:M proteinUniRule annotationAlternative name(s):E1 glycoproteinUniRule annotationMatrix glycoproteinUniRule annotationMembrane glycoproteinUniRule annotation
Gene namesiName:MUniRule annotationORF Names:6
OrganismiHuman coronavirus OC43 (HCoV-OC43)
Taxonomic identifieri31631 [NCBI]
Taxonomic lineageiViruses › Riboviria › Orthornavirae › Pisuviricota › Pisoniviricetes › Nidovirales › Cornidovirineae › Coronaviridae › Orthocoronavirinae › Betacoronavirus › Embecovirus › 
Virus hostiHomo sapiens (Human) [TaxID: 9606]
ProteomesiUP000180344 Componenti: GenomeUP000100580 Componenti: GenomeUP000007552 Componenti: Genome

Subcellular locationi

For All Information on This Protein: https://www.uniprot.org/uniprot/Q01455

Human coronavirus OC43 nucleocapsid protein binds microRNA 9 and potentiates NF-κB activation

Authors: Frances W Lai 1Kyle B StephensonJames MahonyBrian D Lichty

Abstract

The human coronavirus OC43 is a major contributor to the common cold worldwide, though due to its low mortality rate, little research has focused on this human pathogen. The nucleocapsid is an essential structural protein with conserved functions across the coronavirus family. While a multitude of studies have examined nucleocapsid function, none have described the effects of OC43 nucleocapsid on the transcription factor NF-κB. We report that the nucleocapsid protein of OC43 causes potentiation of NF-κB activation. This prolonged activation is the direct result of the ability of the nucleocapsid to bind RNA, specifically microRNA 9 (miR-9), which is a negative regulator of NF-κB. This previously undescribed interaction between virus and host is a potential mechanism of immune evasion in RNA viruses.

For More Information: https://pubmed.ncbi.nlm.nih.gov/24109243/

Bell’s Palsy as a Late Neurologic Manifestation of COVID-19 Infection

Authors: Ibiyemi O. OkeOlubunmi O. OladunjoyeAdeolu O. OladunjoyeAnish PaudelRyan Zimmerman

Abstract

Bell’s palsy is acute peripheral facial nerve palsy; its cause is often unknown but it can be triggered by acute viral infection. Coronavirus disease 2019 (COVID-19) infection commonly presents with respiratory symptoms, but neurologic complications have been reported. A few studies have reported the occurrence of facial nerve palsy during the COVID-19 pandemic. We present a case of Bell’s palsy in a 36-year-old man with COVID-19 infection and a past medical history of nephrolithiasis. He presented to the emergency room with a day history of sudden right facial weakness and difficulty closing his right eye four weeks following a diagnosis of COVID-19 infection. Physical examination revealed right lower motor neuron facial nerve palsy (House-Brackmann grade IV). Serologic screen for Lyme disease, human immunodeficiency virus (HIV), and herpes simplex virus (HSV) 1 and 2 were negative for acute infection; however, neuroimaging with MRI confirmed Bell’s palsy. He made remarkable improvement following treatment with a course of valacyclovir and methylprednisolone. This case adds to the growing body of literature on neurological complications that should be considered when managing patients with COVID-19 infection.

Introduction

Bell’s palsy is an acute peripheral lower motor neuron (LMN) facial nerve palsy leading to weakness on one side of the face without any other neurologic abnormalities on examination. The cause is often unknown; however, herpes simplex virus isoform 1 (HSV 1) and/or herpes zoster virus (HZV) reactivation is thought to be the most likely cause [1]. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the novel virus that causes coronavirus disease 2019 (COVID-19). It was first identified in Wuhan, a city in Hubei province of China, in December 2019.

There are a few theories on the neuropathogenesis of COVID-19, which include the binding of coronavirus to angiotensin-converting enzyme 2 (ACE2) receptors, which are widely distributed on glial cells and neurons [2,3]. Dubé et al. postulated in their study with animal models that there is axonal transport of human coronavirus (HCoV) OC43 protein into the nervous system [4]. These two mechanisms may lead to nerve damage through direct injury, autoimmunity, and ischemia of the vasa nervorum or inflammatory demyelination [5,6].

Facial nerve palsy may be the first presentation of COVID-19 and it may occur within a few days of its diagnosis [7-13]. We present a patient with a unilateral LMN facial nerve palsy four weeks after a diagnosis of COVID-19 infection.

For More Information: https://www.cureus.com/articles/54173-bells-palsy-as-a-late-neurologic-manifestation-of-covid-19-infection