SARS‐CoV‐2 receptor ACE2 protein expression in serum is significantly associated with age

Pavel, Ana B.; Wu, Jianni; Renert‐Yuval, Yael; Duca, Ester Del; Glickman, Jacob W.; Miller, Rachel L.; Paller, Amy S.; Krueger, James G.; Guttman‐Yassky, Emma

doi:10.1111/all.14522

Cited by 30 publications

(35 citation statements)

References 9 publications

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“…Plasma ACE2 was associated with age, which is in line with recent observations showing higher serum levels of ACE2 in adults compared to a pediatric cohort. 38 There were no associations between plasma ACE2 levels and BMI.…”

Section: Discussionmentioning

confidence: 89%

Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

Kragstrup

Singh

Grundberg

et al. 2021

Preprint

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Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to angiotensin converting enzyme 2 (ACE2) enabling entrance of the virus into cells and causing the infection termed coronavirus disease of 2019 (COVID-19). COVID-19 is a disease with a very broad spectrum of clinical manifestations, ranging from asymptomatic and subclinical infection to severe hyperinflammatory syndrome and death. Methods This study used data from a large longitudinal study of 306 COVID-19 positive patients and 78 COVID-19 negative patients (MGH Emergency Department COVID-19 Cohort with Olink Proteomics). Comprehensive clinical data were collected on this cohort, including 28-day outcomes classified according to the World Health Organization (WHO) COVID-19 outcomes scale. The samples were run on the Olink Explore 1536 platform which includes measurement of the ACE2 protein. Findings High baseline levels of ACE2 in plasma from COVID-19 patients were associated with worse WHOmax category at 28 days with OR=0.56, 95%-CI: 0.44-0.71 (P < 0.0001). This association was significant in regression models with correction for baseline characteristics, pre-existing medical conditions, and laboratory test results. High levels of ACE2 in plasma from COVID-19 patients were also significantly associated with worse WHO category at the time of blood sampling at both day 0, day 3, and day 7 (P = 0.0004, P < 0.0001, and P < 0.0001, respectively). The levels of ACE2 in plasma from COVID-19 patients with hypertension were significantly higher compared to patients without hypertension (P = 0.0045). The plasma ACE2 levels were also significantly higher in COVID-19 patients with pre-existing heart conditions and kidney disease compared with patients without these pre-existing conditions (P = 0.0363 and P = 0.0303, respectively). There was no difference in plasma ACE2 levels comparing patients with or without pre-existing lung disease, diabetes, or immunosuppressive conditions (P = 0.953, P = 0.291, and P = 0.237, respectively). The associations between high plasma levels of ACE2 and worse WHOmax category during 28 days were more pronounced in COVID-19 positive patients compared with COVID-19 negative patients but the difference was not significant in the two-way ANOVA analysis. Interpretation This study suggests that measuring ACE2 is potentially valuable in predicting COVID-19 outcomes. Further, ACE2 levels could be a link between severe COVID-19 disease and its risk factors, namely hypertension, pre-existing heart disease and pre-existing kidney disease. The design of the data analysis using the Olink platform does not allow assessment of quantitative differences. However, previous studies have described a positive correlation between plasma ACE2 and ACE1 activity. This is interesting because ACE1 (serum ACE) analysis is a standardized test in most hospital laboratories. Therefore, our study encourages quantitative investigations of both plasma ACE 1 and 2 in COVID-19.

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Section: Discussionmentioning

confidence: 89%

Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

Kragstrup

Singh

Grundberg

et al. 2021

Preprint

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“…18 While the N phosphoprotein ensures the linkage of the viral RNA to the membrane, 19 the S glycoprotein binds to ACE2 and thereby initiates viral entry into the host cell. 13,[20][21][22] Neutralizing antibodies (NAb) are typically generated against the S protein and often target the receptor-binding domain (RBD). 23,24 As demonstrated in a vaccination approach using inactivated virus, the RBD represents an immunodominant viral antigen since at least half of the detectable anti-S IgG antibodies were directed against the RBD.…”

Section: G R a P H I C A L Abstractmentioning

confidence: 99%

“…To date, antibody testing has focused primarily on two highly abundant structural antigens of SARS‐CoV‐2, specifically the nucleoprotein (N) protein and the spike (S) protein 18 . While the N phosphoprotein ensures the linkage of the viral RNA to the membrane, 19 the S glycoprotein binds to ACE2 and thereby initiates viral entry into the host cell 13,20‐22 . Neutralizing antibodies (NAb) are typically generated against the S protein and often target the receptor‐binding domain (RBD) 23,24 .…”

Section: Introductionmentioning

confidence: 99%

Accuracy of serological testing for SARS‐CoV‐2 antibodies: First results of a large mixed‐method evaluation study

Brigger

Horn

Pennington

et al. 2020

Allergy

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Background Serological immunoassays that can identify protective immunity against SARS‐CoV‐2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed‐design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS‐CoV‐2 proteins and assessed the neutralizing activity of antibodies in patient sera. Methods Consecutive patients admitted with confirmed SARS‐CoV‐2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in‐house enzyme‐linked immunosorbent assay utilizing recombinant receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein was developed and compared to three commercially available enzyme‐linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1) and a lateral flow immunoassay (LFI) based on full‐length spike protein. Neutralization assays with live SARS‐CoV‐2 were performed. Results One‐thousand four‐hundred and seventy‐seven individuals were included comprising 112 SARS‐CoV‐2 positives (defined as a positive real‐time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS‐CoV‐2 positive individuals, 96.3% showed full neutralization of live SARS‐CoV‐2 at serum dilutions ≥1:16, while none of the 6 SARS‐CoV‐2 negative sera revealed neutralizing activity. Conclusions ELISAs targeting RBD and S1 protein of SARS‐CoV‐2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS‐CoV‐2.

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“…Another study found that ACE 2 protein expression is significantly higher in adults compared to infants and toddlers (<5 years old). 10 Despite children's tendency to have milder COVID-19 symptoms, it is important to make elderly caregivers aware of the risk of transmission from young children. 2 Real-time RT-PCR is the standard diagnostic method for COVID-19.…”

Section: Discussionmentioning

confidence: 99%

Case report of a COVID-19 family cluster originating from a boarding school

Cesilia

Sudarmaji²,

Setiabudi

et al. 2021

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Since it was first identified in Wuhan City, Hubei Province, China in December 2019, SARS-CoV-2 has spread to 195 countries and infected more than 8 million people globally. Indonesia, an archipelago consisting of thousands of islands and 34 provinces, has the largest number of confirmed cases and mortality in Southeast Asia. A total of 464 districts/cities in Indonesia have been affected by COVID-19, of which 189 districts/cities are considered to be local transmission areas. Riau Province, located in Sumatra Island, consists of 12 districts/cities with a population of more than 6.8 million. This province has the 1st largest number of COVID-19 cases on Sumatra Island. Currently, more than 3000 childrens have been infected with case fatality rate <0.3% and recovery rate >90%. In May 2020, the public health office of Riau reported that just 34 children were confirmed to have COVID-19, with symptoms varying from asymptomatic to moderate with only a few family clusters identified. During the pandemic, contact tracing is the main approach to detect and isolate sources of infection in order to reduce viral transmission. This method has also been used to control transmission of other respiratory diseases such as tuberculosis (TB), MERS, and SARS. We report here on a familial cluster of COVID-19 in the Meranti Island Regency, which is located 145 km from the city of Pekanbaru (Riau Province). The island can only be reached in four hours by speed boat.

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SARS‐CoV‐2 receptor ACE2 protein expression in serum is significantly associated with age

Cited by 30 publications

References 9 publications

Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

Plasma ACE2 levels predict outcome of COVID-19 in hospitalized patients

Accuracy of serological testing for SARS‐CoV‐2 antibodies: First results of a large mixed‐method evaluation study

Case report of a COVID-19 family cluster originating from a boarding school

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