SARS-CoV-2 antibody immunoassays in serial samples reveal earlier seroconversion in acutely ill COVID-19 patients developing ARDS

Objectives During the COVID-19 pandemic, SARS-CoV-2 antibody testing has been suggested for (1) screening populations for disease prevalence, (2) diagnostics, and (3) guiding therapeutic applications. Here, we conducted a detailed clinical evaluation of four Anti-SARS-CoV-2 immunoassays in samples from acutely ill COVID-19 patients and in two negative cohorts. Methods 443 serum specimens from serial sampling of 29 COVID-19 patients were used to determine clinical sensitivities. Patients were stratified for the presence of acute respiratory distress syndrome (ARDS). Individual serum specimens from a pre-COVID-19 cohort of 238 healthy subjects and from a PCR-negative clinical cohort of 257 patients were used to determine clinical specificities. All samples were measured side-by-side with the Anti-SARS-CoV-2-ELISA (IgG), Anti-SARS-CoV-2-ELISA (IgA) and Anti-SARS-CoV-2-NCP-ELISA (IgG) (Euroimmun AG, Lübeck, Germany) and the Elecsys Anti-SARS-CoV-2 ECLIA (Roche Diagnostics International, Rotkreuz, Switzerland). Results Median seroconversion occurred earlier in ARDS patients (8–9 days) than in non-ARDS patients (11–17 days), except for EUR N-IgG. Rates of positivity and mean signal ratios in the ARDS group were significantly higher than in the non-ARDS group. Sensitivities between the four tested immunoassays were equivalent. In the set of negative samples, the specificity of the Anti-SARS-CoV-2-ELISA (IgA) was lower (93.9%) compared to all other assays (≥98.8%) and the specificity of Anti-SARS-CoV-2-NCP-ELISA (IgG) was lower (98.8%) than that of Elecsys Anti-SARS-CoV-2 (100%). Conclusions Serial sampling in COVID-19 patients revealed earlier seroconversion and higher signal ratios of SARS-CoV-2 antibodies as a potential risk marker for the development of ARDS, suggesting a utility for antibody testing in acutely diseased patients.

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SARS-CoV-2 antibody immunoassays in serial samples reveal earlier seroconversion in acutely ill COVID-19 patients developing ARDS

10.1101/2021.02.15.21250916 ◽

2021 ◽

Author(s):

Marie-Luise Buchholtz ◽

Florian M. Arend ◽

Peter Eichhorn ◽

Michael Weigand ◽

Alisa Kleinhempel ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Healthy Subjects ◽

Distress Syndrome ◽

Disease Prevalence ◽

Risk Marker ◽

Antibody Testing ◽

Clinical Cohort ◽

Serial Sampling ◽

Serial Samples ◽

Roche Diagnostics

AbstractObjectivesDuring the COVID-19 pandemic, SARS-CoV-2 antibody testing has been suggested for (1) screening populations for disease prevalence, (2) diagnostics, and (3) guiding therapeutic applications. Here, we conducted a detailed clinical evaluation of four Anti-SARS-CoV-2 immunoassays in samples from acutely ill COVID-19 patients and in two negative cohorts.Methods443 serum specimens from serial sampling of 29 COVID-19 patients were used to determine clinical sensitivities. Patients were stratified for the presence of acute respiratory distress syndrome (ARDS). Individual serum specimens from a pre-COVID-19 cohort of 238 healthy subjects and from a PCR-negative clinical cohort of 257 patients were used to determine clinical specificities. All samples were measured side-by-side with the Anti-SARS-CoV-2-ELISA (IgG), Anti-SARS-CoV-2-ELISA (IgA) and Anti-SARS-CoV-2-NCP-ELISA (IgG) (Euroimmun AG, Lübeck, Germany) and the Elecsys Anti-SARS-CoV-2 ECLIA (Roche Diagnostics International, Rotkreuz, Switzerland).ResultsMedian seroconversion occurred earlier in ARDS patients (8-9 days) than in non-ARDS patients (11-17 days), except for EUR N-IgG. Rates of positivity and mean signal ratios in the ARDS group were significantly higher than in the non-ARDS group. Sensitivities between the four tested immunoassays were equivalent. In the set of negative samples, the specificity of the Anti-SARS-CoV-2-ELISA (IgA) was lower (93.9 %) compared to all other assays (≥98.8 %) and the specificity of Anti-SARS-CoV-2-NCP-ELISA (IgG) was lower (98.8 %) than that of Elecsys Anti-SARS-CoV-2 (100 %).ConclusionsSerial sampling in COVID-19 patients revealed earlier seroconversion and higher signal ratios of SARS-CoV-2 antibodies as a potential risk marker for the development of ARDS, suggesting a utility for antibody testing in acutely diseased patients.

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Distinct Proteasome Subpopulations in the Alveolar Space of Patients with the Acute Respiratory Distress Syndrome

Mediators of Inflammation ◽

10.1155/2012/204250 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 14

Author(s):

S. U. Sixt ◽

R. Alami ◽

J. Hakenbeck ◽

M. Adamzik ◽

A. Kloß ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Healthy Subjects ◽

Distress Syndrome ◽

Distinct Pattern ◽

Alveolar Space ◽

Chromatographic Purification ◽

Cell Pellet ◽

First Time

There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n=28) and healthy subjects (n=10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL±1116 versus59±25;P<0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P=0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation.

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Critical Illness Polyneuropathy and Myopathy in Patients With Acute Respiratory Distress Syndrome

Yearbook of Pulmonary Disease ◽

10.1016/s8756-3452(08)70229-9 ◽

2006 ◽

Vol 2006 ◽

pp. 283-284

Author(s):

J.A. Barker

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Critical Illness ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome ◽

Critical Illness Polyneuropathy

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Acute Respiratory Distress Syndrome

10.1017/cbo9780511575112 ◽

1999 ◽

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome

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COVID-19 – eine vaskuläre Systemerkrankung

Der Klinikarzt ◽

10.1055/a-1261-8676 ◽

2020 ◽

Vol 49 (10) ◽

pp. 418-421

Author(s):

Christopher Werlein ◽

Peter Braubach ◽

Vincent Schmidt ◽

Nicolas J. Dickgreber ◽

Bruno Märkl ◽

...

Keyword(s):

Acute Respiratory Distress Syndrome ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Distress Syndrome

ZUSAMMENFASSUNGDie aktuelle COVID-19-Pandemie verzeichnet mittlerweile über 18 Millionen Erkrankte und 680 000 Todesfälle weltweit. Für die hohe Variabilität sowohl der Schweregrade des klinischen Verlaufs als auch der Organmanifestationen fanden sich zunächst keine pathophysiologisch zufriedenstellenden Erklärungen. Bei schweren Krankheitsverläufen steht in der Regel eine pulmonale Symptomatik im Vordergrund, meist unter dem Bild eines „acute respiratory distress syndrome“ (ARDS). Darüber hinaus zeigen sich jedoch in unterschiedlicher Häufigkeit Organmanifestationen in Haut, Herz, Nieren, Gehirn und anderen viszeralen Organen, die v. a. durch eine Perfusionsstörung durch direkte oder indirekte Gefäßwandschädigung zu erklären sind. Daher wird COVID-19 als vaskuläre Multisystemerkrankung aufgefasst. Vor dem Hintergrund der multiplen Organmanifestationen sind klinisch-pathologische Obduktionen eine wichtige Grundlage der Entschlüsselung der Pathomechanismen von COVID-19 und auch ein Instrument zur Generierung und Hinterfragung innovativer Therapieansätze.

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