Quantitative Measurement of Anti-SARS-CoV-2 Antibodies: Analytical and Clinical Evaluation.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). Molecular-based testing is used to diagnose COVID-19, and serologic testing of antibodies specific to SARS-CoV-2 is used to detect past infection. While most serologic assays are qualitative, a quantitative serologic assay was recently developed that measures antibodies against the S protein, the target of vaccines. Quantitative antibody determination may help determine antibody titer and facilitate longitudinal monitoring of the antibody response, including antibody response to vaccines. We evaluated the quantitative Roche Elecsys anti-SARS-CoV-2 S assay. Specimens from 167 PCR-positive patients and 103 control specimens were analyzed using the Elecsys anti-SARS-CoV-2 S assay on the cobas e411 (Roche Diagnostics). Analytical evaluation included assessing linearity, imprecision, and analytical sensitivity. Clinical evaluation included assessing clinical sensitivity, specificity, cross-reactivity, positive predictive value (PPV), negative predictive value (NPV), and serial sampling from the same patient. The Elecsys anti-SARS-CoV-2 S assay exhibited its highest sensitivity (84.0%) at 15 to 30 days post-PCR positivity and exhibited no cross-reactivity, a specificity and PPV of 100%, and an NPV between 98.3% and 99.8% at ≥14 days post-PCR positivity, depending on the seroprevalence estimate. Imprecision was <2% at 9.06 U/ml across 6 days, the negative quality control (QC) was consistently negative (<0.40 U/ml), the manufacturer's claimed limit of quantitation of 0.40 U/ml was verified, and linearity across the analytical measuring range was observed, except at the low end (<20 U/ml). Lastly, antibody response showed high interindividual variation in level and time of peak antibody titer and trends over time.

Anti-SARS-CoV-2 IgM improves clinical sensitivity early in disease course.

INTRODUCTION: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is diagnosed by molecular-based detection of SARS-CoV-2 RNA. Serologic testing detects antibodies specific to SARS-CoV-2 and IgM specifically may serve as an adjunct test to PCR early in disease. We evaluated the Abbott anti-SARS-CoV-2 IgM and IgG assays along with DiaSorin anti-SARS-CoV-2 IgG and Roche anti-SARS-CoV-2 Total. METHODS: Specimens from 175 PCR-positive patients and 107 control specimens were analyzed using Abbott IgM and IgG, DiaSorin IgG, and Roche Total (IgA, IgG, IgM) assays. Sensitivity, specificity, cross-reactivity, concordance between assays, trends over time, positive predictive value (PPV), and negative predictive value (NPV) were determined. RESULTS: Abbott IgM sensitivity was 63.6% at 0 days post-PCR positivity, 76.5% at 1-5d, 76.3% at 6-14d, 85.2% at 15-30d, and 63.6% at > 30d. All assays exhibited highest sensitivity 15-30d post-PCR positivity (83.3-85.2%). Combining Abbott IgM and IgG improved sensitivity by 22.7% compared to IgG alone when tested 0d post-PCR positivity. All assays had a specificity of 100% and only Abbott IgG exhibited cross-reactivity (anti-dsDNA). Cohen's kappa varied between 0.86 and 0.93. Time to seroconversion from PCR positivity was lowest for Abbott IgM and highest for Abbott IgG. NPV was highest for Abbott IgM < 14 days post-PCR positivity and Abbott IgG ≥ 14 days. CONCLUSION: The Abbott IgM assay exhibited the earliest response and greatest signal in most patients evaluated for serial sampling and had the highest NPV < 14 days post-PCR positivity, suggesting its potential utility as an adjunct test to PCR early in disease course.

COVID-19: from an acute to chronic disease? Potential long-term health consequences.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite pulmonary impairments being the most prevalent, extra-pulmonary manifestations of COVID-19 are abundant. Confirmed COVID-19 cases have now surpassed 57.8 million worldwide as of 22 November 2020. With estimated case fatality rates (number of deaths from COVID-19 divided by number of confirmed COVID-19 cases) varying between 1 and 7%, there will be a large population of recovered COVID-19 patients that may acquire a multitude of long-term health consequences. While the multi-organ manifestations of COVID-19 are now well-documented, the potential long-term implications of these manifestations remain to be uncovered. In this review, we turn to previous similar coronaviruses (i.e. SARS-CoV-1 and Middle East respiratory syndrome coronavirus [MERS-CoV]) in combination with known health implications of SARS-CoV-2 infection to predict potential long-term effects of COVID-19, including pulmonary, cardiovascular, hematologic, renal, central nervous system, gastrointestinal, and psychosocial manifestations, in addition to the well-known post-intensive care syndrome. It is necessary to monitor COVID-19 patients after discharge to understand the breadth and severity of long-term effects. This can be accomplished by repurposing or initiating large cohort studies to not only focus on the long-term consequences of SARS-CoV-2 infection, but also on acquired immune function as well as ethno-racial group and household income disparities in COVID-19 cases and hospitalizations. The future for COVID-19 survivors remains uncertain, and if this virus circulates among us for years to come, long-term effects may accumulate exponentially.