Serological response to SARS-CoV-2 can predict the severity of COVID-19
A recent study published in Virus reported that antibody titers against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may serve as a marker for the severity of coronavirus disease 2019 (COVID-19).
COVID-19 manifests as mild asymptomatic illness up to acute respiratory illness syndrome (ARDS). The disease is often biphasic, with ARDS developing days after mild symptoms due to the release of pro-inflammatory cytokines. Therefore, it has been speculated that the antibody-mediated immune response may contribute to disease severity. Early assessment of COVID-19 severity and prediction of outcomes could help optimize medical care and resources.
About the study
In the present observational study, researchers prospectively assessed immunoglobulin G (IgG) response in a cohort of patients hospitalized with COVID-19. All hospitalized patients with acute respiratory symptoms or polymerase chain reaction (PCR) confirmed COVID-19 were included. Those who acquired nosocomial infection with SARS-CoV-2 and patients with concomitant disease with COVID-19 were excluded.
Patient classification was based on disease severity: a) no oxygen therapy, b) oxygen through masks or nasal prongs, c) high-flow oxygen or non-invasive ventilation, d) mechanical ventilation, e) mechanical ventilation and organ support, and f) death. Patients were stratified into mild, moderate and severe cases.
Patient clinical, demographic, and laboratory data were obtained from electronic health records (EHRs). Serial serum samples were obtained from patients on days 0, 7 and 14 post-baseline. Two serological tests evaluated anti-SARS-CoV-2 IgG in the samples: a chemiluminescent immunoassay (CLIA) and an internal Luminex test.
The target proteins of anti-SARS-CoV-2 antibodies were the nucleocapsid protein (N) and the monomer S1. CLIA results were reported in arbitrary units (AU)/ml, and Luminex results in median fluorescence intensity (MFI). Fischer’s exact or chi-square tests were performed for categorical variables, and one-way analysis of variance (ANOVA) or Wilcoxon’s matched pairs ranking test for continuous variables.
The researchers recruited 70 patients hospitalized with COVID-19 at the Lausanne University Hospital and classified 19 as mild cases, 29 as moderate cases and 22 as severe cases. Half of the serious cases were directly admitted to the intensive care unit (ICU). Men outnumbered women in the cohort and the median age of the subjects was 60 years. Milder cases presented with dyslipidemia and obesity, while severe cases frequently presented with dyspnoea, cough and radiological infiltrate.
C-reactive protein and D-dimer levels were higher in severe cases. Severe cases had symptoms for a median of 13 days after hospitalization, while moderate and mild cases had symptoms for a median of eight and nine days, respectively. A total of 133 serum samples were tested with Luminex and CLIA assays. On day 0 (D0), 84% and 63% of patients showed positive results on the Luminex and CLIA platforms. On D7, 97% of patients had positive results with one or other of the test methods.
Samples from all patients tested at D14 were positive for anti-SARS-CoV-2 antibodies with Luminex assays, while 97% of samples were positive for CLIA. The estimated cumulative seroconversion rate was 25%, 73% and 98% for the Luminex test, and 14%, 62% and 96% for CLIA at D7, D14 and D28, respectively. The median time from symptom onset to seroconversion was 11 days for the Luminex test and 13 days for the CLIA.
IgG titers differed significantly depending on disease severity. In mild cases, IgG titers remained relatively stable and low. In contrast, in moderate/severe cases, IgG titers measured using CLIA increased for up to 14 days (18 days with Luminex) from symptom onset, and elevated levels were maintained through the following.
The authors plotted a receiver operating characteristic (ROC) curve to assess the performance of serological tests at D0 in predicting the need for invasive ventilation. The ROC area under the curve (AUC) was comparable for two tests (0.78 for Luminex and 0.79 for CLIA). The optimal prediction was observed for CLIA IgG titers of 50 AU/ml on D0 with a sensitivity of 82%, a specificity of 79%, a positive predictive value (PPV) of 63% and a negative predictive value (NPV) of 91%.
However, the Luminex test was also able to predict the need for invasive ventilation. Of the 28 patients with titers greater than 50.8 AU/ml on D0, eight were already intubated or required immediate intubation, 10 patients required late ventilation during their hospital stay and the others did not require ventilation.
The research team observed that most patients had positive IgG titers on admission and found two distinct patterns of IgG titers over time. Moderate and severe cases had high and sustained serological responses, while titers were low in mild cases. Notably, severe cases had significantly higher IgG titers on admission than moderate/mild cases.
The optimal performance to predict the need for mechanical ventilation was obtained with the CLIA tests with a PPV of 63% and a NPV of 91% for the threshold > 50.8 AU/ml. In addition, one-third of patients with titers above the threshold already had severe disease on admission and were immediately transferred to the ICU and invasively ventilated. These results suggest that determining IgG titers at admission could help identify patients at risk for serious complications.