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BackgroundSince 1920, a decrease in serum cholesterol has been identified as a marker of severe pneumonia. We have assessed the performance of serum apolipoprotein-A1, the main transporter of HDL-cholesterol, to identify the early spread of coronavirus disease 2019 (Covid-19) in the general population and its diagnostic performance for the Covid-19. MethodsWe compared the daily mean serum apolipoprotein-A1 during the first 30 weeks of 2020 in a population that is routinely followed for a risk of liver fibrosis risk in the USA (183,112 sera) and in France (18,316 sera) in relation to a local increase in confirmed cases, and in comparison to the same period in 2019 (respectively 234,881 and 26,056 sera). We prospectively assessed the sensitivity of this marker in an observational study of 136 consecutive hospitalized cases and retrospectively evaluated its specificity in 7,481 controls representing the general population. ResultsThe mean serum apolipoprotein-A1 levels in these populations began decreasing in January 2020, compared to the same 30 weeks in 2019. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases in the following 30 weeks, in both France and USA, including the June and mid-July recovery periods in France. Apolipoprotein-A1 at the 1.25 g/L cutoff had a sensitivity of 90.6% (95%CI84.2-95.1) and a specificity of 96.1% (95.7-96.6%) for the diagnosis of Covid-19. The area under the characteristics curve was 0.978 (0.957-0.988), and outperformed haptoglobin and liver function tests. The adjusted risk ratio for survival without transfer to intensive care unit was 5.61 (95%CI 1.02-31.0;P=0.04). ConclusionApolipoprotein-A1 could be both a sentinel of the pandemic in existing routine surveillance of the general population with no new blood sample, as well as a candidate predictor of suspected Covid-19 in multivariate analysis in cases with a negative virological test. NCT01927133, CER-2020-14. Key Points QuestionDoes serum apolipoprotein-A1 decrease could be a very early biomarker of SARS-CoV-2 pandemic? FindingsDuring the 30 weeks of 2020 we observed in two large cohorts of patients at risk of liver fibrosis a highly significant decrease of serum apolipoprotein-A1, not observed in previous years. This decrease was highly correlated to and in parallel with the daily increase in confirmed Covid-19 cases, including the recovery period. MeaningApolipoprotein-A1 could be used as a sentinel of the pandemic in existing routine surveillance of the general population.
RESUMO
A major dogma in immunology has it that the IgM antibody response precedes secondary memory responses built on the production of IgG, IgA and, occasionaly, IgE. Here, we measured acute humoral responses to SARS-CoV-2, including the frequency of antibody-secreting cells and the presence of specific, neutralizing, antibodies in serum and broncho-alveolar fluid of 145 patients with COVID-19. Surprisingly, early SARS-CoV-2-specific humoral responses were found to be typically dominated by antibodies of the IgA isotype. Peripheral expansion of IgA-plasmablasts with mucosal-homing potential was detected shortly after the onset of symptoms and peaked during the third week of the disease. While the specific antibody response included IgG, IgM and IgA, the latter contributed to a much larger extent to virus neutralization, as compared to IgG. However, specific IgA serum levels notably decrease after one month of evolution. These results represent a challenging observation given the present uncertainty as to which kind of humoral response would optimally protect against re-infection, and whether vaccine regimens should consider boosting a potent, although, at least in blood, fading IgA response. One sentence SummaryWhile early specific antibody response included IgG, IgM and IgA, the latter contributed to a much larger extent to virus neutralization.
