We determined and compared the humoral immune response in patients with severe (hospitalized) and mild (nonhospitalized) coronavirus disease 2019 (COVID-19). Patients with severe disease (n = 38) develop a robust antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including immunoglobulin G and immunoglobulin A antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infection was found in hospital personnel (n = 24), who developed mild symptoms necessitating leave of absence and self-isolation, but not hospitalization; 75% developed antibodies, but with low/absent virus neutralization (60% with titers <1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long-term monitoring will show whether these responses predict protection against future infections.

Background: The coronavirus disease (COVID-19) situation demands a lot from citizens, health care providers, and governmental institutions. Citizens need to cope with guidelines on social interaction, work, home isolation, and symptom recognition. Additionally, health care providers and policy makers have to cope with unprecedented and unpredictable pressure on the health care system they need to manage. By providing citizens with an app, they always have access to the latest information and can assess their own health. This data could be used to support policy makers and health care providers to get valuable insights in the regional distribution of infection load and health care consumption. Objective: The aim of this observational study is to assess people’s use of an app to support them with COVID-19 education, self-assessment, and monitoring of their own health for a 7-day period. In addition, we aim to assess the usability of this data for health care providers and policy makers by applying it to an interactive map and combining it with hospital data. The secondary outcomes of the study were user’s satisfaction with the information provided in the app, perceived usefulness of the app, health care providers they contacted, and the follow-up actions from this contact. Methods: This observational cohort study was carried out at the nonacademic teaching hospital “Elisabeth Twee Steden” (ETZ) in Tilburg, Netherlands. From April 1, 2020, onwards ETZ offered the COVID-19 education, self-assessment, and symptom tracking diary to their already existing app for patient education and monitoring. Results: Between April 1 and April 20, 2020, a total of 6194 people downloaded the app. The self-assessment functionality was used abundantly to check one’s health status. In total, 5104 people responded to the question about severe symptoms, from which 242 indicated to suffer from severe symptoms. A total of 4929 people responded to the question about mild symptoms, from which 3248 indicated to suffer from these. The data was successfully applied to an interactive map, displaying user demographics and health status. Furthermore, the data was linked to clinical data. App users were satisfied with the information in the app and appreciated the symptom diary functionality. In total, 102 users reached out to a health care provider, leading to 91 contacts. Conclusions: Our study demonstrated the successful implementation and use of an app with COVID-19 education, self-assessment, and a 7-day symptom diary. Data collected with the app were successfully applied to an interactive map. In addition, we were able to link the data to COVID-19 screening results from the hospital’s microbiology laboratory. This data could be used to support policy makers and health care providers to get valuable insights in the regional distribution of infection load and health care consumption. Trial Registration: Netherlands Trial Register NL8501; https://www.trialregister.nl/trial/8501

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infections often cause only mild disease that may evoke relatively low Ab titers compared with patients admitted to hospitals. Generally, total Ab bridging assays combine good sensitivity with high specificity. Therefore, we developed sensitive total Ab bridging assays for detection of SARS-CoV-2 Abs to the receptor-binding domain (RBD) and nucleocapsid protein in addition to conventional isotype-specific assays. Ab kinetics was assessed in PCR-confirmed, hospitalized coronavirus disease 2019 (COVID-19) patients (n = 41) and three populations of patients with COVID-19 symptoms not requiring hospital admission: PCR-confirmed convalescent plasmapheresis donors (n = 182), PCR-confirmed hospital care workers (n = 47), and a group of longitudinally sampled symptomatic individuals highly suspect of COVID-19 (n = 14). In nonhospitalized patients, the Ab response to RBD is weaker but follows similar kinetics, as has been observed in hospitalized patients. Across populations, the RBD bridging assay identified most patients correctly as seropositive. In 11/14 of the COVID-19–suspect cases, seroconversion in the RBD bridging assay could be demonstrated before day 12; nucleocapsid protein Abs emerged less consistently. Furthermore, we demonstrated the feasibility of finger-prick sampling for Ab detection against SARS-CoV-2 using these assays. In conclusion, the developed bridging assays reliably detect SARS-CoV-2 Abs in hospitalized and nonhospitalized patients and are therefore well suited to conduct seroprevalence studies. Key Points We developed a sensitive total Ab bridging assay to detect SARS-CoV-2 Abs. The assay reliably detects SARS-CoV-2 Abs also in nonhospitalized patients. Fewer Abs arise but with similar kinetics compared with hospitalized patients.

Serology is a crucial part of the public health response to the ongoing SARS-CoV-2 pandemic, but there are still many unknowns. Here, we describe the development, validation and clinical evaluation of a protein micro-array as a quantitative multiplex immunoassay that can identify S and N-directed SARS-CoV-2 IgG antibodies with high specificity and sensitivity and distinguish them from all currently circulating human coronaviruses. The method specificity was 100% for SARS-CoV-2 S1 and 96 % for N antigen based on extensive syndromic (n=230 cases) and population panel (n=94) testing that also confirmed the high prevalence of seasonal human coronaviruses. To assess the potential role of the protein micro-array for both SARS-CoV-2 patient diagnostics and population studies, we evaluated a large heterogeneous COVID-19 cohort (n=330) and found an overall sensitivity of 89% (≥ 21 days post onset symptoms (dps)), which ranged from 86% to 96% depending on severity of disease. For a subset of these patients longitudinal samples were provided up to 56 dps. We observed an absent or delayed, and lower SARS-CoV-2 antibody responses in mild cases. Overall, we present the development and extensive clinical validation of a multiplex human coronavirus serological assay that can be used for syndromic testing, to answer research questions regarding human coronavirus antibody responses, to support SARS-CoV-2 diagnostics where RT-PCR lacks in sensitivity and to evaluate epidemiological developments efficiently and with high-throughput.