ABSTRACT
Background: Most data on COVID-19 was collected in hospitalized cases. Much less is known about the spectrum of disease in entire populations including nonhospitalized patients and minors. In this study, we examine a representative cohort in an administrative district in Southern Germany who tested positive for SARS-CoV-2 between February and June of 2020. Methods: We contacted all confirmed SARS-CoV-2 cases in an administrative district in southern Germany. Consenting participants answered a retrospective survey either via a telephone, electronically or via mail. Clinical and sociodemographic features were compared between hospitalized and non-hospitalized patients. Additionally, we assessed potential risk factors for hospitalization and time to hospitalization in a series of regression models. As predictors we assessed age as a continuous variable, sex, smoking as a continuous variable using pack years, living with children (age <18), hypertension (yes/no), coronary heart disease (CHD;yes/no), diabetes (type 1 or type 2;yes/no) and lung conditions (yes/no). Lung conditions were defined as a combined variable of either COPD, asthma treated with medications, any other lung disease or previously performed lung surgery. Secondly, we estimated the influence of the same covariates on the time from symptom onset to hospitalization with a Cox proportional hazard ratio (HR) model. Results: We included 897 participants in our study, 69% out of 1,305 total cases in the district with a mean age of 47 years (range 2-97), 51% of which were female and 47% had a pre-existing illness. The percentage of asymptomatic, mild (symptomatic, no hospitalization), moderate (leading to hospital admission) and critical illness (requiring mechanical ventilation) was 54 patients (6%), 713 (79%), 97 (11%) and 16 (2%), respectively. Seventeen patients (2%) died. The most prevalent symptoms were fatigue (65%), cough (62%) and dysgeusia (60%). The risk factors for hospitalization included older age (OR 1.05 per year increase;95% CI 1.04-1.07) preexisting lung conditions (OR 3.09;95% CI 1.62-5.88). Female sex was a protective factor (OR 0.51;95% CI 0.33-0.77). Conclusion: This population-representative analysis of COVID-19 cases confirms age, male sex and preexisting lung conditions but not cardiovascular disease as risk factors for severe illness. Almost 80% of infection take a mild course, whereas 13% of patients suffer moderate to severe illness.
ABSTRACT
The emerging SARS-CoV-2 pandemic entails an urgent need for specific and sensitive high-throughput serological assays to assess SARS-CoV-2 epidemiology. We, therefore, aimed at developing a fluorescent-bead based SARS-CoV-2 multiplex serology assay for detection of antibody responses to the SARS-CoV-2 proteome. Proteins of the SARS-CoV-2 proteome and protein N of SARS-CoV-1 and common cold Coronaviruses (ccCoVs) were recombinantly expressed in E. coli or HEK293 cells. Assay performance was assessed in a COVID-19 case cohort (n = 48 hospitalized patients from Heidelberg) as well as n = 85 age- and sex-matched pre-pandemic controls from the ESTHER study. Assay validation included comparison with home-made immunofluorescence and commercial enzyme-linked immunosorbent (ELISA) assays. A sensitivity of 100% (95% CI: 86-100%) was achieved in COVID-19 patients 14 days post symptom onset with dual sero-positivity to SARS-CoV-2 N and the receptor-binding domain of the spike protein. The specificity obtained with this algorithm was 100% (95% CI: 96-100%). Antibody responses to ccCoVs N were abundantly high and did not correlate with those to SARS-CoV-2 N. Inclusion of additional SARS-CoV-2 proteins as well as separate assessment of immunoglobulin (Ig) classes M, A, and G allowed for explorative analyses regarding disease progression and course of antibody response. This newly developed SARS-CoV-2 multiplex serology assay achieved high sensitivity and specificity to determine SARS-CoV-2 sero-positivity. Its high throughput ability allows epidemiologic SARS-CoV-2 research in large population-based studies. Inclusion of additional pathogens into the panel as well as separate assessment of Ig isotypes will furthermore allow addressing research questions beyond SARS-CoV-2 sero-prevalence.
ABSTRACT
Introduction: The spectrum of coronavirus disease 2019 (COVID-19) ranges from asymptomatic infection to respiratory failure and death of patients. Severely affected patients may develop a cytokine storm-like clinical syndrome with multi-organ failure and a mortality rate of up to 90%. Case Description: Here we report on five COVID-19 patients with a median age of 67 years who were treated at the intensive care unit due to respiratory failure. Prophylactic antibiotic, antimycotic, and antiviral/immunomodulatory therapy was initiated in all patients upon admission. During the course of the disease, patients developed circulatory shock and persistent fever together with increased interleukin 6-levels compatible with the cytokine storm-like clinical syndrome. In addition, all patients had multi-organ failure with acute respiratory-distress syndrome (ARDS, 4 severe, 1 moderate) and acute kidney injury of at least KDIGO stage 2. A single PE with a median of 3.39 L of fresh frozen plasma was initiated in all patients followed by one additional treatment in patients 1, 3, and 5. During the PE, striking reduction of inflammatory markers C-reactive protein (-47%, P=0.0078) and interleukin 6 (-74%, P=0.0078), as well as significant reduction of ferritin (-49%, P=0.0078), LDH (-41%, P=0.0078), and D-Dimer (-47%, P=0.016) were observed. Due to circulatory shock, four patients received vasopressor treatment at the start of the PE that could be substantially reduced during treatment (-71%, P=0.031). Biochemical and clinical improvement continued over the following days together with an increase in the oxygenation index in 4 out of 5 patients. These improvements were achieved with only 1 to 2 PE, which might be a possible indication of a direct pathophysiological influence of PE on the COVID-19-associated cytokine storm-like clinical syndrome. Three of the 5 most critically ill patients are alive, while a 71-year-old male and a 76-year-old female patient died after the therapy was limited due to persistent severe ARDS. Discussion: PE improved inflammation, microcirculatory clot formation, and hypotension, thereby improving clinical outcomes. Further studies to test whether (repeated) PE can alter the course of critically ill COVID-19 patients are clearly indicated.