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Background Guidelines from the CDC and the IDSA suggest the use of serologic testing to support the diagnosis of COVID-19 in individuals with high clinical suspicion that repeatedly test negative by diagnostic methods. Given that variability in specimen type, collection technique, and time from symptoms all reduce the sensitivity of molecular methods for SARS-CoV-2. The routine use of serology to diagnose and manage patients with symptoms concerning COVID-19 is tempting, despite limited studies in the literature supporting this approach. Here, we assessed the utility of serology testing for diagnosing SARs-CoV-2 in symptomatic, PCR-negative patients. Methods Remnant EDTA plasma specimens were obtained from 393 patients with clinical suspicion for COVID-19 and a negative SARs-COV-2 RNA test by the nasopharyngeal swab. The specimens were analyzed for SARs-CoV-2 IgG on an Abbott Architect i2000 (Abbott diagnostic). Patient information and symptoms adjudication were obtained from patient electronic health records. Results 14 of 393 patients were positive for antibodies to SARS-CoV-2 (seropositivity rate of 3.6%), 6 of which were from patients with previous RT-PCR-confirmed COVID-19 infection. Among patients without previously diagnosed COVID-19, the seropositivity rate in symptomatic patients was 1.2% (2/171), in patients with altered mental status was 4.3% (2/46), and in asymptomatic patients with no known previous COVID-19 diagnoses was 2.6% (4/170). The seropositivity rate among symptomatic patients presenting ≥ 14 days after symptom onset was 0% (0/67), 7-13 days was 5% (1/20), and for patients < 7 days, was 2.1% (1/47). Among the 4 patients with AMS that were serologically positive, 2 were previously diagnosed by PCR. Conclusion There is a low diagnostic utility of SARS-COV-2 serological testing for identifying novel cases of acute SARS-CoV-2 infections in the ED after a negative PCR test.

Background COVID-19 associated hyperviscosity is a potential driver for the increased rates of thrombotic complications and multi-organ failure associated with severe COVID-19. Limited experience suggests a promising role for Therapeutic Plasma Exchange (TPE) in COVID-19 management based on the hypothesis that clinical benefit is derived from reduction in plasma viscosity. However, systematic study evaluating the safety and efficacy of TPE in these patients has not been done. Objective To evaluate the safety and efficacy of TPE in a subset of critically ill patients with COVID-19 and elevated blood viscosity in a randomized controlled trial (RCT). Study Design and Methods This study was conducted in the intensive care units (ICUs) of 3 hospitals in our health system, with a limited initial enrollment target of 20 patients. Participants included adult COVID-19 patients with moderate elevation in plasma viscosity (2.3-3.5 centipoise) or significant hyperfibrinogenemia (>800 mg/dL) that were not improving despite standard supportive care. Patients with bacterial or fungal coinfection or moribund patients were specifically excluded. Upon enrollment, patients were randomized 1:1 to the treatment group (1 plasma volume TPE with frozen plasma (FP) replacement on 2 consecutive days) or control group (continued standard of care (SOC)). Primary measures included the safety/tolerability of TPE and change in plasma viscosity levels after TPE versus SOC. Secondary measures included evaluation of various clinical and laboratory parameters, including fibrinogen and other coagulation-related markers, mortality, bleeding and thromboembolic complications, ICU length of stay and time to discharge after enrollment. Results Preliminary analysis of collected data demonstrates that TPE is safe and well-tolerated in these patients, with adverse events limited to one mild occurrence of tachycardia that improved upon decreasing the flow rate. There was significant decrease in plasma viscosity in the TPE treatment group, compared to the SOC control group. Secondary measures of select laboratory parameters also show a significant decrease in fibrinogen, von Willebrand factor (vWF), Factor VIII, and erythrocyte sedimentation rate in the TPE treatment group. No significant differences were seen in levels of fibrin monomer, total IgG, total IgM, total protein, or total albumin between the two groups. Data collection and analysis for clinical parameters are ongoing. Conclusions and Relevance Here we report preliminary results suggesting that TPE is safe and effective for normalizing plasma viscosity in critically ill COVID-19 patients. Concomitant removal of large plasma proteins (fibrinogen, vWF) hints at their role in driving the increased viscosity associated with severe disease, which may contribute to clotting and end-organ damage in COVID-19. Based on lack of change in total IgG/IgM levels, TPE is not anticipated to hinder the patient’s humoral immunity by removing existing anti-SARS-CoV-2 specific antibodies. These results warrant further studies on the utility of TPE to mitigate critical illness in COVID-19 patients.

Systemic inflammation and coagulopathy are characteristic hallmarks of COVID19. “COVID coagulopathy” manifests mainly as a prothrombotic state affecting both large and small blood vessels, and presenting as arterial, venous, and microangiopathic thrombotic events with von Willebrand factor (VWF) and soluble thrombomodulin increased in hospitalized patients. The causes of coagulopathy are poorly understood. Aim: To investigate the relationship between von Willebrand factor (VWF) biomarkers, intravascular hemolysis, coagulation, and organ damage in COVID19 patients and to study their association with disease severity and mortality. Methods: 181 hospitalized adult COVID19 patients were randomly selected with a balanced distribution of survivors and non-survivors during the period of March 26th 2020 to May 5th 2020. The medical records and laboratory values were reviewed. Statistical analysis was performed using R studio V.3.6.2. Results: Patients who died (n=90) had significantly lower ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity, elevated lactate dehydrogenase levels, increased schistocyte/RBC fragment counts, and elevated VWF antigen and activity levels compared to patients discharged alive (n=91). In 31 patients, we measured several of these biomarkers on two or more occasions. The trending of ADAMTS13 activity illustrated that it is not steady throughout the hospitalization course. ADAMTS13 activity levels tended to improve and/or reach normal levels in patients that survived, yet ADAMTS13 activity levels worsened in most patients that died. Likewise, the VWF antigen and activity levels tended to decrease in patients that survived whereas tended to increase well above the normal range (2-3 folds) in patients that died. D-Dimer levels trended downwards in survivors, sometimes to levels less than 1 µg/ml, yet tended to increase in patients who died. Given the relationship between ADAMTS13 activity and mortality, we wanted to determine a cut-point of initial ADAMTS13 activity (within 72 hours from admission) to predict mortality. 102 patients in our cohort had an ADAMTS13 activity measurement within this timeframe. We determined that this optimal cut-point of initial ADAMTS13 activity was 43% using Youden’s J statistic. Only 30% of patients who had an ADAMTS13 activity level of less than 43% on admission survived, yet 60% of patients survived who had an ADAMTS13 activity level of greater than 43% on admission. Conclusions: COVID-19 may present with low ADAMTS13 activity in a subset of hospitalized patients. Presence of schistocytes/RBC fragment and elevated D-dimer levels on admission may warrant a work-up for ADAMTS13 activity and VWF antigen and activity levels. These findings indicate the need for future investigation to study the relationship between endothelial and coagulation activation and the efficacy of treatments aimed at prevention and/or amelioration of microangiopathy in COVID-19.

During the SARS-CoV-2 pandemic, community-based testing sites have provided free COVID testing to millions of people who would have otherwise faced substantial barriers. In one metropolitan area, over 700,000 tests were performed from September 2020 through February 2021. To make appointments online, people not only provided basic demographic information such as age, gender, and address but also free-text reasons for seeking testing. We sought to examine how reason for testing, coded as free text, in combination with other collected demographic information, correlated with rates of SARS-CoV-2 positivity and measures of infectiousness such as the Real-Time Polymerase Chain Reaction (RT-PCR) Cycle Threshold (Ct) value. Data from the scheduling software used to coordinate the on site testing workflow was extracted and linked to SARS-CoV-2 PCR assay metadata stored in a laboratory data warehouse, including Ct values. We categorized individual text responses into 3 separate categories: symptomatic, exposed but asymptomatic, and asymptomatic without exposure. Symptomatic individuals were identified based on the presence of common keywords and phrases like “symptom”, “fever”, “cough”, and “sore throat.” Similarly, exposed individuals were identified by keywords such as “exposed”, “exposure”, and “roommate.” All others were categorized as asymptomatic. We found that symptomatic individuals had the highest frequency of testing positive at 11.6% (21,150/181,868). Exposed individuals and asymptomatic individuals had lower rates of detection with frequencies of 7.4% (10,266/138,721) and 4.9% (8,987/185,026) respectively. Repeat testing represented 29.9% of the results and positivity rates were calculated using the first result for each individual. In addition, among those who tested positive, symptomatic individuals exhibited the lowest average Ct values, while those who are asymptomatic exhibit the highest average Ct values. Among those who self-reported duration of symptoms, recent onset of symptoms was strongly correlated with lower Ct values. Across more than 700,000 results, self-reported symptomatic people, based on free text responses, have a higher likelihood of testing positive for SARS-CoV-2. People who claim a more recent onset of symptoms are more likely to exhibit higher concentrations of viral RNA.

Background and aimsSerologic assays for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies are being developed and approved rapidly with limited external validation. Accurate diagnostics are an essential component to pandemic management and public health.Materials and methodsResidual serum samples (N=113) from patients who were evaluated for SARS-CoV-2 infection status by polymerase chain reaction (PCR) were retrospectively tested in parallel across three automated SARS-CoV-2 serologic assays: Liaison SARS-CoV-2 S1/S2 IgG, Elecsys anti-SARS-CoV-2 total antibody, and Access SARS-CoV-2 IgG.ResultsTesting of 51 PCR-positive and 62 PCR-negative patients demonstrated qualitative inter-test agreement of 96% overall, 100% in PCR-negative patients, 88% in early positive samples (0-13 days post positive PCR), and 100% in convalescent samples (14+ days post positive PCR).Calculated kappa values for paired inter-test agreement ranged 0.93-0.96. Compared to PCR, overall percent positive agreement ranged from 82-86% (100% for convalescent samples) and percent negative agreement was 100% for each assay.ConclusionThis study demonstrates high diagnostic accuracy and inter-test agreement for three automated SARS-CoV-2 serologic assays. External validation of serologic assays is critical to ensure diagnostic accuracy and appropriate utilization of critical resources.