Alternative Strategies to Provide Actionable Results When a Supply of Urinalysis Strips Is Unavailable.

CONTEXT.­: Urinalysis instrument-specific dip strips offer physicians qualitative results for actionable analytes (protein, glucose, leukocyte esterase, nitrates, hemoglobin, and ketones). OBJECTIVE.­: To explain a strategy implemented to support clinical decision-making by providing urine quantification of protein, glucose, white blood cells (WBCs), and red blood cells because of urine strip shortages. DESIGN.­: During shortages, we implemented an automated algorithm that triggered sending urine samples to the automation line for quantification of protein and glucose and ensured that urine microscopy was performed to obtain WBC and red blood cell counts. The algorithm printed 2 labels so nursing staff would collect 2 specimens. We monitored the turnaround time from the specimen being received in the laboratory to result verification, ensured that the culture reflex order was triggered, and tracked complaints by physicians regarding not having usual urinalysis results. Prior to implementation, correlation between sample types for protein and glucose measurement was found acceptable. RESULTS.­: The algorithm was put in place twice during 2022. The turnaround time of urine microscopic study was identical to that obtained when the urinalysis was done with the strips; however, the quantification of glucose and protein took approximately 30 minutes more. Urine reflex cultures were triggered correctly with the algorithm, as they were derived entirely from a WBC count higher than 10 per high-power field. During the shortage period we had only 1 complaint, by a physician wanting to have results of nitrates. CONCLUSIONS.­: During urine strip shortages, we successfully implemented a diversion algorithm that provided actionable urinalysis analytes in a timely manner with minimal provider complaints.

Comparison of Antibody Class-Specific SARS-CoV-2 Serologies for the Diagnosis of Acute COVID-19.

Accurate diagnosis of acute severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is critical for appropriate management of patients with this disease. We examined the possible complementary role of laboratory-developed class-specific clinical serology in assessing SARS-CoV-2 infection in hospitalized patients. Serological tests for immunoglobulin G (IgG), IgA, and IgM antibodies against the receptor binding domain (RBD) of SARS-CoV-2 were evaluated using samples from real-time reverse transcription-quantitative PCR (qRT-PCR)-confirmed inpatient coronavirus disease 2019 (COVID-19) cases. We analyzed the influence of timing and clinical severity on the diagnostic value of class-specific COVID-19 serology testing. Cross-sectional analysis revealed higher sensitivity and specificity at lower optical density cutoffs for IgA in hospitalized patients than for IgG and IgM serology (IgG area under the curve [AUC] of 0.91 [95% confidence interval {CI}, 0.89 to 0.93] versus IgA AUC of 0.97 [95% CI, 0.96 to 0.98] versus IgM AUC of 0.95 [95% CI, 0.92 to 0.97]). The enhanced performance of IgA serology was apparent in the first 2 weeks after symptom onset and the first week after PCR testing. In patients requiring intubation, all three tests exhibit enhanced sensitivity. Among PCR-negative patients under investigation for SARS-CoV-2 infection, 2 out of 61 showed clear evidence of seroconversion IgG, IgA, and IgM. Suspected false-positive results in the latter population were most frequently observed in IgG and IgM serology tests. Our findings suggest the potential utility of IgA serology in the acute setting and explore the benefits and limitations of class-specific serology as a complementary diagnostic tool to PCR for COVID-19 in the acute setting.

Rapid Generation of Neutralizing Antibody Responses in COVID-19 Patients.

SARS-CoV-2, the virus responsible for COVID-19, is causing a devastating worldwide pandemic, and there is a pressing need to understand the development, specificity, and neutralizing potency of humoral immune responses during acute infection. We report a cross-sectional study of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in a cohort of 44 hospitalized COVID-19 patients. RBD-specific IgG responses are detectable in all patients 6 days after PCR confirmation. Isotype switching to IgG occurs rapidly, primarily to IgG1 and IgG3. Using a clinical SARS-CoV-2 isolate, neutralizing antibody titers are detectable in all patients by 6 days after PCR confirmation and correlate with RBD-specific binding IgG titers. The RBD-specific binding data were further validated in a clinical setting with 231 PCR-confirmed COVID-19 patient samples. These findings have implications for understanding protective immunity against SARS-CoV-2, therapeutic use of immune plasma, and development of much-needed vaccines.

Rapid generation of neutralizing antibody responses in COVID-19 patients.

SARS-CoV-2 is currently causing a devastating pandemic and there is a pressing need to understand the dynamics, specificity, and neutralizing potency of the humoral immune response during acute infection. Herein, we report the dynamics of antibody responses to the receptor-binding domain (RBD) of the spike protein and virus neutralization activity in 44 COVID-19 patients. RBD-specific IgG responses were detectable in all patients 6 days after PCR confirmation. Using a clinical isolate of SARS-CoV-2, neutralizing antibody titers were also detectable in all patients 6 days after PCR confirmation. The magnitude of RBD-specific IgG binding titers correlated strongly with viral neutralization. In a clinical setting, the initial analysis of the dynamics of RBD-specific IgG titers was corroborated in a larger cohort of PCR-confirmed patients (n=231). These findings have important implications for our understanding of protective immunity against SARS-CoV-2, the use of immune plasma as a therapy, and the development of much-needed vaccines.