A study to assess the impact of cobas Liat point-of-care PCR assays (SARS-CoV-2 and Influenza A/B) on patient clinical management in the emergency department of the University of California at Davis Medical Center (preprint)

Background Rapid detection of SARS-CoV-2 is crucial for reduction of transmission and clinical decision-making. The cobas(R) SARS-CoV-2 & Influenza A/B nucleic acid test for use on the cobas Liat(R) System is a rapid (20 minutes) point-of-care (POC) polymerase chain reaction (PCR) method. Methods This unblinded, pre-post study enrolled consecutive patients with symptoms/signs consistent with SARS-CoV-2 infection presenting to the University of California, Davis emergency department (ED). Outcomes following implementation of the cobas Liat SARS-CoV-2 & Influenza A/B test (intervention period: December 2020 to May 2021) were compared with previous standard-of-care using centralized laboratory PCR methods (control period: April 2020 to October 2020). Results Electronic health records of 8879 symptomatic patients were analyzed, comprising 4339 and 4540 patient visits and 538 and 638 positive SARS-CoV-2 PCR test results in the control and intervention periods, respectively. Compared with the control period, turnaround time (TAT) was shorter in the intervention period (median 0.98 vs 12.3 hours; p<0.0001). ED length of stay (LOS) was generally longer in the intervention period compared with the control period, but for those SARS-CoV-2-negative who were admitted, ED LOS was shorter (median 12.53 vs 17.93 hours; p<0.0001). Overall, the rate of anti-infective prescribing was also lower in the intervention period than in the control period (antibiotics only: 38.11% vs 44.55%; p<0.0001 and antivirals only: 3.13% vs 0.94%; p<0.0001). Conclusion This real-world study confirms faster TAT with a POC PCR method in an emergency care setting and highlights the importance of rapid SARS-CoV-2 detection to aid patient management and inform treatment decisions.

COMPARATIVE PERFORMANCE OF TWO AUTOMATED MACHINE LEARNING PLATFORMS FOR COVID-19 DETECTION BY MALDI-TOF-MS (preprint)

The 2019 novel coronavirus infectious disease (COVID-19) pandemic has resulted in an unsustainable need for diagnostic tests. Currently, molecular tests are the accepted standard for the detection of SARS-CoV-2. Mass spectrometry (MS) enhanced by machine learning (ML) has recently been postulated to serve as a rapid, high-throughput, and low-cost alternative to molecular methods. Automated ML is a novel approach that could move mass spectrometry techniques beyond the confines of traditional laboratory settings. However, it remains unknown how different automated ML platforms perform for COVID-19 MS analysis. To this end, the goal of our study is to compare algorithms produced by two commercial automated ML platforms (Platforms A and B). Our study consisted of MS data derived from 361 subjects with molecular confirmation of COVID-19 status including SARS-CoV-2 variants. The top optimized ML model with respect to positive percent agreement (PPA) within Platforms A and B exhibited an accuracy of 94.9%, PPA of 100%, negative percent agreement (NPA) of 93%, and an accuracy of 91.8%, PPA of 100%, and NPA of 89%, respectively. These results illustrate the MS methods robustness against SARS-CoV-2 variants and highlight similarities and differences in automated ML platforms in producing optimal predictive algorithms for a given dataset.

Nasopharyngeal SARS-CoV2 viral loads in young children do not differ significantly from those in older children and adults (preprint)

The role of children in the spread of the SARS-CoV2 coronavirus has become a matter of urgent debate as societies in the US and abroad consider how to safely reopen schools. Small studies have suggested higher viral loads in young children. Here we present a multicenter investigation on over five thousand SARS-CoV-2 cases confirmed by real-time reverse transcription (RT) PCR assay. Notably, we found no discernable difference in amount of viral nucleic acid among young children and adults.

SARS-CoV-2 infection induces germinal center responses with robust stimulation of CD4 T follicular helper cells in rhesus macaques (preprint)

CD4 T follicular helper (Tfh) cells are important for the generation of long-lasting and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. Here we report that, following infection with SARS-CoV-2, adult rhesus macaques exhibited transient accumulation of activated, proliferating Tfh cells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a Th1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center Tfh cells specific for the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and a corresponding early appearance of antiviral serum IgG antibodies but delayed or absent IgA antibodies. Our data suggest that a vaccine promoting Th1-type Tfh responses that target the S protein may lead to protective immunity.