+++ Diagnosis +++
* * * Next update: 24 November. In the meantime, find the global updates at 7 Days. * * *
Gniffke EP, Harrington WE, Dambrauskas N, et al. Plasma From Recovered COVID-19 Patients Inhibits Spike Protein Binding to ACE2 in a Microsphere-Based Inhibition Assay. J Infect Dis. 2020 Nov 13;222(12):1965-1973. PubMed: https://pubmed.gov/32798222 . Full-text: https://doi.org/10.1093/infdis/jiaa508
A new microsphere-based flow cytometry assay that quantifies the ability of plasma to inhibit the binding of spike protein to ACE2. Plasma from 22 patients who had recovered from mild COVID-19 and expressed anti–spike protein trimer immunoglobulin G (IgG) inhibited ACE2–spike protein binding to a greater degree than controls. The degree of inhibition was correlated with anti–spike protein IgG levels, neutralizing titers in a pseudotyped lentiviral assay, and the presence of fever during illness. This inhibition assay may be broadly useful to quantify the functional antibody response of patients recovered from COVID-19 or vaccine recipients in a cell-free assay system.
Escribano P, Álvarez-Uría A, Alonso R, et al. Detection of SARS-CoV-2 antibodies is insufficient for the diagnosis of active or cured COVID-19. Sci Rep 10, 19893 2020. Full-text: https://doi.org/10.1038/s41598-020-76914-5
Using Abbott´s SARS-CoV-2 IgG assay and the PanbioTM COVID-19 IgG/IgM device, the authors found that serum IgG detection alone is insufficient for the diagnosis of active or cured COVID-19, with sensitivity values that range between 60 and 75%, respectively. Detection of IgM adds limited value to the performance of serological strategies.
Wang H, Hogan CA, Miller JA, et al. Performance of nucleic acid amplification tests for detection of severe acute respiratory syndrome coronavirus 2 in prospectively pooled specimens. Emerg Infect Dis. 2012 Jan. Full-text: https://doi.org/10.3201/eid2701.203379
Pooled nucleic acid amplification tests (NATs) could increase availability of testing at a decreased cost. However, it is not that trivial, and the effect of dilution on analytical sensitivity through sample pooling has not been well characterized. Hannah Wang and colleagues from Stanford tested 1648 prospectively pooled specimens by using 3 different NATs. Positive percent agreement (PPA) of pooled versus individual testing ranged from 71,7% to 82,6% for pools of 8 and from 82,9% to 100,0% for pools of 4. PPA was dependent on the proportion of tests with positive results, cycle threshold distribution, and assay limit of detection. False negative results occurred exclusively in pools containing samples with low estimated viral load (Ct > 34).
Manabe YC, Sharfstein JS, Armstrong K. The Need for More and Better Testing for COVID-19. JAMA November 13, 2020. Full-text: https://doi.org/10.1001/jama.2020.21694
In their viewpoint, Yukari C. Manabe, Joshua S. Sharfstein and Katrina Armstrong argue that it is more accurate to consider testing less of a prevention strategy than a mitigation strategy. Testing in the absence of other proven prevention strategies is unable to prevent outbreaks. Even as tests become faster with higher sensitivity and specificity, social distancing, mask wearing, and avoidance of large indoor and outdoor gatherings must remain central to any public health strategy. Even the perfect test cannot go it alone.
Liotti FM, Menchinelli G, Marchetti S, et al. Assessment of SARS-CoV-2 RNA Test Results Among Patients Who Recovered From COVID-19 With Prior Negative Results. JAMA Intern Med, November 12, 2020. Full-text: https://doi.org/10.1001/jamainternmed.2020.7570
Many patients who recovered from COVID-19 may still be positive (albeit at lower levels) for SARS-CoV-2 RNA, but only a minority of the patients may carry replicating SARS-CoV-2 in the respiratory tract. Flora Marzia Liotti and colleagues from Rome, Italy analyzed nasal/oropharyngeal swab samples of 176 recovered patients with no fever and with 2 negative RT-PCR results for SARS-CoV-2 RNA 24 hours apart. In total, 32 of 176 samples (18%) tested positive for total SARS-CoV-2 RNA. All had low viral loads and only one of the 32 samples (3.1%) had replicative SARS-CoV-2 RNA.
Zilla M, Wheeler BJ, Keetch C, et al. Variable Performance in 6 Commercial SARS-CoV-2 Antibody Assays May Affect Convalescent Plasma and Seroprevalence Screening. American Journal of Clinical Pathology, aqaa228. Full-text: https://doi.org/10.1093/ajcp/aqaa228
Megan Zilla and colleagues from Pittsburgh have compared six SARS-CoV-2 antibody assays, namely Beckman Coulter, Euroimmun (IgG, IgA), Roche, and Siemens (Centaur, Vista). Assays were assessed for specificity (n=184), sensitivity (n=154), and seroconversion in a defined cohort with clinical correlates and molecular SARS-CoV-2 results. Assay specificity was 99% or greater for all assays except the Euroimmun IgA (95%). Sensitivity at more than 21 days from symptom onset were 84%, 95%, 72%, 98%, 67%, and 96% for Beckman Coulter, Centaur, Vista, Roche, Euroimmun IgA, and Euroimmun IgG, respectively. These finding raises concerns that seroprevalence studies may vary significantly based on the serologic assay utilized, even when the assays are from reliable manufacturers with proven methodologies and have similar targets and initial specificity and sensitivity measures.
Chan CW, Shahul S, Coleman C, et al. Evaluation of the Truvian Easy Check COVID-19 IgM/IgG Lateral Flow Device for Rapid Anti-SARS-CoV-2 Antibody Detection. American Journal of Clinical Pathology, 02 November 2020, aqaa22. Full-text: https://doi.org/10.1093/ajcp/aqaa221
Clarence W. Chan and colleagues from Chicago evaluated the analytical and clinical performance of the Truvian Easy Check COVID-19 IgM/IgG antibody test. This test was designed to detect the nucleocapsid and S1 spike protein RBD epitopes of SARS-CoV-2. Results are available at 10 minutes after test initiation for serum and possibly fingerstick blood samples. The Easy Check device showed excellent clinical and analytical performance; the test compares well with the Roche Elecsys anti-SARS-CoV-2 antibody assay. Of 99 patient samples that were positively confirmed by PCR for SARS-CoV-2, antibodies against the virus were detected by both tests in 88 of the samples, whereas 9 of the 99 samples eluded detection by both testing modalities. All samples from 41 prepandemic volunteers remained negative.
Ward H, Cooke G, Atchison C, et al. Declining prevalence of antibody positivity to SARS-CoV-2: a community study of 365 000 adults. [Preprint] 2020. Full-text: https://www.imperial.ac.uk/media/imperial-college/institute-of-global-health-innovation/MEDRXIV-2020-219725v1-Elliott.pdfdoi:10.1101/2020.10.26.20219725.
Not yet peer reviewed, but important data. Results from the large, nation-wide REACT (real time assessment of community transmission) antibody study which was led by Imperial College London, show that the national antibody prevalence in the UK was 6% around 12 weeks after the epidemic’s April peak. Since then, the rates had fallen to 4.4% 24 weeks after the peak. These data suggest that antibodies induced by natural infection may be short lived, as is the case for other seasonal coronaviruses.
Henss L, Scholz T, von Rhein C, et al. Analysis of humoral immune responses in SARS-CoV-2 infected patients. J Infect Dis. 2020 Oct 31:jiaa680. PubMed: https://pubmed.gov/33128369 . Full-text: https://doi.org/10.1093/infdis/jiaa680
Do previous coronavirus infections protect from severe courses? Lisa Henss and colleagues from Frankfurt University analyzed the humoral immune response of a cohort of 143 COVID-19 patients, using ELISA and neutralization assays. Disease severity correlated with the amount of SARS-CoV-2 specific IgG and IgA and the neutralization activity of the antibodies. Neutralizing titers of patients with mild disease were very low and higher titers were only detected in severe cases. Of note, compared to patients with mild-moderate disease, patients with severe disease had only weakly neutralizing antibodies against coronavirus-NL63. Although the numbers of severe cases were low, it remains tempting to speculate that preexisting immunity to NL63 or other common cold coronaviruses might reduce the risk of severe disease.
Fontana IC, Bongarzone S, Gee A. PET Imaging as a Tool for Assessing COVID-19 Brain Changes. Trends Neurosc October 29, 2020. Full-text: https://doi.org/10.1016/j.tins.2020.10.010
A brief overview of positron emission tomography (PET) applications that could advance current understanding of CNS pathophysiological alterations associated with SARS-CoV-2 infection. Apart from testing for brain changes during the acute phase of the disease, longitudinal assessment of COVID-19 patients using PET may be conducted to examine whether brain changes are transient or long-lasting.