Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.
In recent years, there has been significant investment from both the private and public sectors in the development of diagnostic technologies to meet the need for human immunodeficiency virus (HIV) and tuberculosis testing in low-resource settings. Future investments should ensure that the most appropriate technologies are adopted in settings where they will have a sustainable impact. Achieving these aims requires the involvement of many stakeholders, as their needs, operational constraints, and priorities are often distinct. Here, we discuss these considerations from different perspectives representing those of various stakeholders involved in the development, introduction, and implementation of diagnostic tests. We also discuss some opportunities to address these considerations.
The effect of an electric field has been measured on the absorption spectrum (Stark effect) of the heterodimer mutant (M)H202L of Rhodobaeter sphaeroides reaction centers, where the primary electron donor consists of one bacteriochlorophyll a and one bacteriopheophytin a. The electronic absorption spectrum of the heterodimer mutant from 820-950 nm is relatively featureless in a poly(vinyl alcohol) film, but it exhibits some structure in a glycerol/water -ass at 77 K. A feature is seen in the Stark effect spectrum of the heterodimer at 77 K centered at 927 and 936 nm in poly(vinyl alcohol) and a glycerol/water glass, respectively. This feature has approximately the same shape and width as the Stark effect for the primary electron donor of the wild type, which consists of a pair of bacteriochlorophyll a molecules. The angle M4 between the transition moment at the frequency of absorption and the difference dipole AIA is 36± + in the wild ty and 32 ± 2 for that feature in the heterodimer. A range of values for IAAI = (13-17)/f Debye units (where f is the local field correction) is obtained for the 936-nm feature in glycerol/water, depending on analysis method. This feature is interpreted as arising from a transition to the lower exciton state of the heterodimer, which is more strongly mixed with a low-lying charge transfer transition than in the wild type.With the recent availability of genes and deletion strains for the photosynthetic bacteria Rhodobacter capsulatus (1, 2) and Rhodobacter sphaeroides (3, 4), amino acid residues in the reaction center (RC) can be manipulated by site-directed mutagenesis to investigate specific aspects of proteinprosthetic group interactions. In R. capsulatus RCs, replacement of the histidine ligand of the M-side bacteriochlorophyll a (BChla) molecule in the special pair primary-electron donor (denoted P) with a noncoordinating side chain leads to loss of the central Mg atom, converting it to a bacteriopheophytin a (BPheoa). This RC, the primary electron donor of which consists of one BChla (DL) and one BPheoa (DM), has been called the heterodimer mutant; the symbol D is used for P in this dimer (2, 5). In contrast to P. in which the lowest singlet electronic absorption band is relatively narrow (full width at half-maximum =500 cm-'), the absorption spectrum of D appears rather featureless and extends from =800-1000 nm. The quantum yield for the initial charge separation step in the heterodimer mutant is =50% of that in wild-type RCs; the remaining 50o of excited RCs decay rapidly to the ground state (5). The mechanism of charge separation in the heterodimer mutant has been suggested (5) to be the following:where HL is the BPheoa electron acceptor. [The notation *D is used to denote the excited state formed upon excitation at 870 nm under conditions ofthe experiments described in refs. 5 and 6. Internal charge transfer (CT) states of D are written as DL+DM-because BPheoa is "-300 meV easier to reduce than BChla (5-7). The hole on D+ may localize on the BChla (DL) half of the ...
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