Background: The COVID-19 pandemic caused >1 million infections during January-March 2020. There is an urgent need for reliable antibody detection approaches to support diagnosis, vaccine development, safe release of individuals from quarantine, and population lock-down exit strategies. We set out to evaluate the performance of ELISA and lateral flow immunoassay (LFIA) devices. Methods: We tested plasma for COVID (severe acute respiratory syndrome coronavirus 2; SARS-CoV-2) IgM and IgG antibodies by ELISA and using nine different LFIA devices. We used a panel of plasma samples from individuals who have had confirmed COVID infection based on a PCR result (n=40), and pre-pandemic negative control samples banked in the UK prior to December-2019 (n=142). Results: ELISA detected IgM or IgG in 34/40 individuals with a confirmed history of COVID infection (sensitivity 85%, 95%CI 70-94%), vs. 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 COVID-positive individuals tested ≥10 days after symptom onset (sensitivity 100%, 95%CI 89-100%). IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions: Currently available commercial LFIA devices do not perform sufficiently well for individual patient applications. However, ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following first symptoms.

1. The role of the microgeometry of planar surfaces in the detection of sliding of the surfaces on human and monkey fingerpads was investigated. By the use of a servo-controlled tactile stimulator to press and stroke glass plates on passive fingerpads of human subjects, the ability of humans to discriminate the direction of skin stretch caused by friction and to detect the sliding motion (slip) of the plates with or without micrometer-sized surface features was determined. To identify the associated peripheral neural codes, evoked responses to the same stimuli were recorded from single, low-threshold mechanoreceptive afferent fibers innervating the fingerpads of anesthetized macaque monkeys. 2. Humans could not detect the slip of a smooth glass plate on the fingerpad. However, the direction of skin stretch was perceived based on the information conveyed by the slowly adapting afferents that respond differentially to the stretch directions. Whereas the direction of skin stretch signaled the direction of impending slip, the perception of relative motion between the plate and the finger required the existence of detectable surface features. 3. Barely detectable micrometer-sized protrusions on smooth surfaces led to the detection of slip of these surfaces, because of the exclusive activation of rapidly adapting fibers of either the Meissner (RA) or the Pacinian (PC) type to specific geometries of the microfeatures. The motion of a smooth plate with a very small single raised dot (4 microns high, 550 microns diam) caused the sequential activation of neighboring RAs along the dot path, thus providing a reliable spatiotemporal code. The stroking of the plate with a fine homogeneous texture composed of a matrix of dots (1 microns high, 50 microns diam, and spaced at 100 microns center-to-center) induced vibrations in the fingerpad that activated only the PCs and resulted in an intensive code. 4. The results show that surprisingly small features on smooth surfaces are detected by humans and lead to the detection of slip of these surfaces, with the geometry of the microfeatures governing the associated neural codes. When the surface features are of sizes greater than the response thresholds of all the receptors, redundant spatiotemporal and intensive information is available for the detection of slip.

Background:The SARS-CoV-2 pandemic caused >1 million infections during January-March 2020. There is an urgent need for robust antibody detection approaches to support diagnostics, vaccine development, safe individual release from quarantine and population lock-down exit strategies. The early promise of lateral flow immunoassay (LFIA) devices has been questioned following concerns about sensitivity and specificity. Methods:We used a panel of plasma samples designated SARS-CoV-2 positive (from SARS-CoV-2 RT-PCR-positive individuals; n=40) and negative (samples banked in the UK prior to December-2019 (n=142)). We tested plasma for SARS-Cov-2 IgM and IgG antibodies by ELISA and using nine different commercially available LFIA devices. Results: ELISA detected SARS-CoV-2 IgM or IgG in 34/40 individuals with an RT-PCR-confirmed diagnosis of SARS-CoV-2 infection (sensitivity 85%, 95%CI 70-94%), vs 0/50 pre-pandemic controls (specificity 100% [95%CI 93-100%]). IgG levels were detected in 31/31 RT-PCRpositive individuals tested ≥10 days after symptom onset (sensitivity 100%, 95%CI 89-100%).IgG titres rose during the 3 weeks post symptom onset and began to fall by 8 weeks, but remained above the detection threshold. Point estimates for the sensitivity of LFIA devices ranged from 55-70% versus RT-PCR and 65-85% versus ELISA, with specificity 95-100% and 93-100% respectively. Within the limits of the study size, the performance of most LFIA devices was similar. Conclusions:The performance of current LFIA devices is inadequate for most individual patient applications. ELISA can be calibrated to be specific for detecting and quantifying SARS-CoV-2 IgM and IgG and is highly sensitive for IgG from 10 days following symptoms onset.

The magnitude and duration of itch sensation produced by intracutaneous injection of histamine were determined for humans with the procedure of magnitude estimation scaling. Thirteen subjects received a 10-microliter intracutaneous injection of histamine at doses of 0.0001, 0.001, 0.01, 0.1, 1, and 10 micrograms into the volar forearm; eight of these subjects also received a 100-microgram dose. One subject received multiple injections over several weeks to determine the reliability of the magnitude estimates of itch. Following each injection, the area of flare and duration of itch were also determined. Intracutaneous injection of histamine produced a pure sensation of itch, without pain. The magnitude of itch increased in a dose-dependent fashion. The lowest histamine dose that produced itch greater than the itch produced by vehicle was 0.01 micrograms. The greatest itch was produced by the 100-microgram dose. A power function fitted to the mean magnitude estimates had an exponent of 0.17, indicating a negatively accelerating relation between the magnitude of itch and histamine dose. The one subject who received histamine over several weeks gave fairly reproducible estimates of itch magnitude. The duration of itch and the area of flare also increased in a dose-dependent fashion. The lowest dose of histamine that produced a duration of itch longer than the itch produced by the vehicle was 0.1 microgram, while the 100-microgram dose produced the longest duration of itch. Although the area of flare increased with each increase in dose from 0.1 to 10 micrograms, the areas of flare produced by 10 and 100 micrograms of histamine did not differ. These results indicate that humans can scale the magnitude of itch produced by histamine in a dose-dependent manner. In addition, the duration of itch and the area of flare produced by histamine are dose-dependent, confirming results of previous investigators. Intracutaneous histamine is easily quantifiable and may thus be a useful stimulus in neurophysiological studies of the peripheral neural mechanisms of itch.

The capacities of humans to detect the presence of a single raised dot of 550 micron diameter on a smooth plate and to judge the magnitude of evoked sensation were determined for dots of different heights, stroked at different velocities across the passive fingerpad. Evoked responses to the same stimuli were recorded from single, slowly adapting (SA), rapidly adapting (RA), and Pacinian (PC) mechanoreceptive peripheral nerve fibers innervating the fingerpad of anesthetized macaque monkeys. When the stroke velocity was 10 mm/s, dot height detection thresholds, as determined from measurements of detection sensitivity were between 1 and 3 microns for all human observers. From fiber recordings in monkeys, the RAs had dot height thresholds of 2-4 microns, i.e., within the range of human detection thresholds. The dot height thresholds were 8 microns or greater for SAs and 21 micron or greater for PCs. In contrast, force thresholds for punctate von Frey filaments did not differ for RAs and SAs and were lowest for PCs. The magnitude of sensation evoked in human increased with increases in dot height above threshold. Similarly, the number of nerve impulses evoked in monkey RAs increased with dot height as did the widths of RA receptive fields. Neither changes in stroke velocity from 10 to 40 mm/s nor changes in vertical force applied by the dot plate to the skin altered sensory magnitude evoked by a 15-microns high dot or the number of impulses evoked in RAs. However, a decrease in stroke velocity from 10 to 1.5 mm/s elevated sensory detection thresholds and, for the 15-microns high dot, decreased sensory magnitude, the number of impulses in RAs, and the widths of RA receptive fields. It was hypothesized that the mechanical event responsible for activating the RA was the lateral deformation of elevated regions of skin. In support of this, the number of impulses evoked in RAs by a dot was greater when the dot was stroked across, as opposed to along, the papillary ridges. Also, under certain stimulus conditions, a correspondence was observed between the occurrence of each action potential in an RA and the passage of the leading edge of the dot across the peak of a papillary ridge. It is concluded that the responses of RAs alone account for the sensory capacity to detect a dot of minimal height on a smooth surface with the fingerpad.(ABSTRACT TRUNCATED AT 400 WORDS)