Plasma-based antigen persistence in the post-acute phase of SARS-CoV-2 infection.

BACKGROUND: Persistent symptoms among some persons who develop COVID-19 has led to the hypothesis that SARS-CoV-2 may, in some form or location, persist for long periods following acute infection. Several studies have shown data in this regard but are limited by non-representative and small study populations, short duration since acute infection, and lack of a true-negative comparator group to assess assay specificity. METHODS: We evaluated adults with RNA-confirmed COVID-19 at multiple time points following acute infection (pandemic-era participants) and adults with specimens collected prior to 2020 (pre-pandemic era). Using once-thawed plasma, we employed the Simoa® (Quanterix) single molecule array detection platform to measure SARS-CoV-2 spike, S1, and nucleocapsid antigens. RESULTS: Compared to 250 pre-pandemic participants who had 2% assay positivity, detection of any SARS-CoV-2 antigen was significantly more frequent among 171 pandemic-era participants at three different time periods in the post-acute phase of infection. The absolute difference in SARS-CoV-2 plasma antigen prevalence was +11% (95% CI: +5.0% to +16%) at 3.0-6.0 months post-onset of COVID-19; +8.7% (95% CI: +3.1% to +14%) at 6.1 to 10.0 months; and +5.4% (95% CI: +0.42% to +10%) at 10.1-14.1 months. Hospitalization for acute COVID-19 and, among the non-hospitalized, worse self-reported health during acute COVID-19 were associated with greater post-acute phase antigen detection. CONCLUSIONS: Compared to uninfected persons, there is an excess prevalence of SARS-CoV-2 antigenemia in SARS-CoV-2-infected individuals up to 14 months after acute COVID-19. These findings motivate an urgent research agenda regarding the short-term and long-term clinical manifestations of this viral persistence.

The importance of response type to the relationship between temporal order and numerical magnitude.

Time, number, and space may be represented in the brain by a common set of cognitive/neural mechanisms. In support of this conjecture, Schwarz and Eiselt (Journal of Experimental Psychology: Human Perception and Performance, 35, 989-1004, 2009) found that numerically smaller digits were perceived to occur earlier than larger digits, and they concluded that this difference reflected faster processing of smaller numbers. This difference, however, could have been related to a response bias, whereby participants map responses of "which first" onto the "first" number along the mental number line. In Experiment 1, participants made temporal order judgements between digits presented to the left or to the right. The point of subjective simultaneity was shifted so that the 9 had to be presented before the 2 in order for simultaneity to be perceived. This difference could reflect either faster processing of the 2 or a response bias. Experiments 2a and 2b eliminated response biases by using simultaneity judgements, which have no logical stimulus mapping. Both of the latter experiments established that the 2 was not processed faster than the 9. Although the present results relate specifically to numerical magnitude and temporal order associations, they also have broader implications. Other studies have reported associations between dimensions such as size, duration, and number and have attributed these to parietal mechanisms. Such associations, however, may also be an artefact of response biases.

Histological changes of an injectable rhBMP-2/calcium phosphate cement in vertebroplasty of rhesus monkey.

STUDY DESIGN: A histologic study of recombinant human bone morphogenetic protein-2/calcium phosphate cement (rhBMP-2/CPC) using adult rhesus monkeys in vivo. OBJECTIVE: To evaluate the histologic changes of rhBMP-2/CPC in vertebroplasty and determine the feasibility of this bone substitution instead of polymethylmethacrylate (PMMA). SUMMARY OF BACKGROUND DATA: Previous studies have shown that the new rhBMP-2/nanoscale CPC has a suitable strength and injection for vertebroplasty. However, the osteoinductive properties and biodegradable characteristics are still unclear. METHODS: Percutaneous vertebroplasty (PVP) was performed in 4 adult rhesus monkeys of 2 groups. Ten vertebral bodies (VBs) from T10-L7 of each rhesus were selected, and the 20 VBs in each group were randomly divided into 3 subgroups. Subgroup A (rhBMP-2/CPC): 8 VBs, filled with rhBMP-2/CPC; Subgroup B (PMMA): 6 VBs, filled with injectable PMMA; Subgroup C (control): 6 VBs, filled with normal saline. The 2 rhesus monkeys from each of the groups were killed at 2 and 6 months after operation, respectively. Individual specimens from the 40 VBs were collected for histologic observation. RESULTS: In subgroup A, radiographic and histologic observations showed that the part of the rhBMP-2/CPC cement degraded with new bone and new vessel ingrowths, into the material, after 2 months. In addition, gaps, fibrous hyperplasia, or sclerotic callus were not found in the interface. After 6 months, the cement was nearly all replaced by mature bone tissue. In subgroup B, the inflammatory cell infiltration and fibrous membrane gapping were found after 2 months, and subsided partly at 6 months. But no new bone formation and material degradation were discovered. In subgroup C, the tunnels were filled with irregular new trabeculae after 2 months and unrecognizable from the surrounding mature bone after 6 months. CONCLUSION: It is confirmed that the rhBMP-2/CPC is an osteoinductive and biodegradable material (in animal trials). It may also be an alternative to PMMA in order to achieve biostabilization in a vertebroplasty.