Seropositivity in blood donors and pregnant women during the first year of SARS-CoV-2 transmission in Stockholm, Sweden.

BACKGROUND: In Sweden, social restrictions to contain SARS-CoV-2 have primarily relied upon voluntary adherence to a set of recommendations. Strict lockdowns have not been enforced, potentially affecting viral dissemination. To understand the levels of past SARS-CoV-2 infection in the Stockholm population before the start of mass vaccinations, healthy blood donors and pregnant women (n = 5,100) were sampled at random between 14 March 2020 and 28 February 2021. METHODS: In this cross-sectional prospective study, otherwise-healthy blood donors (n = 2,600) and pregnant women (n = 2,500) were sampled for consecutive weeks (at four intervals) throughout the study period. Sera from all participants and a cohort of historical (negative) controls (n = 595) were screened for IgG responses against stabilized trimers of the SARS-CoV-2 spike (S) glycoprotein and the smaller receptor-binding domain (RBD). As a complement to standard analytical approaches, a probabilistic (cut-off independent) Bayesian framework that assigns likelihood of past infection was used to analyse data over time. SETTING: Healthy participant samples were randomly selected from their respective pools through Karolinska University Hospital. The study was carried out in accordance with Swedish Ethical Review Authority: registration number 2020-01807. PARTICIPANTS: No participants were symptomatic at sampling, and blood donors were all over the age of 18. No additional metadata were available from the participants. RESULTS: Blood donors and pregnant women showed a similar seroprevalence. After a steep rise at the start of the pandemic, the seroprevalence trajectory increased steadily in approach to the winter second wave of infections, approaching 15% of all individuals surveyed by 13 December 2020. By the end of February 2021, 19% of the population tested seropositive. Notably, 96% of seropositive healthy donors screened (n = 56) developed neutralizing antibody responses at titres comparable to or higher than those observed in clinical trials of SARS-CoV-2 spike mRNA vaccination, supporting that mild infection engenders a competent B-cell response. CONCLUSIONS: These data indicate that in the first year since the start of community transmission, seropositivity levels in metropolitan in Stockholm had reached approximately one in five persons, providing important baseline seroprevalence information prior to the start of vaccination.

Intrapatient viral diversity and treatment outcome in patients with genotype 3a hepatitis C virus infection on sofosbuvir-containing regimens.

Treatment with the direct-acting antiviral agent (DAA) sofosbuvir (SOF), an NS5B inhibitor, and velpatasvir (VEL), an NS5A inhibitor, demonstrates viral cure rates of ≥95% in hepatitis C virus (HCV) genotypes (GT) 1-6. Here, we investigated intrapatient HCV diversity in NS5A and NS5B using Shannon entropy to examine the relationship between viral diversity and treatment outcome. At baseline, HCV diversity was lowest in patients infected with HCV GT3 as compared to the other GTs, and viral diversity was greater in NS5A than NS5B (P < .0001). Treatment outcome with SOF/VEL or the comparator regimen of SOF with ribavirin (RBV) was not correlated with baseline diversity. However, among persons treated with SOF/VEL, a decrease in diversity from baseline was observed at relapse in the majority virologic failures, consistent with a viral bottleneck event at relapse. In contrast, an increase in diversity was observed in 27% of SOF+RBV virologic failures. We investigated whether the increase in diversity was due to an increase in the transition rate, one mode of potential RBV-mediated mutagenesis; however, we found no evidence of this mechanism. Overall, we did not observe that viral diversity at baseline influenced treatment outcome, but the diversity changes observed at relapse can improve our understanding of RBV viral suppression in vivo.

Biomechanical analysis of pedicle screw thread differential design in an osteoporotic cadaver model.

BACKGROUND: Pedicle screw fixation, the standard surgical care for posterior stabilization in the thoraco-lumbar spine has a high rate of failure in osteoporotic individuals. Screw design factors and insertion techniques have been shown to influence the biomechanical performance of pedicle screws. Our objective was to investigate the biomechanical characteristics of pedicle screw fixation in osteoporotic bone by comparing standard screws with newly designed differential crest thickness dual lead screws. METHODS: An in-vitro spinal-level paired factorial study design was used to examine thoraco-lumbar spine biomechanical outcomes for differential pedicle screw thread designs. Six cadaveric human spines (T8-L5) were tested for six groups (n=20) consisting of 2 different crest thickness and 3 different insertion techniques. Bone mineral density was assessed and peak insertion torque measured while placing one screw of new design and control on the contralateral side. Screw pullout properties were measured from classical American Society for Testing and Materials protocols. FINDINGS: The screws designed specifically for osteoporotic bone showed significantly larger insertion torque compared with the standard screw design irrespective of insertion technique. Much of the variability in pullout failure and stiffness was explained by bone mineral density. The osteoporotic screws of different crest thickness were statistically similar to each other in all outcome measures. INTERPRETATION: Compared with standard pedicle screws, the dual lead osteoporotic-specific pedicle screws demonstrated significantly larger insertion torques and similar pullout properties. Non-significant increased biomechanical strength was observed for thin crest compared to thick crest dual lead pedicle screws indicating their enhanced purchase in osteoporotic bone.