Investigating the Marginal and Herd Effects of COVID-19 Vaccination for Reducing Case Fatality Rate: Evidence from the United States between March 2021 to January 2022

Vaccination campaigns have been rolled out in most countries to increase vaccination coverage and protect against case mortality during the ongoing pandemic. To evaluate the effectiveness of COVID-19 vaccination, it is vital to disentangle the herd effect from the marginal effect and parameterize them separately in a model. To demonstrate this, we study the relationship between the COVID-19 vaccination coverage and case fatality rate (CFR) based on U.S. vaccination coverage at county level, with daily records from 11 March 2021 to 26 January 2022 for 3109 U.S. counties. Using segmented regression, we discovered three breakpoints of the vaccination coverage, at which herd effects could potentially exist. Controlling for county heterogeneity, we found the size of the marginal effect was not constant but actually increased as the vaccination coverage increased, and only the herd effect at the first breakpoint to be statistically significant, which implied an indirect benefit of vaccination may exist at the early stage of a vaccination campaign. Our results demonstrated that public-health researchers should carefully differentiate and quantify the herd and marginal effects when analyzing vaccination data, to better inform vaccination-campaign strategies as well as evaluate vaccination effectiveness

Outcomes and Treatment of Lumbosacral Spinal Tuberculosis: A Retrospective Study of 53 Patients.

A retrospective clinic study.To evaluate the efficacy of conservative and surgical treatment for lumbosacral tuberculosis.This study retrospectively reviewed 53 patients with lumbosacral tuberculosis who were treated in our institution between January 2005 and January 2011. There were 29 males and 24 females with average ages of 37.53 ± 17.28 years (range 6-72 years). 11 patients were given only anti-TB drugs; the remainder underwent anterior debridement, interbody fusion with and without instrumentation, or one-stage anterior debridement combined with posterior instrumentation. Outcome data for these patients included neurologic status, lumbosacral angle, erythrocyte sedimentation rate value(ESR) and C-reactive protein value(CRP) were assessed before and after treatment.The mean lumbosacral angles were 23.00°± 2.90° in the conservatively treated patients and 22.36°± 3.92o in the surgically treated patients. At the final follow-up, this had improved to 24.10o ± 2.96° in the conservatively treated patients and 28.13° ± 1.93° in the surgically treated patients (all P < 0.05). There were statistically significant differences before and after treatment in terms of ESR and CRP (all P < 0.05). All patients achieved bone fusion. The mean follow-up period was 32.34 ± 8.13 months (range 18 to 55 months). The neurological deficit did not worsen in any of the patients.It has been proven that conservative and surgical treatments are safe and effective and produce good clinical outcomes for patients with lumbosacral tuberculosis. The advantages of operation include thoroughness of debridement, decompression of the spinal cord, and adequate spinal stabilization

A 56-year-old woman with lumbosacral spinal tuberculosis received conservative anti-TB therapy.

<p>(A)Pretreatment MRI showed destruction of the L4–L5 vertebrae and formation of paravertebral abscess with concomitant compression of the spinal cord. (B) After 6-week anti-TB therapy, the back pain became more serious. (C,D) No recurrence of TB was noted in this patient during the follow-up period.</p

A 28-year-old man with lumbosacral spinal tuberculosis underwent anterior debridement, decompression combined with posterior plate fixation.

<p>(A,B)Pretreatment MRI shown destruction of the L4–S1 vertebrae and paravertebral abscess with concomitant compression of the spinal cord.(C) Immediate postoperative radiographs demonstrating anterolateral debridement, bone graft and internal fixation. (D,E) At 22 months’ follow-up, plain X-ray showed maintenance of the correction and solid fusion.</p

CotA, a Multicopper Oxidase from <i>Bacillus pumilus</i> WH4, Exhibits Manganese-Oxidase Activity

<div><p>Multicopper oxidases (MCOs) are a family of enzymes that use copper ions as cofactors to oxidize various substrates. Previous research has demonstrated that several MCOs such as MnxG, MofA and MoxA can act as putative Mn(II) oxidases. Meanwhile, the endospore coat protein CotA from <i>Bacillus</i> species has been confirmed as a typical MCO. To study the relationship between CotA and the Mn(II) oxidation, the <i>cotA</i> gene from a highly active Mn(II)-oxidizing strain <i>Bacillus pumilus</i> WH4 was cloned and overexpressed in <i>Escherichia coli</i> strain M15. The purified CotA contained approximately four copper atoms per molecule and showed spectroscopic properties typical of blue copper oxidases. Importantly, apart from the laccase activities, the CotA also displayed substantial Mn(II)-oxidase activities both in liquid culture system and native polyacrylamide gel electrophoresis. The optimum Mn(II) oxidase activity was obtained at 53°C in HEPES buffer (pH 8.0) supplemented with 0.8 mM CuCl₂. Besides, the addition of <i>o</i>-phenanthroline and EDTA both led to a complete suppression of Mn(II)-oxidizing activity. The specific activity of purified CotA towards Mn(II) was 0.27 U/mg. The K_m, V_max and k_cat values towards Mn(II) were 14.85±1.17 mM, 3.01×10⁻⁶±0.21 M·min⁻¹ and 0.32±0.02 s⁻¹, respectively. Moreover, the Mn(II)-oxidizing activity of the recombinant <i>E. coli</i> strain M15-pQE-<i>cotA</i> was significantly increased when cultured both in Mn-containing K liquid medium and on agar plates. After 7-day liquid cultivation, M15-pQE-<i>cotA</i> resulted in 18.2% removal of Mn(II) from the medium. Furthermore, the biogenic Mn oxides were clearly observed on the cell surfaces of M15-pQE-<i>cotA</i> by scanning electron microscopy. To our knowledge, this is the first report that provides the direct observation of Mn(II) oxidation with the heterologously expressed protein CotA, Therefore, this novel finding not only establishes the foundation for in-depth study of Mn(II) oxidation mechanisms, but also offers a potential biocatalyst for Mn(II) removal.</p> </div

Mn(II) oxidase activity of purified recombinant CotA in liquid culture system.

<p>Tube 1, 10 mM HEPES (pH 8.0) plus 5 mM MnCl₂ and 0.8 mM CuCl₂ (reaction mixture); tube 2, aliquots (50 µl) of tube 1 reacting with 250 µl Leucoberbelin blue; tube 3, reaction mixture in Tube 1 plus CotA; tube 4, aliquots (50 µl) of tube 3 reacting with 250 µl Leucoberbelin blue.</p

SEM photographs of <i>E. coli</i> cells and biogenic Mn oxides (×20,000 with insert ×10,000).

<p>(A) SEM image showing the morphologies of the mother strain M15 cultivated without Mn(II); (B) SEM image of the mother strain M15 cultivated with Mn(II) and the associated biogenic Mn oxides; (C) SEM image showing the morphologies of the recombinant strain M15-pQE-<i>cotA</i> cultivated without Mn(II); (D) SEM image of the recombinant strain M15-pQE-<i>cotA</i> cultivated with Mn(II) and the aggregated biogenic Mn oxides.</p

The Mn(II) removal percentages from the supernatants by <i>E. coli</i> strains M15-pQE-<i>cotA</i> and M15.

<p>The residual Mn(II) of the 7-day cultivated culture was measured by ICP-OES. The values were means ± standard deviations for triplicate assays.</p

Effect of pH on Mn(II)-oxidizing activity of CotA.

<p>▪ (black square) CotA plus 5 mM MnCl₂ and 0.8 mM CuCl₂ in HEPES buffer (pH 6.8–8.2) at 37°C for about 24 h; □ (red square) control test with 5 mM MnCl₂ and 0.8 mM CuCl₂ in HEPES buffer (pH 6.8–8.2) at 37°C for about 24 h; ▴ (black triangle) CotA plus 5 mM MnCl₂ and 0.8 mM CuCl₂ in CHES buffer (pH 8.6–9.5) at 37°C for about 24 h; △ (red triangle) control test with 5 mM MnCl₂ and 0.8 mM CuCl₂ in CHES buffer (pH 8.6–9.5) at 37°C for about 24 h. The values were means ± standard deviations for triplicate assays.</p

Determination of the Mn(II) oxidation activity of <i>E. coli</i> strains every day.

<p><i>E. coli</i> strains M15-pQE-<i>cotA</i> (▪) (black square) and M15 (•) (red circle) were grown at 37°C in K liquid medium containing HEPES (pH 7.5), 0.5 mM IPTG, 0.25 mM CuCl₂ and 5 mM MnCl₂ for 7 days. The values were means ± standard deviations for triplicate assays.</p