Characterization of the significant decline in humoral immune response six months post-SARS-CoV-2 mRNA vaccination: A systematic review.

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID-19) (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) messenger RNA (mRNA) vaccines such as Pfizer-BioNTech (mRNA BNT161b2) and Moderna (mRNA-1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti-SARS-CoV-2 antibodies after the second dose of a primary cycle of COVID-19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles (N = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21-28 days after the second dose, after which serum levels progressively diminished at 4-6-month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti-receptor binding domain immunoglobulin G (IgG) and anti-spike IgG, ranging from 94% to 95% at 90-180 days and 55%-85% at 140-160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient-related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.

Diversity and Genetic Reassortment of Keystone Virus in Mosquito Populations in Florida.

Keystone orthobunyavirus (KEYV), a member of the genus Orthobunyavirus, was first isolated in 1964 from mosquitoes in Keystone, Florida. Although data on human infections are limited, the virus has been linked to a fever/rash syndrome and, possibly, encephalitis, with early studies suggesting that 20% of persons in the Tampa, Florida, region had antibodies to KEYV. To assess the distribution and diversity of KEYV in other regions of Florida, we collected > 6,000 mosquitoes from 43 sampling sites in St. Johns County between June 2019 and April 2020. Mosquitoes were separated into pools by species and collection date and site. All pools with Aedes spp. (293 pools, 2,171 mosquitoes) were screened with a real-time reverse transcriptase polymerase chain reaction (rRT-PCR) assay that identifies KEYV and other closely related virus species of what was previously designated as the California encephalitis serogroup. In 2020, screening for KEYV was expanded to include 211 pools of Culex mosquitoes from sites where KEYV-positive Aedes spp. had been identified. rRT-PCR-positive samples were inoculated into cell cultures, and five KEYV isolates from Aedes atlanticus pools were isolated and sequenced. Analyses of the KEYV large genome segment sequences revealed two distinct KEYV clades, whereas analyses of the medium and small genome segments uncovered past reassortment events. Our data documented the ongoing seasonal circulation of multiple KEYV clades within Ae. atlanticus mosquito populations along the east coast of Florida, highlighting the need for further studies of the impact of this virus on human health.

Rapid Generation of Circulating and Mucosal Decoy Human ACE2 using mRNA Nanotherapeutics for the Potential Treatment of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause lethal pulmonary damage in humans. It contains spike proteins on its envelope that bind to human angiotensin-converting enzyme 2 (hACE2) expressed on airway cells, enabling entry of the virus, and causing infection. The soluble form of hACE2 binds SARS-CoV-2 spike protein, prevents viral entry into target cells, and ameliorates lung injury; however, its short half-life limits therapeutic utilities. Here, synthetic mRNA is engineered to encode a soluble form of hACE2 (hsACE2) to prevent viral infection. A novel lipid nanoparticle (LNP) is used for packaging and delivering mRNA to cells to produce hsACE2 proteins. Intravenously administered LNP delivers mRNA to hepatocytes, leading to the production of circulatory hsACE2 initiated within 2 h and sustained over several days. Inhaled LNP results in lung transfection and secretion of mucosal hsACE2 to lung epithelia, the primary site of entry and pathogenesis for SARS-CoV-2. Furthermore, mRNA-generated hsACE2 binds to the receptor-binding domain of the viral spike protein. Finally, hsACE2 effectively inhibits SARS-CoV-2 and its pseudoviruses from infecting host cells. The proof of principle study shows that mRNA-based nanotherapeutics can be potentially deployed to neutralize SARS-CoV-2 and open new treatment opportunities for coronavirus disease 2019 (COVID-19).

Genomic Investigation of a Mycobacterium tuberculosis Outbreak Involving Prison and Community Cases in Florida, United States.

We used whole-genome sequencing to investigate a tuberculosis outbreak involving U.S.-born persons in the prison system and both U.S.- and foreign-born persons in the community in Florida over a 7-year period (2009-2015). Genotyping by spacer oligonucleotide typing and 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat suggested that the outbreak might be clonal in origin. However, contact tracing could not link the two populations. Through a multidisciplinary approach, we showed that the cluster involved distinct bacterial transmission networks segregated by country of birth. The source strain is of foreign origin and circulated in the local Florida community for more than 20 years before introduction into the prison system. We also identified novel transmission links involving foreign and U.S.-born cases not discovered during contact investigation. Our data highlight the potential for spread of strains originating from outside the United States into U.S. "high-risk" populations, such as prisoners, with subsequent movement back to the general community.

Effect of active case finding on prevalence and transmission of pulmonary tuberculosis in Dhaka Central Jail, Bangladesh.

BACKGROUND: Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. METHODS: The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). RESULTS: A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as 'modern' and 100 (30%) strains as 'ancestral'. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. CONCLUSIONS: Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh.

Quantitative drug-susceptibility in patients treated for multidrug-resistant tuberculosis in Bangladesh: implications for regimen choice.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) treatment in Bangladesh is empiric or based on qualitative drug-susceptibility testing (DST) by comparative growth in culture media with and without a single drug concentration. METHODS: Adult patients were enrolled throughout Bangladesh during the period of 2011-2013 at MDR-TB treatment initiation. Quantitative DST by minimum inhibitory concentration (MIC) testing for 12 first and second-line anti-TB drugs was compared to pretreatment clinical characteristics and treatment outcomes. MIC values at or one dilution lower than the resistance breakpoint used for qualitative DST were categorized as borderline susceptible, and MIC values one or two dilutions greater as borderline resistant. RESULTS: Seventy-four patients were enrolled with a mean age of 35 ± 15 years, and 51 (69%) were men. Of the rifampin isolates with MIC >1.0 µg/ml, 12 (19%) were fully susceptible or borderline susceptible to rifabutin (MIC ≤ 0.5 µg/ml). Amikacin was fully susceptible in 73 isolates (99%), but kanamycin in only 54 (75%) (p<0.001). Ofloxacin was borderline susceptible in 64%, and fully susceptible in only 14 (19%) compared to 60 (81%) of isolates fully susceptible for moxifloxacin (p<0.001). Kanamycin non-susceptibility and receipt of the WHO Category IV regimen trended with interim treatment failure: adjusted odd ratios respectively of 5.4 [95% CI 0.82-36.2] (p = 0.08) and 7.2 [0.64-80.7] (p = 0.11). CONCLUSIONS: Quantitative MIC testing could impact MDR-TB regimen choice in Bangladesh. Comparative trials of higher dose or later generation fluoroquinolone, within class change from kanamycin to amikacin, and inclusion of rifabutin appear warranted.

Yield of two consecutive sputum specimens for the effective diagnosis of pulmonary tuberculosis.

BACKGROUND: From long instances, it is debatable whether three sputum specimens are required for the diagnosis of pulmonary tuberculosis (TB) or TB can be diagnosed effectively using two consecutive sputum specimens. This study was set out to evaluate the significance of examining multiple sputum specimens in diagnosis of TB. METHODS: We retrospectively reviewed the acid-fast bacillus (AFB) smear and culture results of three consecutive days' sputum specimens from 413 confirmed TB patients which were detected as part of a larger active case finding study in Dhaka Central Jail, the largest correctional facility in Bangladesh. RESULTS: AFB was detected from 81% (n = 334) patients, of which 89% (n = 297) were diagnosed from the first and additional 9% (n = 30) were from the second sputum specimen. M. tuberculosis growth was observed for 406 patients and 85% (n = 343) were obtained from the first sputum and additional 10% (n = 42) were from the second one. The third specimen didn't show significant additional diagnostic value for the detection of AFB by microscopy or growth of the M. tuberculosis. CONCLUSIONS: We concluded from our study results that examining two consecutive sputum specimens is sufficient enough for the effective diagnosis of TB. It can also decrease the laboratory workload and hence improve the quality of work in settings with high TB burden like Bangladesh.