Impact of COVID-19 prevention and control on tuberculosis and scarlet fever in China's Guizhou.

China has implemented a series of long-term measures to control the spread of COVID-19, however, the effects of these measures on other chronic and acute respiratory infectious diseases remain unclear. Tuberculosis (TB) and scarlet fever (SF) serve as representatives of chronic and acute respiratory infectious diseases, respectively. In China's Guizhou province, an area with a high prevalence of TB and SF, approximately 40,000 TB cases and hundreds of SF cases are reported annually. To assess the impact of COVID-19 prevention and control on TB and SF in Guizhou, the exponential smoothing method was employed to establish a prediction model for analyzing the influence of COVID-19 prevention and control on the number of TB and SF cases. Additionally, spatial aggregation analysis was utilized to describe spatial changes in TB and SF before and after the COVID-19 outbreak. The parameters of the TB and SF prediction models are R2 = 0.856, BIC = 10.972 and R2 = 0.714, BIC = 5.325, respectively. TB and SF cases declined rapidly at the onset of COVID-19 prevention and control measures, with the number of SF cases decreasing for about 3-6 months and the number of TB cases remaining in decline for 7 months after the 11th month. The spatial aggregation of TB and SF did not change significantly before and after the COVID-19 outbreak but exhibited a marked decrease. These findings suggest that China's COVID-19 prevention and control measures also reduced the prevalence of TB and SF in Guizhou. These measures may have a long-term positive impact on TB, but a short-term effect on SF. Areas with high TB prevalence may continue to experience a decline due to the implementation of COVID-19 preventive measures in the future.

Spike-Independent Infection of Human Coronavirus 229E in Bat Cells.

Bats are the reservoir for numerous human pathogens, including coronaviruses. Despite many coronaviruses having descended from bat ancestors, little is known about virus-host interactions and broader evolutionary history involving bats. Studies have largely focused on the zoonotic potential of coronaviruses with few infection experiments conducted in bat cells. To determine genetic changes derived from replication in bat cells and possibly identify potential novel evolutionary pathways for zoonotic virus emergence, we serially passaged six human 229E isolates in a newly established Rhinolophus lepidus (horseshoe bat) kidney cell line. Here, we observed extensive deletions within the spike and open reading frame 4 (ORF4) genes of five 229E viruses after passaging in bat cells. As a result, spike protein expression and infectivity of human cells was lost in 5 of 6 viruses, but the capability to infect bat cells was maintained. Only viruses that expressed the spike protein could be neutralized by 229E spike-specific antibodies in human cells, whereas there was no neutralizing effect on viruses that did not express the spike protein inoculated on bat cells. However, one isolate acquired an early stop codon, abrogating spike expression but maintaining infection in bat cells. After passaging this isolate in human cells, spike expression was restored due to acquisition of nucleotide insertions among virus subpopulations. Spike-independent infection of human coronavirus 229E may provide an alternative mechanism for viral maintenance in bats that does not rely on the compatibility of viral surface proteins and known cellular entry receptors. IMPORTANCE Many viruses, including coronaviruses, originated from bats. Yet, we know little about how these viruses switch between hosts and enter human populations. Coronaviruses have succeeded in establishing in humans at least five times, including endemic coronaviruses and the recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In an approach to identify requirements for host switches, we established a bat cell line and adapted human coronavirus 229E viruses by serial passage. The resulting viruses lost their spike protein but maintained the ability to infect bat cells, but not human cells. Maintenance of 229E viruses in bat cells appears to be independent of a canonical spike receptor match, which in turn might facilitate cross-species transmission in bats.

Fixed-length interval estimation of population sizes: sequential adaptive Monte Carlo mark–recapture–mark sampling

Mark–recapture sampling schemes are conventional approaches for population size (N) estimation. In this paper, we mainly focus on providing fixed-length confidence interval estimation methodologies for N under a mark–recapture–mark sampling scheme, where, during the resampling phase, non-marked items are marked before they are released back in the population. Using a Monte Carlo method, the interval estimates for N are obtained through a purely sequential procedure with an adaptive stopping rule. Such an adaptive decision criterion enables the user to "learn” with the subsequent marked and newly tagged items. The method is then compared with a recently developed accelerated sequential procedure in terms of coverage probability and expected number of captured items during the resampling stage. To illustrate, we explain how the proposed procedure could be applied to estimate the number of infected COVID-19 individuals in a near-closed population. In addition, we present a numeric application inspired on the problem of estimating the population size of endangered monkeys of the Atlantic forest in Brazil.

WeChat as a platform for blending problem/case-based learning and paper review methods in undergraduate paediatric orthopaedics internships: a feasibility and effectiveness study.

BACKGROUND: Paediatric orthopaedics is a significant and difficult for undergraduate students to master. During the COVID-19 pandemic, we used the WeChat platform to combine the advantages offered by problem-based learning (PBL), case-based learning (CBL) and paper review teaching methods to establish a new blended online teaching model and demonstrated its feasibility and effectiveness. OBJECTIVE: This study aims to demonstrate the feasibility and effectiveness of a new blended pedagogical method that uses the WeChat platform and combines PBL, CBL and paper review. METHODS: We enrolled 22 students participating in the Department of Paediatric Orthopaedics. They participated in the WeChat blended pedagogy mode. Their departmental rotation examination scores were compared with those of 23 students who participated in the traditional teaching method. Moreover, an anonymous questionnaire was used to evaluate students' perceptions and experiences. RESULTS: The total average scores of students who participated in the WeChat blended pedagogy mode and the traditional teaching method were 47.27 and 44.52, respectively. There were no statistically significant differences between the online teaching mode and the traditional teaching method in terms of possessing professional accomplishment, gaining knowledge and promoting interpersonal skills (P = 0.07, P = 0.12 and P = 0.65, respectively). In terms of independent clinical thinking, self-improving capability and improving clinical skills, the scores associated with the WeChat blended pedagogy mode were 8.00, 8.00 and 6.00, whereas those associated with the traditional teaching method were 6.70, 6.87 and 7.48. The overall satisfaction with the WeChat blended pedagogy mode reached 100%. A total of 64%, 86%, 68%, 64% and 59% of students chose very large or large in response to the items concerning professional accomplishment, knowledge absorption, independent clinical thinking skills, English reading and literature exploring capacity, as well as interpersonal skills, respectively. Fifteen participants claimed that the WeChat blended pedagogy mode was less helpful to them with regard to promoting the improvement of their clinical skills. Nine students claimed that the WeChat blended pedagogy mode was time-consuming. CONCLUSIONS: Our study verified the feasibility and effectiveness of the WeChat blended pedagogy mode for undergraduate paediatric orthopaedics internships. TRIAL REGISTRATION: Retrospectively registered.

Regression model for the reported infected during emerging pandemics under the stochastic SEIR

The COVID-19 pandemic revealed the necessity of measuring the statistical relationship between the transmission rate of epidemic diseases and the social/behavioral, logistical, and economic variables of the affected region. This paper introduces a regression model to estimate the impact of such covariates on the infectious rate of epidemiological agents. Hidden logistical predictor components, such as weekly seasonality of reported data, can also be accessed with the proposed methodology. For this, we assume that the dynamics of officially reported data of emerging pandemics, related to infected groups, follows a stochastic SEIR model. The main advantage of our method is that it is based on a new three-step algorithm that combines the classical likelihood principle, the minimization of the mean squared error, and a tri-section algorithm to estimate, simultaneously, the coefficients of the covariates and the parameters of the compartmental model. Simulation studies are provided to certify the accuracy of the proposed inference methodology. The model is further applied to analyze the official statistical reports of COVID-19 data in the state of São Paulo, Brazil. Supplementary Information The online version contains supplementary material available at 10.1007/s40314-023-02241-w.

The origin and evolution of emerged swine acute diarrhea syndrome coronavirus with zoonotic potential.

Swine acute diarrhea syndrome coronavirus (SADS-CoV) is a newly discovered alphacoronavirus with zoonotic potential that causes diarrhea and vomiting mainly in piglets. Having emerged suddenly in 2017, the prevailing opinion is that the virus originated from HKU2, an alphacoronavirus whose primary host is bats, and at some unknown point achieved interspecies transmission via some intermediate. Here, we further explore the evolutionary history and possible cross-species transmission event for SADS-CoV. Coevolutionary analysis demonstrated that HKU2 may have achieved host switch via SADS-related (SADSr)-CoV, which was isolated from the genus Rhinolophus in 2017. SADS-CoV, HKU2, and SADSr-CoV share similar codon usage patterns and showed a lower tendency to use CpG, which may reflect a method of immune escape. The analyses of virus-host coevolution and recombination support SADSr-CoV is the direct source of SADS-CoV that may have undergone recombination events during its formation. Structure-based spike glycoprotein variance analysis revealed a more nuanced evolutionary pathway to receptor recognition for host switch. We did not find a possible positive selection site, and the dN/dS of the S gene was only 0.29, which indicates that the current SADS-CoV is slowly evolving. These results provide new insights that may help predict future cross-species transmission, and possibly surveil future zoonotic outbreaks and associated public health emergencies.

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults - VISION Network, Nine States, September-November 2022.

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 32% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 59% compared with no vaccination, 42% compared with monovalent vaccination only with last dose 5-7 months earlier, and 48% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.

Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID-19-Associated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults - VISION Network, Nine States, September-November 2022.

During June-October 2022, the SARS-CoV-2 Omicron BA.5 sublineage accounted for most of the sequenced viral genomes in the United States, with further Omicron sublineage diversification through November 2022.* Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the Omicron BA.4/BA.5 sublineages. On September 1, 2022, a single bivalent booster dose was recommended for adults who had completed a primary vaccination series (with or without subsequent booster doses), with the last dose administered ≥2 months earlier (1). During September 13-November 18, the VISION Network evaluated vaccine effectiveness (VE) of a bivalent mRNA booster dose (after 2, 3, or 4 monovalent doses) compared with 1) no previous vaccination and 2) previous receipt of 2, 3, or 4 monovalent-only mRNA vaccine doses, among immunocompetent adults aged ≥18 years with an emergency department/urgent care (ED/UC) encounter or hospitalization for a COVID-19-like illness.† VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated ED/UC encounters was 56% compared with no vaccination, 31% compared with monovalent vaccination only with last dose 2-4 months earlier, and 50% compared with monovalent vaccination only with last dose ≥11 months earlier. VE of a bivalent booster dose (after 2, 3, or 4 monovalent doses) against COVID-19-associated hospitalizations was 57% compared with no vaccination, 38% compared with monovalent vaccination only with last dose 5-7 months earlier, and 45% compared with monovalent vaccination only with last dose ≥11 months earlier. Bivalent vaccines administered after 2, 3, or 4 monovalent doses were effective in preventing medically attended COVID-19 compared with no vaccination and provided additional protection compared with past monovalent vaccination only, with relative protection increasing with time since receipt of the last monovalent dose. All eligible persons should stay up to date with recommended COVID-19 vaccinations, including receiving a bivalent booster dose. Persons should also consider taking additional precautions to avoid respiratory illness this winter season, such as masking in public indoor spaces, especially in areas where COVID-19 community levels are high.

Neutralization Activity against SARS-CoV-2 Variants after Booster Vaccination in Populations without COVID-19: A Meta-Analysis.

A number of SARS-CoV-2 variants that have evolved to have significant immune escape have emerged worldwide since the COVID-19 outbreak. The efficacy of prime vaccination is waning with the evolution of SARS-CoV-2, and the necessity of booster doses is more and more prominent. Therefore, this study aimed to compare the neutralization activity against the wild type and variants (Beta, Delta, and Omicron) in different prime-boost vaccination regimens. Electronic databases including PubMed, the Cochrane Library, Embase, medRxiv, Wanfang and CNKI were used to retrieve original studies. A total of 16 studies, 9 prime-boost vaccination regimes, and 3134 subjects were included in the meta-analysis and random effect models were used to estimate pooled neutralization titers. The neutralization activity against SARS-CoV-2 showed a significant decline with the evolution of the virus, especially in the populations primed with inactivated vaccines. For homologous immunization, only the populations boosted with mRNA vaccines consistently had a significant rise in neutralization titers (Beta: MD = 0.97; Delta: MD = 1.33; Omicron: MD = 0.74). While the heterologous immunization was more effective, the increment of neutralization titers against wild type, Beta, Delta and Omicron was 1.65 (95% CI: 1.32-1.96), 1.03 (95% CI: 0.53-1.54), 1.46 (95% CI: 1.07-1.85) and 1.15 (95% CI: 0.68-1.61), respectively. With the evolution of SARS-CoV-2, the effectiveness of prime immunization is waning. Although the administration of the booster dose could ameliorate the neutralization titers, homologous immunization regimens were gradually losing their effectiveness. Therefore, a heterologous booster dose is required, especially in populations primed with inactivated vaccines.

Time-to-event modeling for hospital length of stay prediction for COVID-19 patients.

Providing timely patient care while maintaining optimal resource utilization is one of the central operational challenges hospitals have been facing throughout the pandemic. Hospital length of stay (LOS) is an important indicator of hospital efficiency, quality of patient care, and operational resilience. Numerous researchers have developed regression or classification models to predict LOS. However, conventional models suffer from the lack of capability to make use of typically censored clinical data. We propose to use time-to-event modeling techniques, also known as survival analysis, to predict the LOS for patients based on individualized information collected from multiple sources. The performance of six proposed survival models is evaluated and compared based on clinical data from COVID-19 patients.

An interpretable multi-task system for clinically applicable COVID-19 diagnosis using CXR.

BACKGROUND: With the emergence of continuously mutating variants of coronavirus, it is urgent to develop a deep learning model for automatic COVID-19 diagnosis at early stages from chest X-ray images. Since laboratory testing is time-consuming and requires trained laboratory personal, diagnosis using chest X-ray (CXR) is a befitting option. OBJECTIVE: In this study, we proposed an interpretable multi-task system for automatic lung detection and COVID-19 screening in chest X-rays to find an alternate method of testing which are reliable, fast and easily accessible, and able to generate interpretable predictions that are strongly correlated with radiological findings. METHODS: The proposed system consists of image preprocessing and an unsupervised machine learning (UML) algorithm for lung region detection, as well as a truncated CNN model based on deep transfer learning (DTL) to classify chest X-rays into three classes of COVID-19, pneumonia, and normal. The Grad-CAM technique was applied to create class-specific heatmap images in order to establish trust in the medical AI system. RESULTS: Experiments were performed with 15,884 frontal CXR images to show that the proposed system achieves an accuracy of 91.94% in a test dataset with 2,680 images including a sensitivity of 94.48% on COVID-19 cases, a specificity of 88.46% on normal cases, and a precision of 88.01% on pneumonia cases. Our system also produced state-of-the-art outcomes with a sensitivity of 97.40% on public test data and 88.23% on a previously unseen clinical data (1,000 cases) for binary classification of COVID-19-positive and COVID-19-negative films. CONCLUSION: Our automatic computerized evaluation for grading lung infections exhibited sensitivity comparable to that of radiologist interpretation in clinical applicability. Therefore, the proposed solution can be used as one element of patient evaluation along with gold-standard clinical and laboratory testing.

Immunogenicity and Safety of Homologous and Heterologous Prime-Boost Immunization with COVID-19 Vaccine: Systematic Review and Meta-Analysis.

A prime-boost strategy of COVID-19 vaccines brings hope to limit the spread of SARS-CoV-2, while the immunogenicity of the vaccines is waning over time. Whether a booster dose of vaccine is needed has become a widely controversial issue. However, no published meta-analysis has focused on the issue. Therefore, this study assessed the immunogenicity and safety of the different combinations of prime-boost vaccinations. Electronic databases including PubMed, the Cochrane Library, Embase, medRxiv, Wanfang and CNKI were used to retrieve the original studies. A total of 28 studies, 9 combinations of prime-boost vaccinations and 5870 subjects were included in the meta-analysis, and random effect models were used to estimate pooled immunogenicity and safety. The immunity against COVID-19 after the prime vaccination waned over time, especially in the populations primed with inactivated vaccines, in which the seropositive rate of antibodies was only 28% (95% CI: 17-40%). Booster vaccination could significantly increase the antibody responses, and heterologous immunization was more effective than homologous immunization (neutralization titers: 1.65 vs. 1.27; anti-RBD IgG: 1.85 vs. 1.15); in particular, the combination of inactivated-mRNA vaccines had the highest antibody responses (neutralization titers: MRAW = 3.64, 95% CI: 3.54-3.74; anti-RBD IgG: 3.73, 95% CI: 3.59-3.87). Moreover, compared with the initial two doses of vaccines, a booster dose did not induce additional or severe adverse events. The administration of the booster dose effectively recalled specific immune responses to SARS-CoV-2 and increased antibody levels, especially in heterologous immunization. Considering the long-term immunogenicity and vaccine equity, we suggest that now, only individuals primed with inactivated vaccines require a booster dose.

Massive image-based single-cell profiling reveals high levels of circulating platelet aggregates in patients with COVID-19.

A characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis of the big image data shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, respiratory condition, and vascular endothelial dysfunction level of COVID-19 patients.

Effectiveness of 2-Dose Vaccination with mRNA COVID-19 Vaccines Against COVID-19-Associated Hospitalizations Among Immunocompromised Adults - Nine States, January-September 2021.

Immunocompromised persons, defined as those with suppressed humoral or cellular immunity resulting from health conditions or medications, account for approximately 3% of the U.S. adult population (1). Immunocompromised adults are at increased risk for severe COVID-19 outcomes (2) and might not acquire the same level of protection from COVID-19 mRNA vaccines as do immunocompetent adults (3,4). To evaluate vaccine effectiveness (VE) among immunocompromised adults, data from the VISION Network* on hospitalizations among persons aged ≥18 years with COVID-19-like illness from 187 hospitals in nine states during January 17-September 5, 2021 were analyzed. Using selected discharge diagnoses,† VE against COVID-19-associated hospitalization conferred by completing a 2-dose series of an mRNA COVID-19 vaccine ≥14 days before the index hospitalization date§ (i.e., being fully vaccinated) was evaluated using a test-negative design comparing 20,101 immunocompromised adults (10,564 [53%] of whom were fully vaccinated) and 69,116 immunocompetent adults (29,456 [43%] of whom were fully vaccinated). VE of 2 doses of mRNA COVID-19 vaccine against COVID-19-associated hospitalization was lower among immunocompromised patients (77%; 95% confidence interval [CI] = 74%-80%) than among immunocompetent patients (90%; 95% CI = 89%-91%). This difference persisted irrespective of mRNA vaccine product, age group, and timing of hospitalization relative to SARS-CoV-2 (the virus that causes COVID-19) B.1.617.2 (Delta) variant predominance in the state of hospitalization. VE varied across immunocompromising condition subgroups, ranging from 59% (organ or stem cell transplant recipients) to 81% (persons with a rheumatologic or inflammatory disorder). Immunocompromised persons benefit from mRNA COVID-19 vaccination but are less protected from severe COVID-19 outcomes than are immunocompetent persons, and VE varies among immunocompromised subgroups. Immunocompromised persons receiving mRNA COVID-19 vaccines should receive 3 doses and a booster, consistent with CDC recommendations (5), practice nonpharmaceutical interventions, and, if infected, be monitored closely and considered early for proven therapies that can prevent severe outcomes.

Spike-independent infection of human coronavirus 229E in bat cells (preprint)

Bats are the reservoir for numerous human pathogens including coronaviruses. The factors leading to the emergence and sustained transmission of coronaviruses in humans are poorly understood. An outstanding question is how coronaviruses can accomplish a host switch with a likely mismatch between the surface protein spike of a bat virus and the human cellular receptor at the time of zoonotic virus transmission. To identify potential novel evolutionary pathways for zoonotic virus emergence, we serially passaged six human 229E isolates in a newly established Rhinolophus lepidus (horseshoe bat) kidney cells and analyzed viral genetic changes. Here we observed extensive deletions within the spike and ORF4 genes of five 229E viruses after passaging in bat cells. As a result, spike protein expression and infectivity of human cells was lost in 5 of 6 viruses but the capability to infect bat cells was maintained. Only viruses that expressed the spike protein could be neutralized by 229E spike-specific antibodies in human cells, whereas there was no neutralizing effect on viruses that do not express the spike protein inoculated on bat cells. However, one isolate acquired an early stop codon abrogating spike expression but maintaining infection in bat cells. Upon passaging this isolate in human cells, spike expression was restored due to acquisition of nucleotide insertions amongst virus subpopulations. Spike-independent infection of coronaviruses provides an alternative mechanism for viral maintenance in bats that does not rely on the compatibility of viral surface proteins and cellular entry receptors.

Effectiveness of Covid-19 Vaccines in Ambulatory and Inpatient Care Settings.

BACKGROUND: There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic. METHODS: We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation. RESULTS: The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit. CONCLUSIONS: Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).

The Potential Role of Extracellular Vesicles in COVID-19 Treatment: Opportunity and Challenge.

SARS-CoV-2 infection has become an urgent public health concern worldwide, severely affecting our society and economy due to the long incubation time and high prevalence. People spare no effort on the rapid development of vaccine and treatment all over the world. Amongst the numerous ways of tackling this pandemic, some approaches using extracellular vesicles (EVs) are emerging. In this review, we summarize current prevalence and pathogenesis of COVID-19, involving the combination of SARS-CoV-2 and virus receptor ACE2, endothelial dysfunction and micro thrombosis, together with cytokine storm. We also discuss the ongoing EVs-based strategies for the treatment of COVID-19, including mesenchymal stem cell (MSC)-EVs, drug-EVs, vaccine-EVs, platelet-EVs, and others. This manuscript provides the foundation for the development of targeted drugs and vaccines for SARS-CoV-2 infections.

Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients.

Virus-specific humoral and cellular immunity act synergistically to protect the host from viral infection. We interrogate the dynamic changes of virological and immunological parameters in 12 patients with symptomatic acute SARS-CoV-2 infection from disease onset to convalescence or death. We quantify SARS-CoV-2 viral RNA in the respiratory tract in parallel with antibodies and circulating T cells specific for various structural (nucleoprotein [NP], membrane [M], ORF3a, and spike) and non-structural (ORF7/8, NSP7, and NSP13) proteins. Although rapid induction and quantity of humoral responses associate with an increase in disease severity, early induction of interferon (IFN)-γ-secreting SARS-CoV-2-specific T cells is present in patients with mild disease and accelerated viral clearance. These findings provide support for the prognostic value of early functional SARS-CoV-2-specific T cells with important implications in vaccine design and immune monitoring.