Characteristic analysis of a local clustered outbreak of COVID-19 pneumonia caused by SARS-CoV-2 omicron BA.2

Objective: To analyze the epidemiological characteristics of a local cluster of corona virus disease 2019 (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron BA.2, and thus provide scientific evidence for the formulation of scientific prevention and control measures. Method: Descriptive epidemiological methods were used to analyze the causes, transmission, vaccination effects and prevention measures of 12 local clustered outbreaks in Haizhu district in March and April 2022 by retrospective investigation. Results: A total of 12 infected patients were reported, all of which were confirmed infected with SARS-CoV-2 Omicron BA.2. Clinical manifestations: 10 cases had fever (83.33%), 7 cases had sore throat (58.33%), 7 cases had cough (58.33%), 5 cases had fatigue (41.67%), and 4 cases had headache or dizziness (33.33%), 2 cases had gastrointestinal symptoms (16.67%), and 1 case had muscle soreness (8.33%). The clinical classification is as follows: 10 cases of mild disease (83.33%), 2 cases of common type (16.67%), no severe disease and no death. The earliest infection time was March 27, and the last case was April 15. The peak incidence was concentrated on April 8 and April 10, with a total of 5 cases (41.67%). The shortest incubation period was 2 days and the longest was 14 days, with an average of 6.55 days. The geographical distribution indicated that 7 cases from Yangyang Clothing Company (58.33%), 3 cases from Guangzhou No. 3 Middle School (25.00%), and 2 cases of family clusters (16.67%). The sex ratio of all patients was 1:3. The youngest age was 18 years old and the oldest was 59 years old. The 12 cases were young adults;of which, 9 cases were 21- < 60 years old (accounting for 75.00%), and 3 cases were 18- < 21 years old (25.00%). Occupational distribution;employees were accounting for 58.33%, followed by unemployed accounting for 25.00%, and students accounting for 16.67%. A 1:3+ matched case-control analysis in 58 high-risk close contacts was conducted, and found that infection and vaccination were not statistically correlated (X2 = 0.861, P > 0.05). Similarly, by conducting a 1:1+ matched case-control analysis, we failed to observed a statistically significantly in the effect of sex on infection (X2 = 0.325, P > 0.05). Conclusions: The outbreak was caused by SARS-CoV-2 Omicron BA.2;the source of infection was still unknown, and there was hidden transmission. Therefore, strengthening personal protection and giving full play to the role of medical units and pharmacies as sentinel points and industry monitoring should be necessary for the normalization of COVID-19 pneumonia prevention and control.

Efficacy and effectiveness of COVID-19 vaccines: progress and prospect

To prevent and control COVID-19, COVID-19 vaccines are being developed, tested, and approved at an unprecedented rate. As of September 24, 2021, 22 types of COVID-19 vaccines have been approved for conditional marketing or emergency use by at least one country worldwide. Vaccine efficacy/effectiveness is a crucial concern for vaccination. This article provides an overview of efficacy of phase III clinical trials, vaccination, effectiveness of real-world studies as well as challenges of COVID-19 vaccine.

Enhancing vaccination of key populations: lessons and actions

Vaccination is effective in preventing the increase of disease, especially emerging infectious diseases (EIDs), and it is particularly important for people in close contact with infected sources and susceptible populations who are at increased risk of getting infectious diseases due to behavior, occupation or health. Despite targeted vaccination guidelines, inadequate vaccination of the key populations fails to receive widespread attention, resulting in a high-risk transition of disease from key populations to general populations. Strengthening the vaccination of the susceptible groups can effectively block the spread of pathogens to general populations, and reduce the consumption of medical resources in universal vaccination, which has significant economic value. In this review, we describe the prevalence of EIDs, analyze the experience and lessons of infectious disease vaccination in key populations through several cases, and further explore the causes for the decline in vaccination rates of key populations. According to the trends of EIDs, a plan to strengthen the vaccination of key populations is proposed to effectively prevent the transition of EIDs from key populations to general populations.

A Multivalent and Thermostable Nanobody Neutralizing SARS-CoV-2 Omicron (B.1.1.529).

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have risen to dominance, which contains far more mutations in the spike protein in comparison to previously reported variants, compromising the efficacy of most existing vaccines or therapeutic monoclonal antibodies. Nanobody screened from high-throughput naïve libraries is a potential candidate for developing preventive and therapeutic antibodies. Methods: Four nanobodies specific to the SARS-CoV-2 wild-type receptor-binding domain (RBD) were screened from a naïve phage display library. Their affinity and neutralizing activity were evaluated by surface plasmon resonance assays, surrogate virus neutralization tests, and pseudovirus neutralization assays. Preliminary identification of the binding epitopes of nanobodies by peptide-based ELISA and competition assay. Then four multivalent nanobodies were engineered by attaching the monovalent nanobodies to an antibody-binding nanoplatform constructed based on the lumazine synthase protein cage nanoparticles isolated from the Aquifex aeolicus (AaLS). Finally, the differences in potency between the monovalent and multivalent nanobodies were compared using the same methods. Results: Three of the four specific nanobodies could maintain substantial inhibitory activity against the Omicron (B.1.1.529), of them, B-B2 had the best neutralizing activity against the Omicron (B.1.1.529) pseudovirus (IC50 = 1.658 µg/mL). The antiviral ability of multivalent nanobody LS-B-B2 was improved in the Omicron (B.1.1.529) pseudovirus assays (IC50 = 0.653 µg/mL). The results of peptide-based ELISA indicated that LS-B-B2 might react with the linear epitopes in the SARS-CoV-2 RBD conserved regions, which would clarify the mechanisms for the maintenance of potent neutralization of Omicron (B.1.1.529) preliminary. Conclusion: Our study indicated that the AaLS could be used as an antibody-binding nanoplatform to present nanobodies on its surface and improve the potency of nanobodies. The multivalent nanobody LS-B-B2 may serve as a potential agent for the neutralization of SARS-CoV-2 variants.

A Multivalent and Thermostable Nanobody Neutralizing SARS-CoV-2 Omicron (B.1.1.529)

Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants have risen to dominance, which contains far more mutations in the spike protein in comparison to previously reported variants, compromising the efficacy of most existing vaccines or therapeutic monoclonal antibodies. Nanobody screened from high-throughput naïve libraries is a potential candidate for developing preventive and therapeutic antibodies. Methods Four nanobodies specific to the SARS-CoV-2 wild-type receptor-binding domain (RBD) were screened from a naïve phage display library. Their affinity and neutralizing activity were evaluated by surface plasmon resonance assays, surrogate virus neutralization tests, and pseudovirus neutralization assays. Preliminary identification of the binding epitopes of nanobodies by peptide-based ELISA and competition assay. Then four multivalent nanobodies were engineered by attaching the monovalent nanobodies to an antibody-binding nanoplatform constructed based on the lumazine synthase protein cage nanoparticles isolated from the Aquifex aeolicus (AaLS). Finally, the differences in potency between the monovalent and multivalent nanobodies were compared using the same methods. Results Three of the four specific nanobodies could maintain substantial inhibitory activity against the Omicron (B.1.1.529), of them, B-B2 had the best neutralizing activity against the Omicron (B.1.1.529) pseudovirus (IC50 = 1.658 μg/mL). The antiviral ability of multivalent nanobody LS-B-B2 was improved in the Omicron (B.1.1.529) pseudovirus assays (IC50 = 0.653 μg/mL). The results of peptide-based ELISA indicated that LS-B-B2 might react with the linear epitopes in the SARS-CoV-2 RBD conserved regions, which would clarify the mechanisms for the maintenance of potent neutralization of Omicron (B.1.1.529) preliminary. Conclusion Our study indicated that the AaLS could be used as an antibody-binding nanoplatform to present nanobodies on its surface and improve the potency of nanobodies. The multivalent nanobody LS-B-B2 may serve as a potential agent for the neutralization of SARS-CoV-2 variants.

Efficacy and effectiveness of COVID-19 vaccines: Progress and prospect

To prevent and control COVID-19, COVID-19 vaccines are being developed, tested, and approved at an unprecedented rate. As of September 24, 2021, 22 types of COVID-19 vaccines have been approved for conditional marketing or emergency use by at least one country worldwide. Vaccine efficacy/effectiveness is a crucial concern for vaccination. This article provides an overview of efficacy of phase III clinical trials, vaccination, effectiveness of real-world studies as well as challenges of COVID-19 vaccine.

Meta-analysis of 16S rRNA microbial data identified alterations of the gut microbiota in COVID-19 patients during the acute and recovery phases.

BACKGROUND: Dozens of studies have demonstrated gut dysbiosis in COVID-19 patients during the acute and recovery phases. However, a consensus on the specific COVID-19 associated bacteria is missing. In this study, we performed a meta-analysis to explore whether robust and reproducible alterations in the gut microbiota of COVID-19 patients exist across different populations. METHODS: A systematic review was conducted for studies published prior to May 2022 in electronic databases. After review, we included 16 studies that comparing the gut microbiota in COVID-19 patients to those of controls. The 16S rRNA sequence data of these studies were then re-analyzed using a standardized workflow and synthesized by meta-analysis. RESULTS: We found that gut bacterial diversity of COVID-19 patients in both the acute and recovery phases was consistently lower than non-COVID-19 individuals. Microbial differential abundance analysis showed depletion of anti-inflammatory butyrate-producing bacteria and enrichment of taxa with pro-inflammatory properties in COVID-19 patients during the acute phase compared to non-COVID-19 individuals. Analysis of microbial communities showed that the gut microbiota of COVID-19 recovered patients were still in unhealthy ecostates. CONCLUSIONS: Our results provided a comprehensive synthesis to better understand gut microbial perturbations associated with COVID-19 and identified underlying biomarkers for microbiome-based diagnostics and therapeutics.

Epidemiological characteristics of imported cases of COVID-19 from outside China in early stage

Objective: The characteristics of imported coronavirus disease 2019(COVID-19) cases from outside China were analyzed to provide evidence for prevention and control backflow of the epidemic.

Effects of COVID-19 Non-Pharmacological Interventions on Dengue Infection: A Systematic Review and Meta-Analysis.

Non-pharmacological interventions (NPIs) implemented during the coronavirus disease 2019 (COVID-19) pandemic have demonstrated significant positive effects on other communicable diseases. Nevertheless, the response for dengue fever has been mixed. To illustrate the real implications of NPIs on dengue transmission and to determine the effective measures for preventing and controlling dengue, we performed a systematic review and meta-analysis of the available global data to summarize the effects comprehensively. We searched Embase, PubMed, and Web of Science in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines from December 31, 2019, to March 30, 2022, for studies of NPI efficacy on dengue infection. We obtained the annual reported dengue cases from highly dengue-endemic countries in 2015-2021 from the European Centre for Disease Prevention and Control to determine the actual change in dengue cases in 2020 and 2021, respectively. A random-effects estimate of the pooled odds was generated with the Mantel-Haenszel method. Between-study heterogeneity was assessed using the inconsistency index (I2 ) and subgroup analysis according to country (dengue-endemic or non-endemic) was conducted. This review was registered with PROSPERO (CRD42021291487). A total of 17 articles covering 32 countries or regions were included in the review. Meta-analysis estimated a pooled relative risk of 0.39 (95% CI: 0.28-0.55), and subgroup revealed 0.06 (95% CI: 0.02-0.25) and 0.55 (95% CI: 0.44-0.68) in dengue non-endemic areas and dengue-endemic countries, respectively, in 2020. The majority of highly dengue-endemic countries in Asia and Americas reported 0-100% reductions in dengue cases in 2020 compared to previous years, while some countries (4/20) reported a dramatic increase, resulting in an overall increase of 11%. In contrast, there was an obvious reduction in dengue cases in 2021 in almost all countries (18/20) studied, with an overall 40% reduction rate. The overall effectiveness of NPIs on dengue varied with region and time due to multiple factors, but most countries reported significant reductions. Travel-related interventions demonstrated great effectiveness for reducing imported cases of dengue fever. Internal movement restrictions of constantly varying intensity and range are more likely to mitigate the entire level of dengue transmission by reducing the spread of dengue fever between regions within a country, which is useful for developing a more comprehensive and sustainable strategy for preventing and controlling dengue fever in the future.

Pre-Existing Cross-Reactive Antibody Responses Do Not Significantly Impact Inactivated COVID-19 Vaccine-Induced Neutralization.

Recent exposure to seasonal coronaviruses (sCoVs) may stimulate cross-reactive antibody responses against severe acute respiratory syndrome CoV 2 (SARS-CoV-2). However, previous studies have produced divergent results regarding protective or damaging immunity induced by prior sCoV exposure. It remains unknown whether pre-existing humoral immunity plays a role in vaccine-induced neutralization and antibody responses. In this study, we collected 36 paired sera samples from 36 healthy volunteers before and after immunization with inactivated whole-virion SARS-CoV-2 vaccines for COVID-19, and analyzed the distribution and intensity of pre-existing antibody responses at the epitope level pre-vaccination as well as the relationship between pre-existing sCoV immunity and vaccine-induced neutralization. We observed large amounts of pre-existing cross-reactive antibodies in the conserved regions among sCoVs, especially the S2 subunit. Excep t for a few peptides, the IgG and IgM fluorescence intensities against S, M and N peptides did not differ significantly between pre-vaccination and post-vaccination sera of vaccinees who developed a neutralization inhibition rate (%inhibition) <40 and %inhibition ≥40 after two doses of the COVID-19 vaccine. Participants with strong and weak pre-existing cross-reactive antibodies (strong pre-CRA; weak pre-CRA) had similar %inhibition pre-vaccination (10.9% ± 2.9% vs. 12.0% ± 2.2%, P=0.990) and post-vaccination (43.8% ± 25.1% vs. 44.6% ± 21.5%, P=0.997). Overall, the strong pre-CRA group did not show a significantly greater increase in antibody responses to the S protein linear peptides post-vaccination compared with the weak pre-CRA group. Therefore, we found no evidence for a significant impact of pre-existing antibody responses on inactivated vaccine-induced neutralization and antibody responses. Our research provides an important basis for inactivated SARS-CoV-2 vaccine use in the context of high sCoV seroprevalence.

A One Health strategy for emerging infectious diseases based on the COVID-19 outbreak.

Coronavirus disease 2019 (COVID-19) is as an emerging infectious disease (EID) that has caused the worst public health catastrophe of the 21st century thus far. In terms of impact, the COVID-19 pandemic is second only to the Spanish Flu pandemic of 1918 in modern world history. As of 7 September 2021, there have been 220 million confirmed cases of COVID-19 and more than 4.5 million deaths. EIDs pose serious public health and socio-economic risks, and 70% of EIDs originate from wildlife. Preventing development of EIDs such as COVID-19 is a pressing concern. Here, taking the COVID-19 pandemic as an example, we illustrate the disastrous effects of EIDs and assess their emergence and evolution from a One Health perspective. We propose a One Health strategy, centered on 'moving the gates forward', for EID prevention and control at the human-animal-environment interface. This strategy may be instructive and provide early warnings of EIDs in the future.

Clinical Treatment Experience in Severe and Critical COVID-19.

Compared with other deadly diseases, the coronavirus disease 2019 (COVID-19) is highly infectious with a relatively low mortality rate. Although critical cases account for only 5% of cases, the mortality rate for the same is nearly 50%. Therefore, the key to the COVID-19 treatment is to effectively treat severe patients and reduce the transition from severe to critical cases. A retrospective study was carried out to evaluate outcomes of treatment in patients with severe and critical COVID-19 admitted to a COVID-19 special hospital in Wuhan, China. A total of 75 severe and critical COVID-19 patients were admitted and treated with immunomodulation as the main strategy combined with anti-inflammatory therapy and appropriate anticoagulation. Leukocyte levels in patients with 7-14 days of onset to diagnosis were significantly lower than in those with >14 days. Higher levels of globulin and D-dimer and lower lymphocyte levels were found in the older age group (>65 years) than in the middle-aged group (50-64 years). Patients with comorbidity had higher levels of inflammatory indicators. After treatment, 65 (86.67%) patients were cured, 7 (9.33%) had improved, and 3 (4.00%) had died. Median hospitalization duration was 23 days. Fatal cases showed continuously increased levels of globulin, dehydrogenase (LDH), hypersensitive C-reactive protein (hs-CRP), D-dimer, and cytokines during treatment. Time from onset to diagnosis, age, and comorbidity are important influencing factors on treatment effects. The occurrence of immunosuppression, "cytokine storm," and thrombosis may be an important cause of death in severely infected cases. In conclusion, high cure rate and low mortality suggested that immunomodulation combined with anti-inflammatory therapy and appropriate anticoagulant therapy is a good strategy for treatment of patients with severe and critical COVID-19.

The characteristics of and responses to the two COVID-19 outbreak waves in Hebei Province of China, January 2020 to February 2021.

Hebei Province was affected by two coronavirus disease 2019 (COVID-19) outbreak waves during the period 22 January 2020 through 27 February 2020 (wave 1) and 2 January 2021 through 14 February 2021 (wave 2). To evaluate and compare the epidemiological characteristics, containment delay, cluster events and social activity, as well as non-pharmaceutical interventions of the two COVID-19 outbreak waves, we examined real-time update information on all COVID-19-confirmed cases from a publicly available database. Wave 1 was closely linked with the COVID-19 pandemic in Wuhan, whereas wave 2 was triggered, to a certain extent, by the increasing social activities such as weddings, multi-household gatherings and church events during the slack agricultural period. In wave 2, the epidemic spread undetected in the rural areas, and people living in the rural areas had a higher incidence rate than those living in the urban areas (5.3 vs. 22.0 per 1 000 000). Furthermore, Rt was greater than 1 in the early stage of the two outbreak waves, and decreased substantially after massive non-pharmaceutical interventions were implemented. In China's 'new-normal' situation, development of targeted and effective intervention remains key for COVID-19 control in consideration of the potential threat of new coronavirus strains.

Immunoreactive peptide maps of SARS-CoV-2.

Serodiagnosis of SARS-CoV-2 infection is impeded by immunological cross-reactivity among the human coronaviruses (HCoVs): SARS-CoV-2, SARS-CoV-1, MERS-CoV, OC43, 229E, HKU1, and NL63. Here we report the identification of humoral immune responses to SARS-CoV-2 peptides that may enable discrimination between exposure to SARS-CoV-2 and other HCoVs. We used a high-density peptide microarray and plasma samples collected at two time points from 50 subjects with SARS-CoV-2 infection confirmed by qPCR, samples collected in 2004-2005 from 11 subjects with IgG antibodies to SARS-CoV-1, 11 subjects with IgG antibodies to other seasonal human coronaviruses (HCoV), and 10 healthy human subjects. Through statistical modeling with linear regression and multidimensional scaling we identified specific peptides that were reassembled to identify 29 linear SARS-CoV-2 epitopes that were immunoreactive with plasma from individuals who had asymptomatic, mild or severe SARS-CoV-2 infections. Larger studies will be required to determine whether these peptides may be useful in serodiagnostics.

The Emergence and Spread of Novel SARS-CoV-2 Variants.

Since severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) began to spread in late 2019, laboratories around the world have widely used whole genome sequencing (WGS) to continuously monitor the changes in the viral genes and discovered multiple subtypes or branches evolved from SARS-CoV-2. Recently, several novel SARS-CoV-2 variants have been found to be more transmissible. They may affect the immune response caused by vaccines and natural infections and reduce the sensitivity to neutralizing antibodies. We analyze the distribution characteristics of prevalent SARS-CoV-2 variants and the frequency of mutant sites based on the data available from GISAID and PANGO by R 4.0.2 and ArcGIS 10.2. Our analysis suggests that B.1.1.7, B.1.351, and P.1 are more easily spreading than other variants, and the key mutations of S protein, including N501Y, E484K, and K417N/T, have high mutant frequencies, which may have become the main genotypes for the spread of SARS-CoV-2.

Altered oral and gut microbiota and its association with SARS-CoV-2 viral load in COVID-19 patients during hospitalization.

The human oral and gut commensal microbes play vital roles in the development and maintenance of immune homeostasis, while its association with susceptibility and severity of SARS-CoV-2 infection is barely understood. In this study, we investigated the dynamics of the oral and intestinal flora before and after the clearance of SARS-CoV-2 in 53 COVID-19 patients, and then examined their microbiome alterations in comparison to 76 healthy individuals. A total of 140 throat swab samples and 81 fecal samples from these COVID-19 patients during hospitalization, and 44 throat swab samples and 32 fecal samples from sex and age-matched healthy individuals were collected and then subjected to 16S rRNA sequencing and viral load inspection. We found that SARS-CoV-2 infection was associated with alterations of the microbiome community in patients as indicated by both alpha and beta diversity indexes. Several bacterial taxa were identified related to SARS-CoV-2 infection, wherein elevated Granulicatella and Rothia mucilaginosa were found in both oral and gut microbiome. The SARS-CoV-2 viral load in those samples was also calculated to identify potential dynamics between COVID-19 and the microbiome. These findings provide a meaningful baseline for microbes in the digestive tract of COVID-19 patients and will shed light on new dimensions for disease pathophysiology, potential microbial biomarkers, and treatment strategies for COVID-19.

A Meta-analysis on the Role of Children in Severe Acute Respiratory Syndrome Coronavirus 2 in Household Transmission Clusters.

The role of children in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains highly controversial. To address this issue, we performed a meta-analysis of the published literature on household SARS-CoV-2 transmission clusters (n = 213 from 12 countries). Only 8 (3.8%) transmission clusters were identified as having a pediatric index case. Asymptomatic index cases were associated with a lower secondary attack in contacts than symptomatic index cases (estimate risk ratio [RR], 0.17; 95% confidence interval [CI], 0.09-0.29). To determine the susceptibility of children to household infections the secondary attack rate in pediatric household contacts was assessed. The secondary attack rate in pediatric household contacts was lower than in adult household contacts (RR, 0.62; 95% CI, 0.42-0.91). These data have important implications for the ongoing management of the COVID-19 pandemic, including potential vaccine prioritization strategies.

Advances in Neutralization Assays for SARS-CoV-2

Abstract The coronavirus disease 2019 (COVID-19) pandemic has triggered a global health emergency and brought disaster to humans. Tremendous efforts have been made to control the pandemic, among which neutralizing antibodies (NAbs) are of specific interest to researchers. Neutralizing antibodies are generated within weeks after infection or immunization, and can protect cells from virus intrusion and confer protective immunity to cells. Thus, production of NAbs is considered as a main goal for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and NAbs may be used for patient treatment in the form of monoclonal antibodies. Neutralization assays are capable of quantitatively detecting NAbs against SARS-CoV-2, allowing to explore the relationship between the level of NAbs and the severity of the disease, and may predict the possibility of re-infection in COVID-19 patients. They can also be used to test the effects of monoclonal antibodies, convalescent plasma and vaccines. At present, wild-type virus neutralization assay remains the gold standard for measuring NAbs;while pseudovirus neutralization assays, Surrogate virus neutralization test (sVNT), and high-throughput versions of neutralization assays are popular alternatives with their own advantages and disadvantages. In this review article, we summarize the characteristics and recent progress of SARS-CoV-2 neutralization assays. Special attention is given to the current limitations of various neutralization assays so as to promote new possible strategies with NAbs by which rapid SARS-CoV-2 serological diagnosis and antiviral screening in the future will be achieved.