COVID-19 breakthrough infection after four doses of the vaccines: a case report

The COVID-19 vaccines provide a high degree of protection against severe disease, hospitalisation, and death. However, no vaccine claimed 100% effectiveness and it is expected that a small proportion of vaccinated individuals may develop a breakthrough infection due to individual differences, virus variants and other factors. We conducted an epidemiological investigation and analysis of an imported case who had finished four doses of vaccination, and in order to provide a relevant reference for regular epidemic prevention and control in the post-pandemic era.

Characteristics and containment of the outbreak caused by the SARS-CoV-2 Omicron variants in Shanghai, China: a retrospective study

Objective: The study aimed to describe the characteristics and containment of the Omicron variants in Shanghai compared with the previous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in China. Methods: We summarized the data retrieved from the Shanghai Municipal Health Commission from January to June 2022 and the National Health Commission of the People's Republic of China from March 2020 to August 2021. Epidemiological analysis was utilized to describe the differences among SARS-CoV-2 variants and the infection situation in the outbreaks in China. Results: The Omicron variants had the characteristics of high insidiousness, rapid transmission, high infectivity, and short incubation period, which were consistent with the characteristics of outbreaks caused by Omicron in other regions in China and abroad. There were 568978 asymptomatic infections in Shanghai from Feburary 26 to June 30, 2022, accounting for 90.73% of the SARS-CoV-2 infections in this outbreak wave. It's significantly different from a total of 23277 SARS-CoV-2 infections in China between March 31, 2020 and August 8, 2021, of which 41.97% of the cases were asymptomatic infections. Conclusions: Compared with previous outbreaks emerged in China, the Omicron outbreak in Shanghai was characterized by multiple point dissemination, wide coverage, a large number of close contacts of confirmed infections and asymptomatic carriers, and difficult source tracing. The lessons from Shanghai's response to Omicron showed that the dynamic zero-COVID policy is still the most suitable response to the virus which can quickly find the infections and curb the transmission route.

Assessing patient safety culture in obstetrics ward: a pilot study using a modified Manchester Patient Safety Framework in China.

AIM: The primary objective of this study was to assess the patient safety culture in a general hospital in Shanghai, China, through a modified Manchester Patient Safety Framework (MaPSaF). DESIGN: This study has a qualitative interview design. Data were collected through group interviews and analyses performed through content analysis. METHODS: The MaPSaF was translated into Chinese and used to assess the patient safety culture in a large general hospital in Shanghai, China. Group interviews using the MaPSaF were conducted with 15 nurses in the obstetric ward. Participants rated their safety practice individually on each of the nine MaPSaF safety culture dimensions. The dimensions and scores were then collectively discussed and a practice-wide consensus score for each dimension was agreed. Discussions were recorded, transcribed and analysed to assess patient safety in the obstetric ward. RESULTS: It took about 2 hr to complete the discussion focusing on patients' safety employing the MaPSaF. Most participants recognized the process as acceptable and useful. The MaPSaF directed team discussion about patient safety issues and facilitated communication, prompting some practice changes. All participants responded positively to the discussion and perceived MaPSaF as a good safety culture assessment tool, with clear, comprehensive and understandable entries. The process demonstrated that the department of obstetrics in the hospital already had a positive patient safety culture, but certain areas were highlighted as still needing improvement. Based on participants' positive experience and perception of the MaPSaF, it can be concluded that there is potential benefit in its adaptation and use in obstetrics wards of Chinese hospitals. The MaPSaF has the potential to strengthen existing safety cultures and improve general safety through collaborative measures.

Reduced binding activity of vaccine serum to omicron receptor-binding domain.

Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). However, the emergence and rapid transmission of the SARS-CoV-2 variant Omicron raise a concern about the efficacy of the current vaccination strategy. Here, we expressed monomeric and dimeric receptor-binding domains (RBDs) of the spike protein of prototype SARS-CoV-2 and Omicron variant in E. coli and investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to these recombinant RBDs. In 106 human blood samples collected from 91 participants from Jiangxi, China, 26 sera were identified to be positive for SARS-CoV-2 spike protein antibodies by lateral flow dipstick (LFD) assays, which were enriched in the ones collected from day 7 to 1 month post-boost (87.0%) compared to those harvested within 1 week post-boost (23.8%) (P < 0.0001). A higher positive ratio was observed in the child group (40.8%) than adults (13.6%) (P = 0.0073). ELISA results showed that the binding activity of anti-SARS-CoV-2 antibody-positive sera to Omicron RBDs dropped by 1.48- to 2.07-fold compared to its homogeneous recombinant RBDs. Thus, our data indicate that current SARS-CoV-2 vaccines provide restricted humoral protection against the Omicron variant.

SARS-CoV-2 neutralizing antibody response after three doses of mRNA1273 vaccine and COVID-19 in hemodialysis patients.

Background: In hemodialysis patients, a third vaccination is frequently administered to augment protection against coronavirus disease 2019 (COVID-19). However, the newly emerged B.1.1.159 (Omicron) variant may evade vaccinal protection more easily than previous strains. It is of clinical interest to better understand the neutralizing activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants after booster vaccine or COVID-19 infection in these mostly immunocompromised patients. Methods: Hemodialysis patients from four dialysis centers were recruited between June 2021 and February 2022. Each patient provided a median of six serum samples. SARS-CoV-2 neutralizing antibodies (nAbs) against wild type (WT) or Omicron were measured using the GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit. Results: Forty-two patients had three doses of mRNA1273. Compared to levels prior to the third dose, nAb-WT increased 18-fold (peak at day 23) and nAb-Omicron increased 23-fold (peak at day 24) after the third dose. Peak nAb-WT exceeded peak nAb-Omicron 27-fold. Twenty-one patients had COVID-19 between December 24, 2021, and February 2, 2022. Following COVID-19, nAb-WT and nAb-Omicron increased 12- and 40-fold, respectively. While levels of vaccinal and post-COVID nAb-WT were comparable, post-COVID nAb-Omicron levels were 3.2 higher than the respective peak vaccinal nAb-Omicron. Four immunocompromised patients having reasons other than end-stage kidney disease have very low to no nAb after the third dose or COVID-19. Conclusions: Our results suggest that most hemodialysis patients have a strong humoral response to the third dose of vaccination and an even stronger post-COVID-19 humoral response. Nevertheless, nAb levels clearly decay over time. These findings may inform ongoing discussions regarding a fourth vaccination in hemodialysis patients.

SARS-COV-2 Neutralizing Antibody Response to Booster Vaccination in Patients on Hemodialysis

BACKGROUND AND AIMS SARS-CoV-2 antibody titers after two doses of vaccination decrease over time. Hemodialysis patients are especially vulnerable to COVID-19 as they are immunocompromised, putting them at higher risk of infection and poorer response to vaccines. Therefore, administrating the third dose (‘booster’) in these patients is key to reduce COVID-19 infections and prevent severe illness. Dialysis patients were among the first group of patients who received booster vaccinations. To study the humoral response to the third injection in this group, we collected serum from 33 patients on hemodialysis and measured neutralizing antibody titers against SARS-CoV-2 before and after their booster doses. METHOD Patients were recruited from a dialysis center in New York City, NY from June to September 2021. Data on COVID-19 vaccination and demographics were collected upon enrollment. Blood samples were taken after enrollment. SARS-CoV-2 neutralization antibodies were assayed using the GenScript SARS-CoV-2 Surrogate Virus Neutralization Test Kit (Cat#L00847-A). Corresponding neutralizing antibody titers are presented as Unit/mL (U/mL). RESULTS A total of 33 in-center hemodialysis patients who had received three doses of vaccination were studied. Patients had a mean age of 61 years, 23 (70%) were male. Out of these, 31 (94%) patients received three doses of mRNA-1273 (Moderna), and two patients received the BNT162b2 (Pfizer BioNTech) vaccine. A total of 138 serum samples were analyzed (ranging from 156 days before to 85 days after the booster). Figure 1 shows the antibody titer distribution of all samples in these 33 patients. Each color indicates an individual patient. Each patient has up to 12 data points before and after the booster. The mean neutralizing antibody titers of all 48 data points pre-booster is 29.291 U/mL (range: 228–188.600). Seven days post-booster, the mean neutralizing antibody titer is 73.088 U/mL (range: 12.401–254.504). Mean titer is 169.826 U/mL (range: 17.830–375.046) at 14–28 days post-booster. After the peak time, we observe a decline of the titers. At 72–85 days, the mean titer is 72.179 (range: 33.702–204.382). We fitted a nonparametric mixed effects model with an adaptive spline and a random intercept for each subject to neutralizing antibody titers on the log10 scale. The estimate of the mean trajectory and its 95% confidence interval are shown in Fig. 2. The estimated peak time is 18.2 days with a 95% confidence interval (0–27.7). CONCLUSION Our results suggest that hemodialysis patients have a strong humoral response to booster vaccination. Neutralizing antibody titers peak at 18 days post-booster and wane to an average of 42% of peak value after 10–12 weeks.FIGURE 1: Time-course of neutralizing antibody titers before and after booster vaccination. The colors identify individual hemodialysis patients.FIGURE 2: A nonparametric mixed effects model with an adaptive spline and a random intercept for each subject to neutralizing antibody titers. The red line indicates the average titer, and the gray area indicates the 95% confidence interval. The circles are means across all data points.

Reduced binding activity of vaccine serum to omicron receptor-binding domain

Coronavirus disease 2019 (COVID-19) vaccination regimens contribute to limiting the spread of severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2). However, the emergence and rapid transmission of the SARS-CoV-2 variant Omicron raise a concern about the efficacy of the current vaccination strategy. Here, we expressed monomeric and dimeric receptor-binding domains (RBDs) of the spike protein of prototype SARS-CoV-2 and Omicron variant in E. coli and investigated the reactivity of anti-sera from Chinese subjects immunized with SARS-CoV-2 vaccines to these recombinant RBDs. In 106 human blood samples collected from 91 participants from Jiangxi, China, 26 sera were identified to be positive for SARS-CoV-2 spike protein antibodies by lateral flow dipstick (LFD) assays, which were enriched in the ones collected from day 7 to 1 month post-boost (87.0%) compared to those harvested within 1 week post-boost (23.8%) (P < 0.0001). A higher positive ratio was observed in the child group (40.8%) than adults (13.6%) (P = 0.0073). ELISA results showed that the binding activity of anti-SARS-CoV-2 antibody-positive sera to Omicron RBDs dropped by 1.48- to 2.07-fold compared to its homogeneous recombinant RBDs. Thus, our data indicate that current SARS-CoV-2 vaccines provide restricted humoral protection against the Omicron variant.

Neuropsychiatric sequelae of long COVID-19: Pilot results from the COVID-19 neurological and molecular prospective cohort study in Georgia, USA.

Background: As the coronavirus disease 2019 (COVID-19) pandemic continues, there has been a growing interest in the chronic sequelae of COVID-19. Neuropsychiatric symptoms are observed in the acute phase of infection, but there is a need for accurate characterization of how these symptoms evolve over time. Additionally, African American populations have been disproportionately affected by the COVID-19 pandemic. The COVID-19 Neurological and Molecular Prospective Cohort Study in Georgia (CONGA) was established to investigate the severity and chronicity of these neurologic findings over the five-year period following infection. Methods: The CONGA study aims to recruit COVID-19 positive adult patients in Georgia, United States from both the inpatient and outpatient setting, with 50% being African American. This paper reports our preliminary results from the baseline visits of the first 200 patients recruited who were on average 125 days since having a positive COVID-19 test. The demographics, self-reported symptoms, comorbidities, and quantitative measures of depression, anxiety, smell, taste, and cognition were analyzed. Cognitive measures were compared to demographically matched controls. Blood and mononuclear cells were drawn and stored for future analysis. Results: Fatigue was the most reported symptom in the study cohort (68.5%). Thirty percent of participants demonstrated hyposmia and 30% of participants demonstrated hypogeusia. Self-reported neurologic dysfunction did not correlate with dysfunction on quantitative neurologic testing. Additionally, self-reported symptoms and comorbidities were associated with depression and anxiety. The study cohort performed worse on cognitive measures compared to demographically matched controls, and African American patients scored lower compared to non-Hispanic White patients on all quantitative cognitive testing. Conclusion: Our results support the growing evidence that there are chronic neuropsychiatric symptoms following COVID-19 infection. Our results suggest that self-reported neurologic symptoms do not appear to correlate with associated quantitative dysfunction, emphasizing the importance of quantitative measurements in the complete assessment of deficits. Self-reported symptoms are associated with depression and anxiety. COVID-19 infection appears to be associated with worse performance on cognitive measures, though the disparity in score between African American patients and non-Hispanic White patients is likely largely due to psychosocial, physical health, and socioeconomic factors.

SARS-CoV-2 in Spent Dialysate from Chronic Peritoneal Dialysis Patients with COVID-19.

Background: To date, it is unclear whether SARS-CoV-2 is present in spent dialysate from patients with COVID-19 on peritoneal dialysis (PD). Our aim was to assess the presence or absence of SARS-CoV-2 in spent dialysate from patients on chronic PD who had a confirmed diagnosis of COVID-19. Methods: Spent PD dialysate samples from patients on PD who were positive for COVID-19 were collected between March and August 2020. The multiplexed, real-time RT-PCR assay contained primer/probe sets specific to different SARS-CoV-2 genomic regions and to bacteriophage MS2 as an internal process control for nucleic acid extraction. Demographic and clinical data were obtained from patients' electronic health records. Results: A total of 26 spent PD dialysate samples were collected from 11 patients from ten dialysis centers. Spent PD dialysate samples were collected, on average, 25±13 days (median, 20; range, 10-45) after the onset of symptoms. The temporal distance of PD effluent collection relative to the closest positive nasal-swab RT-PCR result was 15±11 days (median, 14; range, 1-41). All 26 PD effluent samples tested negative at three SARS-CoV-2 genomic regions. Conclusions: Our findings indicate the absence of SARS-CoV-2 in spent PD dialysate collected at ≥10 days after the onset of COVID-19 symptoms. We cannot rule out the presence of SARS-CoV-2 in spent PD dialysate in the early stage of COVID-19.

Imparting reusable and SARS-CoV-2 inhibition properties to standard masks through metal-organic nanocoatings.

Face masks are effective response to address this havoc pandemic caused by respiratory infection virus, but they are lack of reusable, antibacterial, and antiviral abilities due to their simple filtration mechanism, bringing to a supply shortage and severe plastic pollution globally. Herein, we designed reusable, antiviral, and antibacterial masks (referred to as R2A masks) that transformed from commonly-used standard masks and household fabrics based on the polyphenol-based surface functionalization. R2A nanocoatings are mainly composed of supramolecular complexation of natural polyphenols and metal ions, possessing a high performance of antibacterial property and comprehensive recyclability. Interfacial interaction of R2A nanocoating can effectively capture the spreading of particulate matters and aerosols containing virus-mimic nanoparticles even after 10 recycles. Moreover, R2A masks exist antibacteria and antivirus for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Collectively, this simple functional enhancement of masks provides a sustainable and strategic preparation for combating the infectious respiratory diseases.

Mechanism of Xuanbai Qingfei Jiedu decoction in the treatment of COVID-19 based on network pharmacology

Objective: To explore the pharmacological mechanism of Xuanbai Qingfei Jiedu Decoction in the treatment of coronavirus disease 2019 (COVID-19) on account of network pharmacology.

Single cell atlas for 11 non-model mammals, reptiles and birds.

The availability of viral entry factors is a prerequisite for the cross-species transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Large-scale single-cell screening of animal cells could reveal the expression patterns of viral entry genes in different hosts. However, such exploration for SARS-CoV-2 remains limited. Here, we perform single-nucleus RNA sequencing for 11 non-model species, including pets (cat, dog, hamster, and lizard), livestock (goat and rabbit), poultry (duck and pigeon), and wildlife (pangolin, tiger, and deer), and investigated the co-expression of ACE2 and TMPRSS2. Furthermore, cross-species analysis of the lung cell atlas of the studied mammals, reptiles, and birds reveals core developmental programs, critical connectomes, and conserved regulatory circuits among these evolutionarily distant species. Overall, our work provides a compendium of gene expression profiles for non-model animals, which could be employed to identify potential SARS-CoV-2 target cells and putative zoonotic reservoirs.

Sample pooling: burden or solution?

BACKGROUND: Pool-testing strategies combine samples from multiple people and test them as a group. A pool-testing approach may shorten the screening time and increase the test rate during times of limited test availability and inadequate reporting speed. Pool testing has been effectively used for a wide variety of infectious disease screening settings. Historically, it originated from serological testing in syphilis. During the current coronavirus disease 2019 (COVID-19) pandemic, pool testing is considered across the globe to inform opening strategies and to monitor infection rates after the implementation of interventions. AIMS: This narrative review aims to provide a comprehensive overview of the global efforts to implement pool testing, specifically for COVID-19 screening. SOURCES: Data were retrieved from a detailed search for peer-reviewed articles and preprint reports using Medline/PubMed, medRxiv, Web of Science, and Google up to 21st March 2021, using search terms "pool testing", "viral", "serum", "SARS-CoV-2" and "COVID-19". CONTENT: This review summarizes the history and theory of pool testing. We identified numerous peer-reviewed articles that describe specific details and practical implementation of pool testing. Successful examples as well as limitations of pool testing, in general and specifically related to the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and antibodies, are reviewed. While promising, significant operational, pre-analytical, logistical, and economic challenges need to be overcome to advance pool testing. IMPLICATIONS: The theory of pool testing is well understood and numerous successful examples from the past are available. Operationalization of pool testing requires sophisticated processes that can be adapted to the local medical circumstances. Special attention needs to be paid to sample collection, sample pooling, and strategies to avoid re-sampling.

Positive Rate of Serology and RT-PCR for COVID-19 among Community Residents and Healthcare Workers in Wuhan, China.

This study aimed to evaluate the infection rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among different populations in Wuhan, China. This cross-sectional survey-based study examined the results of SARS-CoV-2-specific serological tests and RT-PCR tests for 4,454 community residents and 4,614 healthcare workers performed from May 15 to May 29, 2020. The healthcare workers were classified as administrative and logistical staff (n = 1,378), non-first-line healthcare workers (n = 2,630), or first-line healthcare workers (n = 606) according to their frequency of contact with coronavirus disease (COVID-19) patients. The positive rates of SARS-CoV-2-specific IgG, IgM, and RNA were 2.9%, 0.4%, and 0.1% for the community residents and 3.3%, 0.6%, and 0.2% for the healthcare workers, respectively. There were no statistically significant differences between the rates of the two groups. Spearman's correlation analysis showed that the frequency of contact with COVID-19 patients negatively correlated with the positive rates of RT-PCR (rs = -0.036, P = 0.016), but did not significantly correlate with the positive rates of IgM (rs = -0.006, P = 0.698) or IgG (rs = 0.017, P = 0.239). There was no statistically significant difference between the SARS-CoV-2-specific IgG, IgM, or RNA positive rates of the community residents and those of the healthcare workers. The positive rate of SARS-CoV-2 RNA was lower for the first-line healthcare workers than for the non-first-line healthcare workers and the administrative and logistical staff.

The trans-omics landscape of COVID-19.

The outbreak of coronavirus disease 2019 (COVID-19) is a global health emergency. Various omics results have been reported for COVID-19, but the molecular hallmarks of COVID-19, especially in those patients without comorbidities, have not been fully investigated. Here we collect blood samples from 231 COVID-19 patients, prefiltered to exclude those with selected comorbidities, yet with symptoms ranging from asymptomatic to critically ill. Using integrative analysis of genomic, transcriptomic, proteomic, metabolomic and lipidomic profiles, we report a trans-omics landscape for COVID-19. Our analyses find neutrophils heterogeneity between asymptomatic and critically ill patients. Meanwhile, neutrophils over-activation, arginine depletion and tryptophan metabolites accumulation correlate with T cell dysfunction in critical patients. Our multi-omics data and characterization of peripheral blood from COVID-19 patients may thus help provide clues regarding pathophysiology of and potential therapeutic strategies for COVID-19.

An Investigation of a Confirmed Imported Case of COVID-19 Infected Abroad - Qingpu District, Shanghai Municipality, China, November 15, 2020.

SUMMARY: What is already known about this topic? A passenger who was from the United States was taken to the hotel for the required isolation on November 13, 2020. During the quarantine she was diagnosed as the COVID-19 patient on November 15, 2020. Controlling the importation of COVID-19 remains a major challenge.What is added by this report? In this study, an epidemiological investigation was conducted for a confirmed case of COVID-19, including the treatment records in the hospital and 14-day travel trajectory before the onset of disease.What are the implications for public health practice? This study described an epidemiological investigation and management process on an imported case of COVID-19 and analyzed the test results, aiming to provide useful warnings to strengthen the capacity of public health system in response to the importation.

Analyzing the potential therapeutic mechanism of Huashi Baidu Decoction on severe COVID-19 through integrating network pharmacological methods.

BACKGROUND AND AIM: Huashi Baidu Decoction (HSBD) is a novel complex prescription which has positive effects on severe COVID-19. This study was aimed to discover key Chinese materia medica, main active compounds, hub therapeutic target proteins and core signal pathways in the potential therapeutic mechanism of HSBD on severe COVID-19 through integrating network pharmacological methods. EXPERIMENTAL PROCEDURE: TCMSP, TCMID and STITCH databases were used to screen out active compounds and target proteins of HSBD. GeneCards database was used to screen out disease genes of severe COVID-19. The potential therapeutic targets of HSBD on severe COVID-19 were used to construct protein-protein interaction network through STRING database and the hub target proteins were discovered. Next, GO and KEGG enrichment analysis were carried out to discover core signal pathways. Finally, the network diagram of "Chinese materia medica-active compounds-therapeutic target proteins" was built, then key Chinese materia medica and main active compounds were selected. RESULTS AND CONCLUSION: HSBD might treat severe COVID-19 through 45 potential target genes, among them, there were 13 hub target genes: RELA, TNF, IL6, IL1B, MAPK14, TP53, CXCL8, MAPK3, MAPK1, IL4, MAPK8, CASP8, STAT1. Meanswhile, GO_BiologicalProcess and KEGG signaling pathways analysis results showed that the core signal pathways were inflammation and immune regulation pathways. Finally, 4 key Chinese materia medica and 11 main active compounds were discovered in the HSBD. In conclusion, the therapeutic mechanism of HSBD on severe COVID-19 might involve its pharmacological effects of anti-inflammation and immune regulation via acting on 45 disease-related proteins of severe COVID-19. TAXONOMY CLASSIFICATION BY EVISE: Viral Pneumonia, COVID-19, Acute Respiratory Distress Syndrome, Septic Shock, Chinese Herbal Medicine.