Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2.

Breakthrough infections by SARS-CoV-2 variants become the global challenge for pandemic control. Previously, we developed the protein subunit vaccine ZF2001 based on the dimeric receptor-binding domain (RBD) of prototype SARS-CoV-2. Here, we developed a chimeric RBD-dimer vaccine approach to adapt SARS-CoV-2 variants. A prototype-Beta chimeric RBD-dimer was first designed to adapt the resistant Beta variant. Compared with its homotypic forms, the chimeric vaccine elicited broader sera neutralization of variants and conferred better protection in mice. The protection of the chimeric vaccine was further verified in macaques. This approach was generalized to develop Delta-Omicron chimeric RBD-dimer to adapt the currently prevalent variants. Again, the chimeric vaccine elicited broader sera neutralization of SARS-CoV-2 variants and conferred better protection against challenge by either Delta or Omicron SARS-CoV-2 in mice. The chimeric approach is applicable for rapid updating of immunogens, and our data supported the use of variant-adapted multivalent vaccine against circulating and emerging variants.

Heterologous prime-boost immunizations with chimpanzee adenoviral vectors elicit potent and protective immunity against SARS-CoV-2 infection.

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is urgently needed to tackle the COVID-19 global pandemic. Here, we describe the development of chimpanzee adenovirus serotypes 6 and 68 (AdC6 and AdC68) vector-based vaccine candidates expressing the full-length transmembrane spike glycoprotein. We assessed the vaccine immunogenicity, protective efficacy, and immune cell profiles using single-cell RNA sequencing in mice. Mice were vaccinated via the intramuscular route with the two vaccine candidates using prime-only regimens or heterologous prime-boost regimens. Both chimpanzee adenovirus-based vaccines elicited strong and long-term antibody and T cell responses, balanced Th1/Th2 cell responses, robust germinal center responses, and provided effective protection against SARS-CoV-2 infection in mouse lungs. Strikingly, we found that heterologous prime-boost immunization induced higher titers of protective antibodies, and more spike-specific memory CD8+ T cells in mice. Potent neutralizing antibodies produced against the highly transmissible SARS-CoV-2 variants B.1.1.7 lineage (also known as N501Y.V1) and B.1.351 lineage (also known as N501Y.V2) were detectable in mouse sera over 6 months after prime immunization. Our results demonstrate that the heterologous prime-boost strategy with chimpanzee adenovirus-based vaccines is promising for further development to prevent SARS-CoV-2 infection.

Prevalence and Impact Factors of COVID-19 Vaccination Hesitancy Among Breast Cancer Survivors: A Multicenter Cross-Sectional Study in China.

Cancer patients are at a high risk of being infected with COVID-19 and have a poor prognosis after infection. Breast cancer is one of the most common cancers. Since vaccination is an effective measure to prevent the spread of COVID-19, we studied the vaccination rate among breast cancer survivors and analyzed their characteristics to provide evidence for boosting the vaccination rate. The researchers conducted a multicenter, cross-sectional study on 747 breast cancer survivors from six hospitals in Wuhan city between June 5, 2021, and June 12, 2021. The self-administrated questionnaires based on relevant studies were distributed. The researchers then compared differences in characteristics among vaccinated patients, hesitant patients, and non-vaccinated patients. Moreover, they performed univariable and multivariable logistic regression analyses to identify potential factors associated with vaccination hesitancy. The researchers assessed a total of 744 breast cancer survivors -94 cases in the vaccinated group, 103 in the planning group, 295 in the hesitancy group, and 252 in the refusal group. The vaccination rate was 12.63% (95% CI 10.25-15.02%) and 37.23% (95% CI 27.48-47.82%) patients reported adverse reactions. The vaccination hesitancy/refusal rate was 73.52% (95% CI 70.19-76.66%), which was independently associated with current endocrine or targeted therapy (odds ratio [OR] = 1.52, 95% CI 1.03-2.24), no notification from communities or units (OR = 2.46, 95% CI 1.69-3.59) and self-perceived feel (general vs. good, OR = 1.46, 95% CI 1.01-2.13; bad vs. good, OR = 4.75, 95% CI 1.85-12.16). In the hesitancy/refusal group, the primary reason was "I did not know who to ask whether I can get vaccinated" (46.07%), the person who would most influence decisions of patients was the doctor in charge of treatment (35.83%). Effective interaction between doctors and patients, simple and consistent practical guidelines on vaccination, and timely and positive information from authoritative media could combat misinformation and greatly reduce vaccine hesitancy among breast cancer survivors.

Negative and positive psychological experience of frontline nurses in combatting COVID-19: A qualitative study.

AIMS: To qualitatively explore potential experience among frontline nurses who had been fighting against the COVID-19 infection since the outbreak. BACKGROUND: Disasters are often sudden and uncertain. Since the COVID-19 outbreak in Wuhan city, local frontline nurses had been responsible for treatment of COVID-19 for several months. Qualitative study was required to assess complex multi-component psychological experiences among frontline nurses. METHODS: Twenty local frontline nurses were recruited from a designated hospital of COVID-19 treatment. We conducted semi-structured interview using phenomenological method. Descriptive phenomenological method was applied for thematic analysis. RESULTS: Twenty female frontline nurses (aged 24 to 43 years old) were interviewed. Two broader themes, negative and positive, were identified. Negative experience included refusal and helpless (refusal to work at frontline, shortage of confidence in working and helpless), fear and anxiety, excessive miss, and other health issues. Positive experience included improved interpersonal relationship, sublimation of personal faith and strength, changes in understanding meaning of life and new possibility. CONCLUSION: Both positive and negative psychological response were observed, which can provide evidence based clues for making essential strategies and policy. IMPLICATIONS FOR NURSING MANAGEMENT: Understand subjective experience of frontline nurses can establish evidence for development of effective psychological intervention. Nursing administrator should consider the nurses' psychological experience comprehensively to promote psychological growth and lower post-traumatic psychological burden.

Recombinant chimpanzee adenovirus AdC7 expressing dimeric tandem-repeat spike protein RBD protects mice against COVID-19.

A safe and effective vaccine is urgently needed to control the unprecedented COVID-19 pandemic. Four adenovirus-vectored vaccines expressing spike (S) protein have been approved for use. Here, we generated several recombinant chimpanzee adenovirus (AdC7) vaccines expressing S, receptor-binding domain (RBD), or tandem-repeat dimeric RBD (RBD-tr2). We found vaccination via either intramuscular or intranasal route was highly immunogenic in mice to elicit both humoral and cellular immune responses. AdC7-RBD-tr2 showed higher antibody responses compared to either AdC7-S or AdC7-RBD. Intranasal administration of AdC7-RBD-tr2 additionally induced mucosal immunity with neutralizing activity in bronchoalveolar lavage fluid. Either single-dose or two-dose mucosal administration of AdC7-RBD-tr2 protected mice against SARS-CoV-2 challenge, with undetectable subgenomic RNA in lung and relieved lung injury. AdC7-RBD-tr2-elicted sera preserved the neutralizing activity against the circulating variants, especially the Delta variant. These results support AdC7-RBD-tr2 as a promising COVID-19 vaccine candidate.

Clinical outcomes of hemodialysis patients infected with severe acute respiratory syndrome coronavirus 2 and impact of proactive chest computed tomography scans.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that first manifested in humans in Wuhan, Hubei Province, China, in December 2019, and has subsequently spread worldwide. METHODS: We conducted a retrospective, single-center case series of the seven maintenance hemodialysis (HD) patients infected with COVID-19 at Zhongnan Hospital of Wuhan University from 13 January to 7 April 2020 and a proactive search of potential cases by chest computed tomography (CT) scans. RESULTS: Of 202 HD patients, 7 (3.5%) were diagnosed with COVID-19. Five were diagnosed by reverse transcription polymerase chain reaction (RT-PCR) because of compatible symptoms, while two were diagnosed by RT-PCR as a result of screening 197 HD patients without respiratory symptoms by chest CT. Thirteen of 197 patients had positive chest CT features and, of these, 2 (15%) were confirmed to have COVID-19. In COVID-19 patients, the most common features at admission were fatigue, fever and diarrhea [5/7 (71%) had all these]. Common laboratory features included lymphocytopenia [6/7 (86%)], elevated lactate dehydrogenase [3/4 (75%)], D-dimer [5/6 (83%)], high-sensitivity C-reactive protein [4/4 (100%)] and procalcitonin [5/5 (100%)]. Chest CT showed bilateral patchy shadows or ground-glass opacity in the lungs of all patients. Four of seven (57%) received oxygen therapy, one (14%) received noninvasive and invasive mechanical ventilation, five (71%) received antiviral and antibacterial drugs, three (43%) recieved glucocorticoid therapy and one (14%) received continuous renal replacement therapy. As the last follow-up, four of the seven patients (57%) had been discharged and three patients were dead. CONCLUSIONS: Chest CT may identify COVID-19 patients without clear symptoms, but the specificity is low. The mortality of COVID-19 patients on HD was high.

A suspected case of COVID-19 turned into a confirmed case: a case report.

COVID-19 (coronavirus disease 2019) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and discovered in 2019. The clinical manifestations include fever, coughing, difficulty in breathing and even death from multiple organ failure. Nucleic acid test is the golden standard method for confirmation of infection. According to the Chinese 'Seventh Edition of the COVID-19 Diagnosis and Treatment Protocol', suspected patients with negative nucleic acid tests from two consecutive airway specimens can be excluded from diagnosis and released from quarantine. The current report describes a suspected COVID-19 case that had a history of close contact with a COVID-19 patient. The diagnosis was confirmed after the SARS-CoV-2 nucleic acid was detected after four sputum sample tests (sampling interval of at least 24 h).

Improving the early diagnosis of suspected patients with COVID-19: a retrospective study of 106 patients.

INTRODUCTION: An outbreak of coronavirus disease 2019 (COVID-19) occurred in Wuhan, Hubei Province, China. This study aimed to analyze the clinical and epidemiologic characteristics of patients with COVID-19 to better differentiate the suspected patients in Beijing, China. METHODOLOGY: This was a retrospective, single-center study. Clinical and epidemiologic data were collected from suspected patients with COVID-19 admitted to Beijing Ditan Hospital from January 29 to February 21, 2020. RESULTS: One hundred and six patients (60 males and 46 females, median age 36 years) were enrolled. Thirty-six patients were ultimately laboratory confirmed. Fifty-three were excluded from the diagnosis of COVID-19. The remaining 17 patients were highly suspected, although their nucleic acid tests were repeatedly negative. The confirmed patients and highly suspected patients had a significantly higher proportion of epidemiologic history than the excluded patients (P < 0.001). There was no significant difference in clinical symptoms or the underlying diseases among the three groups. The confirmed patients had a higher frequency of lymphopenia and eosinopenia than the highly suspected and excluded patients. Chest computed tomography scans showed bilateral lung involvement, and ground-glass opacity was more likely observed in the confirmed patients. CONCLUSION: The clinical features of the confirmed patients with COVID-19 were insufficient for early diagnosis of COVID-19. The epidemiologic history was of great significance in the early diagnosis of COVID-19. More sensitive diagnostic methods are needed to aid the differential diagnosis of suspected patients with COVID-19.

COVID-19 and the case for global development.

COVID-19 accentuates the case for a global, rather than an international, development paradigm. The novel disease is a prime example of a development challenge for all countries, through the failure of public health as a global public good. The COVID-19 pandemic has highlighted the falsity of any assumption that the global North has all the expertise and solutions to tackle global challenges, and has further highlighted the need for multi-directional learning and transformation in all countries towards a more sustainable and equitable world. We illustrate our argument for a global development paradigm by examining the implications of the COVID-19 pandemic across four themes or 'vignettes': global value chains, digitalisation, debt, and climate change. We conclude that development studies must adapt to a very different context from when the field emerged in the mid-20th century.

Coronavirus disease 2019 in children: Characteristics, antimicrobial treatment, and outcomes.

BACKGROUND: At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help pediatricians understand the conditions of COVID-19 in children. METHODS: We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan Children's Hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. RESULTS: As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-α nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. CONCLUSIONS: The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.

A family cluster of severe acute respiratory syndrome coronavirus 2 infections.

Clinical and epidemiological knowledge of 2019 novel coronavirus disease (COVID-19) is limited. We reported a family cluster of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cases in Beijing, China. This family comprised three laboratory confirmed cases with clinical symptoms. All three patients had close contact with a relative from Wuhan, Hubei Province. Throat swab samples were all positive for SARS-CoV-2 using real-time reverse transcriptase-polymerase chain reaction assays. Chest computerized tomography revealed ground-glass opacities and consolidation. SARS-CoV-2 infections tend to clusters. Physicians should be aware of contact history so that infected patients can be identified promptly and further spreading prevented.