DNA-scaffolded multivalent vaccine against SARS-CoV-2.

Short peptides are poor immunogens. One way to increase their immune responses is by arraying immunogens in multivalency. Simple and efficient scaffolds for spatial controlling the inter-antigen distance and enhancing immune activation are required. Here, we report a molecular vaccine design principle that maximally drives potent SARS-CoV-2 RBD subunit vaccine on DNA duplex to induce robust and efficacious immune responses in vivo. We expect that the DNA-peptide epitope platform represents a facile and generalizable strategy to enhance the immune response. STATEMENT OF SIGNIFICANCE: DNA scaffolds offer a biocompatible and convenient platform for arraying immunogens in multivalency antigenic peptides, and spatially control the inter-antigen distance. This can effectively enhance immune response. Peptide (instead of entire protein) vaccines are highly attractive. However, short peptides are poor immunogens. Our DNA scaffolded multivalent peptide immunogen system induced robust and efficacious immune response in vivo as demonstrated by the antigenic peptide against SARS-CoV-2. The present strategy could be readily generalized and adapted to prepare multivalent vaccines against other viruses or disease. Particularly, the different antigens could be integrated into one single vaccine and lead to super-vaccines that can protect the host from multiple different viruses or multiple variants of the same virus.

Neutralizing and Total/IgG Spike Antibody Responses Following Homologous CoronaVac vs. BNT162b2 Vaccination Up to 90 Days Post-Booster.

INTRODUCTION: We documented the total spike antibody (S-Ab), IgG S-Ab and neutralizing antibody (N-Ab) responses of BNT162b2/CoronaVac vaccinees up to 90 days post-booster dose. METHODS: We included 32 homologous regimen CoronaVac vaccinees and 136 BNT162b2 mRNA vaccinees. We tested their total S-Ab (Roche), IgG (Abbott) and N-Ab (Snibe) levels at set time points from January 2021 to April 2022. All subjects were deemed to be COVID-19-naïve either via clinical history (CoronaVac vaccinees) or nucleocapsid antibody testing (BNT162b2 vaccinees). RESULTS: All antibodies peaked 20-30 days post-inoculation. In BNT162b2 vaccinees, all post-booster antibodies were significantly higher than second-dose peaks. In CoronaVac vaccinees, IgG showed no significant differences between peak third-/second-dose titers (difference of 56.0 BAU/mL, 95% CI of -17.1 to 129, p = 0.0894). The post-vaccination titers of all antibodies in BNT162b2 vaccinees were significantly higher than those in CoronaVac vaccinees at all time points. Post-booster, all antibodies declined in 90 days; the final total/IgG/N-Ab titers were 7536 BAU/mL, 1276 BAU/mL and 12.5 µg/mL in BNT162b2 vaccinees and 646 BAU/mL, 62.4 BAU/mL and 0.44 µg/mL in CoronaVac vaccinees. CONCLUSION: The mRNA vaccine generated more robust total S-Ab, IgG and N-Ab responses after the second and third vaccinations.

mRNA Booster Vaccination Enhances Antibody Responses against SARS-CoV2 Omicron Variant in Individuals Primed with mRNA or Inactivated Virus Vaccines.

The advent of the Omicron variant globally has hastened the requirement for a booster vaccination dose to confer continuous protection against symptomatic SARS-CoV2 infection. However, different vaccines are available in different countries, and individuals who had adverse reactions to certain vaccine types require heterologous vaccine boosters. To understand the efficacy of different vaccination regimens in inducing humoral responses to SARS-CoV2, we examined plasma antibodies and frequencies of Omicron RBD-specific B cells in individuals who had different priming-booster vaccination regimens. We found that individuals with three homologous doses of mRNA vaccines had higher levels of IgG of all subclasses against RBD of Omicron than individuals with three homologous doses of inactivated virus vaccine. A booster with mRNA vaccine resulted in significant increases in median levels of RBD-reactive IgG1 (17-19 fold) and IgG3 (2.3-3.3 fold) as compared to individuals receiving inactivated virus booster shots regardless of priming vaccine types. More importantly, individuals who received a booster dose of mRNA vaccine, irrespective of the priming vaccine, had antibodies with higher neutralizing capability against the Omicron variant than those who received a booster dose of inactivated virus vaccine. Corroborating the antibody results, boosting with the mRNA vaccine increased the frequencies of Omicron RBD-binding B cells by (1.5-3.3 fold) regardless of priming vaccine types. Together, our data demonstrate that an mRNA vaccine (BNT162b2 or mRNA-1273) booster enhances humoral responses against the Omicron variant in individuals vaccinated with either two prior doses of mRNA or inactivated virus vaccine (CoronaVac or BBIBP-CorV), potentially providing more effective protection against SARS-CoV-2 infection, particularly by the Omicron variant.

Kinetics of the Neutralizing and Spike SARS-CoV-2 Antibodies following the Sinovac Inactivated Virus Vaccine Compared to the Pfizer mRNA Vaccine in Singapore.

INTRODUCTION: We compared the early total spike antibody (S-Ab) and neutralizing antibody (N-Ab) responses to two vaccines. METHODS: We studied 96 Pfizer and 34 Sinovac vaccinees over a 14-month period from January 2021 to February 2022. All vaccinees received three doses of one type of vaccine. Antibody levels (Roche Elecsys total S-Ab and the Snibe N-Ab) were tested 10 days after the first dose, 20 days after the second dose, and 20 days after the booster dose. RESULTS: At all time points, the mRNA vaccine generated higher S-Ab and N-Ab responses than the inactivated virus vaccine (S-Ab: first dose 2.48 vs. 0.4 BAU/mL, second dose 2174 vs. 98 BAU/mL, third dose 15,004 vs. 525 BAU/mL; N-Ab: first dose 0.05 vs. 0.02 µg/mL, second dose 3.48 vs. 0.38 µg/mL, third dose 19.8 vs. 0.89 µg/mL). mRNA vaccine recipients had a 6.2/22.2/28.6-fold higher S-Ab and 2.5/9.2/22.2-fold higher N-Ab response than inactivated virus vaccine recipients after the first/second/third inoculations, respectively. Mann-Whitney U analysis confirmed the significant difference in S-Ab and N-Ab titers between vaccination groups at each time point. CONCLUSIONS: The mRNA vaccines generated a more robust S-Ab and N-Ab response than the inactivated virus vaccine at all time points after the first, second, and third vaccinations.

User Perception of Public Parks: A Pilot Study Integrating Spatial Social Media Data with Park Management in the City of Chicago

User-generated content (UGC) is a relatively young field of research;however, it has been proven useful in disciplines such as hospitality and tourism, to elicit public opinions of place usage. In landscape architecture and urban planning, UGC has been used to understand people’s emotions and movement in a space, while other areas and additional functions are yet to be discovered. This paper explores the capability of UGC in revealing city-scale park management problems and the applicability of social media as a future tool in bridging visitor feedback to city parks and recreation department staff. This research analyzed the spatial characteristics and patterns of Google Maps review quantity, rating score, and review comments. The results of this pilot study indicate the spatial and structural features of the Chicago parks and demonstrate distribution problems, financial investment priority concerns, park usage characteristics, and user preferences of the park attributes. Findings affirm that user-generated online reviews can be used as an alternative and self-reporting data source to effectively assess the natural performance and users’ experience of city parks and can potentially serve as an evaluative tool for public park management.

Hypophosphatemia is an independent risk factor for AKI among hospitalized patients with COVID-19 infection.

BACKGROUND: This study sought to investigate incidence and risk factors for acute kidney injury (AKI) in hospitalized COVID-19. METHODS: In this retrospective study, we enrolled 823 COVID-19 patients with at least two evaluations of renal function during hospitalization from four hospitals in Wuhan, China between February 2020 and April 2020. Clinical and laboratory parameters at the time of admission and follow-up data were recorded. Systemic renal tubular dysfunction was evaluated via 24-h urine collections in a subgroup of 55 patients. RESULTS: In total, 823 patients were enrolled (50.5% male) with a mean age of 60.9 ± 14.9 years. AKI occurred in 38 (40.9%) ICU cases but only 6 (0.8%) non-ICU cases. Using forward stepwise Cox regression analysis, we found eight independent risk factors for AKI including decreased platelet level, lower albumin level, lower phosphorus level, higher level of lactate dehydrogenase (LDH), procalcitonin, C-reactive protein (CRP), urea, and prothrombin time (PT) on admission. For every 0.1 mmol/L decreases in serum phosphorus level, patients had a 1.34-fold (95% CI 1.14-1.58) increased risk of AKI. Patients with hypophosphatemia were likely to be older and with lower lymphocyte count, lower serum albumin level, lower uric acid, higher LDH, and higher CRP. Furthermore, serum phosphorus level was positively correlated with phosphate tubular maximum per volume of filtrate (TmP/GFR) (Pearson r = 0.66, p < .001) in subgroup analysis, indicating renal phosphate loss via proximal renal tubular dysfunction. CONCLUSION: The AKI incidence was very low in non-ICU patients as compared to ICU patients. Hypophosphatemia is an independent risk factor for AKI in patients hospitalized for COVID-19 infection.

A validation study of UCSD-Mayo risk score in predicting hospital-acquired acute kidney injury in COVID-19 patients.

INTRODUCTION: Acute kidney injury (AKI) in coronavirus disease 2019 (COVID-19) patients is associated with poor prognosis. Early prediction and intervention of AKI are vital for improving clinical outcome of COVID-19 patients. As lack of tools for early AKI detection in COVID-19 patients, this study aimed to validate the USCD-Mayo risk score in predicting hospital-acquired AKI in an extended multi-center COVID-19 cohort. METHODS: Five hundred seventy-two COVID-19 patients from Wuhan Tongji Hospital Guanggu Branch, Wuhan Leishenshan Hospital, and Wuhan No. Ninth Hospital was enrolled for this study. Patients who developed AKI or reached an outcome of recovery or death during the study period were included. Predictors were evaluated according to data extracted from medical records. RESULTS: Of all patients, a total of 44 (8%) developed AKI. The UCSD-Mayo risk score achieved excellent discrimination in predicting AKI with the C-statistic of 0.88 (95%CI: 0.84-0.91). Next, we determined the UCSD-Mayo risk score had good overall performance (Nagelkerke R2 = 0.32) and calibration in our cohort. Further analysis showed that the UCSD-Mayo risk score performed well in subgroups defined by gender, age, and several chronic comorbidities. However, the discrimination of the UCSD-Mayo risk score in ICU patients and patients with mechanical ventilation was not good which might be resulted from different risk factors of these patients. CONCLUSIONS: We validated the performance of UCSD-Mayo risk score in predicting hospital-acquired AKI in COVID-19 patients was excellent except for patients from ICU or patients with mechanical ventilation.

Dynamics and Correlation Among Viral Positivity, Seroconversion, and Disease Severity in COVID-19 : A Retrospective Study.

BACKGROUND: The understanding of viral positivity and seroconversion during the course of coronavirus disease 2019 (COVID-19) is limited. OBJECTIVE: To describe patterns of viral polymerase chain reaction (PCR) positivity and evaluate their correlations with seroconversion and disease severity. DESIGN: Retrospective cohort study. SETTING: 3 designated specialty care centers for COVID-19 in Wuhan, China. PARTICIPANTS: 3192 adult patients with COVID-19. MEASUREMENTS: Demographic, clinical, and laboratory data. RESULTS: Among 12 780 reverse transcriptase PCR tests for severe acute respiratory syndrome coronavirus 2 that were done, 24.0% had positive results. In 2142 patients with laboratory-confirmed COVID-19, the viral positivity rate peaked within the first 3 days. The median duration of viral positivity was 24.0 days (95% CI, 18.9 to 29.1 days) in critically ill patients and 18.0 days (CI, 16.8 to 19.1 days) in noncritically ill patients. Being critically ill was an independent risk factor for longer viral positivity (hazard ratio, 0.700 [CI, 0.595 to 0.824]; P < 0.001). In patients with laboratory-confirmed COVID-19, the IgM-positive rate was 19.3% in the first week, peaked in the fifth week (81.5%), and then decreased steadily to around 55% within 9 to 10 weeks. The IgG-positive rate was 44.6% in the first week, reached 93.3% in the fourth week, and then remained high. Similar antibody responses were seen in clinically diagnosed cases. Serum inflammatory markers remained higher in critically ill patients. Among noncritically ill patients, a higher proportion of those with persistent viral positivity had low IgM titers (<100 AU/mL) during the entire course compared with those with short viral positivity. LIMITATION: Retrospective study and irregular viral and serology testing. CONCLUSION: The rate of viral PCR positivity peaked within the initial few days. Seroconversion rates peaked within 4 to 5 weeks. Dynamic laboratory index changes corresponded well to clinical signs, the recovery process, and disease severity. Low IgM titers (<100 AU/mL) are an independent risk factor for persistent viral positivity. PRIMARY FUNDING SOURCE: None.

Six Gynecological Cancer Patients Infected With SARS-CoV-2 After Surgery or Radio-/Chemo-Therapy Treatment: Case Series.

OBJECTIVE: Recently, the number of gynecological cancer patients infected with SARS-CoV-2 has been increasing. This article was committed to studying the influence of gynecological tumor treatment history compared to the Coronavirus Disease 2019 (COVID-19), which was of great significance for the treatment of gynecological cancer patients during the outbreak of COVID-19. METHODS: We retrospectively analyzed the diagnosis and treatment of six gynecological cancer patients infected with SARS-CoV-2 in Tongji Hospital in Wuhan from January 30 to March 25, 2020. To better explain the treatment of gynecological cancer patients during the epidemic of COVID-19, we summarized the case characteristics, auxiliary examination, treatment plan, and outcome of these six patients. RESULTS: We observed a high rate of nosocomial SARS-CoV-2 infection among these six gynecological cancer patients, who were in a low immune state. Also, due to the influence of cancer treatment history, COVID-19-related atypical symptoms became the first symptom of COVID-19 in some cases, which increased the difficulty of diagnosis. Furthermore, in terms of treatment for these cases, immune boosters and reagents that raised white blood cells were applied, except for in symptomatic antiviral treatment. At present, all patients in this study were discharged from the hospital with a good prognosis. CONCLUSION: After cancer-related treatment, the gynecological cancer patients became more susceptible to COVID-19. Besides, the history of cancer treatment made the diagnosis of COVID-19 difficult, which also affected the treatment of COVID-19. Therefore, we put forward the corresponding therapy suggestions for gynecological cancer patients during the outbreak of COVID-19.

[Correlation between hyponatremia and the severity of coronavirus disease 2019].

OBJECTIVE: To investigate the correlation between hyponatremia and the severity of coronavirus disease 2019 (COVID-19). METHODS: Clinical data of 12 patients with COVID-19 admitted to Shantou Central Hospital from January 23 to February 5 in 2020 were retrospectively analyzed, including gender, age, symptoms, lab test and clinical outcomes, to analyze the change trend of blood Na+ level in the patients with COVID-19. RESULTS: Among the 12 patients with COVID-19, there were 8 males and 4 females with the mean age of (38.0±16.3) years old, most of them were admitted to the hospital with cough and/or fever. All patients had a positive nucleic acid test for 2019 novel coronavirus (2019-nCoV), and were discharged after clinical treatment with oxygen therapy, antiviral, antibacterial, anti-inflammatory, and nutritional support. All patients were of ordinary type when they were admitted to the hospital. Among them, 1 patient turned into a severe case during the course of the disease, and 1 patient showed a tendency to become severe case. It was found that 10 patients without severe conversion had an average blood Na+ of (138.3±1.3) mmol/L at admission, and the lowest blood Na+ during the course of disease was (135.9±3.1) mmol/L. However, 2 patients who became severe and had a tendency to become severe disease (Na+ levels at admission were 140.0 mmol/L and 138.0 mmol/L, respectively) experienced hyponatremia during the course of the disease (the lowest blood Na+ levels were 129.0 mmol/L and 122.0 mmol/L). Further analysis showed that the lower serum Na+ level, the higher level of white blood cell count (WBC) and C-reactive protein (CRP), but serum Na+ level was consistent with the change trend of lymphocytes, suggesting that hyponatremia was closely correlated with severe inflammation reaction. CONCLUSIONS: Serum Na+ showed decreasing tendency during the development of COVID-19, and hyponatremia was closely related to the severity of COVID-19. It was necessary to pay great attention to the change trend of blood Na+ level. However, further research was needed to obtain more reliable conclusions and explorer the pathophysiological mechanisms.

Cancer history is an independent risk factor for mortality in hospitalized COVID-19 patients: a propensity score-matched analysis.

BACKGROUND: Although research on the effects of comorbidities on coronavirus disease 2019 (COVID-19) patients is increasing, the risk of cancer history has not been evaluated for the mortality of patients with COVID-19. METHODS: In this retrospective study, we included 3232 patients with pathogen-confirmed COVID-19 who were hospitalized between January 18th and March 27th, 2020, at Tongji Hospital in Wuhan, China. Propensity score matching was used to minimize selection bias. RESULTS: In total, 2665 patients with complete clinical outcomes were analyzed. The impacts of age, sex, and comorbidities were evaluated separately using binary logistic regression analysis. The results showed that age, sex, and cancer history are independent risk factors for mortality in hospitalized COVID-19 patients. COVID-19 patients with cancer exhibited a significant increase in mortality rate (29.4% vs. 10.2%, P < 0.0001). Furthermore, the clinical outcomes of patients with hematological malignancies were worse, with a mortality rate twice that of patients with solid tumors (50% vs. 26.1%). Importantly, cancer patients with complications had a significantly higher risk of poor outcomes. One hundred nine cancer patients were matched to noncancer controls in a 1:3 ratio by propensity score matching. After propensity score matching, the cancer patients still had a higher risk of mortality than the matched noncancer patients (odds ratio (OR) 2.98, 95% confidence interval (95% CI) 1.76-5.06). Additionally, elevations in ferritin, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, procalcitonin, prothrombin time, interleukin-2 (IL-2) receptor, and interleukin-6 (IL-6) were observed in cancer patients. CONCLUSIONS: We evaluated prognostic factors with epidemiological analysis and highlighted a higher risk of mortality for cancer patients with COVID-19. Importantly, cancer history was the only independent risk factor for COVID-19 among common comorbidities, while other comorbidities may act through other factors. Moreover, several laboratory parameters were significantly different between cancer patients and matched noncancer patients, which may indicate specific immune and inflammatory reactions in COVID-19 patients with cancer.