Using the Actor-Partner Interdependence Model to explore the psychological impact of COVID-19 on anxiety in dyads of patients with cancer and caregivers.

BACKGROUND: Delineating the compound psychological effect of the pandemic on cancer care, and the interdependency across cancer patient-caregiver dyads have yet to be explored. This study examines the levels of psychological impact of COVID-19 on patient-caregiver dyads anxiety, and the interdependent associations between their COVID-19 and cancer concerns, and risk perceptions. METHOD: There were 352 patients and caregivers (patient-caregiver dyads, N = 176) included in this study (43.2% spousal dyads). Generalized Anxiety Disorder-7 and questionnaires regarding risk perception, perceived confidence in healthcare system, COVID-19, and cancer-related concerns were administered. Actor-Partner Interdependence Model (APIM) analyses were used to determine the interdependent effects. Indirect effects were tested using mediation pathway analyses. RESULTS: Patients reported significantly higher levels of risk perceptions and anxiety than their caregivers (p < 0.01). Anxiety rates (GAD-7 ≥ 10) were also significantly higher (26.7% vs 18.2%, p < 0.01). Dyads' anxiety, "general COVID-19 concerns," "cancer-related concerns," and risk perceptions were correlated (ps < 0.01). APIM showed only actor effects of general COVID-19 concerns, cancer-related COVID-19 concerns, and risk perceptions on anxiety (ßs = 0.19-0.53, ps < 0.01). No partner effects were observed. Similar results were found in the composite APIM. Indirect effects of the patient/caregiver's variables on their partner's anxiety were observed in the mediation analyses. CONCLUSION: Concerns about COVID-19 and cancer care could be indirectly associated in patient-caregiver dyads and need to be proactively addressed. As pandemic evolves into endemicity, engagement with patients and caregivers should strive to be sensitive to their differential needs and messages should be tailored to the informational needs of each.

Building Digital Literacy in Older Adults of Low Socioeconomic Status in Singapore (Project Wire Up): Nonrandomized Controlled Trial.

BACKGROUND: In a rapidly digitalizing world, the inability of older adults to leverage digital technology has been associated with weaker social connections and poorer health outcomes. Despite the widespread digital adoption in Singapore, older adults, especially those of lower socioeconomic status (SES), still face difficulties in adopting information and communications technology and are typically digitally excluded. OBJECTIVE: We aimed to examine the impact of the volunteer-led, one-on-one, and home-based digital literacy program on digital literacy and health-related outcomes such as self-reported loneliness, social connectedness, quality of life, and well-being for older adults of low SES. METHODS: A nonrandomized controlled study was carried out in Singapore between July 2020 and November 2021 involving 138 digitally excluded community-dwelling older adults aged ≥55 years and of lower SES. Older adults awaiting participation in the program served as controls. Older adults under the intervention were equipped with a smartphone and cellular data, underwent fortnightly to monthly digital literacy training with volunteers to learn digital skills, and digitally connected to their existing social networks. Primary outcome was the improvement in self-reported digital literacy. Secondary outcomes included improvements in University of California, Los Angeles 3-item loneliness scale, Lubben Social Network Scale-6, EQ-5D-3L and EQ visual analogue scale scores, and Personal Wellbeing Score. RESULTS: There were significant improvements in digital literacy scores in the intervention group as compared to controls (mean difference 2.28, 95% CI 1.37-3.20; P<.001). Through multiple linear regression analyses, this difference in digital literacy scores remained independently associated with group membership after adjusting for differences in baseline scores, age, gender, education, living arrangement, housing type, and baseline social connectivity and loneliness status. There was no statistically significant difference in University of California, Los Angeles 3-item loneliness scale, Lubben Social Network Scale-6, Personal Wellbeing Score, or EQ-5D Utility and visual analogue scale score. CONCLUSIONS: This study adds to the growing research on digital inclusion by showing that a volunteer-led, one-on-one, and home-based digital literacy program contributed to increase digital literacy in older adults of low SES. Future studies should look into developing more older adult-friendly digital spaces and technology design to encourage continued digital adoption in older adults and, eventually, impact health-related outcomes.

Evolution of anti-SARS-CoV-2 spike protein titers after two-dose of COVID-19 vaccination among people living with HIV.

Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89). Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.

Surface translocation of ACE2 and TMPRSS2 upon TLR4/7/8 activation is required for SARS-CoV-2 infection in circulating monocytes.

Infection of human peripheral blood cells by SARS-CoV-2 has been debated because immune cells lack mRNA expression of both angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease type 2 (TMPRSS2). Herein we demonstrate that resting primary monocytes harbor abundant cytoplasmic ACE2 and TMPRSS2 protein and that circulating exosomes contain significant ACE2 protein. Upon ex vivo TLR4/7/8 stimulation, cytoplasmic ACE2 was quickly translocated to the monocyte cell surface independently of ACE2 transcription, while TMPRSS2 surface translocation occurred in conjunction with elevated mRNA expression. The rapid translocation of ACE2 to the monocyte cell surface was blocked by the endosomal trafficking inhibitor endosidin 2, suggesting that endosomal ACE2 could be derived from circulating ACE2-containing exosomes. TLR-stimulated monocytes concurrently expressing ACE2 and TMPRSS2 on the cell surface were efficiently infected by SARS-CoV-2, which was significantly mitigated by remdesivir, TMPRSS2 inhibitor camostat, and anti-ACE2 antibody. Mass cytometry showed that ACE2 surface translocation in peripheral myeloid cells from patients with severe COVID-19 correlated with its hyperactivation and PD-L1 expression. Collectively, TLR4/7/8-induced ACE2 translocation with TMPRSS2 expression makes circulating monocytes permissive to SARS-CoV-2 infection.

Smartphone Ownership, Digital Literacy, and the Mediating Role of Connectedness and Loneliness In Improving The Wellbeing among Community-Dwelling Singaporean Older Adults of Low Socio-Economic Status (preprint)

Importance: Safe-distancing measures used during the COVID-19 pandemic may exacerbate social isolation and loneliness with their attending negative consequences. Digital technology may mitigate the negative impact of safe-distancing measures; however, older adults of low socioeconomic status (SES) who may not be digitally literate remain a vulnerable population. Objective: To examine the relationship between digital literacy and social connectedness, loneliness, wellbeing, and quality of life (QOL) amongst older adults. To identify demographic factors associated with smartphone ownership, digital literacy, and willingness to enroll in a home-based digital literacy program. Design: Cross-sectional study. Setting: Convenience sampling of older adults receiving financial aid or living in rental flat referred to a volunteer-led digital literacy program.Participants: 302 community dwelling older adults who are ≥55 years old. Main Outcomes: Smartphone ownership, self-reported digital literacy, willingness to enroll in a digital literacy program; social connectedness (Lubben Social Connectedness Scale, LSNS-6), loneliness (UCLA 3-item scale, UCLA-3), wellbeing (Personal Wellbeing Score), and QOL (EQ-5D-3L [utility index], EQ VAS). Results: Social digital literacy had a positive indirect effect on both the wellbeing and QOL (mediated by social connectedness and perceived loneliness) of older adults, while instrumental digital literacy had a negative indirect effect on the two outcomes. 59.9% of participants owned an internet-enabled phone (smartphone). The median digital literacy index is 3 (score ranging from 0 to 13). Older adults who are younger and more educated were more likely to own a smartphone; while older adults who are more educated, Chinese (ethnic majority), have a smartphone, and lower digital literacy index were more likely to enroll in a home-based digital literacy education program.Conclusions and Relevance: During the COVID-19 pandemic, community dwelling older adults of low SES are socially isolated, lonely, and have low digital literacy. Interventions to improve digital literacy (especially the social domain) may help to reduce social isolation and loneliness, ultimately improving wellbeing and QOL.

Effectiveness of Inactivated COVID-19 Vaccines Against COVID-19 Pneumonia and Severe Illness Caused by the B.1.617.2 (Delta) Variant: Evidence from an Outbreak in Guangdong, China (preprint)

Background: Real-world evidence (RWE) of a vaccine supplements clinical trial data by providing information in populations differing from clinical trial populations, under different epidemiological situations, on alternative outcomes, or against different pathogen lineages. To date, RWE on inactivated COVID-19 vaccines against the highly transmissible SARS-CoV-2 B.1.617.2 (Delta) variant is limited, leaving an important gap in the evidence base of inactivated COVID-19 vaccines for use by immunization programs. Methods: Between May and June 2021, an outbreak of the B.1.617.2 variant was discovered and traced in Guangdong, China. Before this outbreak, Guangdong province had started mass vaccination using inactivated vaccines approved by China’s regulator for use in adults. Using surveillance and vaccination data from the outbreak, we assessed the real-world effectiveness of inactivated vaccines against pneumonia and severe illness caused by the B.1.617.2 variant. We enrolled 10813 subjects who were close contacts of laboratory-confirmed cases, categorizing them as an unvaccinated group, a partially vaccinated (1-dose) group, and a fully vaccinated (2-dose) group. We estimated relative risk (RR) and vaccine effectiveness (VE) of the vaccinated groups in relation to the unvaccinated group. Findings: Unadjusted and adjusted VE of full vaccination against pneumonia were 77·7% (95% CI 45·1–90·9) and 69·5% (95% CI 42·8–96·3), respectively. Full vaccination was 100% effective against severe illness. Unadjusted and adjusted VE of partial vaccination against pneumonia were 1·4% (95% CI -79·7–45·9) and 8·4% (95% CI -47·6–64·4). Interpretation Full vaccination with inactivated vaccines is effective against pneumonia, severe, and critical illness caused by the B.1.617.2 variant. Effort should be placed to ensure full vaccination of target populations. Funding: National Natural Science Foundation of China and Key-Area Research and Development Program of Guangdong.Declaration of Interest: None to declare. Ethical Approval: This study was approved by the institutional ethics committee of the Guangdong Provincial Center for Disease Control and Prevention (GDCDC). Data in the study were collected per administrative requirements of disease control and surveillance, and were anonymized for analysis. Participants were informed about the requirements of disease surveillance and provided oral consents.

The relationship of perceived social support to feelings of hopelessness under COVID-19 pandemic: The effects of epidemic risk and meaning in life.

Lockdown orders were issued on January 23, 2020 in Wuhan, China, for the purpose of preventing and controlling COVID-19, which led to severe psychological problems for residents. The present study aimed to investigate the recovery model of hopelessness through interpersonal pathways during the COVID-19 epidemic. An online survey was conducted in 34 provinces (those in autonomous regions and municipalities) of China. This survey investigated residents' hopelessness and the impact of three factors on it, including their perceived social support, meaning in life, and epidemic risk levels. Results showed that both perceived social support and meaning in life negatively predicted hopelessness, while meaning in life played a partial mediating role between perceived social support and hopelessness. Further, epidemic risk level played a moderating role between perceived social support and meaning in life, indicating a "marginal zone effect." Specifically, when comparing other province, perceived social support showed a stronger positive relationship with meaning in life among residents living in other regions of Hubei province. In sum, this study extends the recovery model of hopelessness through interpersonal pathways, and has important implications for public health emergency management.

Individualized model for predicting COVID-19 deterioration in patients with cancer: A multicenter retrospective study.

The 2019 novel coronavirus has spread rapidly around the world. Cancer patients seem to be more susceptible to infection and disease deterioration, but the factors affecting the deterioration remain unclear. We aimed to develop an individualized model for prediction of coronavirus disease (COVID-19) deterioration in cancer patients. The clinical data of 276 cancer patients diagnosed with COVID-19 in 33 designated hospitals of Hubei, China from December 21, 2019 to March 18, 2020, were collected and randomly divided into a training and a validation cohort by a ratio of 2:1. Cox stepwise regression analysis was carried out to select prognostic factors. The prediction model was developed in the training cohort. The predictive accuracy of the model was quantified by C-index and time-dependent area under the receiver operating characteristic curve (t-AUC). Internal validation was assessed by the validation cohort. Risk stratification based on the model was carried out. Decision curve analysis (DCA) were used to evaluate the clinical usefulness of the model. We found age, cancer type, computed tomography baseline image features (ground glass opacity and consolidation), laboratory findings (lymphocyte count, serum levels of C-reactive protein, aspartate aminotransferase, direct bilirubin, urea, and d-dimer) were significantly associated with symptomatic deterioration. The C-index of the model was 0.755 in the training cohort and 0.779 in the validation cohort. The t-AUC values were above 0.7 within 8 weeks both in the training and validation cohorts. Patients were divided into two risk groups based on the nomogram: low-risk (total points ≤ 9.98) and high-risk (total points > 9.98) group. The Kaplan-Meier deterioration-free survival of COVID-19 curves presented significant discrimination between the two risk groups in both training and validation cohorts. The model indicated good clinical applicability by DCA curves. This study presents an individualized nomogram model to individually predict the possibility of symptomatic deterioration of COVID-19 in patients with cancer.

Managing cancer in context of pandemic: a qualitative study to explore the emotional and behavioural responses of patients with cancer and their caregivers to COVID-19.

OBJECTIVES: Having to access life-sustaining treatment during the emerging COVID-19 outbreak has placed patients with cancer at an especially vulnerable position notwithstanding their immunocompromised condition. The present study aimed to elucidate cancer patients' and their caregivers' experiences during this outbreak. DESIGN: Face-to-face semistructured interviews were conducted. SETTING: A tertiary cancer care facility. PARTICIPANTS: 16 patients with cancer and 14 caregivers. Inclusions criteria were: (A) diagnosed with cancer, (B) receiving active treatment or follow-ups, (C) aged 21 years and above and (D) fluent in English or Mandarin. RESULTS: Thematic analysis was conducted. Five themes were identified: heightened sense of threat, impact on healthcare experience, responsibility falls on oneself, striving for normalcy and sense of safety and trust. Heightened threat of COVID-19 was more pronounced in patients and linked to vulnerability and fear, uncertainty and actions of socially irresponsible others. Dominant in their healthcare experience was prioritising cancer and treatment amidst heightened threat and anticipatory worry about treatment disruptions. Both noted on the importance of taking responsibility for one's health, with caregivers reporting a reinforced sense of duty towards patients. They strived to maintain normalcy by viewing COVID-19 as beyond personal control, downplaying and living life as usual. Their resolve was supported by a sense of safety from the actions of authorities, hospitals and trust towards healthcare providers. CONCLUSIONS: Cancer intensifies threat and the emotional impact of COVID-19 and may trigger specific concerns related to treatment. Psychoeducation interventions led by healthcare providers over digital platforms could help address cancer-specific concerns and support patients and caregivers during the pandemic.

Understanding the Psychological Impact of COVID-19 Pandemic on Patients With Cancer, Their Caregivers, and Health Care Workers in Singapore.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has had a global impact, and Singapore has seen 33,000 confirmed cases. Patients with cancer, their caregivers, and health care workers (HCWs) need to balance the challenges associated with COVID-19 while ensuring that cancer care is not compromised. This study aimed to evaluate the psychological effect of COVID-19 on these groups and the prevalence of burnout among HCWs. METHODS: A cross-sectional survey of patients, caregivers, and HCWs at the National Cancer Centre Singapore was performed over 17 days during the lockdown. The Generalized Anxiety Disorder-7 and Maslach Burnout Inventory were used to assess for anxiety and burnout, respectively. Self-reported fears related to COVID-19 were collected. RESULTS: A total of 624 patients, 408 caregivers, and 421 HCWs participated in the study, with a response rate of 84%, 88%, and 92% respectively. Sixty-six percent of patients, 72.8% of caregivers, and 41.6% of HCWs reported a high level of fear from COVID-19. The top concern of patients was the wide community spread of COVID-19. Caregivers were primarily worried about patients dying alone. HCWs were most worried about the relatively mild symptoms of COVID-19. The prevalence of anxiety was 19.1%, 22.5%, and 14.0% for patients, caregivers, and HCWs, respectively. Patients who were nongraduates and married, and caregivers who were married were more anxious. The prevalence of burnout in HCWs was 43.5%, with more anxious and fearful HCWs reporting higher burnout rates. CONCLUSION: Fears and anxiety related to COVID-19 are high. Burnout among HCWs is similar to rates reported prepandemic. An individualized approach to target the specific fears of each group will be crucial to maintain the well-being of these vulnerable groups and prevent burnout of HCWs.

A nomogram for predicting mortality in patients with COVID-19 and solid tumors: a multicenter retrospective cohort study.

BACKGROUND: Individualized prediction of mortality risk can inform the treatment strategy for patients with COVID-19 and solid tumors and potentially improve patient outcomes. We aimed to develop a nomogram for predicting in-hospital mortality of patients with COVID-19 with solid tumors. METHODS: We enrolled patients with COVID-19 with solid tumors admitted to 32 hospitals in China between December 17, 2020, and March 18, 2020. A multivariate logistic regression model was constructed via stepwise regression analysis, and a nomogram was subsequently developed based on the fitted multivariate logistic regression model. Discrimination and calibration of the nomogram were evaluated by estimating the area under the receiver operator characteristic curve (AUC) for the model and by bootstrap resampling, a Hosmer-Lemeshow test, and visual inspection of the calibration curve. RESULTS: There were 216 patients with COVID-19 with solid tumors included in the present study, of whom 37 (17%) died and the other 179 all recovered from COVID-19 and were discharged. The median age of the enrolled patients was 63.0 years and 113 (52.3%) were men. Multivariate logistic regression revealed that increasing age (OR=1.08, 95% CI 1.00 to 1.16), receipt of antitumor treatment within 3 months before COVID-19 (OR=28.65, 95% CI 3.54 to 231.97), peripheral white blood cell (WBC) count ≥6.93 ×109/L (OR=14.52, 95% CI 2.45 to 86.14), derived neutrophil-to-lymphocyte ratio (dNLR; neutrophil count/(WBC count minus neutrophil count)) ≥4.19 (OR=18.99, 95% CI 3.58 to 100.65), and dyspnea on admission (OR=20.38, 95% CI 3.55 to 117.02) were associated with elevated mortality risk. The performance of the established nomogram was satisfactory, with an AUC of 0.953 (95% CI 0.908 to 0.997) for the model, non-significant findings on the Hosmer-Lemeshow test, and rough agreement between predicted and observed probabilities as suggested in calibration curves. The sensitivity and specificity of the model were 86.4% and 92.5%. CONCLUSION: Increasing age, receipt of antitumor treatment within 3 months before COVID-19 diagnosis, elevated WBC count and dNLR, and having dyspnea on admission were independent risk factors for mortality among patients with COVID-19 and solid tumors. The nomogram based on these factors accurately predicted mortality risk for individual patients.

Recombinant SARS-CoV-2 RBD molecule with a T helper epitope as a built in adjuvant induces strong neutralization antibody response (preprint)

Without approved vaccines and specific treatment, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading around the world with above 20 million COVID-19 cases and approximately 700 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of Spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5), and prokaryotic expression, chromatography purification and the rational renaturation of the protein were performed. The antigenicity and immunogenicity of S1-4 protein was evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency of it was measured by virus neutralization test in Vero E6 cells with SARS-CoV-2. S1-4 protein was prepared to high homogeneity and purity by prokaryotic expression and chromatography purification. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity compared with S1-5 protein. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralization antibody GMT 256. The candidate subunit vaccine molecule could stimulate strong humoral and Th1 and Th2-type cellular immune response in mice, giving us solid evidence that S1-4 protein could be a promising subunit vaccine candidate.