Psychological interventions for loneliness and social isolation among older adults during medical pandemics: a systematic review and meta-analysis.

OBJECTIVES: There is little research conducted to systematically synthesize the evidence on psychological interventions for social isolation and loneliness among older adults during medical pandemics. This systematic review aims to address this information gap and provides guidance for planning and implementing interventions to prevent and reduce loneliness and social isolation for older adults, especially during medical pandemics. METHODS: Four electronic databases (EMBASE, PsychoInfo, Medline and Web of Science) and grey literature from 1 January 2000 to 13 September 2022 were searched for eligible studies on loneliness and social isolation. Data extraction and methodological quality assessment on key study characteristics were conducted independently by two researchers. Both qualitative synthesis and meta-analysis were used. RESULTS: The initial search yielded 3,116 titles. Of the 215 full texts reviewed, 12 intervention articles targeting loneliness during the COVID-19 pandemic met the inclusion criteria. No studies were found concerning intervention with respect to social isolation. Overall, interventions targeting social skills and the elimination of negativities effectively alleviated the feelings of loneliness in the older population. However, they had only short-term effects. CONCLUSION: This review systematically summarised the key characteristics and the effectiveness of existing interventions addressing loneliness in older adults during the COVID-19 pandemic. Future interventions should focus on social skills and eliminating negativities and be tailored to the needs and characteristics of older people. Repeated larger-scale randomized controlled trials and long-term effectiveness evaluations on this topic are warranted.

Prevalence of loneliness and social isolation among older adults during the COVID-19 pandemic: A systematic review and meta-analysis.

OBJECTIVES: Pandemics and their public health control measures have generally substantially increased the level of loneliness and social isolation in the general population. Because of the circumstances of aging, older adults are more likely to experience social isolation and loneliness during pandemics. However, no systematic review has been conducted or published on the prevalence of loneliness and/or social isolation among the older population. This systematic review and meta-analysis aims to provide up-to-date pooled estimates of the prevalence of social isolation and loneliness among older adults during the COVID-19 pandemic and other pandemics in the last two decades. DESIGN: EMBASE, PsychoINFO, Medline, and Web of Science were searched for relevant studies from January 1, 2000 to November 31, 2021 published in a variety of languages. Only studies conducted during the COVID-19 pandemic were selected in the review. RESULTS: A total of 30 studies including 28,050 participants met the inclusion criteria. Overall, the pooled period prevalence of loneliness among older adults was 28.6% (95% CI: 22.9-35.0%) and 31.2% for social isolation (95% CI: 20.2-44.9%). Prevalence estimates were significantly higher for those studies conducted post 3-month from the start of the COVID-19 pandemic compared to those conducted within the first 3 months of the pandemic. CONCLUSIONS: This review identifies the need for good quality longitudinal studies to examine the long-term impact of pandemics on loneliness and social isolation among older populations. Health policymaking and healthcare systems should proactively address the rising demand for appropriate psychological services among older adults.

The duration and breadth of antibody responses to 3-dose of inactivated COVID-19 vaccinations in healthy blood donors: An observational study.

Objectives: We aimed to evaluate the duration and breadth of antibodies elicited by inactivated COVID-19 vaccinations in healthy blood donors. Methods: We performed serological tests on 1,417 samples from 658 blood donors who received two (n=357), or three (n=301) doses of COVID-19 inactivated vaccine. We also accessed the change in antibody response before and after booster vaccination in 94 participants and their neutralization breadth to the current variants after the booster. Results: Following vaccination, for either the 2- or 3-dose, the neutralizing antibodies (nAbs) peaked with about 97% seropositivity approximately within one month but subsequently decreased over time. Of plasmas collected 6-8 months after the last immunization, the nAb seropositivities were 37% and 85% in populations with 2-dose and 3-dose vaccinations, respectively. The nAbs of plasma samples (collected between 2-6 weeks after the 3rd dose) from triple-vaccinated donors (n=94) showed a geometric mean titer of 145.3 (95% CI: 117.2 to 180.1) against the ancestral B.1, slightly reduced by 1.7-fold against Delta variant, but markedly decreased by 4-6 fold in neutralizing Omicron variants, including the sub-lineages of BA.1 (5.6-fold), BA.1.1 (6.0-fold), BA.2 (4.2-fold), B.2.12.1 (6.2-fold) and BA.4/5 (6.5-fold). Conclusion: These findings suggested that the 3rd dose of inactivated COVID-19 vaccine prolongs the antibody duration in healthy populations, but the elicited-nAbs are less efficient in neutralizing circulating Omicron variants.

Toll-Like Receptor Signaling in Severe Acute Respiratory Syndrome Coronavirus 2-Induced Innate Immune Responses and the Potential Application Value of Toll-Like Receptor Immunomodulators in Patients With Coronavirus Disease 2019.

Toll-like receptors (TLRs) are key sensors that recognize the pathogen-associated molecular patterns (PAMPs) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to activate innate immune response to clear the invading virus. However, dysregulated immune responses may elicit the overproduction of proinflammatory cytokines and chemokines, resulting in the enhancement of immune-mediated pathology. Therefore, a proper understanding of the interaction between SARS-CoV-2 and TLR-induced immune responses is very important for the development of effective preventive and therapeutic strategies. In this review, we discuss the recognition of SARS-CoV-2 components by TLRs and the downstream signaling pathways that are activated, as well as the dual role of TLRs in regulating antiviral effects and excessive inflammatory responses in patients with coronavirus disease 2019 (COVID-19). In addition, this article describes recent progress in the development of TLR immunomodulators including the agonists and antagonists, as vaccine adjuvants or agents used to treat hyperinflammatory responses during SARS-CoV-2 infection.

Safety and immunogenicity of a live-attenuated influenza virus vector-based intranasal SARS-CoV-2 vaccine in adults: randomised, double-blind, placebo-controlled, phase 1 and 2 trials.

BACKGROUND: All currently available SARS-CoV-2 vaccines are administered by intramuscular injection. We aimed to evaluate the safety and immunogenicity of a live-attenuated influenza virus vector-based SARS-CoV-2 vaccine (dNS1-RBD) administered by intranasal spray in healthy adults. METHODS: We did double-blind, randomised, placebo-controlled phase 1 and 2 trials, followed by a phase 2 extension trial, at a single centre in Jiangsu, China. Healthy adults (≥18 years) who had negative serum or fingertip blood total antibody tests for SARS-CoV-2 (in phases 1 and 2), with no prevalent SARS-CoV-2 infection or history of infection and no SARS-CoV-2 vaccination history (in all three trials reported here), were enrolled. Participants were randomly allocated (4:1 in phase 1, 2:1 in phase 2, and 1:1 in the extension trial) to receive two intranasal doses of the dNS1-RBD vaccine or placebo on days 0 and 14 or, for half of the participants in phase 2, on days 0 and 21. To avoid cross-contamination during administration, vaccine and placebo recipients were vaccinated in separate rooms in the extension trial. The phase 1 primary outcome was safety (adverse events recorded on days 0-44; serious adverse events recorded from day 0 until 12 months after the second dose). In the phase 2 and extension trials, the primary immunogenicity outcomes were SARS-CoV-2-specific T-cell response in peripheral blood (measured by IFN-γ ELISpot), proportion of participants with positive conversion for SARS-CoV-2 receptor-binding domain (RBD)-specific IgG and secretory IgA (s-IgA) antibodies, and concentration of SARS-CoV-2 RBD IgG in serum and SARS-CoV-2 RBD s-IgA in the nasopharynx (measured by ELISA) at 1 month after the second dose in the per-protocol set for immunogenicity. χ2 test and Fisher's exact test were used to analyse categorical data, and t test and Wilcoxon rank sum test to compare the measurement data between groups. These trials were registered with the Chinese Clinical Trial Registry (ChiCTR2000037782, ChiCTR2000039715, and ChiCTR2100048316). FINDINGS: Between Sept 1, 2020, and July 4, 2021, 63, 724, and 297 participants without a history of SARS-CoV-2 vaccination were enrolled in the phase 1, phase 2, and extension trials, respectively. At least one adverse reaction after vaccination was reported in 133 (19%) of 684 participants in the vaccine groups. Most adverse reactions were mild. No vaccine-related serious adverse event was noted. Specific T-cell immune responses were observed in 211 (46% [95% CI 42-51]) of 455 vaccine recipients in the phase 2 trial, and in 48 (40% [31-49]) of 120 vaccine recipients compared with one (1% [0-5]) of 111 placebo recipients (p<0·0001) in the extension trial. Seroconversion for RBD-specific IgG was observed in 48 (10% [95% CI 8-13]) of 466 vaccine recipients in the phase 2 trial (geometric mean titre [GMT] 3·8 [95% CI 3·4-4·3] in responders), and in 31 (22% [15-29]) of 143 vaccine recipients (GMT 4·4 [3·3-5·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. 57 (12% [95% CI 9-16]) of 466 vaccine recipients had positive conversion for RBD-specific s-IgA (GMT 3·8 [95% CI 3·5-4·1] in responders) in the phase 2 trial, as did 18 (13% [8-19]) of 143 vaccine recipients (GMT 5·2 [4·0-6·8]) and zero (0% [0-2]) of 147 placebo recipients (p<0·0001) in the extension trial. INTERPRETATION: dNS1-RBD was well tolerated in adults. Weak T-cell immunity in peripheral blood, as well as weak humoral and mucosal immune responses against SARS-CoV-2, were detected in vaccine recipients. Further studies are warranted to verify the safety and efficacy of intranasal vaccines as a potential supplement to current intramuscular SARS-CoV-2 vaccine pools. Steps should be taken in future studies to reduce the potential for cross-contamination caused by the vaccine strain aerosol during administration. FUNDING: National Key Research and Development Program of China, National Science, Fujian Provincial Science, CAMS Innovation Fund for Medical Sciences, and Beijing Wantai Biological Pharmacy Enterprise.

A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2.

Remarkable progress has been made in developing intramuscular vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, they are limited with respect to eliciting local immunity in the respiratory tract, which is the primary infection site for SARS-CoV-2. To overcome the limitations of intramuscular vaccines, we constructed a nasal vaccine candidate based on an influenza vector by inserting a gene encoding the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2, named CA4-dNS1-nCoV-RBD (dNS1-RBD). A preclinical study showed that in hamsters challenged 1 d after single-dose vaccination or 9 months after booster vaccination, dNS1-RBD largely mitigated lung pathology, with no loss of body weight. Moreover, such cellular immunity is relatively unimpaired for the most concerning SARS-CoV-2 variants, especially for the latest Omicron variant. In addition, this vaccine also provides cross-protection against H1N1 and H5N1 influenza viruses. The protective immune mechanism of dNS1-RBD could be attributed to the innate immune response in the nasal epithelium, local RBD-specific T cell response in the lung, and RBD-specific IgA and IgG response. Thus, this study demonstrates that the intranasally delivered dNS1-RBD vaccine candidate may offer an important addition to the fight against the ongoing coronavirus disease 2019 pandemic and influenza infection, compensating limitations of current intramuscular vaccines.

Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants.

Mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) may alter viral host tropism and affect the activities of neutralizing antibodies. Here, we investigated 153 RBD mutants and 11 globally circulating variants of concern (VOCs) and variants of interest (VOIs) (including Omicron) for their antigenic changes and cross-species tropism in cells expressing 18 ACE2 orthologs. Several RBD mutations strengthened viral infectivity in cells expressing ACE2 orthologs of non-human animals, particularly those less susceptible to the ancestral strain. The mutations surrounding amino acids (aas) 439-448 and aa 484 are more likely to cause neutralization resistance. Strikingly, enhanced cross-species infection potential in the mouse and ferret, instead of the neutralization-escape scores of the mutations, account for the positive correlation with the cumulative prevalence of mutations in humans. These findings present insights for potential drivers of circulating SARS-CoV-2 variants and provide informative parameters for tracking and forecasting spreading mutations.

Protection Duration of COVID-19 Vaccines: Waning Effectiveness and Future Perspective.

The coronavirus disease 2019 (COVID-19) vaccines have very successfully decreased the disease risk as we know; some key information remains unknown due to the short development history and the lack of long-term follow-up studies in vaccinated populations. One of the unanswered issues is the protection duration conferred after COVID-19 vaccination, which appears to play a pivotal role in the future impact of pathogens and is critical to inform the public health response and policy decisions. Here, we review current information on the long-term effectiveness of different COVID-19 vaccines, persistence of immunogenicity, and gaps in knowledge. Meanwhile, we also discuss the influencing factors and future study prospects on this topic.

Mechanism of SARS-CoV-2 Invasion into the Liver and Hepatic Injury in Patients with COVID-19.

Many studies have shown that patients with Coronavirus disease 2019 (COVID-19) have different degrees of liver injury. However, the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) invasion into the liver are still not fully understood. This review mainly summarizes the recently published works on the abnormal liver biochemical indicators and the mechanism of viral invasion with liver injury in COVID-19 patients. Generally, SARS-CoV-2 infection of the liver was caused by blood circulation or retrograde infection of the digestive tract, which led to the liver injury through direct cytopathic effect induced by virus or immunopathological effect caused by excessive inflammation. Besides these, hypoxia, endothelial injury and drug-induced jury were also the main reasons of liver injury in COVID-19 patients. In the liver function indicators, elevated alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and lactate dehydrogenase levels with reduced albumin levels were observed in COVID-19 patients.

Protection Duration of COVID-19 Vaccines: Waning Effectiveness and Future Perspective

The coronavirus disease 2019 (COVID-19) vaccines have very successfully decreased the disease risk as we know;some key information remains unknown due to the short development history and the lack of long-term follow-up studies in vaccinated populations. One of the unanswered issues is the protection duration conferred after COVID-19 vaccination, which appears to play a pivotal role in the future impact of pathogens and is critical to inform the public health response and policy decisions. Here, we review current information on the long-term effectiveness of different COVID-19 vaccines, persistence of immunogenicity, and gaps in knowledge. Meanwhile, we also discuss the influencing factors and future study prospects on this topic.

Cross-species tropism and antigenic landscapes of circulating SARS-CoV-2 variants

Zhang et al. show in vitro cross-species infectivity and neutralization-escape characteristics of 153 SARS-CoV-2 RBD mutants and 11 globally circulating VOC/VOI variants. They reveal an association between enhanced cross-species infection potential and the current cumulative prevalence of mutations, which can inform surveillance and forecasting of SARS-CoV-2 spike mutations.

A review of the safety and efficacy of current COVID-19 vaccines.

Vaccination is the most effective and feasible way to contain the Coronavirus disease 2019 (COVID-19) pandemic. The rapid development of effective COVID-19 vaccines is an extraordinary achievement. This study reviewed the efficacy/effectiveness, immunogenicity, and safety profile of the 12 most progressed COVID-19 vaccines and discussed the challenges and prospects of the vaccine-based approaches in a global crisis. Overall, most of the current vaccines have shown safety and efficacy/effectiveness during actual clinical trials or in the real-world studies, indicating a development of pandemic control. However, many challenges are faced by pandemic control in terms of maximizing the effect of vaccines, such as rapid vaccine coverage, strategies to address variants with immune escape capability, and surveillance of vaccine safety in the medium- and long-terms.

Inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Concerns about vaccine safety are an important reason for vaccine hesitancy, however, limited information is available on whether common adverse reactions following vaccination affect the immune response. Data from three clinical trials of recombinant vaccines were used in this post hoc analysis to assess the correlation between inflammation-related solicited adverse reactions (ISARs, including local pain, redness, swelling or induration and systematic fever) and immune responses after vaccination. In the phase III trial of the bivalent HPV-16/18 vaccine (Cecolin®), the geometric mean concentrations (GMCs) for IgG anti-HPV-16 and -18 (P<0.001) were significantly higher in participants with any ISAR following vaccination than in those without an ISAR. Local pain, induration, swelling and systemic fever were significantly correlated with higher GMCs for IgG anti-HPV-16 and/or anti-HPV-18, respectively. Furthermore, the analyses of the immunogenicity bridging study of Cecolin® and the phase III trial of a hepatitis E vaccine yielded similar results. Based on these results, we built a scoring model to quantify the inflammation reactions and found that the high score of ISAR indicates the strong vaccine-induced antibody level. In conclusion, this study suggests inflammation-related adverse reactions following vaccination potentially indicate a stronger immune response.

Antibody response in COVID-19 patients with and without re-positive RT-PCR results during the convalescent phase.

Nucleic acid testing and antibody testing data from 143 recovered COVID-19 patients during the convalescent phase were retrospectively analyzed. A total of 23 (16.1%) recovered patients re-tested positive for SARS-CoV-2 RNA by RT-PCR. Three months after symptom onset, 100% and 99.3% of the patients remained positive for total and IgG antibodies, and the antibody levels remained high. IgM antibodies declined rapidly, with a median time to seroconversion of 67 (95% CI: 59, 75) days after onset. Approximately 25% of patients were seronegative for IgA antibodies at three months after onset. There was no statistically significant difference in antibody kinetics between patients with and without re-positive RT-PCR results during the convalescent phase.

Antibody Responses to SARS-CoV-2 in Patients With Novel Coronavirus Disease 2019.

BACKGROUND: The novel coronavirus SARS-CoV-2 is a newly emerging virus. The antibody response in infected patients remains largely unknown, and the clinical value of antibody testing has not been fully demonstrated. METHODS: 173 patients with SARS-CoV-2 infection were enrolled. Their serial plasma samples (n = 535) collected during hospitalization were tested for total antibodies (Ab), IgM, and IgG against SARS-CoV-2. The dynamics of antibodies with disease progress were analyzed. RESULTS: Among 173 patients, the seroconversion rates for Ab, IgM, and IgG were 93.1%, 82.7%, and 64.7%, respectively. The reason for the negative antibody findings in 12 patients might be due to the lack of blood samples at the later stage of illness. The median seroconversion times for Ab, IgM, and then IgG were days 11, 12, and 4, respectively. The presence of antibodies was <40% among patients within 1 week of onset, and rapidly increased to 100.0% (Ab), 94.3% (IgM), and 79.8% (IgG) by day 15 after onset. In contrast, RNA detectability decreased from 66.7% (58/87) in samples collected before day 7 to 45.5% (25/55) during days 15-39. Combining RNA and antibody detection significantly improved the sensitivity of pathogenic diagnosis for COVID-19 (P < .001), even in the early phase of 1 week from onset (P = .007). Moreover, a higher titer of Ab was independently associated with a worse clinical classification (P = .006). CONCLUSIONS: Antibody detection offers vital clinical information during the course of SARS-CoV-2 infection. The findings provide strong empirical support for the routine application of serological testing in the diagnosis and management of COVID-19 patients.

The prevalence of antibodies to SARS-CoV-2 among blood donors in China.

In this study, we investigate the seroprevalence of SARS-CoV-2 antibodies among blood donors in the cities of Wuhan, Shenzhen, and Shijiazhuang in China. From January to April 2020, 38,144 healthy blood donors in the three cities were tested for total antibody against SARS-CoV-2 followed by pseudotype SARS-CoV-2 neutralization tests, IgG, and IgM antibody testing. Finally, a total of 398 donors were confirmed positive. The age- and sex-standardized SARS-CoV-2 seroprevalence among 18-60 year-old adults (18-65 year-old in Shenzhen) was 2.66% (95% CI: 2.24%-3.07%) in Wuhan, 0.033% (95% CI: 0.0029%-0.267%) in Shenzhen, and 0.0028% (95% CI: 0.0001%-0.158%) in Shijiazhuang, respectively. Female sex and older-age were identified to be independent risk factors for SARS-CoV-2 seropositivity among blood donors in Wuhan. As most of the population of China remained uninfected during the early wave of the COVID-19 pandemic, effective public health measures are still certainly required to block viral spread before a vaccine is widely available.

Early diagnosis and population prevention of coronavirus disease 2019.

PURPOSE OF REVIEW: To discuss the diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection by nucleic acid and antibody testing as well as its contribution to mitigating the spread of coronavirus disease 2019. RECENT FINDINGS: Nucleic acid testing (NAT) is the firstly developed and most widely used diagnostic technique for SARS-CoV-2 infection. However, the sensitivity of SARS-CoV-2 RNA NAT assays is always unsatisfactory, mainly due to insufficient viral RNA in samples, especially when upper respiratory samples were used. Compared with NAT assays, serological tests are more convenient and less dependent on the quality of sample collection. But the sensitivity of antibody assays varies largely to test samples collected at different time after onset of symptoms. The diagnostic sensitivity can be significantly improved by combination of RNA and antibody testing. Due to the lack of effective drugs and vaccines, population prevention results mainly from timely triage and quarantine of SARS-CoV-2 infected individuals. Thus, extensive testing with NAT and antibody assays simultaneously is very important to constrain coronavirus disease 2019 epidemic. SUMMARY: Viral RNA testing combining with serological testing could improve the early diagnosis of SARS-CoV-2 infection, which has great value for clinical practice and public health.

Public Voice via Social Media: Role in Cooperative Governance during Public Health Emergency.

With the development of the Internet, social networking sites have empowered the public to directly express their views about social issues and hence contribute to social change. As a new type of voice behavior, public voice on social media has aroused wide concern among scholars. However, why public voice is expressed and how it influences social development and betterment in times of public health emergencies remains unstudied. A key point is whether governments can take effective countermeasures when faced with public health emergencies. In such situation, public voice is of great significance in the formulation and implementation of coping policies. This qualitive study uses China's Health Code policy under COVID-19 to explore why the public performs voice behavior on social media and how this influences policy evolution and product innovation through cooperative governance. A stimulus-cognition-emotion-behavior model is established to explain public voice, indicating that it is influenced by cognitive processes and public emotions under policy stimulus. What is more, as a form of public participation in cooperative governance, public voice plays a significant role in promoting policy evolution and product innovation, and represents a useful form of cooperation with governments and enterprises to jointly maintain social stability under public health emergencies.