An Entertainment-Education Video and Written Messages to Alleviate Loneliness in Germany: Pilot Randomized Controlled Study.

BACKGROUND: More than half of adults in Germany have felt lonely during the COVID-19 pandemic. Previous studies highlight the importance of boosting positive emotions and social connectedness to combat loneliness. However, interventions targeting these protective psychosocial resources remain largely untested. OBJECTIVE: In this study, we aim to test the feasibility of a short animated storytelling video, written messages boosting social connectedness, and a combination of both for alleviating loneliness. METHODS: We enrolled 252 participants who were 18 years or older and spoke fluent German. Participants were recruited from a previous study on loneliness in Germany. We measured the effects of a combination of an animated video and written messages (intervention A), an animated video (intervention B), and written messages (intervention C) on loneliness, self-esteem, self-efficacy, and hope. We compared these with a control arm, which did not receive any intervention. The animated video was developed by Stanford University School of Medicine to reflect experiences of social isolation during the COVID-19 pandemic and convey messages of hope and solidarity. The written messages communicate four findings from recent studies on loneliness in Germany: (1) over a period of 6 months, 66% of respondents in Germany reported feeling lonely (feelings of loneliness are surprisingly common); (2) physical activity can ease feelings of loneliness; (3) focusing on "what really matters" in one's life can help to ease feelings of loneliness; and (4) turning to friends for companionship and support can ease feelings of loneliness. Participants were randomized 1:1:1:1 to interventions A, B, C, and the control condition, using the randomization feature of the web-based platform "Unipark," on which our trial takes place. Both the study investigators and analysts were blinded to the trial assignments. The primary outcome, loneliness, was measured using the short-form UCLA Loneliness Scale (ULS-8). Our secondary outcomes included the scores of the Coping with Loneliness Questionnaire, the 10-item Rosenberg Self-Esteem Scale (RSE), the 10-item General Self-Efficacy Scale, and the 12-item Adult Hope Scale (AHS). RESULTS: We observed no statistically significant effect of the tested interventions on loneliness scores, controlling for the baseline loneliness score before an intervention (all P values >.11). However, we observed significantly greater intention to cope with loneliness after exposure to an animated video when compared with the control (ß=4.14; t248=1.74; 1-tailed P=.04). CONCLUSIONS: Our results provide meaningful evidence for the feasibility of a full-scale study. Our study sheds light on the intention to cope with loneliness and explores the potential for creative digital interventions to enhance this psychological precursor, which is integral to overcoming loneliness. TRIAL REGISTRATION: German Clinical Trials Register DRKS00027116; https://drks.de/search/en/trial/DRKS00027116.

The negative impact of loneliness and perceived stress on mental health during two-month lockdown in Shanghai.

BACKGROUND: Shanghai undergone COVID-19 lockdown for 2 months in 2022, affecting >25 million population. We aim to find changes in mental health during Shanghai lockdown and if mental health was associated with Shanghai lockdown, loneliness, and perceived stress. METHODS: We conducted two cross-sectional online surveys in China, which were before and at the end of Shanghai lockdown (survey 1 in January 2022, N = 1123; survey 2 in June 2022, N = 2139). Participants reported mental health, loneliness, and perceived stress through the 12-item General Health Questionnaire (GHQ-12), the short-form UCLA Loneliness Scale (ULS-8), and the 10-item Perceived Stress Scale (PSS-10). We compared data between survey 1 and 2. We ran a multiple linear regression model to investigate the impact of Shanghai lockdown, loneliness and perceived stress on mental health. RESULTS: There's an increase in the proportion of lonely people during Shanghai lockdown (49.77 % to 65.26 %). During Shanghai lockdown, the proportion of lonely people (68.97 % VS. 61.35 %, p < 0.001) and risk for mental health conditions (50.50 % VS. 43.27 %, p < 0.001) were higher among residents in Shanghai than outside Shanghai. Shanghai lockdown (b = 0.556, p = 0.02), higher ULS-8 (b = 0.284, p < 0.001) and higher PSS-10 (b = 0.365, p < 0.001) were associated with higher GHQ-12. LIMITATIONS: Participants reported their mental health status during Shanghai lockdown retrospectively. CONCLUSION: Shanghai lockdown had psychological impacts not only on residents in Shanghai but also outside Shanghai. Addressing loneliness and perceived stress accommodated to the lockdown situation should be considered.

Positive and negative experiences with the COVID-19 pandemic among lonely and non-lonely populations in Germany.

The COVID-19 pandemic is causing an epidemic of loneliness. Previous studies have shown the differences in positive and negative experiences of lonely and non-lonely people in a non-pandemic setting. However, it is unclear how the drastic alteration of the COVID-19 pandemic may influence peoples' reactions and beliefs, especially among those who feel lonely. Our study aims to examine the positive and negative experiences among lonely and non-lonely people. We undertook a cross-sectional online survey of the general population in Germany (N = 1,758) from May 2020 to May 2022. We assessed their feelings of loneliness with the short eight-item UCLA Loneliness Scale (ULS-8), their positive and negative experience of living in the COVID-19 pandemic as well as their psychological distress regarding the pandemic with the COVID-19 Peritraumatic Distress Index (CPDI). We found lonely individuals (ULS-8 score ≥ 16) reported fewer positive experiences of living in the COVID-19 pandemic, for example, less time with loved ones [z (1, 756) = -2.5, p = 0.012] and less sense of togetherness [z (1, 756) = -2.39, p = 0.017] as compared to non-lonely individuals. Meanwhile, they experienced more negative experiences, for example, worry and fear [z (1, 756) = 6.31, p < 0.001] compared with non-lonely individuals. Interestingly, lonely people were less likely to view the pandemic as a conspiracy than non-lonely people were [z (1, 756) = -3.35, p < 0.001]. Our results may give insight into attribution bias and the negative affect of lonely people during the COVID-19 pandemic as well as highlight the experience of non-lonely people and raise the question of differences in conspiracy beliefs. For pandemic preparedness and response, decision-makers may focus on interventions to foster social cohesion, empower people, build resilience, and most importantly provide timely social care.

Positive and negative experiences with the COVID-19 pandemic among lonely and non-lonely populations in Germany

The COVID-19 pandemic is causing an epidemic of loneliness. Previous studies have shown the differences in positive and negative experiences of lonely and non-lonely people in a non-pandemic setting. However, it is unclear how the drastic alteration of the COVID-19 pandemic may influence peoples' reactions and beliefs, especially among those who feel lonely. Our study aims to examine the positive and negative experiences among lonely and non-lonely people. We undertook a cross-sectional online survey of the general population in Germany (N = 1,758) from May 2020 to May 2022. We assessed their feelings of loneliness with the short eight-item UCLA Loneliness Scale (ULS-8), their positive and negative experience of living in the COVID-19 pandemic as well as their psychological distress regarding the pandemic with the COVID-19 Peritraumatic Distress Index (CPDI). We found lonely individuals (ULS-8 score ≥ 16) reported fewer positive experiences of living in the COVID-19 pandemic, for example, less time with loved ones [z(1, 756) = −2.5, p = 0.012] and less sense of togetherness [z(1, 756) = −2.39, p = 0.017] as compared to non-lonely individuals. Meanwhile, they experienced more negative experiences, for example, worry and fear [z(1, 756) = 6.31, p < 0.001] compared with non-lonely individuals. Interestingly, lonely people were less likely to view the pandemic as a conspiracy than non-lonely people were [z(1, 756) = −3.35, p < 0.001]. Our results may give insight into attribution bias and the negative affect of lonely people during the COVID-19 pandemic as well as highlight the experience of non-lonely people and raise the question of differences in conspiracy beliefs. For pandemic preparedness and response, decision-makers may focus on interventions to foster social cohesion, empower people, build resilience, and most importantly provide timely social care.

Baricitinib inhibits type I IFN-signaling during SARS-CoV-2 infection in vitro

Objective: To explore the antiviral effect of baricitinib in the SARS-CoV-2 infection and influence on cytokine levels.

The effects of momentary loneliness and COVID-19 stressors on hypothalamic-pituitary adrenal (HPA) axis functioning: A lockdown stage changes the association between loneliness and salivary cortisol.

The COVID-19 pandemic can be characterized as a chronic stressor affecting the hypothalamic-pituitary-adrenal (HPA) axis, indexed by glucocorticoids (e.g., cortisol). We investigated whether salivary cortisol level is increased during a lockdown and whether a lockdown condition affects the association between loneliness, specific COVID-19 related stressors and salivary cortisol level. We conducted a smartphone-based ecological momentary assessment (EMA) study with 280 participants in Germany who experienced at least mild loneliness and distress amid COVID-19 from August 2020 to March 2021. We measured their momentary loneliness and COVID-related stressors including worries, information seeking behaviors and feelings of restriction during "no-lockdown" or "lockdown" stages amid COVID-19. Their salivary cortisol was measured 4 times on the last day of a 7-day EMA study. We found a significant increase in salivary cortisol levels during lockdown compared to no-lockdown. Lockdown stage was found to moderate the relationship between momentary loneliness and salivary cortisol level, i.e., loneliness was positively related to cortisol level specifically during lockdown. Mechanisms explaining the effect of forced social isolation on the association between loneliness and salivary cortisol need to be investigated in future studies.

Patterns of Alcohol Consumption Among Individuals With Alcohol Use Disorder During the COVID-19 Pandemic and Lockdowns in Germany.

Importance: Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence. Objective: To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms. Design, Setting, and Participants: This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021). Main Outcomes and Measures: Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates. Results: Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (ß = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (ß = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year's Eve (ß = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (ß = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (ß = -5.45; 95% CI, -8.00 to -2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (ß = -11.10; 95% CI, -13.63 to -8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (ß = -6.14; 95% CI, -9.96 to -2.31; P = .002) and in participants with severe AUD (ß = -6.26; 95% CI, -10.18 to -2.34; P = .002). Conclusions and Relevance: This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.

Smartphone-Based Ecological Momentary Assessment of Coping with Loneliness amid COVID-19 in Germany.

The COVID-19 pandemic may have caused people to feel isolated, left out, and in need of companionship. Effective strategies to cope with such unrelenting feelings of loneliness are needed. In times of COVID-19, we conducted a smartphone-based ecological momentary assessment (EMA) study with 280 lonely participants in Germany over 7 months, where a long and hard second national lockdown was in place. Each participant reported their daily loneliness and coping strategies for loneliness once in the evening for 7 consecutive days. We found that managing emotions and social relationships were associated with decreased feelings of loneliness, while using a problem-focused coping strategy was associated with increased feelings of loneliness amid COVID-19. Interestingly, managing emotions was particularly effective for easing loneliness during the second lockdown. Females tend to use more emotion-focused coping strategies to overcome their loneliness compared to males. Our study highlights the importance of managing emotions against loneliness throughout the COVID-19 pandemic in Germany. Designing technology that provides emotional support to people may be one of the keys to easing loneliness and promoting well-being.

Smartphone-Based Ecological Momentary Assessment of Coping with Loneliness amid COVID-19 in Germany

The COVID-19 pandemic may have caused people to feel isolated, left out, and in need of companionship. Effective strategies to cope with such unrelenting feelings of loneliness are needed. In times of COVID-19, we conducted a smartphone-based ecological momentary assessment (EMA) study with 280 lonely participants in Germany over 7 months, where a long and hard second national lockdown was in place. Each participant reported their daily loneliness and coping strategies for loneliness once in the evening for 7 consecutive days. We found that managing emotions and social relationships were associated with decreased feelings of loneliness, while using a problem-focused coping strategy was associated with increased feelings of loneliness amid COVID-19. Interestingly, managing emotions was particularly effective for easing loneliness during the second lockdown. Females tend to use more emotion-focused coping strategies to overcome their loneliness compared to males. Our study highlights the importance of managing emotions against loneliness throughout the COVID-19 pandemic in Germany. Designing technology that provides emotional support to people may be one of the keys to easing loneliness and promoting well-being.

Assessment of S-Specific IgG and IgM Positive Rates in Healthy Hospital Staff Members Vaccinated with the Inactivated SARS-CoV-2 Vaccine.

Widespread vaccination of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine makes the assessment of antibodies' positive rates essential. In this study, a total of 378 hospital staff members vaccinated with the vaccine were selected as research subjects. Serum-specific IgG and IgM against the SARS-CoV-2 spike protein (S) were detected, and S-specific IgG and IgM positive rates were analyzed in different age and sex groups, as was the serological pattern of IgG/IgM. The positive rates of IgG and IgM were 92.06% and 44.44%, respectively. The percentage of both IgG and IgM positive (IgG+IgM+) was 43.92%. A total of 182 vaccinees (46.90%) were IgG positive and IgM negative (IgG+IgM-), and 28 vaccinees (7.41%) were negative for both IgG and IgM (IgG-IgM-); 2 participants were positive for IgM alone (IgG-IgM+). In sex subgroups, the rate of IgM positivity was significantly higher in the male group than in the female group (p = 0.027). In different age subgroups, positive rates for IgG in the young group were significantly higher than those in the other group (p = 0.035). Furthermore, ratios of sample values to cutoff values (S/CO values) for IgG in vaccinees who were S-specific IgG positive were compared, and the S/CO values of IgG were significantly higher in the younger group than in the other group (p < 0.001). When comparing the influence of sex on two specific serological patterns (IgG+IgM- and IgG+IgM+), a significant difference in positivity rates was detected (p = 0.011). Male vaccinees were more likely than females to have an IgG+IgM+ pattern.

Antiviral drugs arbidol and interferon alpha-1b contribute to reducing the severity of COVID-19 patients: a retrospective cohort study.

OBJECTIVES: The aim of this study was to evaluate the role of antiviral drugs in reducing the risk of developing severe illness in patients with moderate COVID-19 pneumonia. METHODS: This retrospective cohort study included 403 adult patients with moderate COVID-19 pneumonia who were admitted to Shenzhen Third People's Hospital, China. The antiviral drugs arbidol, interferon alpha-1b, lopinavir-ritonavir and ribavirin were distributed to the patients for treatment. The primary endpoint of this study was the time to develop severe illness. RESULTS: Of the 462 patients admitted, 403 had moderate COVID-19 symptoms at hospital admission and were included in this study. 90 of the 403 (22.3%) patients progressed to severe illness. The use of arbidol was associated with a lower severity rate 3.5% compared to control group 30.5%, p-value < 0.0001; the adjusted hazard ratio was 0.28 (95% CI: 0.084-0.90, p = 0.033). The use of interferon alpha-1b was associated with a lower severity rate 15.5% compared to control group 29.3%, with p-value < 0.0001; the adjusted hazard ratio was 0.30 (95% CI: 0.15-0.58, p =  0.0005). The use of lopinavir-itonavir and ribavirin did not show significant differences in adjusted regression models. Early use of arbidol within 7 days of symptom onset was significantly associated with a reduced recovery time of - 5.2 days (IQR - 3.0 to - 7.5, p = 4e-06) compared with the control group. CONCLUSION: Treatment with arbidol and interferon alpha-1b contributes to reducing the severity of illness in patients with moderate COVID-19 pneumonia. Early use of arbidol may reduce patients' recovery time.

Long-Term Impact of Economic Downturn and Loneliness on Psychological Distress: Triple Crises of COVID-19 Pandemic.

BACKGROUND: The COVID-19 crisis poses global mental health and global economy challenges. However, there is a lack of longitudinal research investigating whether financial instability and social disruption may increase the risk of developing mental health problems over time that may potentially outlast the pandemic. METHODS: We conducted an online survey for members of the general population (n = 2703) in Germany during the twelve months spanning from April 2020 to March 2021. We investigated the development of COVID-19 related psychological distress, the number of unemployed people, federal government debt, income distribution, and loneliness over the time period. RESULTS: Over a period of twelve months, 53.6% of respondents in Germany reported experiencing psychological distress, varying from mild levels, 34.2%, to severe levels, 19.4%, of distress. High federal government debt, high incident COVID-19 cases, low incomes, and the prevalence of loneliness were found to be associated with increased long-term mental health problems. Psychological distress scores were most strongly increased in female and young respondents as well as those who reported fewer years of education, low income, and higher loneliness. CONCLUSIONS: Our study highlights factors that have a long-term impact on mental health amid the COVID-19 pandemic. We suggest that specific mental-health services could be offered to support high-risk groups experiencing financial fragility and loneliness. For purposes of safeguarding their mental health there is a need to monitor and track such risk factors in real time.

The Persistence of the Impact of COVID-19-Related Distress, Mood Inertia, and Loneliness on Mental Health During a Postlockdown Period in Germany: An Ecological Momentary Assessment Study.

BACKGROUND: The first wave of the COVID-19 pandemic in early 2020 increased mental health problems globally. However, little is known about mental health problems during a low-incidence period of the pandemic without strict public health measures. OBJECTIVE: We aim to investigate whether COVID-19-related risk factors for mental health problems persist beyond lockdown measures. We targeted a vulnerable population that is at risk of developing low mental health and assessed their daily dynamics of mood and emotion regulation after a strict lockdown. METHODS: During a postlockdown period in Germany (between August 8, 2020, and November 1, 2020), we conducted an ecological momentary assessment with 131 participants who experienced at least mild COVID-19-related distress and loneliness. To estimate negative mood inertia, we built a lag-1 three-level autoregressive model. RESULTS: We found that information exposure and active daily COVID-19 cases did not have an impact on negative mood amid a postlockdown period. However, there was a day-to-day carryover effect of negative mood. In addition, worrying about COVID-19, feeling restricted by COVID-19, and feeling lonely increased negative mood. CONCLUSIONS: The mental health of a vulnerable population is still challenged by COVID-19-related stressors after the lifting of a strict lockdown. This study highlights the need to protect mental health during postpandemic periods.

[The global impact of the COVID-19 pandemic on the care provision for people with mental health problems]. / Globale Auswirkungen der COVID-19-Pandemie auf die Versorgung von Menschen mit psychischen Erkrankungen.

There are increasingly comprehensive data on recognition of the psychological impact of the coronavirus disease 2019 (COVID 19) pandemic on global populations. In most regions of the world, the economic and psychological burden on the general population and persons with mental disorders has risen sharply over the course of the pandemic. Beyond anxieties regarding severe acute respiratory syndromes due to coronavirus type 2 (SARS-CoV-2) infections, in many countries the measures for containing the pandemic also led to psychological burdens. It was shown that social distancing and contact restrictions were risk factors for the development or deterioration of mental health problems on a global scale. Simultaneously, the COVID-19 pandemic has disrupted or reduced mental health services in many countries. Thus, there is a substantial need for low threshold offers of assistance and for coping strategies. Current studies could show that certain coping strategies, such as virtual social contacts and physical activity, appear to be useful in counteracting the negative psychological sequelae of the pandemic; however, in order to improve care provision for people with psychological burden and mental illness in the medium term, it is necessary to offer targeted treatment, such as online psychotherapy in particular. Collaborative research tackles poverty, social isolation and loneliness.

The complex structure of GRL0617 and SARS-CoV-2 PLpro reveals a hot spot for antiviral drug discovery.

SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease (PLpro) has been implicated in playing important roles in virus maturation, dysregulation of host inflammation, and antiviral immune responses. The multiple functions of PLpro render it a promising drug target. Therefore, we screened a library of approved drugs and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising in vitro IC50 of 2.1 µM and an effective antiviral inhibition in cell-based assays. The co-crystal structure of SARS-CoV-2 PLproC111S in complex with GRL0617 indicates that GRL0617 is a non-covalent inhibitor and it resides in the ubiquitin-specific proteases (USP) domain of PLpro. NMR data indicate that GRL0617 blocks the binding of ISG15 C-terminus to PLpro. Using truncated ISG15 mutants, we show that the C-terminus of ISG15 plays a dominant role in binding PLpro. Structural analysis reveals that the ISG15 C-terminus binding pocket in PLpro contributes a disproportionately large portion of binding energy, thus this pocket is a hot spot for antiviral drug discovery targeting PLpro.

Increased Psychological Distress, Loneliness, and Unemployment in the Spread of COVID-19 over 6 Months in Germany.

Background: The COVID-19 pandemic poses a challenge to global mental health. Loneliness and isolation may put people at higher risk for increased psychological distress. However, there is a lack of research investigating the development of COVID-19-related distress over time. Materials and Methods: We undertook an online survey among general population (N = 1903) in Germany throughout 6 months from the peak transmission period in April to the off-peak period by September 2020. Results: We found that the average prevalence of psychological distress caused by the COVID-19 pandemic significantly rose from 24% to 66% between the peak and off-peak transmission period, respectively. Unemployment rate and loneliness increased negative mental health outcomes, although the number of active COVID-19 cases decreased from April to September. Psychological distress scores increased mostly in female, young, and lonely people. Conclusions: Our results underline the importance of considering innovative alternatives to facilitate employment opportunities, distant contacts, and self-help over the course of the pandemic. Our study highlights the urgent need to pay attention to mental health services specifically targeting female, young, unemployed, and lonely people.