A 16-Month Longitudinal Investigation of Risk and Protective Factors for Mental Health Outcomes Throughout Three National Lockdowns and a Mass Vaccination Campaign: Evidence from a Weighted Israeli Sample During COVID-19

Background COVID-19 is an ongoing global crisis, with a multitude of factors that affect mental health worldwide. We explored potential predictors for the emergence and maintenance of depression, anxiety, and posttraumatic stress symptoms (PTSS) in the general population in Israel. Methods Across the span of 16 months, 2,478 people completed a repeated self-report survey which inquired psychiatric symptoms and pandemic related stress factors (PRSF). We applied mixed-effects models to assess how each stressor contributes to depression, anxiety and PTSS at each time point, and longitudinally assessed participants who completed at least two consecutive surveys (n=400). Results Fatigue was the strongest predictor for depression, anxiety and PTSS at all time points, and predicted deterioration overtime. Financial concerns associated with depression and anxiety at all time points, and with their deterioration overtime. Health related concerns were uniquely associated with anxiety and PTSS at all time points and their deterioration, but not with depression. Improvement in sense of protection overtime associated with decrease in depression and anxiety. Hesitancy towards vaccination was associated to higher financial concerns and lower sense of protection by the authorities. Conclusions Our findings accentuate the multitude of risk factors for psychiatric morbidity during COVID-19, and the centrality of fatigue in determining mental health outcomes.

A 16-month longitudinal investigation of risk and protective factors for mental health outcomes throughout three national lockdowns and a mass vaccination campaign: Evidence from a weighted Israeli sample during COVID-19.

BACKGROUND: COVID-19 is an ongoing global crisis, with a multitude of factors that affect mental health worldwide. We explored potential predictors for the emergence and maintenance of depression, anxiety, and posttraumatic stress symptoms (PTSS) in the general population in Israel. METHODS: Across the span of 16 months, 2478 people completed a repeated self-report survey which inquired psychiatric symptoms and pandemic related stress factors (PRSF). We applied mixed-effects models to assess how each stressor contributes to depression, anxiety and PTSS at each time point, and longitudinally assessed participants who completed at least two consecutive surveys (n = 400). We weighted our sample to increase representativeness of the population. RESULTS: Fatigue was the strongest predictor for depression, anxiety and PTSS at all time points, and predicted deterioration overtime. Financial concerns associated with depression and anxiety at all time points, and with their deterioration overtime. Health related concerns were uniquely associated with anxiety and PTSS at all time points and their deterioration, but not with depression. Improvement in sense of protection overtime associated with decrease in depression and anxiety. Hesitancy towards vaccination was associated to higher financial concerns and lower sense of protection by the authorities. CONCLUSIONS: Our findings accentuate the multitude of risk factors for psychiatric morbidity during COVID-19, and the centrality of fatigue in determining mental health outcomes.

Real-World Immunogenicity and Reactogenicity of Two Doses of Pfizer-BioNTech COVID-19 Vaccination in Children Aged 5-11 Years.

There are limited data concerning the immunogenicity and reactogenicity of COVID-19 vaccines in children. A total of 110 children, 5-11 years old were vaccinated with two doses (with a 3-week interval between doses) of the Pfizer-BioNTech COVID-19 vaccine and were followed for 21, 90, and 180 days after vaccination for immunogenicity, adverse events, and breakthrough infections. Ninety days after the first vaccine dose, the GeoMean (CI 95%) of IgG ascended to 1291.0 BAU (929.6-1790.2) for uninfected children and 1670.0 BAU (1131.0-2466.0) for Infected children. One hundred and eighty days after receiving the first dose of the vaccine, the titers decreased to 535.5 BAU (288.4-993.6) for the uninfected children, while only a small decline was detected among infected children-1479.0 (878.2-2490.0). The neutralizing antibodies titer almost did not change over time in the uninfected children, and even elevated for the infected children. Of the 110 vaccinated children, 75.5% were infected, with only mild COVID-19 infection symptoms. Child vaccination was found to be safe, with mild, mostly local, and of short duration, reported AEs. No serious adverse events (SAEs) were reported after vaccination. The durability of two doses of vaccine in children is longer, thus a booster may not be needed as early as in adults.

Prevalence and clinical implication of thrombocytopenia and heparin-induced thrombocytopenia in patients who are critically ill with COVID-19.

As the COVID-19 pandemic continues to evolve, different clinical manifestations are better understood and studied. These include various haematologic disorders that have been shown to be associated with increased morbidity and mortality. We studied the prevalence of one unusual manifestation, heparin-induced thrombocytopenia (HIT) and its clinical implications in patients who are severely ill with COVID-19 in a single tertiary centre in Israel. The presence of thrombocytopenia, disseminated intravascular coagulation (DIC) and HIT, and their association with clinical course and outcomes were studied. One-hundred and seven patients with COVID-19 were included. Fifty-seven (53.2%) patients developed thrombocytopenia, which was associated with the worst outcomes (ventilation, DIC and increased mortality). Sixteen (28.0%) patients with thrombocytopenia were positive for HIT, all of which were supported by extracorporeal devices. HIT was independently associated with ventilation days, blood product transfusions, longer hospitalisation and mortality.Platelet abnormalities and HIT are common in patients who are critically ill with COVID-19 and are associated with the worst clinical outcomes. The mechanisms underlying HIT in COVID-19 are yet to be studied; HIT may contribute to the dysregulated immunologic response associated with COVID-19 critical illness and may play a significant part in the coagulopathy seen in these patients. As many patients with COVID-19 require aggressive thromboprophylaxis, further understanding of HIT and the implementation of appropriate protocols are important.

A Practical Clinical Score Predicting Respiratory Failure in COVID-19 Patients.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic resulted in repeated surges of patients, sometimes challenging triage protocols and appropriate control of patient flow. Available models, such as the National Early Warning Score (NEWS), have shown significant limitations. Still, they are used by some centers to triage COVID-19 patients due to the lack of better tools. OBJECTIVES: To establish a practical and automated triage tool based on readily available clinical data to rapidly determine a distinction between patients who are prone to respiratory failure. METHODS: The electronic medical records of COVID-19 patients admitted to the Sheba Medical Center March-April 2020 were analyzed. Population data extraction and exploration were conducted using a MDClone (Israel) big data platform. Patients were divided into three groups: non-intubated, intubated within 24 hours, and intubated after 24 hours. The NEWS and our model where applied to all three groups and a best fit prediction model for the prediction of respiratory failure was established. RESULTS: The cohort included 385 patients, 42 of whom were eventually intubated, 15 within 24 hours or less. The NEWS score was significantly lower for the non-intubated patients compared to the two other groups. Our improved model, which included NEWS elements combined with other clinical data elements, showed significantly better performance. The model's receiver operating characteristic curve had area under curve (AUC) of 0.92 with of sensitivity 0.81, specificity 0.89, and negative predictive value (NPV) 98.4% compared to AUC of 0.63 with NEWS. As patients deteriorate and require further support with supplemental O2, the need for re-triage emerges. Our model was able to identify those patients on supplementary O2 prone to respiratory failure with an AUC of 0.86 sensitivity 0.95, and specificity 0.7 NPV 98.9%, whereas NEWS had an AUC of 0.76. For both groups positive predictive value was approximately 35. CONCLUSIONS: Our model, based on readily available and simple clinical parameters, showed an excellent ability to predict negative outcome among patients with COVID-19 and therefore might be used as an initial screening tool for patient triage in emergency departments and other COVID-19 specific areas of the hospital.

Sleep Difficulties Among COVID-19 Frontline Healthcare Workers.

Objective: To identify COVID-19 work-related stressors and experiences associated with sleep difficulties in HCW, and to assess the role of depression and traumatic stress in this association. Methods: A cross-sectional study of HCW using self-report questionnaires, during the first peak of the pandemic in Israel (April 2020), conducted in a large tertiary medical center in Israel. Study population included 189 physicians and nurses working in designated COVID-19 wards and a comparison group of 643 HCW. Mean age of the total sample was 41.7 ± 11.1, 67% were female, 42.1% physicians, with overall mean number of years of professional experience 14.2 ± 20. The exposure was working in COVID-19 wards and related specific stressors and negative experiences. Primary outcome measurement was the Insomnia Severity Index (ISI). Secondary outcomes included the Primary Care-Post Traumatic Stress Disorder Screen (PC-PTSD-5); the Patient Health Questionnaire-9 (PHQ-9) for depression; the anxiety module of the Patient-Reported Outcomes Measurement Information System (PROMIS); Pandemic-Related Stress Factors (PRSF) and witnessing patient suffering and death. Results: Compared with non-COVID-19 HCW, COVID-19 HCW were more likely to be male (41.3% vs. 30.7%) and younger (36.91 ± 8.81 vs. 43.14 ± 11.35 years). COVID-19 HCW reported higher prevalence of sleep difficulties: 63% vs. 50.7% in the non-COVID group (OR 1.62, 95% CI 1.15-2.29, p = 0.006), mostly difficulty maintaining sleep: 26.5% vs. 18.5% (OR 1.65, 95% CI 1.11-2.44, p = 0.012). Negative COVID-19 work-related experiences, specifically witnessing patient physical suffering and death, partially explained the association. Although past psychological problems and current depression and PTSD were associated with difficulty maintaining sleep, the main association remained robust also after controlling for those conditions in the full model. Conclusion and Relevance: COVID-19 frontline HCW were more likely to report sleep difficulties, mainly difficulty maintaining sleep, as compared with non-COVID-19 HCW working at the same hospital. Negative patient-care related experiences likely mediated the increased probability for those difficulties. Future research is needed to elucidate the long-term trajectories of sleep difficulties among HCW during large scale outbreaks, and to identify risk factors for their persistence.

Rapid Antigen Tests For Safe School Opening in the COVID-19 Pandemic Era.

BACKGROUND: Since the beginning of the Sever Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, school closure as a mitigating measure was at the center of a public and professional debate. While the negative effects of school closure cannot be ignored, accumulating data suggested that it is necessary for reducing community transmission. Our study presents an optional strategy for safe school opening during a pandemic, implemented in selected Israeli high schools by a special task force constructed by the Sheba Medical Center (SMC). METHODS: The study took place between November 2020 and April 2021. Three schools from different areas of Israel were enrolled. The participants were asked to undergo bi-weekly SARS-CoV-2 rapid diagnostic antigen tests (Ag-RDT). Those who tested positive were requested to self-isolate, whereas their school contacts were tested daily by Ag-RDT. Participants with a previously documented SARS-CoV-2 infection or who were found to be SARS-CoV-2 seropositive upon enrollment were exempted from screening. RESULTS: Of a total of 361 participants who enrolled in the study, 12.3% were found to be seropositive. Fourteen SARS-CoV-2 cases were detected (3.5%), 12 of them in one single school located in an endemic area for SARS-CoV-2. The 14 cases resulted in 84 days of COVID-19-related absence from school, comparing with 1775 potential days of COVID-19-related absence under a strategy implementing self-isolation instead of testing. CONCLUSIONS: Safe continuation of academic routine during the pandemic is possible when using rapid Ag-RDT as a screening tool, while allowing swab collection by trained students and teachers.

The Predictive Value of Serum ACE2 and TMPRSS2 Concentrations in Patients with COVID-19-A Prospective Pilot Study.

One of the major challenges for healthcare systems during the Coronavirus-2019 (COVID-19) pandemic was the inability to successfully predict which patients would require mechanical ventilation (MV). Angiotensin-Converting Enzyme 2 (ACE2) and TransMembrane Protease Serine S1 member 2 (TMPRSS2) are enzymes that play crucial roles in SARS-CoV-2 entry into human host cells. However, their predictive value as biomarkers for risk stratification for respiratory deterioration requiring MV has not yet been evaluated. We aimed to evaluate whether serum ACE2 and TMPRSS2 levels are associated with adverse outcomes in COVID-19, and specifically the need for MV. COVID-19 patients admitted to an Israeli tertiary medical center between March--November 2020, were included. Serum samples were obtained shortly after admission (day 0) and again following one week of admission (day 7). ACE2 and TMPRSS2 concentrations were measured with ELISA. Of 72 patients included, 30 (41.6%) ultimately required MV. Serum ACE2 concentrations >7.8 ng/mL at admission were significantly associated with the need for MV (p = 0.036), inotropic support, and renal replacement therapy. In multivariate logistic regression analysis, elevated ACE2 at admission was associated with the need for MV (OR = 7.49; p = 0.014). To conclude, elevated serum ACE2 concentration early in COVID-19 illness correlates with respiratory failure necessitating mechanical ventilation. We suggest that measuring serum ACE2 at admission may be useful for predicting the risk of severe disease.

Left alone outside: A prospective observational cohort study on mental health outcomes among relatives of COVID-19 hospitalized patients.

Hospitalization due to COVID-19 bears many psychological challenges. While focusing on infected patients, their relatives are being largely neglected. Here, we investigated the mental health implications of hospitalization among relatives, over a one-month course. A single center study was conducted to assess relatives of COVID-19 patients during the first month from their admission to the hospital, and elucidate risk and protective factors for mental health deterioration. Ninety-one relatives of the first patients to be hospitalized in Israel were contacted by phone and screened for anxiety, depression, and posttraumatic stress symptoms (PTSS) at three time points (25-72 hours, 7-18 days, and one month). We found that anxiety and depression decreased significantly during the first month from their admission. Risk factors for deteriorated mental health at one month included feelings of mental exhaustion, financial concerns, and social disconnection. Being an ultra-orthodox was a protective factor for anxiety and depression but not for PTSS. Our findings emphasize the importance of addressing the mental health status of close relatives and adjust support for the unique setting of COVID-19.

Inpatient Telemedicine and New Models of Care during COVID-19: Hospital Design Strategies to Enhance Patient and Staff Safety.

The challenges of the COVID-19 pandemic have led to the development of new hospital design strategies and models of care. To enhance staff safety while preserving patient safety and quality of care, hospitals have created a new model of remote inpatient care using telemedicine technologies. The design of the COVID-19 units divided the space into contaminated and clean zones and integrated a control room with audio-visual technologies to remotely supervise, communicate, and support the care being provided in the contaminated zone. The research is based on semi-structured interviews and observations of care processes that implemented a new model of inpatient telemedicine at Sheba Medical Center in Israel in different COVID-19 units, including an intensive care unit (ICU) and internal medicine unit (IMU). The study examines the impact of the diverse design layouts of the different units associated with the implementation of digital technologies for remote care on patient and staff safety. The results demonstrate the challenges and opportunities of integrating inpatient telemedicine for critical and intermediate care to enhance patient and staff safety. We contribute insights into the design of hospital units to support new models of remote care and suggest implications for Evidence-based Design (EBD), which will guide much needed future research.

Telemedicine Implementation in COVID-19 ICU: Balancing Physical and Virtual Forms of Visibility.

OBJECTIVE: This case study examines the implementation of inpatient telemedicine in COVID-19 intensive care units (ICUs) and explores the impact of shifting forms of visibility on the management of the unit, staff collaboration, and patient care. BACKGROUND: The COVID-19 crisis drove healthcare institutions to rapidly develop new models of care based on integrating digital technologies for remote care with transformations in the hospital-built environment. The Sheba Medical Center in Israel created COVID-19 ICUs in an underground structure with an open-ward layout and telemedicine control rooms to remotely supervise, communicate, and support the operations in the contaminated zones. One unit had a physical visual connection between the control room and the contaminated zone through a window, while the other had only a virtual connection with digital technologies. METHODS: The findings are based on semistructured interviews with Sheba medical staff, telemedicine companies, and the architectural design team and observations at the COVID-19 units during March-August 2020. RESULTS: The case study illustrates the implications of virtual and physical visibility on the management of the unit, staff collaboration, and patient care. It demonstrates the correlations between patterns of visibility and the users' sense of control, orientation in space, teamwork, safety, quality of care, and well-being. CONCLUSIONS: The case study demonstrates the limitations of current telemedicine technologies that were not designed for inpatient care to account for the spatial perception of the unit and the dynamic use of the space. It presents the potential of a hybrid model that balances virtual and physical forms of visibility and suggests directions for future research and development of inpatient telemedicine.

Association among income loss, financial strain and depressive symptoms during COVID-19: Evidence from two longitudinal studies.

BACKGROUND: COVID-19 pandemic has major ramifications for global health and economy, with growing concerns about economic recession and implications for mental health. Here we investigated the associations between pandemic-related income loss with financial strain and mental health trajectories over a 1-month course, in two independent cohorts. METHODS: Two independent studies were conducted in the U.S and in Israel at the beginning of the outbreak (March-April 2020, T1; study I: N = 2904, study II: N = 1267) and at a 1-month follow-up (T2; study I: N = 1318, study II: N = 241). Mixed-effects models were applied to assess associations among COVID-19-related income loss, financial strain, and pandemic-related worries about health, with anxiety and depression, controlling for multiple covariates including pre-COVID-19 income. RESULTS: In both studies, income loss and financial strain were associated with greater depressive symptoms at T1, above and beyond T1 anxiety, worries about health, and pre-COVID-19 income. Worsening of income loss was associated with exacerbation of depression at T2 in both studies. Worsening of subjective financial strain was associated with exacerbation of depression at T2 in one study (US). CONCLUSIONS: Income loss and financial strain were uniquely associated with depressive symptoms and their exacerbation over time, above and beyond pandemic-related anxiety. In times when a myriad of stressors are affecting mental health worldwide, our findings reveal specific links between the economic impact of COVID-19 and psychiatric outcomes.

Trajectories of post-traumatic stress symptoms, anxiety, and depression in hospitalized COVID-19 patients: A one-month follow-up.

OBJECTIVES: Little is known about the mental health outcomes of hospitalized COVID-19 patients. The aims of the study were: (1) to examine the trajectories of anxiety, depression, and pandemic-related stress factors (PRSF) of COVID-19 hospitalized patients one-month following hospitalization; (2) to assess the presence of post-traumatic stress symptoms (PTSS) a month after hospitalization; (3) to identify baseline risk and protective factors that would predict PTSS one month after hospitalization. METHODS: We contacted hospitalized COVID-19 patients (n = 64) by phone, at three time-points: during the first days after admission to the hospital (T1); after ~two weeks from the beginning of hospitalization (T2), and one month after hospitalization (T3). At all time-points we assessed the levels of anxiety and depression symptoms, as well as PRSF. At T3, PTSS were assessed. RESULTS: The levels of depressive and anxiety symptoms decreased one-month following hospitalization. Moreover, higher levels of anxiety (standardized ß = 1.15, 95% CI = 0.81-1.49, p < 0.001) and depression (ß = 0.97, 95% CI = 0.63-1.31 p < 0.001) symptoms during the first week of hospitalization, feeling socially disconnected (ß = 0.59, 95% CI = 0.37-0.81 p < 0.001) and experiencing a longer hospitalization period (ß = 0.25, 95% CI = 0.03-0.47 p = 0.026) predicted higher PTSS scores a month post-hospitalization. CONCLUSIONS: We identified early hospitalization risk factors for the development of PTSS one month after hospitalization that should be targeted to reduce the risk for PTSS.

The association between witnessing patient death and mental health outcomes in frontline COVID-19 healthcare workers.

BACKGROUND: Healthcare workers (HCW) treating coronavirus disease 2019 (COVID-19) patients face high levels of psychological stress. We aimed to compare mental health outcomes, risk and protective factors for posttraumatic stress symptoms (PTSS), probable depression, and anxiety between HCW working in COVID-19 and non-COVID-19 wards. METHODS: A self-report survey, administered in a large tertiary hospital in Israel during the peak of the COVID-19 outbreak was completed by 828 HCW (42.2% physicians, 57.8% nurses. Patient-Reported Outcomes Measurement Information System; the Patient Health Questionnaire-9; the Primary Care-Post Traumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) were used for assessing anxiety, depression, and PTSS, respectively. Pandemic-related stress factors, negative experiences, and potential protective factors were also assessed. RESULTS: Median PC-PTSD scores differed significantly between study teams (χ2 [5] = 17.24; p = .004). Prevalence of probable depression and anxiety were similar in both groups. Risk factors for mental health outcomes included mental exhaustion, anxiety about being infected and infecting family. Overall, higher proportion of the COVID-19 team witnessed patient deaths as compared to the non-COVID-19 team (50.2% vs. 24.7%). Witnessing patient death at the COVID-19 wards was associated with a four-fold increased likelihood of PTSS (odds ratio [OR] = 3.97; 95% confidence interval [CI], 1.58-9.99; p = .0007), compared with the non-COVID-19 wards (OR 0.91; 95% CI, 0.51-1.61; p = .43). CONCLUSIONS: Witnessing patient death appears to be a risk factor for PTSS unique to HCW directly engaged in treating patients with COVID-19. Our findings suggest that helping HCW cope with COVID-19 related deaths might reduce their risk of posttraumatic stress.

Anxiety and Depression Symptoms in COVID-19 Isolated Patients and in Their Relatives.

Background: While focusing on the management and care of COVID-19 patients, the mental health of these patients and their relatives is being overlooked. The aim of the current study was to measure anxiety and depression, and to assess their association with socio-demographic and pandemic-related stress factors in COVID-19 patients and their relatives during the initial stage of hospitalization. Methods: We assessed isolated hospitalized patients (N = 90) and their relatives (adults and children, N = 125) by phone, 25-72 h following patients' admission. The quantitative measures included the Anxiety and Depression modules of the Patient-Reported Outcomes Measurement Information System (PROMIS) and pandemic-related stress factors. Qualitative measures included questions exploring worries, sadness, and coping modes. Results: Both patients and relatives suffer from high levels of anxiety and related pandemic worries, with lower levels of depressive symptoms. Compared to adult relatives, child relatives reported significantly lower anxiety. The multivariable logistic regression analysis revealed an increased risk for anxiety among females and a decreased risk among ultra-orthodox participants. While increased anxiety among patients was associated with feelings of isolation, increased anxiety among relatives was associated with a feeling of not being protected by the hospital. Conclusions: Patients and relatives experience similar high anxiety levels which are more robust in women and lower in ultra-orthodox participants. Our findings indicate that anxiety symptoms of both patients and adult relatives should be addressed.

COVID-19 in the Pediatric Population-Review and Current Evidence.

PURPOSE OF REVIEW: Coronavirus disease 2019 (COVID-19) pandemic has major health and economic impacts. We review disease characteristics in children. RECENT FINDINGS: Children comprise 1-2% of the diagnosed cases, and typically suffer mild disease. The median age of infected children is 3.3-11 years, and male/female ratio is 1.15-1.55. Common symptoms in children include upper respiratory symptoms (26-54%), cough (44-54%), fever (32-65%), and gastrointestinal (15-30%) symptoms. Substantial proportion (4-23%) are asymptomatic. Death rates are up to 0.7%. Risk factors associated with severe disease are neonatal age group, male gender, lower respiratory tract disease, and pre-existing medical conditions. Vertical transmission was reported. Multisystem inflammatory syndrome (MIS), characterized by fever, multisystem organ involvement, and laboratory markers of inflammation, causes critical illness in > 50% of cases and is increasingly reported from endemic countries. Indirect effects of the coronavirus epidemic include higher rates of psychiatric morbidities, education loss, unhealthy lifestyle changes, and increased child neglect. Vaccines are in clinical trials and immunogenicity has not yet been shown in children. SUMMARY: Overall, COVID-19 has lower incidence and causes milder disease in children compared with adult patients. MIS is a rare severe complication more common in children. More data on the efficacy and safety of antivirals in children are needed.

Anxiety, pandemic-related stress and resilience among physicians during the COVID-19 pandemic.

BACKGROUND: Physicians play a crucial frontline role in the COVID-19 pandemic, which may involve high levels of anxiety. We aimed to investigate the association between pandemic-related stress factors (PRSF) and anxiety and to evaluate the potential effect of resilience on anxiety among physicians. METHODS: A self-report digital survey was completed by 1106 Israeli physicians (564 males and 542 females) during the COVID-19 outbreak. Anxiety was measured by the 8-item version of the Patient-Reported Outcomes Measurement Information System. Resilience was evaluated by the 10-item Connor-Davidson Resilience Scale. Stress was assessed using a PRSF inventory. RESULTS: Physicians reported high levels of anxiety with a mean score of 59.20 ± 7.95. We found an inverse association between resilience and anxiety. Four salient PRSF (mental exhaustion, anxiety about being infected, anxiety infecting family members, and sleep difficulties) positively associated with anxiety scores. CONCLUSIONS: Our study identified specific PRSF including workload burden and fear of infection that are associated with increased anxiety and resilience that is associated with reduced anxiety among physicians.