Pandemic fatigue fueled political discontent during the COVID-19 pandemic.

Health authorities have highlighted "pandemic fatigue" as a psychological consequence of the COVID-19 pandemic and warned that "fatigue" could demotivate compliance with health-related policies and mandates. Yet, fatigue from following the policies of authorities may have consequences far beyond the health domain. Theories from the social sciences have raised that real and perceived costs of policies can also drive sentiments of discontent with the entire political establishment. Integrating theories from the health and social sciences, we ask how pandemic fatigue (i.e., perceived inability to "keep up" with restrictions) developed over the pandemic and whether it fueled political discontent. Utilizing longitudinal and panel surveys collected from September 2020 to July 2021 in eight Western countries (N = 49,116), we analyze: 1) fatigue over time at the country level, 2) associations between pandemic fatigue and discontent, and 3) the effect of pandemic fatigue on political discontent using panel data. Pandemic fatigue significantly increased with time and the severity of interventions but also decreased with COVID-19 deaths. When triggered, fatigue elicited a broad range of discontent, including protest support and conspiratorial thinking. The results demonstrate the significant societal impact of the pandemic beyond the domain of health and raise concerns about the stability of democratic societies, which were already strained by strife prior to the pandemic.

Low Prevalence of Mild Alpha-1-Antitrypsin Deficiency in Hospitalized COVID-19-Patients.

Introduction: Alpha-1-antitrypsin (AAT) has been shown to inhibit SARS-CoV-2 cell entry and suggested as a therapeutic agent for COVID-19. Furthermore, epidemiological association of high prevalence of Alpha-1-antitrypsin deficiency (AATD) and regional severity of COVID-19-impact has been hypothesized. In our study setting, the estimated prevalence rates of mild (PI*MZ, PI*SS or PI*MS) and moderate-to-severe AATD (PI*ZZ or PI*SZ) are high, 9% and 0.2%, respectively. Our primary aim was to examine the prevalence rate of AATD among hospitalized COVID-19-patients. Methods: In this prospective observational study, enrollment occurred from December 2020 to January 2021 in two COVID-19-units at Skåne University Hospital, Lund, Sweden. Case definition was a patient hospitalized due to COVID-19. Patients were screened for AATD with PI-typing and if results were inconclusive, PCR for the S- and Z-genes were performed. Patients were categorized as severe or moderate COVID-19 and 30-day-mortality data were collected. The primary outcome was prevalence rate of AATD. The secondary outcome investigated association between presence of mild AATD and severe COVID-19. Results: We enrolled 61 patients with COVID-19. Two patients out of 61 (3%) had mild AATD (PI*MZ) and none had moderate-to-severe AATD. 30/61 (49%) had severe COVID-19. Both patients with mild AATD developed severe COVID-19. Yet, presence of AATD was not significantly associated with severe COVID-19 (p=0.24). Conclusion: Mild AATD (PI*MS or PI*MZ) was rare in a small cohort of hospitalized patients with COVID-19 in a study setting with a high background prevalence of AATD.

Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line

Preclinical studies of COVID-19 mRNA vaccine BNT162b2, developed by Pfizer and BioNTech, showed reversible hepatic effects in animals that received the BNT162b2 injection. Furthermore, a recent study showed that SARS-CoV-2 RNA can be reverse-transcribed and integrated into the genome of human cells. In this study, we investigated the effect of BNT162b2 on the human liver cell line Huh7 in vitro. Huh7 cells were exposed to BNT162b2, and quantitative PCR was performed on RNA extracted from the cells. We detected high levels of BNT162b2 in Huh7 cells and changes in gene expression of long interspersed nuclear element-1 (LINE-1), which is an endogenous reverse transcriptase. Immunohistochemistry using antibody binding to LINE-1 open reading frame-1 RNA-binding protein (ORFp1) on Huh7 cells treated with BNT162b2 indicated increased nucleus distribution of LINE-1. PCR on genomic DNA of Huh7 cells exposed to BNT162b2 amplified the DNA sequence unique to BNT162b2. Our results indicate a fast up-take of BNT162b2 into human liver cell line Huh7, leading to changes in LINE-1 expression and distribution. We also show that BNT162b2 mRNA is reverse transcribed intracellularly into DNA in as fast as 6 h upon BNT162b2 exposure.

COVID-19 vaccine effectiveness against severe disease from SARS-CoV-2 Omicron BA.1 and BA.2 subvariants - surveillance results from southern Sweden, December 2021 to March 2022.

We compared vaccine effectiveness against severe COVID-19 between December 2021 and March 2022 when Omicron BA.1 and BA.2 were the dominating SARS-CoV-2 variants in Scania county, Sweden. Effectiveness remained above 80% after the transition from BA.1 to BA.2 among people with at least three vaccine doses but the point estimate decreased markedly to 54% among those with only two doses. Protection from prior infection was also lower after the transition to BA.2. Booster vaccination seems necessary to maintain sufficient protection.

Risk of severe COVID-19 from the Delta and Omicron variants in relation to vaccination status, sex, age and comorbidities - surveillance results from southern Sweden, July 2021 to January 2022.

We compared the risk of severe COVID-19 during two periods 2021 and 2022 when Delta and Omicron, respectively, were the dominating virus variants in Scania county, Sweden. We adjusted for differences in sex, age, comorbidities, prior infection and vaccination. Risk of severe disease from Omicron was markedly lower among vaccinated cases. It was also lower among the unvaccinated but remained high (> 5%) for older people and middle-aged men with two or more comorbidities. Efforts to increase vaccination uptake should continue.

Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2.

Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.

Convalescent plasma treatment in severely immunosuppressed patients hospitalized with COVID-19: an observational study of 28 cases.

BACKGROUND: Immunosuppressed patients are particularly vulnerable to severe infection from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), risking prolonged viremia and symptom duration. In this study we describe clinical and virological treatment outcomes in a heterogeneous group of patients with severe immunosuppression due to various causes suffering from COVID-19 infection, who were all treated with convalescent plasma (CCP) along with standard treatment. METHODS: We performed an observational, retrospective case series between May 2020 to March 2021 at three sites in Skåne, Sweden, with a population of nearly 1.4 million people. All patients hospitalized for COVID-19 who received CCP with the indication severe immunosuppression as defined by the treating physician were included in the study (n = 28). RESULTS: In total, 28 severely immunocompromised patients, half of which previously had been treated with rituximab, who had received in-hospital convalescent plasma treatment of COVID-19 were identified. One week after CCP treatment, 13 of 28 (46%) patients had improved clinically defined as a decrease of at least one point at the WHO-scale. Three patients had increased score points of whom two had died. For 12 patients, the WHO-scale was unchanged. CONCLUSION: As one of only few studies on CCP treatment of COVID-19 in hospitalized patients with severe immunosuppression, this study adds descriptive data. The study design prohibits conclusions on safety and efficacy, and the results should be interpreted with caution. Prospective, randomized trials are needed to investigate this further.

Convalescence plasma treatment of COVID-19: results from a prematurely terminated randomized controlled open-label study in Southern Sweden.

OBJECTIVE: Convalescent plasma has been tried as therapy for various viral infections. Early observational studies of convalescent plasma treatment for hospitalized COVID-19 patients were promising, but randomized controlled studies were lacking at the time. The objective of this study was to investigate if convalescent plasma is beneficial to hospitalized patients with COVID-19. RESULTS: Hospitalized patients with confirmed COVID-19 and an oxygen saturation below 94% were randomized 1:1 to receive convalescent plasma in addition to standard of care or standard of care only. The primary outcome was number of days of oxygen treatment to keep saturation above 93% within 28 days from inclusion. The study was prematurely terminated when thirty-one of 100 intended patients had been included. The median time of oxygen treatment among survivors was 11 days (IQR 6-15) for the convalescent plasma group and 7 days (IQR 5-9) for the standard of care group (p = 0.4, median difference -4). Two patients in the convalescent plasma group and three patients in the standard of care group died (p = 0.64, OR 0.49, 95% CI 0.08-2.79). Thus no significant differences were observed between the groups. Trial registration ClinicalTrials NCT04600440, retrospectively registered Oct 23, 2020.

Detection of SARS-CoV-2 by rapid antigen tests on saliva in hospitalized patients with COVID-19.

BACKGROUND: The COVID-19 pandemic presents great challenges on transmission prevention, and rapid diagnosis is essential to reduce the disease spread. Various diagnostic methods are available to identify an ongoing infection by nasopharyngeal (NPH) swab sampling. However, the procedure requires handling by health care professionals, and therefore limits the application in household and community settings. OBJECTIVES: In this study, we aimed to determine if the detection of SARS-CoV-2 can be performed alternatively on saliva specimens by rapid antigen test. STUDY DESIGN: Saliva and NPH specimens were collected from 44 patients with confirmed COVID-19. To assess the diagnostic accuracy of point-of-care SARS-CoV-2 rapid antigen test on saliva specimens, we compared the performance of four test products. RESULTS: RT-qPCR was performed and NPH and saliva sampling had similar Ct values, which associated with disease duration. All four antigen tests showed similar trend in detecting SARS-CoV-2 in saliva, but with variation in the ability to detect positive cases. The rapid antigen test with the best performance could detect up to 67% of the positive cases with Ct values lower than 25, and disease duration shorter than 10 days. CONCLUSION: Our study therefore supports saliva testing as an alternative diagnostic procedure to NPH testing, and that rapid antigen test on saliva provides a potential complement to PCR test to meet increasing screening demand.

High level of protection against COVID-19 after two doses of BNT162b2 vaccine in the working age population - first results from a cohort study in Southern Sweden.

BACKGROUND: Vaccine effectiveness against COVID-19 needs to be assessed in diverse real-world population settings. METHODS: A cohort study of 805,741 residents in Skåne county, Southern Sweden, aged 18-64 years, of whom 26,587 received at least one dose of the BNT162b2 vaccine. Incidence rates of COVID-19 were estimated in sex- and age-adjusted analysis and stratified in two-week periods with substantial community spread of the disease. RESULTS: The estimated vaccine effectiveness in preventing infection ≥7 days after second dose was 86% (95% CI 72-94%) but only 42% (95% CI 14-63%) ≥14 days after a single dose. No difference in vaccine effectiveness was observed between females and males. Having a prior positive test was associated with 91% (95% CI 85-94%) effectiveness against new infection among the unvaccinated. CONCLUSION: A satisfactory effectiveness of BNT162b2 after the second dose was suggested, but with possibly substantially lower effect before the second dose.

Distinct phenotypes of platelet, monocyte, and neutrophil activation occur during the acute and convalescent phase of COVID-19.

SARS-CoV-2 has spread rapidly worldwide, causing the COVID-19 pandemic. Platelet activation and platelet-leukocyte complex formation are proposed to contribute to disease progression. Here, we report platelet and leukocyte activation during acute and convalescent COVID-19 in patients recruited between May-July 2020. Blood samples were analyzed by flow cytometry and ELISA using paired comparison between inclusion (day 0) and 28 days later. The majority of patients were mildly or moderately ill with significantly higher cytokine levels (IL-6 and IL-10) on day 0 as compared with day 28. Platelet activation and granule release were significantly higher on day 0 compared with day 28, as determined by ADP- or thrombin-induced surface CD62P expression, baseline released CD62P, and thrombin-induced platelet-monocyte complex formation. Monocyte activation and procoagulant status at baseline and post activation were heterogeneous but generally lower on day 0 compared with day 28. Baseline and thrombin- or fMLF-induced neutrophil activation and procoagulant status were significantly lower on day 0 compared with day 28. We demonstrate that during the acute phase of COVID-19 compared with the convalescent phase, platelets are more responsive while neutrophils are less responsive. COVID-19 is associated with thromboembolic events where platelet activation and interaction with leukocytes may play an important role.

Post-outbreak serological screening for SARS-CoV-2 infection in healthcare workers at a Swedish University Hospital.

BACKGROUND: Nosocomial outbreaks of coronavirus disease 2019 (COVID-19) can have devastating consequences from both a resource cost and patient healthcare perspective. Relying on reverse transcription-polymerase chain reaction (RT-PCR) for identifying infected individuals may result in missed cases. Screening for antibodies after an outbreak can help to find missed cases and better illuminate routes of transmission. METHODS: In this study, we present the results of a serological screening of the healthcare workers (HCWs) on a ward for infectious diseases in Sweden with a point-of-care antibody test 8 weeks after an outbreak of COVID-19. In all, 107/123 (87%) of HCWs who were tested with RT-PCR in the outbreak investigation participated in this study on seroprevalence. Participants were also asked to fill out a questionnaire entailing epidemiological data. The cohort was stratified by RT-PCR result and the resulting groups were compared to each other. RESULTS: Six (8%) HCWs who were tested RT-PCR negative during the outbreak investigation had developed specific IgG antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These HCWs had all worked shifts with colleagues who later were tested RT-PCR positive during the outbreak. CONCLUSIONS: Our results indicate that a serological follow-up screening after an outbreak may be used as a complement to virus detection in an outbreak situation. However, immunoglobulin (Ig) G-detection should also be performed at the start of an outbreak, to facilitate interpretation of the results.

Antibody kinetics and clinical course of COVID-19 a prospective observational study.

BACKGROUND: Serological response and association to clinical manifestation is important for understanding the pathogenesis of COVID-19. MATERIALS AND METHODS: A prospective observational study was conducted where antibody responses of IgG and IgA towards SARS-CoV-2 spike protein were studied over time in patients with COVID-19. Possible associations between antibody titers and outcome were analyzed. RESULTS: Forty patients with COVID-19, hospitalized at Skåne University hospital, Sweden, between April and June 2020 were included. IgG antibody responses were detected for all patients with the highest levels four weeks after COVID-19 diagnosis. Levels of IgA were generally higher at diagnosis and decreased towards baseline 4 weeks after confirmed COVID-19. Patients with severe COVID-19 had higher levels of antibodies directed against SARS-CoV-2 spike protein compared with patients with mild disease. CONCLUSION: IgG and IgA antibodies towards the spike protein follow different kinetics during COVID-19 and patients with severe disease develop higher antibody levels.

Association between SARS-CoV-2 and exposure risks in health care workers and university employees - a cross-sectional study.

BACKGROUND: In health care workers SARS-CoV-2 has been shown to be an occupational health risk, often associated with transmission between health care workers. Yet, insufficient information on transmission dynamics has been presented to elucidate the precise risk factors for contracting SARS-CoV-2 in this group. METHODS: In this cross-sectional study, we investigated association between questionnaire answers on potential exposure situations and SARS-CoV-2-positivity. Health care workers with and without COVID-19-patient contact at nine units at Skåne University Hospitals in Malmö and Lund, Sweden and university employees from Lund University, Sweden were enrolled. To limit impact of health care worker to health care worker transmission, units with known outbreaks were excluded. A SARS-CoV-2-positive case was defined by a previous positive PCR or anti-SARS-CoV-2 IgG in the ZetaGene COVID-19 Antibody Test. RESULTS: SARS-CoV-2-positivity was detected in 11/51 (22%) health care workers in COVID-19-units, 10/220 (5%) in non-COVID-19-units and 11/192 (6%) University employees (p = .001, Fischer's exact). In health care workers, SARS-CoV-2-positivity was associated with work in a designated COVID-19-unit (OR 5.7 (95CI 2.1-16)) and caring for COVID-19-patients during the majority of shifts (OR 5.4 (95CI 2.0-15)). In all participants, SARS-CoV-2-positivity was associated with a confirmed COVID-19 case (OR 10 (95CI 2.0-45)) in the household. CONCLUSION: Our study confirmed previous findings of elevated risk of acquiring SARS-CoV-2 in health care workers in COVID-19-units, despite exclusion of units with known outbreaks. Interestingly, health care workers in non-COVID-19-units had similar risk as University employees. Further measures to improve the safety of health care workers might be needed.KEY POINTSPrevious findings of elevated risk of contracting SARS-CoV-2 in health care workers with COVID-19 patient contact was confirmed, despite exclusion of wards with known SARS-CoV-2 outbreaks. Further measures to improve the safety of health care workers might be needed.

Rapid diagnostic testing for SARS-CoV-2: Validation and comparison of three point-of-care antibody tests.

With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a need for diagnostic tests has surfaced. Point-of-care (POC) antibody tests can detect immunoglobulin (Ig) G and M against SARS-CoV-2 in serum, plasma, or whole blood and give results within 15 min. Validation of the performance of such tests is needed if they are to be used in clinical practice. In this study, we evaluated three POC antibody tests. Convalescent serum samples from 47 reverse transcription-polymerase chain reaction (RT-PCR) verified patients with coronavirus disease 2019 (COVID-19) collected at least 28 days post RT-PCR diagnosis as well as 50 negative pre-COVID-19 controls were tested. The three tests (denoted the J-, N-, and Z-tests) displayed the sensitivities of 87%, 96%, and 85%, respectively, for the detection of IgG. All tests had the same specificity for IgG (98%). The tests did not differ significantly for the detection of IgG. The sensitivities for IgM were lower (15%, 67%, and 70%) and the specificities were 90%, 98%, and 90%, respectively. The positive and negative predictive values were similar among the tests. Our results indicate that these POC antibody tests might be accurate enough to use in routine clinical practice.

Serology assessment of antibody response to SARS-CoV-2 in patients with COVID-19 by rapid IgM/IgG antibody test.

The coronavirus disease 2019 (COVID-19) pandemic has created a global health- and economic crisis. Detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which causes COVID-19 by serological methods is important to diagnose a current or resolved infection. In this study, we applied a rapid COVID-19 IgM/IgG antibody test and performed serology assessment of antibody response to SARS-CoV-2. In PCR-confirmed COVID-19 patients (n = 45), the total antibody detection rate is 92% in hospitalized patients and 79% in non-hospitalized patients. The total IgM and IgG detection is 63% in patients with <2 weeks from disease onset; 85% in non-hospitalized patients with >2 weeks disease duration; and 91% in hospitalized patients with >2 weeks disease duration. We also compared different blood sample types and suggest a higher sensitivity by serum/plasma over whole blood. Test specificity was determined to be 97% on 69 sera/plasma samples collected between 2016-2018. Our study provides a comprehensive validation of the rapid COVID-19 IgM/IgG serology test, and mapped antibody detection patterns in association with disease progress and hospitalization. Our results support that the rapid COVID-19 IgM/IgG test may be applied to assess the COVID-19 status both at the individual and at a population level.

[Large differences in excess mortality in March-May 2020 by country of birth in Sweden]

The Swedish strategy for dealing with covid-19 has been criticized for not accounting for difficulties of conducting voluntary social distancing in settings with household overcrowding, dependence on public transport and large proportion of service sector workers. In such neighbourhoods there is typically a larger proportion of immigrants. We compared all-cause-mortality data in Sweden by country of origin from 2020 and 2016-2019 and found large disparities. The number of deaths among persons born in countries from which many refugees have migrated to Sweden in the last decades was 220% higher in March-May 2020 compared to the mean in 2016-2019. In contrast, there was no increased mortality among persons aged 40-64 years and a 19% increased number of deaths of those aged above 65 years born in Sweden, EU or North America during these three months. These observations further illustrate the need for a dedicated and more diverse strategy in dealing with the covid-19 pandemic.