Role of the interaction between lumbar kinematics and accelerometer-measured physical activity in bodily pain, physical functioning and work ability among health care workers with low back pain.

The aim of this study was to examine the associations of spinal kinematics and physical activity (PA) with bodily pain, physical functioning, and work ability among health care workers with low back pain (LBP). Spinal kinematics and PA were measured with a wireless Inertial Measurement Unit system (ValedoMotion®) and a waist-worn tri-axial accelerometer (Hookie AM20), respectively. Their association was assessed in relation to Work Ability Index (WAI), bodily pain and physical functioning (RAND-36) in 210 health care workers with recurrent LBP. Greater lumbar movement variability/less deterministic lumbar movement (in angular velocity) during a "Pick Up a Box" functional task was correlated with higher amounts of step counts (r = -0.29, p = 0.01) and moderate PA (r = -0.24, p = 0.03). A higher amount of PA (p = 0.03) as well as less movement control impairment (p = 0.04) and movement variability (p = 0.03) were associated with greater work ability, whilst greater vigorous PA was the only parameter to explain higher physical functioning (p = 0.02). PA and movement variability were relative to each other to explain bodily pain (p = 0.01). These findings show the importance of considering the interaction between lumbar kinematics and physical activity while planning strategies to improve bodily pain, physical functioning and work ability among health care workers with LBP.

Non-patient related SARS-CoV-2 exposure to colleagues and household members impose the highest infection risk for hospital employees with and without patient contact in a German university hospital: follow-up of the prospective Co-HCW Seroprevalence study

BackgroundThe Co-HCW study is a prospective, longitudinal single center observational study on the SARS-CoV-2 seroprevalence and infection status in staff members of Jena University Hospital (JUH) in Jena, Germany. Material and MethodsThis follow-up study covers the observation period from 19th May 2020 to 22nd June 2021. At each out of three voluntary study visits, participants filled out a questionnaire on individual SARS-CoV-2 exposure. In addition, serum samples to assess specific SARS-CoV-2 antibodies were collected. Participants with antibodies against nucleocapsid and/or spike protein without previous vaccination and/or a reported positive SARS-CoV-2 PCR test were regarded as participants with detected SARS-CoV-2 infection. Multivariable logistic regression modeling was applied to identify potential risk factors for infected compared to non-infected participants. ResultsOut of 660 participants that were included during the first study visit, 406 participants (61.5%) were eligible for final analysis as they did not change the COVID-19 risk area (high-risk n=76; intermediate-risk n=198; low-risk n=132) during the study. Forty-four participants (10.8%, 95% confidence interval (95%CI) 8.0%-14.3%) had evidence of a current or past SARS-CoV-2 infection detected by serology (n=40) and/or PCR (n=28). No association of any SARS-CoV-2 infection with the COVID-19 risk group according to working place could be detected. But exposure to a SARS-CoV-2 positive household member (adjusted OR (AOR) 4.46, 95%CI 2.06-9.65) or colleague (AOR 2.30, 95%CI 1.10-4.79) significantly increased the risk of a SARS-CoV-2 infection. ConclusionOur results demonstrate that non-patient-related SARS-CoV-2 exposure imposed the highest infection risk in hospital staff members of JUH.

Arrayed multicycle drug screens identify broadly acting chemical inhibitors for repurposing against SARS CoV 2

Coronaviruses (CoVs) circulate in humans and animals, and expand their host range by zoonotic and anthroponotic transmissions. Endemic human CoVs, such as 229E and OC43 cause limited respiratory disease, and elicit short term anti-viral immunity favoring recurrent infections. Yet, severe acute respir-atory syndrome (SARS)-CoV-2 spreads across the globe with unprecedented impact on societies and economics. The world lacks broadly effective and affordable anti-viral agents to fight the pandemic and reduce the death toll. Here, we developed an image-based multicycle replication assay for focus for-mation of -coronavirus hCoV-229E-eGFP infected cells for screening with a chemical library of 5440 compounds arrayed in 384 well format. The library contained about 39% clinically used compounds, 26% in phase I, II or III clinical trials, and 34% in preclinical development. Hits were counter-selected against toxicity, and challenged with hCoV-OC43 and SARS-CoV-2 in tissue culture and human bronchial and nasal epithelial explant cultures from healthy donors. Fifty three compounds inhibited hCoV-229E-GFP, 39 of which at 50% effective concentrations (EC50) < 2M, and were at least 2-fold separated from toxicity. Thirty nine of the 53 compounds inhibited the replication of hCoV-OC43, while SARS-CoV-2 was inhibited by 11 compounds in at least two of four tested cell lines. Six of the 11 compounds are FDA-approved, one of which is used in mouth wash formulations, and five are systemic and orally available. Here, we demonstrate that methylene blue (MB) and mycophenolic acid (MPA), two broadly available low cost compounds, strongly inhibited shedding of infectious SARS-CoV-2 at the apical side of the cultures, in either pre- or post-exposure regimens, with somewhat weaker effects on viral RNA release indicated by RT-qPCR measurements. Our study illustrates the power of full cycle screens in repurposing clinical compounds against SARS-CoV-2. Importantly, both MB and MPA reportedly act as immunosuppressants, making them interesting candidates to counteract the cytokine storms affecting COVID-19 patients.

Seroprevalence of SARS CoV-2 antibodies in healthcare workers and administration employees: a prospective surveillance study at a 1,400-bed university hospital in Germany

Background: Healthcare workers (HCWs) are at particular risk to acquire SARS-CoV-2 infections. Aim: The objectives of this study were to compare SARS-CoV-2 IgG seroprevalence and compliance to wear personal protective equipment (PPE) between HCWs working within (high-risk) or outside (intermediate-risk) units treating suspected or confirmed COVID-19 patients. In addition, administration staff (low-risk) was included. Materials: Co-HCW is a prospective cohort study among employees at the Jena University Hospital, Germany. Since 16th March 2020, 50 SARS-CoV-2 inpatients and 73 outpatients were treated in our hospital. Mandatory masking was implemented on 20th March 2020. We here evaluated seroprevalence using two IgG detecting immunoassays, assessed COVID-19 exposure, clinical symptoms and compliance to wear PPE. Findings: Between 19th May and 19th June 2020 we analysed 660 employees [out of 3,228; 20.4%]. Eighteen participants (2.7%) had SARS-CoV-2 antibodies in at least one immunoassay. Among them, 13 (72.2%) were not aware of direct COVID-19 exposure and 9 (50.0%) did not report any clinical symptoms. We observed no evidence for an association between seroprevalence and risk area (high-risk: 2 of 137 HCWs (1.5%), intermediate-risk: 10 of 343 HCWs (2.9%), low-risk: 6 of 180 administration employees (3.3%); p=0.574). Reported compliance to wear PPE differed (p<0.001) between working in high-risk (98.3%) and in intermediate-risk areas (69.8%). Conclusion: No evidence for higher seroprevalence against SARS-CoV-2 in HCWs working in high-risk COVID-19 areas could be observed, probably due to high compliance to wear PPE. Compared to administration employees, we observed no additional risk to acquire SARS-CoV-2 infections by patient care.

Early postmortem mapping of SARS-CoV-2 RNA in patients with COVID-19 and correlation to tissue damage

Clinical observations indicate that COVID-19 is a systemic disease. An investigation of the viral distribution within the human body in correlation to tissue damage can help understanding the pathophysiology of SARS-CoV-2 infection.We present a detailed mapping of viral RNA in 61 tissues and organs of 11 deceased patients with the diagnosis COVID-19. The autopsies were performed within the (very) early postmortem interval (mean: 5.6 hours) to avoid bias due to viral RNA and tissue degradation. Viral loads, blood levels of cytokines, prothrombotic factors as well as macro- and micro-morphology were correlated.Very high (> 104 copies/ml) viral loads were detected in the lungs of most patients and then correlated to severe tissue damage. Intact viral particles could be verified in the lung tissue by transmission electron microscopy. Viral loads in the lymph nodes were associated with a loss of follicular architecture. Viral RNA was detected throughout further extra-pulmonary tissues and organs without visible tissue damage. Inflammatory cytokines as well as the prothrombotic factors were elevated in all patients.In conclusion, the dissemination of SARS-CoV-2-RNA throughout the body supports the hypothesis of a maladaptive host response with viremia and multi-organ dysfunction.View Full Text

Neuropilin-1 is a host factor for SARS-CoV-2 infection

SARS-CoV-2 is the causative agent of COVID-19, a coronavirus disease that has infected more than 6.6 million people and caused over 390,000 deaths worldwide1,2. The Spike (S) protein of the virus forms projections on the virion surface responsible for host cell attachment and penetration. This viral glycoprotein is synthesized as a precursor in infected cells and, to be active, must be cleaved to two associated polypeptides: S1 and S2(3,4). For SARS-CoV-2 the cleavage is catalysed by furin, a host cell protease, which cleaves the S protein precursor at a specific sequence motif that generates a polybasic Arg-Arg-Ala-Arg (RRAR) C-terminal sequence on S1. This sequence motif conforms to the C-end rule (CendR), which means that the C-terminal sequence may allow the protein to associate with cell surface neuropilin-1 (NRP1) and neuropilin-2 (NRP2) receptors5. Here we demonstrate using immunoprecipitation, site-specific mutagenesis, structural modelling, and antibody blockade that, in addition to engaging the known receptor ACE2, S1 can bind to NRP1 through the canonical CendR mechanism. This interaction enhances infection by SARS-CoV-2 in cell culture. NRP1 thus serves as a host factor for SARS-CoV-2 infection, and provides a therapeutic target for COVID-19.