Syrian hamster convalescence from prototype SARS-CoV-2 confers measurable protection against the attenuated disease caused by the Omicron variant.

The mutation profile of the SARS-CoV-2 Omicron (lineage BA.1) variant posed a concern for naturally acquired and vaccine-induced immunity. We investigated the ability of prior infection with an early SARS-CoV-2 ancestral isolate (Australia/VIC01/2020, VIC01) to protect against disease caused by BA.1. We established that BA.1 infection in naïve Syrian hamsters resulted in a less severe disease than a comparable dose of the ancestral virus, with fewer clinical signs including less weight loss. We present data to show that these clinical observations were almost absent in convalescent hamsters challenged with the same dose of BA.1 50 days after an initial infection with ancestral virus. These data provide evidence that convalescent immunity against ancestral SARS-CoV-2 is protective against BA.1 in the Syrian hamster model of infection. Comparison with published pre-clinical and clinical data supports consistency of the model and its predictive value for the outcome in humans. Further, the ability to detect protection against the less severe disease caused by BA.1 demonstrates continued value of the Syrian hamster model for evaluation of BA.1-specific countermeasures.

Within and between-day variation and associations of symptoms in Long Covid: Intensive longitudinal study.

BACKGROUND: People with Long Covid (Post Covid-19 Condition) describe multiple symptoms which vary between and within individuals over relatively short time intervals. We aimed to describe the real-time associations between different symptoms and between symptoms and physical activity at the individual patient level. METHODS AND FINDINGS: Intensive longitudinal study of 82 adults with self-reported Long Covid (median duration 12-18 months). Data collection involved a smartphone app with 5 daily entries over 14 days and continuous wearing of a wrist accelerometer. Data items included 7 symptoms (Visual Analog Scales) and perceived demands in the preceding period (Likert scales). Activity was measured using mean acceleration in the 3-hour periods preceding and following app data entry. Analysis used within-person correlations of symptoms pairs and both pooled and individual symptom networks derived from graphical vector autoregression. App data was suitable for analysis from 74 participants (90%) comprising 4022 entries representing 77.6% of possible entries. Symptoms varied substantially within individuals and were only weakly autocorrelated. The strongest between-subject symptom correlations were of fatigue with pain (partial coefficient 0.5) and cognitive difficulty with light-headedness (0.41). Pooled within-subject correlations showed fatigue correlated with cognitive difficulty (partial coefficient 0.2) pain (0.19) breathlessness (0.15) and light-headedness (0.12) but not anxiety. Cognitive difficulty was correlated with anxiety and light-headedness (partial coefficients 0.16 and 0.17). Individual participant correlation heatmaps and symptom networks showed no clear patterns indicative of distinct phenotypes. Symptoms, including fatigue, were inconsistently correlated with prior or subsequent physical activity: this may reflect adjustment of activity in response to symptoms. Delayed worsening of symptoms after the highest activity peak was observed in 7 participants. CONCLUSION: Symptoms of Long Covid vary within individuals over short time scales, with heterogenous patterns of symptom correlation. The findings are compatible with altered central symptom processing as an additional factor in Long Covid.

‘Function First’: how to promote physical activity and physical function in people with long-term conditions managed in primary care? A study combining realist and co-design methods

ObjectivesTo develop a taxonomy of interventions and a programme theory explaining how interventions improve physical activity and function in people with long-term conditions managed in primary care. To co-design a prototype intervention informed by the programme theory.DesignRealist synthesis combining evidence from a wide range of rich and relevant literature with stakeholder views. Resulting context, mechanism and outcome statements informed co-design and knowledge mobilisation workshops with stakeholders to develop a primary care service innovation.ResultsA taxonomy was produced, including 13 categories of physical activity interventions for people with long-term conditions.Abridged realist programme theoryRoutinely addressing physical activity within consultations is dependent on a reinforcing practice culture, and targeted resources, with better coordination, will generate more opportunities to address low physical activity. The adaptation of physical activity promotion to individual needs and preferences of people with long-term conditions helps affect positive patient behaviour change. Training can improve knowledge, confidence and capability of practice staff to better promote physical activity. Engagement in any physical activity promotion programme will depend on the degree to which it makes sense to patients and professions, and is seen as trustworthy.Co-designThe programme theory informed the co-design of a prototype intervention to: improve physical literacy among practice staff;describe/develop the role of a physical activity advisor who can encourage the use of local opportunities to be more active;and provide materials to support behaviour change.ConclusionsPrevious physical activity interventions in primary care have had limited effect. This may be because they have only partially addressed factors emerging in our programme theory. The co-designed prototype intervention aims to address all elements of this emergent theory, but needs further development and consideration alongside current schemes and contexts (including implications relevant to COVID-19), and testing in a future study. The integration of realist and co-design methods strengthened this study.

Virucidal efficacy of guanidine-free inactivants and rapid test buffers against SARS-CoV-2.

A pathogen inactivation step during collection or processing of clinical samples has the potential to reduce infectious risks associated with diagnostic procedures. It is essential that these inactivation methods are demonstrated to be effective, particularly for non-traditional inactivation reagents or for commercial products where the chemical composition is undisclosed. This study assessed inactivation effectiveness of twenty-four next-generation (guanidine-free) nucleic acid extraction lysis buffers and twelve rapid antigen test buffers against SARS-CoV-2, the causative agent of COVID-19. These data have significant safety implications for SARS-CoV-2 diagnostic testing and support the design and evidence-based risk assessment of these procedures.

Performance and impact of disposable and reusable respirators for healthcare workers during pandemic respiratory disease: a rapid evidence review.

OBJECTIVES: To synthesise evidence concerning the range of filtering respirators suitable for patient care and guide the selection and use of different respirator types. DESIGN: Comparative analysis of international standards for respirators and rapid review of their performance and impact in healthcare. DATA SOURCES: Websites of international standards organisations, Medline and Embase, hand-searching of references and citations. STUDY SELECTION: Studies of healthcare workers (including students) using disposable or reusable respirators with a range of designs. We examined respirator performance, clinician adherence and performance, comfort and impact, and perceptions of use. RESULTS: We included standards from eight authorities across Europe, North and South America, Asia and Australasia and 39 research studies. There were four main findings. First, international standards for respirators apply across workplace settings and are broadly comparable across jurisdictions. Second, effective and safe respirator use depends on proper fitting and fit testing. Third, all respirator types carry a burden to the user of discomfort and interference with communication which may limit their safe use over long periods; studies suggest that they have little impact on specific clinical skills in the short term but there is limited evidence on the impact of prolonged wearing. Finally, some clinical activities, particularly chest compressions, reduce the performance of filtering facepiece respirators. CONCLUSION: A wide range of respirator types and models is available for use in patient care during respiratory pandemics. Careful consideration of performance and impact of respirators is needed to maximise protection of healthcare workers and minimise disruption to care.

The effect of heat-treatment on SARS-CoV-2 viability and detection.

The development of safe diagnostic protocols for working with SARS-CoV-2 clinical samples at Biosafety Level 2 (BSL2) requires understanding of the effect of heat-treatment on SARS-CoV-2 viability and downstream RT-PCR sensitivity. In this study heating SARS-CoV-2/England/2/2020 to 56 °C and 60 °C for 15, 30 and 60 min reduced the virus titre by between 2.1 and 4.9 log10 pfu/mL (as determined by plaque assay). Complete inactivation did not occur and there was significant variability between replicates. Viable virus was detected by plaque assay after heat-treatment at 80 °C for 15 or 30 min but not 60 or 90 min. After heat-treatment at 80 °C for 60 min infectious virus was only detected by more sensitive virus culture. No viable virus was detected after heating to 80 °C for 90 min or 95 °C for 1 or 5 min. RT-PCR sensitivity was not compromised by heating to 56 °C and 60 °C. However, RT-PCR sensitivity was reduced (≥3 Ct value increase) after heating the virus to 80 °C for 30 min or longer, or 95 °C for 1 or 5 min. In summary we found that the efficacy of heat-inactivation varies greatly depending on temperature and duration. Local validation of heat-inactivation and its effects downstream is therefore essential for molecular testing.

Considerations of the impacts of COVID-19 on domestic violence in the United States.

"Stay home, save lives" has been shown to reduce the impacts of COVID-19; however, it is crucial to recognize that efforts not to stress healthcare systems may have unintended social consequences for domestic violence. This commentary addresses domestic violence as an important social and public health implication of COVID-19. As a pandemic with a high contagion level, necessary social distancing measures have been put in place across the world to slow transmission and protect medical services. We first present literature that shows that among the effects of social distancing are social and functional isolation and economic stress, which are known to increase domestic violence. We then present preliminary observations from a content analysis conducted on over 300 news articles from the first six weeks of COVID-19 "lockdown" in the United States: articles predict an increase in domestic violence, report an increase in domestic violence, and inform victims on how to access services. Assessing the intersection of the early news media messaging on the effect of COVID-19 on DV and the literature on social isolation and crisis situations, we conclude the commentary with implications for current policy related to (1) increased media attention, (2) increased attention in healthcare systems, (3) promoting social and economic security, and (4) long-term efforts to fund prevention and response, as well as research implications to consider. The research is presented as ongoing, but the policy and procedure recommendations are presented with urgency.

Analysis of Inactivation of SARS-CoV-2 by Specimen Transport Media, Nucleic Acid Extraction Reagents, Detergents, and Fixatives.

The COVID-19 pandemic has necessitated a multifaceted rapid response by the scientific community, bringing researchers, health officials, and industry together to address the ongoing public health emergency. To meet this challenge, participants need an informed approach for working safely with the etiological agent, the novel human coronavirus SARS-CoV-2. Work with infectious SARS-CoV-2 is currently restricted to high-containment laboratories, but material can be handled at a lower containment level after inactivation. Given the wide array of inactivation reagents that are being used in laboratories during this pandemic, it is vital that their effectiveness is thoroughly investigated. Here, we evaluated a total of 23 commercial reagents designed for clinical sample transportation, nucleic acid extraction, and virus inactivation for their ability to inactivate SARS-CoV-2, as well as seven other common chemicals, including detergents and fixatives. As part of this study, we have also tested five filtration matrices for their effectiveness at removing the cytotoxic elements of each reagent, permitting accurate determination of levels of infectious virus remaining following treatment. In addition to providing critical data informing inactivation methods and risk assessments for diagnostic and research laboratories working with SARS-CoV-2, these data provide a framework for other laboratories to validate their inactivation processes and to guide similar studies for other pathogens.