Distinct evolutionary trajectories of SARS-CoV-2-interacting proteins in bats and primates identify important host determinants of COVID-19.

The coronavirus disease 19 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a coronavirus that spilled over from the bat reservoir. Despite numerous clinical trials and vaccines, the burden remains immense, and the host determinants of SARS-CoV-2 susceptibility and COVID-19 severity remain largely unknown. Signatures of positive selection detected by comparative functional genetic analyses in primate and bat genomes can uncover important and specific adaptations that occurred at virus-host interfaces. We performed high-throughput evolutionary analyses of 334 SARS-CoV-2-interacting proteins to identify SARS-CoV adaptive loci and uncover functional differences between modern humans, primates, and bats. Using DGINN (Detection of Genetic INNovation), we identified 38 bat and 81 primate proteins with marks of positive selection. Seventeen genes, including the ACE2 receptor, present adaptive marks in both mammalian orders, suggesting common virus-host interfaces and past epidemics of coronaviruses shaping their genomes. Yet, 84 genes presented distinct adaptations in bats and primates. Notably, residues involved in ubiquitination and phosphorylation of the inflammatory RIPK1 have rapidly evolved in bats but not primates, suggesting different inflammation regulation versus humans. Furthermore, we discovered residues with typical virus-host arms race marks in primates, such as in the entry factor TMPRSS2 or the autophagy adaptor FYCO1, pointing to host-specific in vivo interfaces that may be drug targets. Finally, we found that FYCO1 sites under adaptation in primates are those associated with severe COVID-19, supporting their importance in pathogenesis and replication. Overall, we identified adaptations involved in SARS-CoV-2 infection in bats and primates, enlightening modern genetic determinants of virus susceptibility and severity.

Distinct evolutionary trajectories of SARS-CoV-2 interacting proteins in bats and primates identify important host determinants of COVID-19 (preprint)

The COVID-19 pandemic is caused by SARS-CoV-2, a novel coronavirus that spilled from the bat reservoir. Despite numerous clinical trials and vaccines, the burden remains immense, and the host determinants of SARS-CoV-2 susceptibility and COVID-19 severity remain largely unknown. Signatures of positive selection detected by comparative functional-genetic analyses in primate and bat genomes can uncover important and specific adaptations that occurred at virus-host interfaces. Here, we performed high-throughput evolutionary analyses of 334 SARS-CoV-2 interacting proteins to identify SARS-CoV adaptive loci and uncover functional differences between modern humans, primates and bats. Using DGINN (Detection of Genetic INNovation), we identified 38 bat and 81 primate proteins with marks of positive selection. Seventeen genes, including the ACE2 receptor, present adaptive marks in both mammalian orders, suggesting common virus-host interfaces and past epidemics of coronaviruses shaping their genomes. Yet, 84 genes presented distinct adaptations in bats and primates. Notably, residues involved in ubiquitination and phosphorylation of the inflammatory RIPK1 have rapidly evolved in bats but not primates, suggesting different inflammation regulation versus humans. Furthermore, we discovered residues with typical virus-host arms-race marks in primates, such as in the entry factor TMPRSS2 or the autophagy adaptor FYCO1, pointing to host-specific in vivo important interfaces that may be drug targets. Finally, we found that FYCO1 sites under adaptation in primates are those associated with severe COVID-19, supporting their importance in pathogenesis and replication. Overall, we identified functional adaptations involved in SARS-CoV-2 infection in bats and primates, critically enlightening modern genetic determinants of virus susceptibility and severity.

Learning about COVID-19 across borders: public health information and adherence among international travellers to the UK.

OBJECTIVE: Public health control measures at borders have long been central to national strategies for the prevention and containment of infectious diseases. Travel was inevitably associated with the rapid global transmission of COVID-19. In the UK, public health authorities tried to reduce the risks of travel-associated spread by providing public health information at ports of entry. This study investigates risk assessment processes, decision-making and adherence to official advice among international travellers, to provide evidence for future policy on the provision of public health information to facilitate safer international travel. STUDY DESIGN: This study is a qualitative study evaluation. METHOD: International air passengers arriving at the London Heathrow Airport on scheduled flights from China and Singapore were approached for interview after consenting to contact in completed surveys. Semi-structured interviews were conducted by telephone, using two topic guides to explore views of official public health information and self-isolation. Interview transcripts were coded and analysed thematically. RESULTS: Participants regarded official advice from Public Health England as adequate at the time, despite observing differences with intervention measures implemented in their countries of departure. Most participants also described adopting precautionary measures, including self-isolation and the use of face coverings that went beyond official advice, but reported adherence to guidance on contacting health authorities was more variable. Adherence to the official guidance was informed by the perceived salience of specific transmission possibilities and containment measures assessed in relation to participants' local social and institutional environments. CONCLUSION: Analysis of study findings demonstrates that international air travellers' responses to public health advice constitute a proactive process of risk assessment and rationalised decision-making to guide preventive action. This process incorporates consideration of the current living situation, trust in information sources, correspondence with cultural logics and willingness to accept potential risk to self and significant others. Our findings concerning international passengers' understanding of, and compliance with, official advice and mitigation measures provide valuable evidence to inform future policy and generate recommendations on the presentation of public health information to facilitate safer international travel. Access to a central source of regularly updated official information would help minimise confusion between different national guidelines. Greater attention to the differentiated information needs of diverse groups in creating future public-facing guidance would help to minimise the uncertainties generated by the receipt of generic information.

Outcomes and characteristics of COVID-19 patients treated with continuous positive airway pressure/high-flow nasal oxygen outside the intensive care setting.

BACKGROUND: Continuous positive airway pressure (CPAP) and high-flow nasal oxygen (HFNO) have been used to manage hypoxaemic respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia. Limited data are available for patients treated with noninvasive respiratory support outside of the intensive care setting. METHODS: In this single-centre observational study we observed the characteristics, physiological observations, laboratory tests and outcomes of all consecutive patients with COVID-19 pneumonia between April 2020 and March 2021 treated with noninvasive respiratory support outside of the intensive care setting. RESULTS: We report the outcomes of 140 patients (mean±sd age: 71.2±11.1, 65% male (n=91)) treated with CPAP/HFNO outside of the intensive care setting. Overall mortality was 59% and was higher in those deemed unsuitable for mechanical ventilation (72%). The mean age of survivors was significantly lower than those who died (66.1 versus 74.4 years, p<0.001). Those who survived their admission also had a significantly lower median Clinical Frailty Score than the non-survivor group (2 versus 4, p<0.001). We report no significant difference in mortality between those treated with CPAP (n=92, mortality: 60%) or HFNO (n=48, mortality: 56%). Treatment was well tolerated in 86% of patients receiving either CPAP or HFNO. CONCLUSIONS: CPAP and HFNO delivered outside of the intensive care setting are viable treatment options for patients with hypoxaemic respiratory failure secondary to COVID-19 pneumonia, including those considered unsuitable for invasive mechanical ventilation. This provides an opportunity to safeguard intensive care capacity for COVID-19 patients requiring invasive mechanical ventilation.

Determining the acceptability of testing contacts of confirmed COVID-19 cases to improve secondary case ascertainment.

BACKGROUND: UK asymptomatic contacts of confirmed COVID-19 cases are not routinely tested for SARS-CoV-2. Testing contacts may improve case ascertainment and reduce onward transmission. This study investigated the acceptability of SARS-CoV-2 testing among contacts of confirmed cases as an integral part of the contact-tracing process. METHODS: A cross-sectional descriptive survey of case contacts was conducted in the UK. All contacts who completed a telephone call with the NHS Test and Trace Agile Lighthouse team were eligible for inclusion and were offered a molecular test. Consenting participants were sent a self-swab kit. RESULTS: Of the 1523 individuals contacted, 602 (39.5%) accepted the test offer. Of the 240 (39.9%) samples returned for testing, 16.3% tested polymerase chain reaction-positive for SARS-CoV-2.Most individuals who declined with a reason (638/905; 70.5%) reported they had already taken or booked a SARS-CoV-2 test, or were part of a testing programme. Matched laboratory records confirmed 73.1% of those who declined were tested by another route. CONCLUSIONS: Most case contacts were tested, either through arranging a test by themselves or by accepting the study offer. Results demonstrate high acceptability, with substantial test positivity, indicating that there is public health benefit in offering tests to contacts as a routine part of the contact-tracing process.

COVID-19 progression, frailty, and use of prolonged continuous positive airway pressure as a ward-based treatment: Lessons to be learnt from a case.

Coronavirus disease 19 (COVID-19) poses the greatest public health threat in 100 years, with cases rising rapidly in many countries around the world. We report a case of a 78-year-old female who exhibited a biphasic course of COVID-19; showing initial clinical improvement followed by deterioration before making a full recovery. The patient was managed with prolonged continuous positive airway pressure (CPAP) and supportive care. In total, 24 days of treatment with CPAP was administered. We emphasize the role of CPAP in the management of severely hypoxemic patients who are inappropriate for mechanical ventilation and describe the role of adequate nutrition and hydration for such patients.

Public health information on COVID-19 for international travellers: lessons learned from a mixed-method evaluation.

OBJECTIVES: In the containment phase of the response to the COVID-19 outbreak, Public Health England (PHE) delivered advice to travellers arriving at major UK ports. We aimed to rapidly evaluate the impact and effectiveness of these communication materials for passengers in the early stages of the pandemic. STUDY DESIGN: The study design used is the mixed-methods evaluation. METHODS: A questionnaire survey and follow-up interviews with passengers arriving at London Heathrow Airport on scheduled flights from China and Singapore. The survey assessed passengers' knowledge of symptoms, actions to take, and attitudes towards PHE COVID-19 public health information; interviews explored their views of official public health information and self-isolation. RESULTS: One hundred and twenty-one passengers participated in the survey and 15 in follow-up interviews. Eighty three percentage of surveyed passengers correctly identified all three COVID-19 associated symptoms listed in PHE information at that time. Most could identify the recommended actions and found the advice understandable and trustworthy. Interviews revealed that passengers shared concerns about the lack of wider official action, and that passengers' knowledge had been acquired elsewhere as much from PHE. Respondents also noted their own agency in choosing to self-isolate, partially as a self-protective measure. CONCLUSION: PHE COVID-19 public health information was perceived as clear and acceptable, but we found that passengers acquired knowledge from various sources and they saw the provision of information alone on arrival as an insufficient official response. Our study provides fresh insights into the importance of taking greater account of diverse information sources and of the need for public assurance in creating public health information materials to address global health threats.

Factors associated with adherence to self-isolation and lockdown measures in the UK: a cross-sectional survey.

OBJECTIVES: To investigate factors associated with adherence to self-isolation and lockdown measures due to COVID-19 in the UK. STUDY DESIGN: Online cross-sectional survey. METHODS: Data were collected between 6th and 7th May 2020. A total of 2240 participants living in the UK aged 18 years or older were recruited from YouGov's online research panel. RESULTS: A total of 217 people (9.7%) reported that they or someone in their household had symptoms of COVID-19 (cough or high temperature/fever) in the last 7 days. Of these people, 75.1% had left the home in the last 24 h (defined as non-adherent). Men were more likely to be non-adherent, as were people who were less worried about COVID-19, and who perceived a smaller risk of catching COVID-19. Adherence was associated with having received help from someone outside your household. Results should be taken with caution as there was no evidence for associations when controlling for multiple analyses. Of people reporting no symptoms in the household, 24.5% had gone out shopping for non-essentials in the last week (defined as non-adherent). Factors associated with non-adherence and with a higher total number of outings in the last week included decreased perceived effectiveness of government 'lockdown' measures, decreased perceived severity of COVID-19 and decreased estimates of how many other people were following lockdown rules. Having received help was associated with better adherence. CONCLUSIONS: Adherence to self-isolation is poor. As we move into a new phase of contact tracing and self-isolation, it is essential that adherence is improved. Communications should aim to increase knowledge about actions to take when symptomatic or if you have been in contact with a possible COVID-19 case. They should also emphasise the risk of catching and spreading COVID-19 when out and about and the effectiveness of preventative measures. Using volunteer networks effectively to support people in isolation may promote adherence.