Incidence and severity of SARS-CoV-2 infections in people with primary ciliary dyskinesia (preprint)

ImportanceEarly in the COVID-19 pandemic, chronic respiratory disease was considered a risk factor for severe COVID-19 disease. Studies have confirmed a higher risk of intensive care unit admission and mortality in people with chronic pulmonary obstructive disease and cystic fibrosis, but there is little data in people with primary ciliary dyskinesia (PCD). ObjectiveTo study incidence of SARS-CoV-2 and its risk factors in people with PCD from May 2020 to May 2022. We also describe the severity of COVID-19 symptoms in this population and factors associated with severity. Design, setting, and participantsWe used data from COVID-PCD, an international participatory cohort study following people with PCD through the COVID-19 pandemic. The study is based on self-reported weekly online questionnaires, available in five languages, adapted to children, adolescents, and adults. COVID-PCD invites people with PCD of any age to participate. ExposuresSARS-CoV-2 Main OutcomesIncidence of reported positive test of SARS-CoV-2 and reported severity of symptoms. ResultsBy May 2022, 728 people with PCD participated (40% male, median age 27 years; range 0-85). The median weeks of follow-up was 60 (range 1-100). Eighty-seven (12%) reported a SARS-CoV-2 infection at baseline or during follow-up and 62 people reported an incident SARS-CoV-2 infection during 716 person-years of follow-up (incidence rate 9 per 100 person years; 95%CI 7-11). Using Poisson regression, we found that age above 14 years was associated with lower risk of infection (IRR 0.42, 95%CI 0.21-0.85) but the strongest predictors were exposure to Delta (IRR 4.52, 95%CI 1.92-10.6) and Omicron variants (IRR 13.3, 95%CI 5.2-33.8) compared to the original strain. Severity of disease was mainly mild; 12 (14%) were asymptomatic and 75 (86%) had symptoms among whom 4 were hospitalized. None needed intensive care and nobody died. Using Poisson regression, we found that comorbidity (IRR 1.93, 95%CI 1.40-2.64) and being infected during the period when the Delta variant was predominant (IRR 1.43, 95%CI 1.07-1.92) were associated with more reported symptoms. Conclusion and RelevancePeople with PCD do not seem to have a higher incidence of SARS-CoV-2 infections nor higher risk of severe COVID-19 disease than people from the general population. Key PointsO_ST_ABSQuestionC_ST_ABSWhat is the incidence and severity of COVID-19 in people with primary ciliary dyskinesia and which factors are associated with reporting a SARS-CoV-2 infection and risk of severe disease? FindingsThis international cohort of 728 people with primary ciliary dyskinesia followed for two years during the COVID-19 pandemic found a low incidence of reported SARS-CoV-2 in people with primary ciliary dyskinesia and mainly mild disease. The strongest predictor of incidence and severity was virus variant. MeaningPeople with PCD do not seem to have a higher incidence of SARS-CoV-2 infections nor higher risk of severe COVID-19 disease than people from the general population.

COVID-19 vaccinations: perceptions and behaviours in people with primary ciliary dyskinesia (preprint)

Primary ciliary dyskinesia (PCD) is a rare genetic disease that causes recurrent respiratory infections. People with PCD may be at high risk of severe COVID-19 and vaccination against SARS-CoV-2 is therefore important. We studied vaccination willingness, speed of vaccination uptake, side effects, and changes in social contact behavior after vaccination in people with PCD. We used data from COVID-PCD, an international participatory cohort study. A questionnaire was e-mailed to participants in May 2021 that asked about COVID-19 vaccinations. 423 participants from 31 countries replied (median age: 30 years; 261 (62%) female). Vaccination uptake and willingness was high with 273 of 287 adults (96%) being vaccinated or willing to be in June 2021; only 4% were hesitant. The most common reasons for hesitancy were fear of side effects (reported by 88%). Mild side effects were common but no participant reported severe side effects. Half of participants changed their social contact behaviour after vaccination by seeing friends and family more often. The high vaccination willingness in the study population might reflect the extraordinary effort taken by PCD support groups to inform people about COVID-19 vaccination. Clear and specific public information and involvement of representatives is important for high vaccine uptake.

Distinct immune responses in patients infected with influenza or SARS-CoV-2, and in COVID-19 survivors, characterised by transcriptomic and cellular abundance differences in blood. (preprint)

Background The worldwide pandemic caused by SARS-CoV-2 has claimed millions of lives and has had a profound effect on global life. Understanding the pathogenicity of the virus and the body's response to infection is crucial in improving patient management, prognosis, and therapeutic strategies. To address this, we performed functional transcriptomic profiling to better understand the generic and specific effects of SARS-CoV-2 infection. Methods Whole blood RNA sequencing was used to profile a well characterised cohort of patients hospitalised with COVID-19, during the first wave of the pandemic prior to the availability of approved COVID-19 treatments and who went on to survive or die of COVID-19, and patients hospitalised with influenza virus infection between 2017 and 2019. Clinical parameters between patient groups were compared, and several bioinformatic tools were used to assess differences in transcript abundances and cellular composition. Results The analyses revealed contrasting innate and adaptive immune programmes, with transcripts and cell subsets associated with the innate immune response elevated in patients with influenza, and those involved in the adaptive immune response elevated in patients with COVID-19. Topological analysis identified additional gene signatures that differentiated patients with COVID-19 from patients with influenza, including insulin resistance, mitochondrial oxidative stress and interferon signalling. An efficient adaptive immune response was furthermore associated with patient survival, while an inflammatory response predicted death in patients with COVID-19. A potential prognostic signature was found based on a selection of transcript abundances, associated with circulating immunoglobulins, nucleosome assembly, cytokine production and T cell activation, in the blood transcriptome of COVID-19 patients, upon admission to hospital, which can be used to stratify patients likely to survive or die. Conclusions The results identified distinct immunological signatures between SARS-CoV-2 and influenza, prognostic of disease progression and indicative of different targeted therapies. The altered transcript abundances associated with COVID-19 survivors can be used to predict more severe outcomes in patients with COVID-19.

Facemask usage during the COVID-19 pandemic among people with primary ciliary dyskinesia: a participatory project (preprint)

BackgroundFacemasks help prevent transmission of SARS-CoV-2 and are particularly important for people with chronic respiratory disease such as primary ciliary dyskinesia (PCD). We studied the usage of facemasks and its consequences among people with PCD in an international context. MethodsWe used data from COVID-PCD, an international observational cohort study which collects longitudinal data from people with PCD during the COVID-19 pandemic via weekly online questionnaires. An online questionnaire investigating use of facemasks was posted in October 2020. It asked about frequency of facemask usage in different public places, problems experienced with use of facemasks, affordability of masks, and beliefs regarding their effectiveness. Results282 participants (50%) completed the questionnaire. Participants came from 27 different countries; median age was 32 years (interquartile range 17-48), and 63% were female. Almost all wore a facemask whenever they left their house. In addition, many avoided public places altogether. For example, 159 (57%) did not use public transport at all, 108 (39%) always wore a facemask in public transport, 4 (1%) sometimes, and 7 (3%) never. 81% agreed with the statement that facemasks protect the person who wears the mask, and 91% agreed that facemasks protect others. One third reported that it was uncomfortable to wear a mask because of their runny nose, 31% because of cough, and 22% because of difficulty breathing. Participants less often wore facemasks in public when there was no national requirement. Only two persons had a personal exemption from wearing a facemask prescribed by a physician. ConclusionsThis international study found that people with PCD carefully shield themselves, and most wear facemasks everywhere in public. People who did not wear facemasks in public came from countries without a national facemask requirement. National policies mandating facemask use in public are important for universal use to protect high-risk populations from SARS-CoV-2 infections.

SARS-CoV-2 infections in people with PCD: neither frequent, nor particularly severe (preprint)

People with pre-existing chronic health conditions are reportedly at high risk of getting the coronavirus disease (COVID-19) and of having a severe disease course but little data exist on rare diseases such as Primary Ciliary Dyskinesia (PCD). We studied risk and severity of SARS-CoV-2 infections among people with PCD using data from the COVID-PCD, a participatory study that collects data in real-time directly from people with PCD. Data was collected using online questionnaires. A baseline questionnaire collected information on demographic data, information about the PCD diagnosis and severity. A short weekly questionnaire collected information about current symptoms and incident SARS-CoV-2 infections. 578 people participated in the COVID-PCD by December 7, 2020, with a median number of follow-up weeks of 9 (interquartile range: 4-19 weeks). 256 (45%) of the participants had been tested for SARS-CoV-2 and 12 tested positive prior to study entry or during study follow up (2.1% of the total included population, 95% confidence interval (CI) 1.1-3.6%). 4 people tested positive during the study follow-up, corresponding to an incidence rate of 2.5 per 100 person-years (95% CI: 0.9-6.5). Overall, reported severity was mild with two reporting no symptoms, eight reporting mild symptoms, one reporting severe symptom without hospitalisation, and one reporting hospitalisation for 9 days. The study suggests that with careful personal protection, people with PCD do not seem to have an increased risk of infection with SARS-COV-2, nor an especially severe disease course. Take home messageIn this longitudinal study of people with PCD followed weekly via online questionnaires, the incidence rate of COVID-19 and the proportion of participants infected were low, and the observed severity mostly mild.

COVID-PCD a participatory research study on the impact of COVID-19 in people with Primary Ciliary Dyskinesia (preprint)

Introduction COVID-PCD is a participatory study initiated by people with PCD who have an essential vote in all stages of the research from the design of the study to the recruitment of participants, and interpretation and communication of the study results. COVID-PCD aims to collect epidemiological data in real time from people with PCD throughout the pandemic to describe incidence of COVID-19, symptoms, and course of disease; identify risk factors for prognosis; and assess experiences, wishes, and needs. Methods The study is advertised through patient support groups and participants register online on the study website (www.covid19pcd.ispm.ch). The study invites persons of any age from anywhere in the world with a suspected or confirmed PCD. A baseline questionnaire assesses details on PCD diagnosis, habitual symptoms, and COVID-19 episodes that occurred before study entry. Afterwards, participants receive a weekly follow-up questionnaire with questions on incident SARS-CoV-2 infections, current symptoms, social contact behaviour, and physical activity. Occasional thematic questionnaires are sent out focusing on emerging questions of interest chosen by people with PCD. In case of hospitalisation, patients or family members are asked to obtain a hospital report. Results are continuously analysed and summaries put online. Conclusion The study started recruitment on April 30, 2020, and 556 people with PCD completed the baseline questionnaire by November 2, 2020. The COVID-PCD study is a participatory study that follows people with PCD during the COVID-19 pandemic, helps to empower affected persons, and serves as a platform for communication between patients, physicians, and researchers.

A novel isoform of ACE2 is expressed in human nasal and bronchial respiratory epithelia and is upregulated in response to RNA respiratory virus infection (preprint)

Angiotensin-converting enzyme 2 (ACE2) is the main entry point in the airways for SARS-CoV-2. ACE2 binding to SARS-CoV-2 protein Spike triggers viral fusion with the cell membrane, resulting in viral RNA genome delivery into the host. Despite ACE2s critical role in SARS-CoV-2 infection, an understanding of ACE2 expression, including in response to viral infection, remains unclear. Until now ACE2 was thought to encode five transcripts and one 805 amino acid protein. Here we identify a novel short isoform of ACE2. Short ACE2 is expressed in the airway epithelium, the main site of SARS-CoV-2 infection; it is substantially upregulated in response to interferon stimulation and RV infection, but not in response to SARS-CoV-2 infection, and it shows differential regulation in asthma patients. This short isoform lacks SARS-CoV-2 spike glycoprotein high-affinity binding sites and altogether, our data are consistent with a model where short ACE2 may influence host susceptibility to SARS-CoV-2 infection.