Risk factors and vectors for SARS-CoV-2 household transmission: a prospective, longitudinal cohort study.

BACKGROUND: Despite circumstantial evidence for aerosol and fomite spread of SARS-CoV-2, empirical data linking either pathway with transmission are scarce. Here we aimed to assess whether the presence of SARS-CoV-2 on frequently-touched surfaces and residents' hands was a predictor of SARS-CoV-2 household transmission. METHODS: In this longitudinal cohort study, during the pre-alpha (September to December, 2020) and alpha (B.1.1.7; December, 2020, to April, 2021) SARS-CoV-2 variant waves, we prospectively recruited contacts from households exposed to newly diagnosed COVID-19 primary cases, in London, UK. To maximally capture transmission events, contacts were recruited regardless of symptom status and serially tested for SARS-CoV-2 infection by RT-PCR on upper respiratory tract (URT) samples and, in a subcohort, by serial serology. Contacts' hands, primary cases' hands, and frequently-touched surface-samples from communal areas were tested for SARS-CoV-2 RNA. SARS-CoV-2 URT isolates from 25 primary case-contact pairs underwent whole-genome sequencing (WGS). FINDINGS: From Aug 1, 2020, until March 31, 2021, 620 contacts of PCR-confirmed SARS-CoV-2-infected primary cases were recruited. 414 household contacts (from 279 households) with available serial URT PCR results were analysed in the full household contacts' cohort, and of those, 134 contacts with available longitudinal serology data and not vaccinated pre-enrolment were analysed in the serology subcohort. Household infection rate was 28·4% (95% CI 20·8-37·5) for pre-alpha-exposed contacts and 51·8% (42·5-61·0) for alpha-exposed contacts (p=0·0047). Primary cases' URT RNA viral load did not correlate with transmission, but was associated with detection of SARS-CoV-2 RNA on their hands (p=0·031). SARS-CoV-2 detected on primary cases' hands, in turn, predicted contacts' risk of infection (adjusted relative risk [aRR]=1·70 [95% CI 1·24-2·31]), as did SARS-CoV-2 RNA presence on household surfaces (aRR=1·66 [1·09-2·55]) and contacts' hands (aRR=2·06 [1·57-2·69]). In six contacts with an initial negative URT PCR result, hand-swab (n=3) and household surface-swab (n=3) PCR positivity preceded URT PCR positivity. WGS corroborated household transmission. INTERPRETATION: Presence of SARS-CoV-2 RNA on primary cases' and contacts' hands and on frequently-touched household surfaces associates with transmission, identifying these as potential vectors for spread in households. FUNDING: National Institute for Health Research Health Protection Research Unit in Respiratory Infections, Medical Research Council.

Telemedicine interventions in six conflict-affected countries in the WHO Eastern Mediterranean region: a systematic review.

BACKGROUND: The COVID-19 pandemic has escalated the use of telemedicine in both high and low resource settings however its use has preceded this, particularly in conflict-affected settings. Several countries in the WHO Eastern Mediterranean (EMR) region are affected by complex, protracted crises. Though telemedicine has been used in such settings, there has been no comprehensive assessment of what interventions are used, their efficacy, barriers, or current research gaps. MAIN BODY: A systematic search of ten academic databases and 3 grey literature sources from January 1st 2000 to December 31st 2020 was completed, identifying telemedicine interventions in select EMR conflict-affected settings and relevant enablers and barriers to their implementation. Included articles reported on telemedicine use in six conflict-affected EMR countries (or territories) graded as WHO Health Emergencies: Afghanistan, Gaza, Iraq, Libya, Syria and Yemen. Data were extracted and narratively synthesised due to heterogeneity in study design and outcomes. Of 3419 articles identified, twenty-one peer-reviewed and three grey literature sources met the inclusion criteria. We analysed these by context, intervention, and evaluation. CONTEXT: eight related to Afghanistan, eight to Syria and seven to Iraq with one each in Yemen and Gaza. Most were implemented by humanitarian or academic organisations with projects mostly initiated in the United States or Europe and mostly by physicians. The in-country links were mostly health professionals rather than patients seeking specialist inputs for specialities not locally available. INTERVENTIONS: these included both SAF (store and forward) and RT (real-time) with a range of specialities represented including radiology, histopathology, dermatology, mental health, and intensive care. EVALUATION: most papers were observational or descriptive with few describing quality measures of interventions. CONCLUSIONS: Telemedicine interventions are feasible in conflict-affected settings in EMR using low-cost, accessible technologies. However, few implemented interventions reported on evaluation strategies or had these built in. The ad hoc nature of some of the interventions, which relied on volunteers without sustained financial or academic investment, could pose challenges to quality and sustainability. There was little exploration of confidentiality, ethical standards, data storage or local healthcare worker and patient acceptability.

Onset and window of SARS-CoV-2 infectiousness and temporal correlation with symptom onset: a prospective, longitudinal, community cohort study.

BACKGROUND: Knowledge of the window of SARS-CoV-2 infectiousness is crucial in developing policies to curb transmission. Mathematical modelling based on scarce empirical evidence and key assumptions has driven isolation and testing policy, but real-world data are needed. We aimed to characterise infectiousness across the full course of infection in a real-world community setting. METHODS: The Assessment of Transmission and Contagiousness of COVID-19 in Contacts (ATACCC) study was a UK prospective, longitudinal, community cohort of contacts of newly diagnosed, PCR-confirmed SARS-CoV-2 index cases. Household and non-household exposed contacts aged 5 years or older were eligible for recruitment if they could provide informed consent and agree to self-swabbing of the upper respiratory tract. The primary objective was to define the window of SARS-CoV-2 infectiousness and its temporal correlation with symptom onset. We quantified viral RNA load by RT-PCR and infectious viral shedding by enumerating cultivable virus daily across the course of infection. Participants completed a daily diary to track the emergence of symptoms. Outcomes were assessed with empirical data and a phenomenological Bayesian hierarchical model. FINDINGS: Between Sept 13, 2020, and March 31, 2021, we enrolled 393 contacts from 327 households (the SARS-CoV-2 pre-alpha and alpha variant waves); and between May 24, 2021, and Oct 28, 2021, we enrolled 345 contacts from 215 households (the delta variant wave). 173 of these 738 contacts were PCR positive for more than one timepoint, 57 of which were at the start of infection and comprised the final study population. The onset and end of infectious viral shedding were captured in 42 cases and the median duration of infectiousness was 5 (IQR 3-7) days. Although 24 (63%) of 38 cases had PCR-detectable virus before symptom onset, only seven (20%) of 35 shed infectious virus presymptomatically. Symptom onset was a median of 3 days before both peak viral RNA and peak infectious viral load (viral RNA IQR 3-5 days, n=38; plaque-forming units IQR 3-6 days, n=35). Notably, 22 (65%) of 34 cases and eight (24%) of 34 cases continued to shed infectious virus 5 days and 7 days post-symptom onset, respectively (survival probabilities 67% and 35%). Correlation of lateral flow device (LFD) results with infectious viral shedding was poor during the viral growth phase (sensitivity 67% [95% CI 59-75]), but high during the decline phase (92% [86-96]). Infectious virus kinetic modelling suggested that the initial rate of viral replication determines the course of infection and infectiousness. INTERPRETATION: Less than a quarter of COVID-19 cases shed infectious virus before symptom onset; under a crude 5-day self-isolation period from symptom onset, two-thirds of cases released into the community would still be infectious, but with reduced infectious viral shedding. Our findings support a role for LFDs to safely accelerate deisolation but not for early diagnosis, unless used daily. These high-resolution, community-based data provide evidence to inform infection control guidance. FUNDING: National Institute for Health and Care Research.

Broadening symptom criteria improves early case identification in SARS-CoV-2 contacts.

BACKGROUND: The success of case isolation and contact tracing for the control of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission depends on the accuracy and speed of case identification. We assessed whether inclusion of additional symptoms alongside three canonical symptoms (CS), i.e. fever, cough and loss or change in smell or taste, could improve case definitions and accelerate case identification in SARS-CoV-2 contacts. METHODS: Two prospective longitudinal London (UK)-based cohorts of community SARS-CoV-2 contacts, recruited within 5 days of exposure, provided independent training and test datasets. Infected and uninfected contacts completed daily symptom diaries from the earliest possible time-points. Diagnostic information gained by adding symptoms to the CS was quantified using likelihood ratios and area under the receiver operating characteristic curve. Improvements in sensitivity and time to detection were compared with penalties in terms of specificity and number needed to test. RESULTS: Of 529 contacts within two cohorts, 164 (31%) developed PCR-confirmed infection and 365 (69%) remained uninfected. In the training dataset (n=168), 29% of infected contacts did not report the CS. Four symptoms (sore throat, muscle aches, headache and appetite loss) were identified as early-predictors (EP) which added diagnostic value to the CS. The broadened symptom criterion "≥1 of the CS, or ≥2 of the EP" identified PCR-positive contacts in the test dataset on average 2 days earlier after exposure (p=0.07) than "≥1 of the CS", with only modest reduction in specificity (5.7%). CONCLUSIONS: Broadening symptom criteria to include individuals with at least two of muscle aches, headache, appetite loss and sore throat identifies more infections and reduces time to detection, providing greater opportunities to prevent SARS-CoV-2 transmission.

Subcutaneous Emphysema, Pneumomediastinum, and Pneumothorax in Critically Ill Patients With Coronavirus Disease 2019: A Retrospective Cohort Study.

IMPORTANCE: Management of severe coronavirus disease 2019 relies on advanced respiratory support modalities including invasive mechanical ventilation, continuous positive airway pressure, and noninvasive ventilation, all of which are associated with the development of subcutaneous emphysema, pneumomediastinum, and pneumothorax (herein collectively termed barotrauma). OBJECTIVES: To assess the occurrence rate of barotrauma in severe coronavirus disease 2019 and to explore possible associated factors. DESIGN SETTING AND PARTICIPANTS: A retrospective, single-center cohort study with nested case series, conducted at University Hospital Lewisham: a 450-bed general hospital in London, United Kingdom. All patients with confirmed coronavirus disease 2019 admitted to the critical care department from March 12, to April 12, 2020, were included. MAIN OUTCOMES AND MEASURES: Patients were retrospectively screened for radiological evidence of barotrauma. Admission characteristics, modalities of respiratory support, and outcomes were compared between barotrauma and nonbarotrauma groups. Respiratory parameters in the period preceding barotrauma identification were recorded. RESULTS: Of 83 admissions with coronavirus disease 2019, eight suffered barotrauma (occurrence rate 9.6%; 95% CI 4.3%-18.1%). Barotrauma cases had longer illness duration prior to critical care admission (10 vs 7 d; interquartile range, 8-14 and 6-10, respectively; p = 0.073) and were more often treated with continuous positive airway pressure or noninvasive ventilation as the initial modality of advanced respiratory support (87.5% vs 36.0%; p = 0.007). Patients managed with continuous positive airway pressure or noninvasive ventilation prior to the development of barotrauma had median minute ventilation of 16.2-19.9 and 21.3-22.7 L/min, respectively. Compared with the nonbarotrauma group, a higher proportion of patients with barotrauma had died (62.5% vs 43.2%), and a lower proportion of patients had been discharged (25.0% vs 53.3%) at 3-month follow-up. CONCLUSIONS AND RELEVANCE: Barotrauma appears to be a common complication of severe coronavirus disease 2019. Determining whether high minute ventilation while using continuous positive airway pressure or noninvasive ventilation predisposes patients to barotrauma requires further investigation.