§COPE Consortium members and affiliations are listed in the supplementary materials.The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.8 million users as of May 2, 2020. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.

BACKGROUND:Circulating biomarkers, such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA), are both considered for blood-based mutation detection, but limited studies have compared them in a head-to-head manner. Using KRAS (Kirsten rat sarcoma viral oncogene homolog), we performed such a comparison in patients who underwent surgery for suspected lung cancer.

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Background: The association between current tobacco smoking, the risk of developing COVID-19 and the severity of illness is an important information gap. Methods: UK users of the COVID Symptom Study app provided baseline data including demographics, anthropometrics, smoking status and medical conditions, were asked to log symptoms daily from 24th March 2020 to 23rd April 2020. Participants reporting that they did not feel physically normal were taken through a series of questions, including 14 potential COVID-19 symptoms and any hospital attendance. The main study outcome was the association between current smoking and the development of classic symptoms of COVID-19 during the pandemic defined as fever, new persistent cough and breathlessness. The number of concurrent COVID-19 symptoms was used as a proxy for severity. In addition, association of subcutaneous adipose tissue expression of ACE2, both the receptor for SARS-CoV-2 and a potential mediator of disease severity, with smoking status was assessed in a subset of 541 twins from the TwinsUK cohort. Results: Data were available on 2,401,982 participants, mean(SD) age 43.6(15.1) years, 63.3% female, overall smoking prevalence 11.0%. 834,437 (35%) participants reported being unwell and entered one or more symptoms. Current smokers were more likely to develop symptoms suggesting a diagnosis of COVID-19; classic symptoms adjusted OR[95%CI] 1.14[1.10 to 1.18]; >5 symptoms 1.29[1.26 to 1.31]; >10 symptoms 1.50[1.42 to 1.58]. Smoking was associated with reduced ACE2 expression in adipose tissue (Beta(SE)= -0.395(0.149); p=7.01x10-3). Interpretation: These data are consistent with smokers having an increased risk from COVID-19.

Background: Routine clinical application of circulating tumour cells (CTCs) for blood based diagnostics is yet to be established. Despite growing evidence of their clinical utility for diagnosis, prognosis and treatment monitoring, the efficacy of a robust platform and universally accepted diagnostic criteria remain uncertain. We evaluate the diagnostic performance of a microfluidic CTC isolation platform using cytomorphologic criteria in patients undergoing lung cancer surgery.Methods: Blood was processed from 51 patients undergoing surgery for known or suspected lung cancer using the ClearBridge ClearCell FX system TM (ClearBridge Biomedics, Singapore). Captured cells were stained on slides with haematoxylin and eosin (H&E) and independently assessed by two pathologist teams. Diagnostic performance was evaluated against the pathologists reported diagnosis of cancer from surgically obtained specimens.Results: Cancer was diagnosed in 43.1% and 54.9% of all cases. In early stage primary lung cancer, between the two reporting teams, a positive diagnosis of CTCs was made for 50% and 66.7% of patients. The agreement between the reporting teams was 80.4%, corresponding to a kappa-statistic of 0.61±0.11 (P<0.001), indicating substantial agreement. Sensitivity levels for the two teams were calculated as 59% (95% CI, 41-76%) and 41% (95% CI, 24-59%), with a specificity of 53% for both. Conclusions:The performance of the tested microfluidic antibody independent device to capture CTCs using standard cytomorphological criteria provides the potential of a diagnostic blood test for lung cancer.

Молекулярные и фармакогенетические механизмы тяжелой бронхиальной астмы В обзоре обобщены результаты исследований по определению доминирующих механизмов формирования и персистенции воспаления при тяжелой бронхиальной астме и результаты фармакогенетических исследований детерминации ответа на лекарственные средства. Данные механизмы в перспективе могут быть использованы как в диагностических целях, так и стать новыми таргетными мишенями терапии бронхиальной астмы. Применение фармакогенетической информации сделает возможным использование персонифицированного подхода к терапии бронхиальной астмы, что позволит скорректировать технологии ведения пациента и повысить вероятность достижения контроля болезни. Ключевые слова: бронхиальная астма, терапия, тяжелая бронхиальная астма, терапевтическая резистентность, молекулярные механизмы.

Objectives: Cytological analysis of peripheral blood circulating tumour cells (CTCs) is a potential method of confirmatory clinical diagnosis of cancer. However, cell capture methods tend to be biased and captured cells are not usually portable resulting in difficulties in pathology reporting. We evaluated unbiased cell capture through depletion of unwanted normal cells and conventional clinical analyses of captured cells. Methods: Blood was sampled from 29 patients who underwent surgery for suspected lung cancer. It was processed using two different depletion cocktails. After depletion of unwanted cells, the resultant cell pellet was processed onto glass slides or embedded into FFPE blocks and stained using standard haematoxylin and eosin staining followed by cytopathologic assessment. Two pathologists performed the assessment independently. Results: The CTCs were identified in 38-45% of cases using CD45 depletion cocktail with the cell pellet processed on a glass slide, while other combinations of methods produced poorer results. Overall, there was a good concordance between the pathologists (up to 91.3%). The sensitivity of cancer diagnosis was 42% (95% CI 23-63%), while the specificity was 100% (95% CI 29-100%). Conclusion: Negative depletion can be used to isolate CTCs in standard clinical settings; however, more effective ways of detection are required to increase the sensitivity of the diagnosis.

Background The objectives of the current study were to develop an initial blood‐based circulating tumor DNA (ctDNA) gene signature and to validate the clinical test performance in patients with early primary and secondary lung cancer. Methods Between January 2009 and October 2014, a total of 211 patients with known or suspected lung cancer donated their blood prior to surgery and were followed up to May 2018. ctDNA was extracted from plasma and from corresponding formalin‐fixed, paraffin‐embedded tissues. The blood was analyzed in a blinded manner and pathology reports were issued that were blinded to the blood test results. The reference standard was histopathology confirmed cancer in the resected surgical specimens as reported according to World Health Organization criteria and staged using the eighth edition of the TNM Classification of Malignant Tumors criteria. Results Of 211 consenting patients, 19 (9.0%) were excluded, leaving 192 participants, consisting of 95 men (49%) and with a mean age of 63 years (SD, 15 years). The clinical test performance for the blood‐based diagnostic signature demonstrated a sensitivity of 75% (95% CI, 67%‐81%), specificity of 89% (95% CI, 70%‐98%), positive predictive value of 98% (95% CI, 93%‐100%), and negative predictive value of 35% (95% CI, 24%‐48%) when compared with conventional clinical histopathology reporting of the resected tissue. Conclusions The results of the current study suggested that blood‐based ctDNA analysis of cancer mutations is a specific, noninvasive test for the diagnosis of cancer.