Risk factors for persistent abnormality on chest radiographs at 12-weeks post hospitalisation with PCR confirmed COVID-19.

BACKGROUND: The long-term consequences of COVID-19 remain unclear. There is concern a proportion of patients will progress to develop pulmonary fibrosis. We aimed to assess the temporal change in CXR infiltrates in a cohort of patients following hospitalisation for COVID-19. METHODS: We conducted a single-centre prospective cohort study of patients admitted to University Hospital Southampton with confirmed SARS-CoV2 infection between 20th March and 3rd June 2020. Patients were approached for standard-of-care follow-up 12-weeks after hospitalisation. Inpatient and follow-up CXRs were scored by the assessing clinician for extent of pulmonary infiltrates; 0-4 per lung (Nil = 0, < 25% = 1, 25-50% = 2, 51-75% = 3, > 75% = 4). RESULTS: 101 patients with paired CXRs were included. Demographics: 53% male with a median (IQR) age 53.0 (45-63) years and length of stay 9 (5-17.5) days. The median CXR follow-up interval was 82 (77-86) days with median baseline and follow-up CXR scores of 4.0 (3-5) and 0.0 (0-1) respectively. 32% of patients had persistent CXR abnormality at 12-weeks. In multivariate analysis length of stay (LOS), smoking-status and obesity were identified as independent risk factors for persistent CXR abnormality. Serum LDH was significantly higher at baseline and at follow-up in patients with CXR abnormalities compared to those with resolution. A 5-point composite risk score (1-point each; LOS ≥ 15 days, Level 2/3 admission, LDH > 750 U/L, obesity and smoking-status) strongly predicted risk of persistent radiograph abnormality (0.81). CONCLUSION: Persistent CXR abnormality 12-weeks post COVID-19 was common in this cohort. LOS, obesity, increased serum LDH, and smoking-status were risk factors for radiograph abnormality. These findings require further prospective validation.

Comparisons in early and late presentation to Hospital in covid-19 patients

Background The clinical presentation and disease severity in SARS-Cov-2 infection ranges from asymptomatic carriage to death. There is little data regarding the timeframe of symptom onset to presentation to hospital, and disease outcomes. Therefore, we aim to investigate differences between 'early presenters' (< 7 days of symptom onset) and 'late presenters' (>7 days) and their clinical and radiological outcomes. Methods In this retrospective cohort study, symptom onset, epidemiological, and clinical characteristics were collected from patient electronic medical records at University Hospital Southampton Foundation Trust with laboratory confirmed SARS-Cov-2 infection. Logistical regression models were used to explore the relationships between these data and time of presentation to hospital. Results Between March and July 2020, symptom onset data was collected for 626 SARS-Cov-2 positive patients, 574 of whom had chest radiographs (CXR). Early presenters comprised 388 (62%) and 238 (38%) were late presenters. Early presenters were significantly older (p<0.001), more likely to have significant comorbidities-hypertension, thromboembolic and renal disease (p<0.001)- A nd also significantly less likely to report cardinal symptoms of Covid-19;fever, cough, SOB, myalgia, fatigue/malaise, headache (p<0.001). In the cohort overall, the presence of infiltrates was not predictive of adverse outcome (ICU admission, ventilation or death) (p=0.214). Although early presenters were less likely to have infiltrates on their CXR (58% vs 76.8%), (p<0.001), the presence of CXR infiltrates in early presenters demonstrated an increased risk of adverse outcome (OR 1.90, 95% CI 1.11, 3.25). Conclusion We have demonstrated that SARS-Cov-2 infection presents in an heterogenous manner that varies with symptom duration. Atypical presentation of SARS-Cov-2 infection is more common earlier on in disease course, where viral shedding is likely to be higher, and this finding is of note in the context of national criteria for self-isolation and testing. Late presentation is more likely to be associated with radiological change, but this does not reflect an increased likelihood of adverse outcome. Patients who present early in their illness with radiological changes are at increased risk of adverse clinical outcome, suggesting that symptom onset and detection of CXR infiltrates are important for clinical assessment of severity at presentation to hospital in Covid-19.

S3 Comparisons in early and late presentation to hospital in COVID-19 patients

BackgroundThe clinical presentation and disease severity in SARS-Cov-2 infection ranges from asymptomatic carriage to death. There is little data regarding the timeframe of symptom onset to presentation to hospital, and disease outcomes. Therefore, we aim to investigate differences between ‘early presenters’ (< 7 days of symptom onset) and ‘late presenters’ (>7 days) and their clinical and radiological outcomes.MethodsIn this retrospective cohort study, symptom onset, epidemiological, and clinical characteristics were collected from patient electronic medical records at University Hospital Southampton Foundation Trust with laboratory confirmed SARS-Cov-2 infection. Logistical regression models were used to explore the relationships between these data and time of presentation to hospital.ResultsBetween March and July 2020, symptom onset data was collected for 626 SARS-Cov-2 positive patients, 574 of whom had chest radiographs (CXR). Early presenters comprised 388 (62%) and 238 (38%) were late presenters. Early presenters were significantly older (p<0.001), more likely to have significant comorbidities – hypertension, thromboembolic and renal disease (p<0.001) – and also significantly less likely to report cardinal symptoms of Covid-19;fever, cough, SOB, myalgia, fatigue/malaise, headache (p<0.001). In the cohort overall, the presence of infiltrates was not predictive of adverse outcome (ICU admission, ventilation or death) (p=0.214). Although early presenters were less likely to have infiltrates on their CXR (58% vs 76.8%), (p<0.001), the presence of CXR infiltrates in early presenters demonstrated an increased risk of adverse outcome (OR 1.90, 95% CI 1.11, 3.25).ConclusionWe have demonstrated that SARS-Cov-2 infection presents in an heterogenous manner that varies with symptom duration. Atypical presentation of SARS-Cov-2 infection is more common earlier on in disease course, where viral shedding is likely to be higher, and this finding is of note in the context of national criteria for self-isolation and testing. Late presentation is more likely to be associated with radiological change, but this does not reflect an increased likelihood of adverse outcome. Patients who present early in their illness with radiological changes are at increased risk of adverse clinical outcome, suggesting that symptom onset and detection of CXR infiltrates are important for clinical assessment of severity at presentation to hospital in Covid-19.

Inflammatory phenotyping predicts clinical outcome in COVID-19.

BACKGROUND: The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. METHODS: We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1ß, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. RESULTS: Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1ß and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). CONCLUSIONS: A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19.