Natural history of COVID-19 recovery: Changes in physiologic, radiologic and patient-reported outcomes 12 months after symptom onset

RATIONALE: The long-term trajectory of people recovering from COVID-19 and the cause of COVID-19;imaging;patient persistent symptoms remains poorly understood. OBJECTIVE: We sought to determine how pulmonary function tests (PFTs), patient-reported outcome pulmonary function measures (PROMs) and radiologic features change over 12months in people hospitalized with COVID-19. METHODS: A prospective, consecutive cohort of patients hospitalized with PCR-confirmed SARS-CoV-2 were recruited. Longitudinal clinical data, PROMs, PFTs and computed tomography (CT) chests were collected at 3, 6 and/or 12months after symptom onset. Repeated analysis of variance (ANOVA) and Friedman tests were used to compare changes in outcomes over time. MEASUREMENT AND MAIN RESULTS: Eighty-one patients were enrolled with 70 completing the 12-month visit. At 3months, the mean diffusing capacity of the lung for carbon monoxide was reduced at 76 +/- 16%-predicted and improved to 80 +/- 16%-predicted at 6months (p<0.001). The median values for dyspnea, cough, sleep and quality of life (QoL) were abnormal at 3months, with QoL being the only PROM that significantly improved at 6 months. There was no further statistically significant change in PFT parameters or PROMs between 6 and 12 months. The percentages of lung affected by ground glass and reticulation at 3months were 11.3% (IQR 5.6-19.6) and 4.4% (IQR 1.6-7.9), respectively. These improved at 12months with ground glass being 0% (IQR 0-3.3) and reticulation 1.7% (IQR 0-3.3). CONCLUSIONS: PFTs improve between 3 and 6 months, with no change over the subsequent 6months in patients hospitalized with COVID-19. Despite improved and nearly normal physiologic and radiologic results in most patients, 60% report abnormal PROMs at 12months.

Longitudinal characterisation of haematological and biochemical parameters in cancer patients prior to and during COVID-19 reveals features associated with outcome.

BACKGROUND: Cancer patients are at increased risk of death from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cancer and its treatment affect many haematological and biochemical parameters, therefore we analysed these prior to and during coronavirus disease 2019 (COVID-19) and correlated them with outcome. PATIENTS AND METHODS: Consecutive patients with cancer testing positive for SARS-CoV-2 in centres throughout the United Kingdom were identified and entered into a database following local governance approval. Clinical and longitudinal laboratory data were extracted from patient records. Data were analysed using Mann-Whitney U test, Fisher's exact test, Wilcoxon signed rank test, logistic regression, or linear regression for outcomes. Hierarchical clustering of heatmaps was performed using Ward's method. RESULTS: In total, 302 patients were included in three cohorts: Manchester (n = 67), Liverpool (n = 62), and UK (n = 173). In the entire cohort (N = 302), median age was 69 (range 19-93 years), including 163 males and 139 females; of these, 216 were diagnosed with a solid tumour and 86 with a haematological cancer. Preinfection lymphopaenia, neutropaenia and lactate dehydrogenase (LDH) were not associated with oxygen requirement (O2) or death. Lymphocyte count (P < 0.001), platelet count (P = 0.03), LDH (P < 0.0001) and albumin (P < 0.0001) significantly changed from preinfection to during infection. High rather than low neutrophils at day 0 (P = 0.007), higher maximal neutrophils during COVID-19 (P = 0.026) and higher neutrophil-to-lymphocyte ratio (NLR; P = 0.01) were associated with death. In multivariable analysis, age (P = 0.002), haematological cancer (P = 0.034), C-reactive protein (P = 0.004), NLR (P = 0.036) and albumin (P = 0.02) at day 0 were significant predictors of death. In the Manchester/Liverpool cohort 30 patients have restarted therapy following COVID-19, with no additional complications requiring readmission. CONCLUSION: Preinfection biochemical/haematological parameters were not associated with worse outcome in cancer patients. Restarting treatment following COVID-19 was not associated with additional complications. Neutropaenia due to cancer/treatment is not associated with COVID-19 mortality. Cancer therapy, particularly in patients with solid tumours, need not be delayed or omitted due to concerns that treatment itself increases COVID-19 severity.

Longitudinal analysis of biochemical and haematological features of cancer patients with COVID-19

Background: Cancer patients (pts) are at increased risk of severe COVID-19 infection and death. Older pts, men and those with haematological malignancies and receiving anti-tumour therapy within 14 days appear to be at highest risk for poor outcomes. In general populations, severe COVID-19 infection has been associated with neutrophilia, raised lactate dehydrogenase (LDH) and C-reactive protein (CRP). Cancer and its treatment affect many haematological and biochemical parameters. We examined whether COVID-19 infection affected these compared to pts’ baseline parameters by longitudinal tracking. We also investigated whether changes were associated with poor outcome. Methods: Consecutive pts with solid or haematological malignancies presenting with index symptoms and testing positive for SARS-CoV-2 at a tertiary oncology centre were identified following institutional board approval. Clinical and laboratory data were extracted from the pt record. Paired T-tests were used for longitudinal sampling and ANOVA/Chi squared for outcomes. Results: 52 pts tested positive (27 male, 25 female;median age 63). 80.5% had solid cancers, and 19.5% haematological. 31/52 pts were lymphopenic prior to infection. Comparing mean pre-infection counts (6 months-14 days=PRE) with mean counts from the 5 days following positive test (DURING) lymphocyte counts significantly decreased during infection (p<0.0001). Platelets were significantly reduced DURING vs. PRE COVID-19 (p=0.0028). 17/52 pts developed transient (median 2 days) neutropenia (<2x109/L) DURING infection (6 pts <1x109/L, 2 pts <0.5x109/L), 8/17 attributed to cancer/cancer therapy, the rest had no underlying cause. 8/17 pts received growth factor support. Reduced lymphocytes/neutrophils/platelets at diagnosis were not associated with oxygen requirement (O2) or death. Different CRP trajectories were observed when comparing pts grouped by discharge/ O2/death. Higher CRP and LDH at diagnosis were associated with admission (p=0.02 CRP/0.2 LDH), O2 (p=0.0002 CRP/p<0.01 LDH) and death (p=0.069 CRP/p=0.04 LDH). Updated analysis will be presented. Conclusions: Infection with SARS-CoV-2 commonly affects haematological parameters in cancer pts. High CRP and LDH are associated with poor outcomes. Legal entity responsible for the study: The Christie NHS Foundation Trust. Funding: Has not received any funding. Disclosure: R. Lee: Speaker Bureau/Expert testimony, Research grant/Funding (self): Bristol Myers Squibb;Speaker Bureau/Expert testimony: Astra Zeneca. A. Armstrong: Shareholder/Stockholder/Stock options, Husband has shares: Astra Zeneca. T. Cooksley: Speaker Bureau/Expert testimony: Bristol Myers Squibb. All other authors have declared no conflicts of interest.