Post-Discharge Health Status and Symptoms in Patients with Severe COVID-19.

BACKGROUND: Little is known about long-term recovery from severe COVID-19 disease. Here, we characterize overall health, physical health, and mental health of patients 1 month after discharge for severe COVID-19. METHODS: This was a prospective single health system observational cohort study of patients ≥ 18 years hospitalized with laboratory-confirmed COVID-19 disease who required at least 6 l of oxygen during admission, had intact baseline cognitive and functional status, and were discharged alive. Participants were enrolled between 30 and 40 days after discharge. Outcomes were elicited through validated survey instruments: the PROMIS® Dyspnea Characteristics and PROMIS® Global Health-10. RESULTS: A total of 161 patients (40.6% of eligible) were enrolled; 152 (38.3%) completed the survey. Median age was 62 years (interquartile range [IQR], 50-67); 57 (37%) were female. Overall, 113/152 (74%) participants reported shortness of breath within the prior week (median score 3 out of 10 [IQR 0-5]), vs 47/152 (31%) pre-COVID-19 infection (0, IQR 0-1), p < 0.001. Participants also rated their physical health and mental health as worse in their post-COVID state (43.8, standard deviation 9.3; mental health 47.3, SD 9.3) compared to their pre-COVID state, (54.3, SD 9.3; 54.3, SD 7.8, respectively), both p < 0.001. Physical and mental health means in the general US population are 50 (SD 10). A total of 52/148 (35.1%) patients without pre-COVID oxygen requirements needed home oxygen after hospital discharge; 20/148 (13.5%) reported still using oxygen at time of survey. CONCLUSIONS: Patients with severe COVID-19 disease typically experience sequelae affecting their respiratory status, physical health, and mental health for at least several weeks after hospital discharge.

Post-discharge health status and symptoms in patients with severe COVID-19.

BACKGROUND: Little is known about long-term recovery from severe COVID-19 disease. Here, we characterize overall health, physical health and mental health of patients one month after discharge for severe COVID-19. METHODS: This was a prospective single health system observational cohort study of patients ≥18 years hospitalized with laboratory-confirmed COVID-19 disease who required at least 6 liters of oxygen during admission, had intact baseline cognitive and functional status and were discharged alive. Participants were enrolled between 30 and 40 days after discharge. Outcomes were elicited through validated survey instruments: the PROMIS Dyspnea Characteristics and PROMIS Global Health-10. RESULTS: A total of 161 patients (40.6% of eligible) were enrolled; 152 (38.3%) completed the survey. Median age was 62 years (interquartile range [IQR], 50-67); 57 (37%) were female. Overall, 113/152 (74%) participants reported shortness of breath within the prior week (median score 3 out of 10 [IQR 0-5]), vs. 47/152 (31%) pre-COVID-19 infection (0, IQR 0-1), p<0.001. Participants also rated their physical health and mental health as worse in their post-COVID state (43.8, standard deviation 9.3; mental health 47.3, SD 9.3) compared to their pre-COVID state, (54.3, SD 9.3; 54.3, SD 7.8, respectively), both p <0.001. A total of 52/148 (35.1%) patients without pre-COVID oxygen requirements needed home oxygen after hospital discharge; 20/148 (13.5%) reported still using oxygen at time of survey. CONCLUSIONS: Patients with severe COVID-19 disease typically experience sequelae affecting their respiratory status, physical health and mental health for at least several weeks after hospital discharge.

Novel Small Molecule MEK Inhibitor URML-3881 Enhances Cisplatin Sensitivity in Clear Cell Ovarian Cancer.

Advanced clear cell ovarian cancer (CCOC) is a highly fatal malignancy with a scarcity of effective treatment options. CCOC is inherently chemotherapy resistance, but the exact mechanism of this resistance has yet to be established. Prosurvival signaling, such as through the MAPK cascade, is one way in which cancer cells can evade chemotherapy. We have determined that CCOC exhibits baseline elevated levels of MAPK activity, which increase further upon cisplatin exposure. We have developed a novel MEK inhibitor, URML-3881, to test the effect of MAPK inhibition in CCOC. URML-3881 was found to reduce in vitro CCOC viability through apoptosis and proliferation inhibition, yet it failed to induce in vivo tumor regression. Similarly, cisplatin alone had minimal impact on tumor growth, but remarkably, the combination of MEK inhibition and cisplatin led to a significant and prolonged tumor regression. These studies confirm that the combination of MEK inhibition with URML-3881 and cisplatin is superior to either agent alone in CCOC. Our data support the design of future preclinical and clinical studies into the combination of MEK inhibition and platinum-based chemotherapy as a treatment strategy for CCOC.