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BackgroundSevere acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection has disproportionately affected older individuals and those with underlying medical conditions. Research has focused on short-term outcomes in hospital, and single organ involvement. Consequently, impact of long COVID (persistent symptoms three months post-infection) across multiple organs in low-risk individuals is yet to be assessed. MethodsAn ongoing prospective, longitudinal, two-centre, observational study was performed in individuals symptomatic after recovery from acute SARS-CoV-2 infection. Symptoms and organ function (heart, lungs, kidneys, liver, pancreas, spleen) were assessed by standardised questionnaires (EQ-5D-5L, Dyspnoea-12), blood investigations and quantitative magnetic resonance imaging, defining single and multi-organ impairment by consensus definitions. FindingsBetween April and September 2020, 201 individuals (mean age 44 (SD 11.0) years, 70% female, 87% white, 31% healthcare workers) completed assessments following SARS-CoV-2 infection (median 140, IQR 105-160 days after initial symptoms). The prevalence of pre-existing conditions (obesity: 20%, hypertension: 6%; diabetes: 2%; heart disease: 4%) was low, and only 18% of individuals had been hospitalised with COVID-19. Fatigue (98%), muscle aches (88%), breathlessness (87%), and headaches (83%) were the most frequently reported symptoms. Ongoing cardiorespiratory (92%) and gastrointestinal (73%) symptoms were common, and 42% of individuals had ten or more symptoms. There was evidence of mild organ impairment in heart (32%), lungs (33%), kidneys (12%), liver (10%), pancreas (17%), and spleen (6%). Single (66%) and multi-organ (25%) impairment was observed, and was significantly associated with risk of prior COVID-19 hospitalisation (p<0.05). InterpretationIn a young, low-risk population with ongoing symptoms, almost 70% of individuals have impairment in one or more organs four months after initial symptoms of SARS-CoV-2 infection. There are implications not only for burden of long COVID but also public health approaches which have assumed low risk in young people with no comorbidities. FundingThis work was supported by the UKs National Consortium of Intelligent Medical Imaging through the Industry Strategy Challenge Fund, Innovate UK Grant 104688, and also through the European Unions Horizon 2020 research and innovation programme under grant agreement No 719445.
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BackgroundIn COVID-19, high levels of granulocyte macrophage-colony stimulating factor (GM-CSF) and inflammatory myeloid cells correlate with disease severity, cytokine storm, and respiratory failure. With this rationale, we used lenzilumab, an anti-human GM-CSF monoclonal antibody, to treat patients with severe and critical COVID-19 pneumonia. MethodsHospitalized patients with COVID-19 pneumonia and risk factors for poor outcomes were treated with lenzilumab 600 mg intravenously for three doses through an emergency single-use IND application. Patient characteristics, clinical and laboratory outcomes, and adverse events were recorded. All patients receiving lenzilumab through May 1, 2020 were included in this report. ResultsTwelve patients were treated with lenzilumab. Clinical improvement was observed in 11 out of 12 (92%), with a median time to discharge of 5 days. There was a significant improvement in oxygenation: The proportion of patients with SpO2/FiO2 < 315 at the end of observation was 8% vs. compared to 67% at baseline (p=0.00015). A significant improvement in mean CRP and IL-6 values on day 3 following lenzilumab administration was also observed (137.3 mg/L vs 51.2 mg/L, p = 0.040; 26.8 pg/mL vs 16.1 pg/mL, p = 0.035; respectively). Cytokine analysis showed a reduction in inflammatory myeloid cells two days after lenzilumab treatment. There were no treatment-emergent adverse events attributable to lenzilumab, and no mortality in this cohort of patients with severe and critical COVID-19 pneumonia. ConclusionsIn high-risk COVID-19 patients with severe and critical pneumonia, GM-CSF neutralization with lenzilumab was safe and associated with improved clinical outcomes, oxygen requirement, and cytokine storm.
