ABSTRACT
Background: In the acute phase, patients with severe COVID-19 exhibit pulmonary inflammation and vascular injury, as well as an exaggerated cytokine response. Aim(s): To describe the inflammatory cytokine and vascular injury mediator profiles in patients previously hospitalised with COVID-19, and to compare these profiles with those in healthy controls and in patients recovering from severe sepsis of other aetiology. Method(s): Plasma levels of 28 different cytokine, chemokine, angiogenic and vascular injury markers were measured by MSD V-PLEX multiplex assays in 49 post-COVID patients 5.0+/-1.9 (mean+/-SD) months after hospitalisation with COVID-19 pneumonia, 11 post-sepsis patients (5.4+/-2.9 months after hospitalised non-COVID sepsis) and 18 healthy controls. Kruskal-Wallis or ANOVA were used to compare groups;false discovery rate correction (Benjamini Hochberg) allowed for multiple testing. Result(s): In the post-COVID group, IL-6, TNFalpha, SAA, MCP1, Tie-2, Flt1, PIGF and CRP were significantly elevated, whereas IL-7 and bFGF were significantly depressed. The differences in TNFalpha, SAA, MCP1, Tie-2, Flt1, IL-7 and bFGF appeared unique to the post-COVID group, but increased IL-6, PIGF and CRP levels were also seen in postsepsis patients compared with controls. In post-COVID patients we found strong negative spearman correlations between each of IL-6 (r=-0.51) and CRP (r=-0.57) with TLCO %predicted (p<0.001) and positive correlations with post-recovery CT abnormality scores: IL-6 (r=0.28) and CRP (r=0.46), p<0.05. Conclusion(s): A unique signature of inflammatory and vascular damage markers is seen months after acute COVID19 infection. Further research is needed to determine their pathophysiological significance.
ABSTRACT
Background: Cardiac magnetic resonance (CMR) and cardiopulmonary exercise testing (CPET) have provided important insights into the prevalence of early cardiopulmonary abnormalities in COVID-19 patients. It is currently unknown whether such abnormalities persist over time and relate to ongoing symptoms. Purpose: To describe the longitudinal trajectory of cardiopulmonary abnormalities on CMR and CPET in moderate to severe COVID-19 patients and assess their relationship with ongoing symptoms. Methods: Fifty-eight previously hospitalised COVID-19 patients and 30 age, sex, body mass index, comorbidity-matched controls underwent CMR, CPET and a symptom-based questionnaire at 2-3 months (2-3m). Repeat assessments (including gas transfer) were performed in 46 patients at 6 months (6m). Results: During admission, 1/3rd of patients needed ventilation or intensive care (Table 1) and three (5%) had a raised troponin. On CMR, patients had preserved left (LV) and right ventricular (RV) volumes and function at 2-3m from infection. By 6m, LV function did not change but RV end diastolic volume decreased (mean difference -4.3 mls/m2, p=0.005) and RV function increased (mean difference +3.2%, p<0.001, Fig. 1A). Patients had higher native T1 (a marker of fibroinflammation) at 2-3m compared to controls (Table 1, Fig. 1B), which normalised by 6m. Extracellular volume was normal and improved by 6m. Native T2, a marker of myocardial oedema, did not differ between patients and controls on serial CMR. At 2- 3m, late gadolinium enhancement (LGE) was higher in patients (p=0.023) but became comparable to controls by 6m (p=0.62). Six (12%) patients had LGE in a myocarditis pattern and one (2%) had myocardial infarction. None had active myocarditis using the Modified Lake Louise Criteria. Lung imaging (T2-weighted) revealed parenchymal abnormalities in 2/3rds of patients at 2-3 and 6 months. The extent of abnormalities improved on serial imaging (Table 1). Gas transfer (DLco) was worse in those with lung abnormalities (77% vs 91% of predicted, p=0.009). CPET revealed reduced peak oxygen consumption (pVO2) in patients at 2-3m, which normalised by 6m (80.5% to 93.3% of predicted, p=0.001) (Table 1, Fig. 1C). At 2-3m, 49% of patients had submaximal tests (respiratory exchange ratio <1.1), reducing to 25% by 6m (p=0.057). VE/VCO2 slope, a marker of lung efficiency, was abnormal in patients but improved on serial CPET (Table 1, Fig. 1D). Cardiac symptoms (chest pain, dyspnoea, palpitations, dizziness or syncope) were present in 83% of patients at 2-3m, reducing to 52% by 6m (p<0.001). There was no significant association between CMR or CPET parameters and persistent cardiac symptoms at 6m (Fig. 1E). Conclusions: Cardiopulmonary parameters (on CMR and CPET) improved in moderate-severe COVID-19 patients from 2-3 to 6 months post infection. Despite this, patients continued to experience cardiac symptoms which had no relationship with measured parameters. (Figure Presented).
ABSTRACT
P217 Table 1A comparison of first and second wave characteristics, treatment and outcome data First wave Second wave Mean difference (95%CI) X2 (df) P value Age (years) 69.0 (52.0, 80.0) 62.0 (52.0, 71.0) -3.4 (-7.8 to +1.1) - 0.14 Sex: - Male - Female 49 (69.0%) 22 (31.0%) 180 (65.0%) 97 (35.0%) - 0.4 (1) 0.52 BMI (kg/m2) 28.5 (24.9, 33.6) 29.6 (24.8, 34.9) +0.6 (-1.7 to +2.9) - 0.63 Clinical Frailty Score: - 1 to 2 (fit) 18 (25.4%) 132 (47.7%) - 15.6 (5) 0.008 CT severity score - Moderate/severe - Severe 11 (29.7%) 23 (62.2%) 131 (52.2%) 113 (45.0%) - 16.0 (3) 0.0012 CRP prior to rHDU admission (mg/L) 180.6 (118.0, 210.0) 124.1 (78.1, 175.6) -44.1 (-66.9 to -21.3) - 0.0002 Spike gene testing - VOC B.1.1.7 variant - Wild-type - Ambiguous - - - 143 (67.1%) 57 (26.8%) 13 (6.1%) - - - Dexamethasone 3 (4.2%) 266 (96.0%) - 271.4 (1) <0.0001 Remdesivir 4 (5.6%) 198 (71.5%) - 100.6 (1) <0.0001 CPAP as primary respiratory support 32 (45.1%) 248 (89.5%) - 71.1 (1) <0.0001 Able to adopt semi- or full- prone position 42 (59.2%) 237 (85.6%) - 24.8 (1) <0.0001 Admission outcome (all) - Died - Discharged 36 (50.7%) 35 (49.3%) 74 (26.7%) 201 (72.5%) - 14.7 (1) 0.0001 rHDU outcome (‘For Intubation’) - Died - Off respiratory support - Intubated 0 (0.0%) 14 (41.2%) 20 (58.8%) 7 (3.3%) 152 (72.4%) 51 (24.3%) - 17.3 (2) 0.0002 ConclusionOur single centre experience shows that rHDU mortality and intubation rates have improved over time in spite of the emergence of new variants. Improvements in outcome are likely to be multi-factorial. Our data support the benefit of pharmacological COVID-19 therapies in a rHDU population as well as the use of CPAP and awake proning. Other potential causes for improved outcomes are lower serological and radiological COVID-19 severity in our wave two cohort as well as reduced rates of frailty.Referencehttps://medrxiv.org/content/10.1101/2021.03.11.21253364v1