PMC:7784786 / 4307-11788 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7784786","sourcedb":"PMC","sourceid":"7784786","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7784786","text":"Cases description\nPatient 1: A 53-year old woman with a personal history of essential hypertension and Type 2 diabetes mellitus presented with symptoms of polypnea of more than 40 rpm, use of respiratory ancillary musculature and dry cough. She arrived from a foreign country where COVID-19 was spreading. Symptoms started on 23 March and COVID-19 was diagnosed on 26 March on the basis of positive real time PCR (RT-PCR) for SARS-CoV-2. Initial gasometry showed moderate hypoxemia and respiratory alkalosis with a partial pressure of oxygen/fraction of inspired oxygen (PO2/FiO2) ratio of 191. Chest x-rays showed interstitial lesions in both lung fields. She started therapy with lopinavir/ritonavir, chloroquine, recombinant IFN α-2b and rocephin. In spite of treatment, the illness subsequently progressed to hypoxemic respiratory failure warranting the initiation of invasive mechanical ventilation. At day 13 of her admission in the ICU, she showed radiologic worsening of the interstitial multifocal pneumonia, with elevation of ALP, LDH, erythrocyte sedimentation rate and D-dimer. Physicians administered itolizumab at a dose of 200 mg. After 48 h of the first itolizumab dose, PO2/FiO2 improved and there were evidences of radiological improvement (Figure 1A \u0026 B). Patient was extubated after the first dose of the antibody and her status changed from critical to severe. She received a second dose of the antibody (200 mg), 48 h after the first infusion. 3 days after the first administration, patient was hemodynamically stable and has spontaneous ventilation. IL-6 levels were evaluated before itolizumab administration and after 2 and 7 days of the first administration. IL-6 levels reduced overtime from 172 pg/ml to 60 pg/ml (day 7) as depicted in Figure 2A. IL-1 was evaluated at the same time intervals, but it was undetectable. In addition, aspartate amino transferase (AST) concentrations were evaluated at different time points showing a reduction from 43 U/l to 24 U/l after 7 days (Figure 2B). No adverse events related with itolizumab were reported.\nFigure 1. Radiological images before and after one dose of itolizumab.\nPatient 1 (A) Before itolizumab (D0): diffuse Interstitial-alveolar infiltrate in both lung fields, predominantly in the bases. Minor left pleural effusion. (B) After itolizumab (48 h): radiological improvement with decreased diffuse infiltrate and radio-opacity at the top of both lungs and in both lung bases, in less proportion. The minor pleural effusion persists. Patient 3 (C) Before itolizumab (D0): alveolar interstitial inflammatory infiltrate in both lung fields, predominantly on the right side. (D) After itolizumab (48 h): radiological improvement with significant decrease of the alveolar interstitial infiltrate of both lungs.\nFigure 2. Circulating biomarkers in patient's sera.\nIL-6 and AST concentrations kinetics (A \u0026 B, respectively) measured in patients during itolizumab treatment. Patient 2: An 89-year old man with a personal history of chronic ischemic cardiopathy, permanent atrial fibrillation, hypertension and hypothyroidism. He has a previous history of alcoholism and several hospital admissions in the last 3 months on account of infectious respiratory diseases. He came to the hospital on 2 April after 7 days of shortness of breath, fever, asthenia and dry cough. He was in contact with a person who returned from a foreign country, where COVID-19 was extending. Physical examination shows signs of respiratory failure characterized by tachycardia, polypnea, intercostal and supraclavicular muscle retraction, high blood pressure, oxygen saturation of 82%, poor diuresis and drowsiness. Chest x-rays showed bilateral pulmonary inflammatory infiltrates, predominantly in the right lung. Admission ECG showed an atrial fibrillation with rapid ventricular response and the initial gasometry showed severe hypoxemia and respiratory alkalosis. Patient also had leukocytosis, altered globular sedimentation rate as well as elevated values of AST, LDH, D-dimer and positive C-reactive protein. He was admitted into the ICU requiring invasive mechanical ventilation. Treatment with lopinavir–ritonavir, chloroquine, IFN α-2b, meropenem and linezolid was initiated. 3 days after his admission into the ICU, itolizumab was prescribed, due to worsening of the bilateral pulmonary infiltrates together with a deterioration of the ventilatory function (PO2/FiO2 = 173). After the first antibody infusion, PO2/FiO2 significantly increased (PO2/FiO2 = 320) and there were evidences of radiological improvement. 3 days after, patient showed radiological worsening of the left lung, characterized by alveolar hypoventilation and atelectasis; then, a 70% pneumothorax was established. Treatment of the pneumothorax with minimal pleurotomy was very demanding and required 3 days for the resolution. The patient received a second infusion of the monoclonal antibody 72 h after the first, while a third dose was administered at the discretion of the treating physicians, 2 days after the second. In total, patient received three doses of itolizumab (200 mg) without any related adverse event. IL-6 levels were evaluated before itolizumab administration and after 2, 4 and 7 days of the first administration. IL-6 was extremely high at baseline (623 pg/ml) and even though cytokine levels reduced roughly 50%, the lowest value remained above 300 pg/ml after 7 days. IL-6 kinetics is shown in Figure 2A. Apart from IL-6, IL-1 was undetectable at this time point of the disease. Interesting, in the case of AST, a significant reduction is detecting at day 7 (pretreatment: 156 U/l, D7: 40 U/l) as is showed in Figure 2B. After 10 days of admission into the ICU, patient presented a myocardial dysfunction and shock that required vasoactive support with norepinephrine. On day 13, he finally died, on account of a mixed cardiovascular and respiratory failure.\nPatient 3: An 81-year old female, who is COVID-19 positive contact was not identified at the moment of hospitalization. She started symptoms on 2 April and entered the ICU on 5 April. Patient has a previous history of hypertension, diabetes mellitus, glaucoma and smoking habit. She was admitted with frequent cough, wheezing and diarrhea. The diagnosis of viral pneumonia by COVID-19 was confirmed by RT-PCR on 7 April. Oxygen support at 5 l/min and treatment with ceftriaxone, lopinavir–ritonavir, chloroquine and IFN α-2b was indicated. Chest images showed bilateral interstitial infiltration in both lungs. Patient condition was classified as severe, although she did not require invasive mechanical ventilation. A dose of itolizumab (200 mg) was given the day after her admission into the ICU. Two days after the antibody administration, together with the rest of the therapy, there was an improvement of the respiratory distress while the chest image showed a decrease of the alveolar interstitial infiltrate of both lungs (Figure 1C \u0026 D). Patient left the ICU after a favorable clinical and radiological evolution. IL-6 concentration was measured prior and after the antibody administration. IL-6 level at baseline was lower than in previous cases (30 pg/ml), but also decreased 48 h and 168 h after itolizumab infusion, in parallel with patient recovery (Figure 2A). IL-1 and TNF-α were untraceable before and 48 h after the antibody administration. Regarding to AST concentration, the values were in the normal range during the treatment period 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