RangerJoe
Posts: 13450
Joined: 11/16/2015 From: My Mother, although my Father had some small part. Status: offline
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Published by PNAS. Proceedings of the National Academy of Sciences of the United States of America. There is a lot more technical stuff in the article as well as x-rays. Effectiveness of convalescent plasma therapy in severe COVID-19 patients March 18, 2020 quote:
Significance COVID-19 is currently a big threat to global health. However, no specific antiviral agents are available for its treatment. In this work, we explore the feasibility of convalescent plasma (CP) transfusion to rescue severe patients. The results from 10 severe adult cases showed that one dose (200 mL) of CP was well tolerated and could significantly increase or maintain the neutralizing antibodies at a high level, leading to disappearance of viremia in 7 d. Meanwhile, clinical symptoms and paraclinical criteria rapidly improved within 3 d. Radiological examination showed varying degrees of absorption of lung lesions within 7 d. These results indicate that CP can serve as a promising rescue option for severe COVID-19, while the randomized trial is warranted. Abstract Currently, there are no approved specific antiviral agents for novel coronavirus disease 2019 (COVID-19). In this study, 10 severe patients confirmed by real-time viral RNA test were enrolled prospectively. One dose of 200 mL of convalescent plasma (CP) derived from recently recovered donors with the neutralizing antibody titers above 1:640 was transfused to the patients as an addition to maximal supportive care and antiviral agents. The primary endpoint was the safety of CP transfusion. The second endpoints were the improvement of clinical symptoms and laboratory parameters within 3 d after CP transfusion. The median time from onset of illness to CP transfusion was 16.5 d. After CP transfusion, the level of neutralizing antibody increased rapidly up to 1:640 in five cases, while that of the other four cases maintained at a high level (1:640). The clinical symptoms were significantly improved along with increase of oxyhemoglobin saturation within 3 d. Several parameters tended to improve as compared to pretransfusion, including increased lymphocyte counts (0.65 × 109/L vs. 0.76 × 109/L) and decreased C-reactive protein (55.98 mg/L vs. 18.13 mg/L). Radiological examinations showed varying degrees of absorption of lung lesions within 7 d. The viral load was undetectable after transfusion in seven patients who had previous viremia. No severe adverse effects were observed. This study showed CP therapy was well tolerated and could potentially improve the clinical outcomes through neutralizing viremia in severe COVID-19 cases. The optimal dose and time point, as well as the clinical benefit of CP therapy, needs further investigation in larger well-controlled trials. . . . Convalescent plasma (CP) therapy, a classic adaptive immunotherapy, has been applied to the prevention and treatment of many infectious diseases for more than one century. Over the past two decades, CP therapy was successfully used in the treatment of SARS, MERS, and 2009 H1N1 pandemic with satisfactory efficacy and safety (9⇓⇓–12). A meta-analysis from 32 studies of SARS coronavirus infection and severe influenza showed a statistically significant reduction in the pooled odds of mortality following CP therapy, compared with placebo or no therapy (odds ratio, 0.25; 95% confidence interval, 0.14–0.45) (13). However, the CP therapy was unable to significantly improve the survival in the Ebola virus disease, probably due to the absence of data of neutralizing antibody titration for stratified analysis (14). Since the virological and clinical characteristics share similarity among SARS, Middle East Respiratory Syndrome (MERS), and COVID-19 (15), CP therapy might be a promising treatment option for COVID-19 rescue (16). Patients who have recovered from COVID-19 with a high neutralizing antibody titer may be a valuable donor source of CP. Nevertheless, the potential clinical benefit and risk of convalescent blood products in COVID-19 remains uncertain. Hence, we performed this pilot study in three participating hospitals to explore the feasibility of CP treatment in 10 severe COVID-19 patients. . . . Results Neutralizing Activity of CP against SARS-CoV-2. The neutralizing activity against SARS-CoV-2 was evaluated by classical plaque reduction test using a recently isolated viral strain (1). Among the first batch of CP samples from 40 recovered COVID-19 patients, 39 showed high antibody titers of at least 1:160, whereas only one had an antibody titer of 1:32. This result laid the basis for our pilot clinical trial using CP in severe patients. General Characteristics of Patients in the Trial. From January 23, 2020, to February 19, 2020, 10 severe COVID-19 patients (six males and four females) were enrolled and received CP transfusion. The median age was 52.5 y (interquartile range [IQR], 45.0 y to 59.5 y) (Table 1). None of the patients had direct exposure to Huanan Seafood Wholesale Market. The median time from onset of symptoms to hospital admission and CP transfusion was 6 d (IQR, 2.5 d to 8.5 d) and 16.5 d (IQR, 11.0 d to 19.3 d), respectively. Three patients were affected by clustering infection. The most common symptoms at disease onset were fever (7 of 10 patients), cough (eight cases), and shortness of breath (eight cases), while less common symptoms included sputum production (five cases), chest pain (two cases), diarrhea (two cases), nausea and vomiting (two cases), headache (one case), and sore throat (one case). Four patients had underlying chronic diseases, including cardiovascular and/or cerebrovascular diseases and essential hypertension. Nine patients received arbidol monotherapy or combination therapy with remdesivir (in one case not included in the current clinical trial), or ribavirin, or peramivir, while one patient received ribavirin monotherapy (Table 2). Antibacterial or antifungal treatment was used when patients had coinfection. Six patients received intravenous (i.v.) methylprednisolone (20 mg every 24 h). . . . Effects of CP Transfusion. Improvement of clinical symptoms. All symptoms in the 10 patients, especially fever, cough, shortness of breath, and chest pain, disappeared or largely improved within 1 d to 3 d upon CP transfusion. Prior to CP treatment, three patients received mechanical ventilation, three received high-flow nasal cannula oxygenation, and two received conventional low-flow nasal cannula oxygenation. After treatment with CP, two patients were weaned from mechanical ventilation to high-flow nasal cannula, and one patient discontinued high-flow nasal cannula. Besides, in one patient treated with conventional nasal cannula oxygenation, continuous oxygenation was shifted to intermittent oxygenation (Table 2). Reduction of pulmonary lesions on chest CT examinations. According to chest CTs, all patients showed different degrees of absorption of pulmonary lesions after CP transfusion. Representative chest CT images of patient 9 and patient 10 are shown on Fig. 1. Patient 9, a 49-y-old female admitted 1 day postonset of illness (dpoi), showed the most obvious pulmonary image improvement. At 10 dpoi, one dose of 200-mL transfusion of CP was given. The SARS-CoV-2 RNA converted to negative at 12 dpoi. Compared with the result at 7 dpoi, massive infiltration and ground-glass attenuation disappeared on CT image performed at 13 dpoi, accompanied by a much better pulmonary function. Patient 10, a 50-y-old male, was admitted 3 dpoi and was given a 200-mL transfusion of CP at 20 dpoi. His chest CT presented massive infiltration and widespread ground-glass attenuation on admission and started to show a gradual absorption of lung lesions 5 d after CP transfusion. The SARS-CoV-2 RNA became negative at 25 dpoi. . . . Outcome of patients treated with CP as compared to a recent historic control group. A historic control group was formed by random selection of 10 patients from the cohort treated in the same hospitals and matched by age, gender, and severity of the diseases to the 10 cases in our trial. Baseline characteristics of patients between CP treatment group and control group showed no significant differences, while clinical outcomes of these two groups were different: three cases discharged while seven cases in much improved status and ready for discharge in CP group, as compared to three deaths, six cases in stabilized status, and one case in improvement in the control group (P < 0.001; SI Appendix, Table S1). Adverse Effects of CP Transfusions. Patient 2 showed an evanescent facial red spot. No serious adverse reactions or safety events were recorded after CP transfusion. https://www.pnas.org/content/early/2020/04/02/2004168117 There are tests in the US on going, I think they just started recently.
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Seek peace but keep your gun handy. I'm not a complete idiot, some parts are missing! “Illegitemus non carborundum est (“Don’t let the bastards grind you down”).” ― Julia Child
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