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      Successful pulsed methylprednisolone and convalescent plasma treatment in a case of a renal transplant recipient with COVID-19 positive pneumonia: a case report

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          Abstract

          Coronavirus 2019 disease (COVID-19) is a deadly disease that was first seen in Wuhan, China, and primarily affects the respiratory system, but also has different systemic involvements. It has caused 89 million cases and 1.9 million deaths worldwide. COVID-19 positive renal transplant recipients have a higher mortality rate than COVID-19 patients in the normal population. There is no specific treatment and follow-up protocol for COVID-19 infection in transplant recipients. COVID-19 treatment and immunosuppressive therapy choices are controversial. Recently, pulse steroid therapies have been used in cases with severe COVID-19 pneumonia. Convalescent plasma therapy is used limitedly in COVID-19 patients. Our 49-year-old male patient has been a recipient of a renal transplant from a cadaver for 6 years. We aimed to make an additional contribution by presenting our patient to the literature whose COVID-19 PCR-RT test performed in the emergency department due to the complaints of fever, shortness of breath, and cough for five days was positive and had moderate COVID-19 pneumonia in thorax tomography and had serious clinical and radiological improvement after pulsed methylprednisolone and convalescent plasma therapy in the early period.

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          Convalescent plasma as a potential therapy for COVID-19

          The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which originated in Wuhan, China, has become a major concern all over the world. The pneumonia induced by the SARS-CoV-2 is named coronavirus disease 2019 (COVID-19). By Feb 22, 2020, this virus has affected more than 77 700 people worldwide and caused more than 2300 deaths. To date, no specific treatment has been proven to be effective for SARS-CoV-2 infection. Apart from supportive care, such as oxygen supply in mild cases and extracorporeal membrane oxygenation for the critically ill patients, specific drugs for this disease are still being researched. In the USA, the first patient infected with SARS-CoV-2 was treated by supportive care and intravenous remdesivir, before the patient recovered and was discharged. 1 However, randomised clinical trials are needed to evaluate the safety and efficacy of remdesivir in the treatment of COVID-19. Convalescent plasma or immunoglobulins have been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite treatment with pulsed methylprednisolone. Moreover, several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with convalescent plasma.2, 3, 4 In 2014, the use of convalescent plasma collected from patients who had recovered from Ebola virus disease was recommended by WHO as an empirical treatment during outbreaks. 5 A protocol for the use of convalescent plasma in the treatment of Middle East respiratory syndrome coronavirus was established in 2015. 6 In terms of patients with pandemic 2009 influenza A H1N1 (H1N1pdm09) virus infection, a prospective cohort study by Hung and colleagues showed a significant reduction in the relative risk of mortality (odds ratio 0·20 [95% CI 0·06–0·69], p=0·01) for patients treated with convalescent plasma. 7 Additionally, in a subgroup analysis, viral load after convalescent plasma treatment was significantly lower on days 3, 5, and 7 after intensive care unit admission. No adverse events were observed. A multicentre, prospective, double-blind, randomised controlled trial by Hung and colleagues showed that using convalescent plasma from patients who recovered from the influenza A H1N1pdm09 virus infection to treat patients with severe influenza A H1N1 infection was associated with a lower viral load and reduced mortality within 5 days of symptom onset. 8 A meta-analysis by Mair-Jenkins and colleagues showed that the mortality was reduced after receiving various doses of convalescent plasma in patients with severe acute respiratory infections, with no adverse events or complications after treatment. 9 Another meta-analysis by Luke and colleagues identified eight studies involving 1703 patients with 1918 influenzapneumonia from 1918 to 1925 who received an infusion of influenza-convalescent human blood products, which showed a pooled absolute reduction of 21% (95% CI 15–27; p<0·001) in the overall crude case-fatality rate at low risk of bias. 10 One possible explanation for the efficacy of convalescent plasma therapy is that the antibodies from convalescent plasma might suppress viraemia. Schoofs and colleagues reported that 3BNC117-mediated immunotherapy, which is a broad neutralising antibody to HIV-1, enhances host humoral immunity to HIV-1. 11 An in vivo trial also showed that the effects of this antibody were not only limited to free viral clearance and blocking new infection, but also included acceleration of infected cell clearance. 12 Viraemia peaks in the first week of infection in most viral illnesses. The patient usually develops a primary immune response by days 10–14, which is followed by virus clearance. 4 Therefore, theoretically, it should be more effective to administer the convalescent plasma at the early stage of disease. 4 However, other treatments might have an effect on the relationship between convalescent plasma and antibody level, including antiviral drugs, steroids, and intravenous immunoglobulin. 10 According to WHO, 13 management of COVID-19 has mainly focused on infection prevention, case detection and monitoring, and supportive care. However, no specific anti-SARS-CoV-2 treatment is recommended because of the absence of evidence. Most importantly, the current guidelines emphasise that systematic corticosteroids should not be given routinely for the treatment of COVID-19, which was also the recommendation in a a Commnt in The Lancet. 14 Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used as a treatment without the occurrence of severe adverse events. Therefore, it might be worthwhile to test the safety and efficacy of convalescent plasma transfusion in SARS-CoV-2-infected patients.
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            Deployment of convalescent plasma for the prevention and treatment of COVID-19

            Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), has spurred a global health crisis. To date, there are no proven options for prophylaxis for those who have been exposed to SARS-CoV-2, nor therapy for those who develop COVID-19. Immune (i.e., "convalescent") plasma refers to plasma that is collected from individuals following resolution of infection and development of antibodies. Passive antibody administration through transfusion of convalescent plasma may offer the only short-term strategy for conferring immediate immunity to susceptible individuals. There are numerous examples in which convalescent plasma has been used successfully as postexposure prophylaxis and/or treatment of infectious diseases, including other outbreaks of coronaviruses (e.g., SARS-1, Middle East respiratory syndrome [MERS]). Convalescent plasma has also been used in the COVID-19 pandemic; limited data from China suggest clinical benefit, including radiological resolution, reduction in viral loads, and improved survival. Globally, blood centers have robust infrastructure for undertaking collections and constructing inventories of convalescent plasma to meet the growing demand. Nonetheless, there are nuanced challenges, both regulatory and logistical, spanning donor eligibility, donor recruitment, collections, and transfusion itself. Data from rigorously controlled clinical trials of convalescent plasma are also few, underscoring the need to evaluate its use objectively for a range of indications (e.g., prevention vs. treatment) and patient populations (e.g., age, comorbid disease). We provide an overview of convalescent plasma, including evidence of benefit, regulatory considerations, logistical work flow, and proposed clinical trials, as scale-up is brought underway to mobilize this critical resource.
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              Covid-19 and Kidney Transplantation

              To the Editor: Kidney-transplant recipients appear to be at particularly high risk for critical Covid-19 illness due to chronic immunosuppression and coexisting conditions. 1 At Montefiore Medical Center, we identified 36 consecutive adult kidney-transplant recipients who tested positive for Covid-19 between March 16 and April 1, 2020. A total of 26 recipients (72%) were male, and the median age was 60 years (range, 32 to 77). Fourteen recipients (39%) were black, and 15 recipients (42%) were Hispanic. Twenty-seven recipients (75%) had received a deceased-donor kidney; 34 recipients (94%) had hypertension, 25 (69%) had diabetes mellitus, 13 (36%) had a history of smoking tobacco or were current smokers, and 6 (17%) had heart disease. Thirty-five of the patients (97%) were receiving tacrolimus, 34 (94%) were receiving prednisone, and 31 (86%) were receiving mycophenolate mofetil or mycophenolic acid. The most common initial symptom was fever (in 21 patients [58%]), and diarrhea was observed in 8 patients (22%). Eight patients who were in stable condition without major respiratory symptoms (22%) were monitored at home, and 28 patients (78%) were admitted to the hospital. Twenty-seven of the hospitalized patients (96%) had radiographic findings that were consistent with viral pneumonia, and 11 (39%) received mechanical ventilation. Six patients (21%) received renal replacement therapy. At a median follow-up of 21 days (range, 14 to 28), 10 of the 36 kidney-transplant recipients (28%) and 7 of the 11 patients who were intubated (64%) had died. Two of the 8 patients who were monitored as outpatients died at home; both were recent kidney-transplant recipients who had received antithymocyte globulin within the previous 5 weeks (see the Supplementary Appendix, available with the full text of this article at NEJM.org). Table 1 summarizes the initial laboratory results in the 28 hospitalized patients. Twenty-two (79%) were lymphopenic, 12 (43%) had thrombocytopenia, 19 (68%) had low CD3 cell counts, 20 (71%) had low CD4 cell counts, and 8 (29%) had low CD8 cell counts. Inflammatory markers were measured, and 10 patients (36%) had ferritin levels higher than 900 ng per milliliter, 13 (46%) had C-reactive protein levels higher than 5 mg per deciliter, 12 (43%) had procalcitonin levels higher than 0.2 ng per milliliter, and 16 (57%) had d-dimer levels higher than 0.5 μg per milliliter. Although effective treatment of Covid-19 is currently unknown, 2 immunosuppressive management included withdrawal of an antimetabolite in 24 of 28 patients (86%). In addition, tacrolimus was withheld in 6 of the 28 severely ill patients (21%). Hydroxychloroquine was administered to 24 of these 28 patients (86%). Apixaban was administered to patients with d-dimer levels higher than 3.0 μg per milliliter. Six severely ill patients received the CCR5 inhibitor leronlimab (PRO 140, CytoDyn) on a compassionate-use basis, and 2 received the interleukin-6 receptor antagonist tocilizumab. Interleukin-6 levels were very elevated (range, 83 to 8175 pg per milliliter) when leronlimab was initiated (on day 0) in the 5 patients with elevated interleukin-6 levels; these levels decreased markedly 3 days later (range, 37 to 2022 pg per milliliter) (see Table S2 in the Supplementary Appendix). However, only the 1 patient who had the lowest interleukin-6 level (at 83 pg per milliliter) remained in stable condition without intubation. In conclusion, at our institution, kidney-transplant recipients with Covid-19 had less fever as an initial symptom, 3 lower CD3, CD4, and CD8 cell counts, 4 and more rapid clinical progression than persons with Covid-19 in the general population. The number of our patients with very low CD3, CD4, and CD8 cell counts indirectly supports the need to decrease doses of immunosuppressive agents in patients with Covid-19, especially in those who have recently received antithymocyte globulin, which decreases all T-cell subsets for many weeks. Our results show a very high early mortality among kidney-transplant recipients with Covid-19 — 28% at 3 weeks as compared with the reported 1% to 5% mortality among patients with Covid-19 in the general population who have undergone testing in the United States and the reported 8 to 15% mortality among patients with Covid-19 who are older than 70 years of age.
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                Author and article information

                Contributors
                Journal
                Pan Afr Med J
                Pan Afr Med J
                PAMJ
                The Pan African Medical Journal
                The African Field Epidemiology Network
                1937-8688
                16 March 2021
                2021
                : 38
                : 273
                Affiliations
                [1 ]Department of Internal Medicine, Erzurum Regional Training and Research Hospital, Health Sciences University, Erzurum, Turkey
                Author notes
                Corresponding author: Muharrem Bayrak, Department of Internal Medicine, Erzurum Regional Training and Research Hospital, Health Sciences University, Erzurum, Turkey. muhabayrak@ 123456hotmail.com
                Article
                PAMJ-38-273
                10.11604/pamj.2021.38.273.28577
                8179983
                2464a7c2-152c-48ae-a71f-e2844009e332
                Copyright: Muharrem Bayrak et al.

                The Pan African Medical Journal (ISSN: 1937-8688). This is an Open Access article distributed under the terms of the Creative Commons Attribution International 4.0 License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 February 2021
                : 02 March 2021
                Categories
                Case Report

                Medicine
                covid-19,renal transplantation,methylprednisolone,convalescent plasma,case report
                Medicine
                covid-19, renal transplantation, methylprednisolone, convalescent plasma, case report

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