Clinical application of and nursing practices for convalescent plasma transfusion in patients with COVID-19


 Background: This study aimed to examine the effect of convalescent plasma transfusion on patient with severe coronavirus disease ( COVID-19 ) and discussed the main nursing practices.
Methods: We retrospectively analyzed the clinical data of 21 patients with severe COVID-19 who had received convalescent plasma transfusion therapy between March 1 and April 1, 2020. The observation indicators included leukocyte, lymphocyte, C-reactive protein (CRP), interleukin-6 (IL-6), and viral antibody levels; test results from pharyngeal swabs; nucleic acid test results; chest CT results; and respiratory symptoms. Further, we summarized the nursing practices related to plasma transfusion.
Results: Neither death nor transfusion-related adverse reactions were observed in patients treated with convalescent plasma transfusion. Their antibody levels, especially IgG (P < 0.05), were increased to different levels, whereas the levels of inflammatory markers (CRP), white blood cells, and lymphocytes were significantly decreased (P < 0.05). Respiratory symptoms showed an improvement, and chest CT showed stable findings.
Conclusions: Convalescent plasma transfusion is safe and feasible. It can increase antibody levels, reduce inflammatory factor levels, improve white blood cell and lymphocyte counts, and improve respiratory symptoms in patients with severe COVID-19. Thus, plasma transfusion can be used as a new, effective COVID-19 treatment method that requires cooperation from nursing.


Background
Coronavirus disease 2019 , caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly around the world since December 2019, with high transmission rate and mortality. The clinical manifestations range from no symptoms to respiratory failure [1]. Current, there are no speci c effective antiviral treatments for COVID-19, limited to general supportive care, with provision of critical care. Therefore, as an unprecedented global public health crisis, safe and effective treatment is urgently needed.
Convalescent plasma treatment is the process of obtaining safe, high-titer neutralizing antibodies and infusing them into patients, which is done by collecting the plasma of patients under rehabilitation under strict preparation procedures. Convalescent blood products could be a valid option for the treatment of infectious diseases in conjunction with other drugs, or as the only therapy when a speci c treatment is not available [2]. Convalescent plasma transfusion, that is, passive antibody transfusion from a previous human survivor, used to be the only known effective treatment for Ebola infection [3]. Additionally, it has been used to treat Middle East respiratory syndrome (MERS) coronavirus in 2015, SARS-CoV, H5N1 avian in uenza, and H1N1 in uenza [4][5][6][7][8]. A study of 80 patients with SARS has reported that patients who received convalescent plasma had better outcomes than did those who did not receive convalescent plasma [9]. A meta-analysis study evaluated the clinical e cacy of convalescent plasma and other treatments on severe viral acute respiratory infections and showed that the mortality rate was signi cantly reduced with convalescent plasma treatment [10]. Recently, convalescent plasma has also been used in patients with COVID-19, but some study identi ed no signi cant differences in clinical status or overall mortality between patients treated with convalescent plasma and those who received placebo [1].
In this study, we evaluated the safety and e cacy of convalescent plasma infusion in the treatment of 21 patients with COVID-19, and summarized the nursing points.

Patients
From March 1 to April 1, 2020, total 21 patients with laboratory-con rmed COVID-19 were recruited, including 12 male and 9 female patients (average age 63.67 ± 12.82 years). All 21 patients had fever and/or respiratory symptoms at admission. Additionally, they had imaging features of COVID-19, and 7 of them had oxygenation index of less than 300 mmHg. These patients were diagnosed and classi ed into three clinical types according to the New Coronavirus Pneumonia Diagnosis and Treatment Program (7 th edition) published by the National Health Commission of China [11], including 10 patients with common type, 8 with severe type and 3 with critical type early stage. Additionally, among these patients, 12 patients had hypertension, coronary heart disease, diabetes or other underlying diseases, and 9 patients had no underlying diseases. The inclusion criteria were as follows: 1) positive nucleic acid test or clinical expert determination of the patient with viremia; 2) with common, severe or critical early stage disease with rapid disease progression; 3) patients who were evaluated by clinical specialists for the need of convalescent plasma treatment. This study was approved by the Ethics Committee of our institution and informed consent was obtained from each patient or candidate.

Intervention
The plasma containing speci c antibodies for COVID-19 were performed virus inactivation and multiple negative pathogens biological tests. The plasma infusion dose was determined by the clinical status, patient weight, etc. Accordingly, each received 1 or 2 consecutive transfusions of 100 to 500 mL of convalescent plasma (4-5 ml/kg). In addition to standard treatment, all patients allowed to receive general therapies including bed rest, intensive supportive treatment, close monitoring of vital signs, adequate energy intake, oxygen therapy, treating other underlying diseases, antiviral therapy (chloroquine phosphate 500 mg orally twice daily or abidore 200 mg orally 3 times daily (no more than 10 days)), and Chinese medicine decoction treatment.

Observation index
The average length of hospital stay, mortality rate, and incidence of adverse transfusion reactions of patients who underwent plasma transfusion were recorded. Blood samples were collected before and after plasma transfusion to measure white blood cells, lymphocytes, C-reactive protein (CRP), interleukin-6 (IL-6), viral antibodies, and so on. Simultaneously, nucleic acid assay of throat swabs, chest CT scans, and respiratory tract symptom assessments were conducted.

Informed consent
The purpose and risks of convalescent plasma transfusion were communicated with the patients and their families in detail. All patients provided consent in accordance with Informed Consent for Plasma Treatment in the Rehabilitation Period of New Coronary Pneumonia Patients. If the patient had no capacity for civil conduct or could not sign the consent form because of other circumstances, the treating physician would communicate with the family over the telephone and obtain detailed information, such as the family name, relationship, and main opinions, while recording the call.

Preparation before infusion
According to indications, we carefully screened the patients and completed preparations for blood group, blood group antibody, infectious disease, viral antibody IgM and IgG, and nucleic acid testing one day in advance. Infusion was performed according to the principle of cross-matching blood secondary compatibility.

Application
The doctor in charge of the bed lled out the "Application Form for Plasma in the Rehabilitation Period of New Coronary Pneumonia Rehabilitation Persons." Following a discussion by the expert team of the department, the paper application form was submitted to the laboratory by the team leader, and the relevant information was reported to the hospital for review.

Plasma distribution
After examination and approval by the hospital, the laboratory held the "Notice of Blood Dispensing for Plasma Therapy in Rehabilitation of New Coronary Pneumonia", applied to the blood center for the recovery period plasma in a clean ambulance, and distributed it to clinical departments in strict accordance with the relevant system of blood distribution management.

Control of the infusion process
(1) Checking the system accurately Before infusion, 2 medical staff members checked the patient's bed number, name, hospitalization number, blood type, blood volume, blood bag number, blood expiration date, blood appearance quality, blood transfusion device, and delivery results of the cross-matching blood test. Before transfusion, antiallergic drugs, such as dexamethasone (5-10 mg push), promethazine (25 mg intramuscular injection), and so on, were given according to doctor's orders.
(2) Speed control During the rst 15 minutes, slow infusion with no more than 20 drops/min was performed. If there was no discomfort, speed was adjusted to normal rate. The infusion process was closely observed. If an adverse reaction occurred, infusion was suspended.

(3) Infusion time and volume
Administration of the infusion was divided into 1 or 2 times. If the infusion was divided into 2 times, the interval time was >15 min. The number of plasma infusions was not more than 2, and the interval between two infusion was not less than 2 days. For adults and children weighing less than 45 kg, the total infusion dose was calculated at 4-5 mL/kg.

(4) Observation of adverse reactions
Before, during, and after plasma transfusion, any potential adverse reactions of blood transfusion were closely monitored, promptly handled, and recorded in detail.

(5) Evaluation
After treatment, the doctor's instructions for close monitoring were followed, the effectiveness of the intervention was evaluated, and the changes in the corresponding review indicators were recorded in a timely manner.

Improvement of respiratory symptoms by convalescent plasma transfusion
The average length of hospital stay of the patients who received plasma transfusion was 22.05 ± 12.45 days. None of the patients died, and no adverse reaction occurred during the transfusion. Four of the cases (19%) were positive for nucleic acid before plasma transfusion but turned negative after 2, 3, 4, and 8 days with transfusion, respectively; The other 17 cases were negative for nucleic acid before plasma transfusion. Moreover, chest CT showed a decrease in the area of infected lesions in 17 of the cases (81%), and reports prompted improvement or obvious improvement; The other 4 cases had higher absorption or remained stable compared with pre-transfusion (Table S1). After 2 to 5 days of transfusion, 16 cases showed obvious improvement on respiratory symptoms including cough, wheezing, chest discomfort and so on; the other 5 had no obvious respiratory symptoms. In addition, PO 2 /FiO 2 in all patients was over 300 before discharge.

Convalescent plasma transfusion-induced increase in antibody levels
After convalescent plasma transfusion, the serum SARS-CoV-2 IgG and IgM in most patients increased to varying degrees ( Figure 1). Among them, IgG showed a statistically signi cant change (P < 0.05), whereas IgM exhibited no signi cant difference (P > 0.1).

Convalescent plasma transfusion-induced decrease in in ammation
Convalescent plasma transfusion dramatically decreased the level of in ammatory factor (CRP) and improved the levels of white blood cells and lymphocytes in patients (P < 0.05) ( Table 1 and Table S2). This study was approved by the Ethics Committee of our institution (Ethics Approval No. HSSLL015). Early in the epidemic of coronavirus disease 2019, the Chinese government recruited a proportion of healthcare workers to support the designated hospital (Huoshenshan Hospital) in Wuhan, China. That hospital has been disbanded and all the documents has been sealed, so we cannot provide the copy of the ethics committee approval.

Consent for publication
Not applicable.

Availability of data and materials
All data generated or analysed during this study are included in this published article. Tables   Table 1 Comparison of laboratory test results before and after Figure 1 IgG and IgM levels. Before and after convalescent plasma transfusion, the levels of SARS-CoV-2 IgG (A) and IgM (B) in serum were detected by Elisa.

Supplementary Files
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