2. Material and method
2.1 Determination of the study group
2.2 Study population
2.3 Selection of peptide plasma donor candidates
- 1.Age 50 years and over (Days over 50 and not over 61 years old).
- 2.In case of female gender, no pregnancy history (birth/miscarriage/abortion).
- 4.Having a chronic disease (Hypertension, Diabetes, Heart disease, Asthma, COPD).
- 5.Using ACE inhibitor or ARB antihypertensive medication.
- 6.Not in an active period of any kind of chronic disease.
- 1.Individuals who have COPD or asthma but have an attack at the time of donation.
- 2.Cancer patients, diabetes patients using insulin.
- 3.Those with organ failure (such as cirrhosis, dialysis patient).
- 4.People who have been infected with COVID-19.
- 5.People who have received blood transfusions cannot be accepted as a donor.
- 1.Appendix 1 Inquiry Form will be fulfilled for Peptide Plasma Volunteer Donors.
- 2.The peptide plasma to be given to the patient must be compatible with the patient's ABO blood group (AB blood group is the general donor in plasma transfusion). Rh blood group can be ignored.
- 3.They will be checked for COVID-19 IgG Negativeness to make sure they don't have the disease.
- 4.The donor will be asked to fulfill in the Appendix2-Plasma Volunteer Donor Consent Form stating that he has donated plasma on a voluntary basis.
- 5.Microbiological screening tests of donor candidates (serologically HBsAg, anti-HCV, anti-HIV 1–2 and anti-syphilis Ab tests and, if possible, HBV-DNA, HCV-RNA, HIV 1,2-RNA, Nucleic tests in accordance with national legislation Acid Scan (NAT) tests) should be negative.
- 6.1 ml of the volunteer's plasma will be taken by the researcher, and blood will be taken into an Eppendorf tube to determine the serum Angiotensin (1−7) level and stored at − 80 degrees.
- 7.Peptide plasma donation can be made up to 3 times in a month, once every 7–10 days, provided that the date of the first donation is accepted as the start date.
- 8.Plasma will be separated from the volunteer by apheresis.
- 9.Preferred delivery/transfusion timing: Plasma is given within 6 h of collection. If it cannot be given within 6 h after collection, it will be frozen and stored.
2.4 Peptide plasma clinical use criteria
- 1.Hospitalization in the COVID-19 inpatient clinic of our hospital.
- 2.Compatibility of CT findings with COVID-19 and presence of bilateral diffuse involvement.
- 3.Oxygen saturation of 93% or less despite nasal oxygen support of 5 liters/minute or more
- 4.Patients with expected rapid clinical progression, with poor prognostic parameters (lymphopenia, thrombocytopenia, CRP, ferritin, LDH, D-dimer elevation)
- 5.Progression despite standard treatment in the national guideline
2.5 Peptide plasma transfusion application
- 1.For each patient, 400ml/day of ABO-compatible peptid plasma was administered for 2 days (without interruption) on the same day it was obtained from the donor.
- 2.The patient's inflammation markers and changes in lung imaging were monitored and recorded after 48h of transfusion.
- 3.Since the aim is to increase the patient's serum Ang-(1−7) level, plasma infusion should not be interrupted. Therefore, infusions should be started after the adequate plasma is supplied.
2.6 Plasma peptide level measurement
2.7 Statistical analysis
|Case number||Age (year)||Gender||Smoking||Other diseases||Symptom||Blood pressure on admission (mmHg)||PCR|
|1||57.4||M||+||Diabetes + Asthma + Sleep apnea||Respiratory distress||130/80||Multifocal, bilateral ground glass||negative|
|2||54.3||M||–||Hypertension||Respiratory distress||160/100||Multifocal, bilateral ground glass and opasity||positive|
|3||85.7||F||+||Hypertension||Fever, respiratory distress, muscle pain||120/80||Multifocal, bilateral ground glass and opasity||positive|
|4||78.2||M||–||–||Respiratory distress, muscle pain||130/80||Multifocal, bilateral ground glass||positive|
|5||51||F||–||Diabetes and Hypertension||Fever, respiratory distress, headache, muscle pain||130/85||Multifocal, bilateral ground glass and opasity||positive|
|6||75.6||F||–||–||Fever, respiratory distress, fatigue||118/68||Multifocal, bilateral ground glass and opasity||positive|
|7||54.4||M||+||Sleep apnea||Fever, respiratory distress, insomnia, fatigue, back pain, head ache, muscle pain||130/80||Multifocal, bilateral ground glass and opasity||positive|
|8||52.2||M||–||–||Respiratory distress, fatigue||145/80||Multifocal, bilateral ground glass and opasity||positive|
|9||36.6||M||–||–||Fever, respiratory distress, fatigue||110/60||Multifocal, bilateral ground glass and opasity||positive|
|Donor number||Gender||Age||Smoking||Smoking Duration (years)||Co-Morbidities||Existence of Co-Morbidities (years)||Medications||Duration of using blood pressure medication (years)|
|4||M||55||0||Prostate cancer||25||ACE Inhibitor||25|
|5||F||55||1||40||Coronary artery disease||6||ACE Inhibitor||6|
|6||M||50||1||10||Coronary artery disease||5||ACE Inhibitor||4|
|Number||Day of hospitalization||Plasma therapy||Saturation||Need for Oxygen||Blood Pressure||Lung stage||Blood Glucose Level||CRP||LDH||Ferritin||D-Dimer||Lymphocyte||Platelet count|
|Data for days before plasma||Plasma administration day||72 h after plasma|
(min: 80- max:99)
High flow oxygen
(min:84- maks: 99)
|Systolic blood pressure||118|
(min:76- max: 160)
|Diastolic blood pressure||70|
(min:40- max: 100)
(min:60- max: 97)
(min:54- max: 97)
(min:75- max: 286)
(min:111- max: 193)
(min:79- max: 221)
(min:17- max: 82)
(min:15- max: 80)
(min:17- max: 82)
(min:0.43- max: 1.2)
(min:11- max: 55)
(min:34- max: 135)
(min:26- max: 101)
(min:13- max: 46)
(min:27- max: 72)
(min:31- max: 104)
(min:18- max: 132)
(min:20- max: 80)
(min:19- max: 202)
(min:63- max: 105)
(min:61- max: 85)
(min:48- max: 113)
(min:203- max: 485)
(min:168- max: 300)
(min:222- max: 530)
(min:38- max: 799)
(min:32- max: 63)
(min:35- max: 156)
(min:14- max: 130)
(min:49- max: 137)
(min:34- max: 115)
(min:4.6- max: 77)
(min:20- max: 114)
(min:19.7- max: 76)
(min:128- max: 140)
(min:131- max: 138)
(min:134- max: 142)
(min:3- max: 5.8)
(min:4- max: 4.8)
(min:3- max: 4.8)
(min:90- max: 108)
(min:91- max: 93)
(min:93- max: 106)
(min:17- max: 355)
(min:6.3- max: 223)
(min:7.1- max: 97)
(min:8.3- max: 2993)
(min:364- max: 3531)
(min:227- max: 1707)
- ●Case 1 was given peptide plasma on the 10th day, while the saturation was < 93% under oxygen support from the 9th day. On the day the plasma was given, his saturation increased to 97%, eliminating the need for oxygen support. This patient was discharged on the 13th day.
- ●Case 2 was admitted to the hospital with 80% saturation, oxygen support was started, and he was planned to be follow-up in the intensive care unit. On the second day, peptide plasma was obtained and administered. His saturation increased to 90%. Oxygen support did not end in our 72-hour follow-up after plasma. However, the patient was discharged on the 11th day without the need for intensive care.
- ●Case 3 had a saturation of 93% on the 14th day of hospitalization, and peptide plasma therapy was administered when oxygen support was initiated. With the treatment, the saturation increased and the need for oxygen disappeared. However, on the 16th day, their re-saturation dropped to 90%. Oxygen support was re-started. Our patient was finally discharged on the 18th day without oxygen support.
- ●Case 4 is being followed up with oxygen support, and peptide plasma treatment was applied on the day when the saturation decreased to 91%. After peptide plasma treatment, the need for oxygen support disappeared. He was discharged on the 14th day of his hospitalization.
- ●While case 5 was receiving oxygen support, peptide plasma treatment was applied, with a saturation of 91% on the 5th day. Saturation increased with treatment. On the eighth day, the need for oxygen disappeared.
- ●While case 6 was being followed in oxygen support, peptide plasma therapy was applied when saturation was measured as 93% on the 4th day. However, a similar response was not obtained in this case. Oxygen requirement increased gradually and, he died on the 6th day after the intensive care process (Table 5).Table 5Recovery status of the cases.
Patient Number Hospital stay (days) Recovery/Final status 1 13 Discharge 2 11 Discharge 3 18 Discharge 4 14 Discharge 5 12 Discharge 6 6 Exitus 7 30 Discharge 8 11 Discharge 9 13 Discharge
- ●While patient number 7 was being followed up with oxygen support, peptide plasma therapy was administered when the saturation dropped below 90%. Response to treatment was obtained, saturation increased. The discharge took place on the 30th day.
- ●While case 8 was being followed up with oxygen support, peptide plasma therapy was applied when the saturation fell below 90% on the 4th day. Response to treatment was obtained, saturation increased. The discharge occurred on the 11th day.
- ●On the 7th day of follow-up case 9, peptide plasma was administered when the saturation was 92 mmHg despite oxygen support. On the day of treatment, the saturation increased to 95 mmHg. The patient was discharged on the 13th day.
|Plasma Angiotensin (1–7) level|
|Cardiac fibrosis, hypertrophy, Atrial Arrhythmia|
|Increased peripheral vascular resistance|
|Disruption of baroreceptor sensitivity|
|Insulin resistance, dyslipidemia|
|Weakening of blood-brain barrier integrity, learning, disability, amnesia, ischaemic stroke|
|Decrease in spermatogenesis and ovulationDecreased sexual steroids synthesis|
|Increase in inflammation and oxidative stress, Increased tendency to thrombosis, Endotelitis|
|Facilitating the formation and spread of cancer|
|Fibrosis and inflammation in organs such as lungs, liver and kidney.|
|Chronic disease||Chronic disease and ACE inhibitor/ARB use||COVID with chronic disease||Healthy Individuals||Smoker||Pregnancy (2–3.trimaster)||Preeclampsia|
CRediT authorship contribution statement
Conflict of Interest Statement
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