key: cord-0749138-t0uzhdcw
authors: Muttamba, W.; Lusiba, J.; Namakula, O. L.; Kibwika, P. B.; Ssali, F.; Ddungu, H.; Mugenyi, L.; Kiwanuka, N.; Sekibira, R.; Kityo, C.; Kyeyune, D.; Acana, S.; Musinguzi, A.; Masasi, A.; Byamugisha, J.; Mpanju, D.; Musoki, W. J.; Tukamuhebwa, H. A.; Nakwagala, F.; Bagaya, B. S.; Kayongo, A.; Kimuli, I.; Nantanda, R.; Katagira, W.; Buregyeya, E.; Byanyima, R.; Byarugaba, B.; Siddharthan, T.; Mwebesa, H.; Charles, O.; Joloba, M. L.; Bazeyo, W.; Kirenga, B.
title: Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda
date: 2020-11-03
journal: nan
DOI: 10.1101/2020.10.29.20222067
sha: a13ab4f625fccb681a11aadfb2d3cbf5880e258a
doc_id: 749138
cord_uid: t0uzhdcw

Introduction Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda. Methods In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors. Results 192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant. Conclusion CCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.

Evidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of 31 COVID-19 is increasingly emerging. However, very few African countries have undertaken 32 the collection and processing of CCP. The aim of this study was to assess the feasibility of 33 collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for 34 treatment of COVID-19 in Uganda.

In a cross-sectional study, persons with documented evidence of recovery from COVID-19 in 37 Uganda were contacted and screened for blood donation via telephone calls. Those found 38 eligible were asked to come to the blood donation centre for further screening and consent.

Whole blood collection was undertaken from which plasma was processed. Plasma was 40 tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers.

SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors.

192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 44 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 45 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma 46 in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack 47 of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and 48 females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for 49 different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 50 samples tested. Age greater than 46 years and female gender were associated with higher 51 titers though not statistically significant. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020.

There have been over 41 million cases of COVID-19 reported, and more than one million 58 deaths recorded (1). In Uganda, the first confirmed case of COVID-19 was reported on 21 st 59 March 2020 (2). Up till mid-May, the local COVID-19 epidemic spread at a slow pace and 60 mainly comprised of imported cases, majority of whom were asymptomatic. There were limited 61 foci of transmission with no evidence of community transmission (2). From mid-May to early 62 August, the local epidemic progressed to more foci and clusters of transmission. However, 63 starting from mid-August, there has been a rapid rise in the number of cases detected daily 64 and rapid progression to community transmission and increasing mortality. As of 5 th October 65 2020, up to 8,808 cases have been recorded with 81 deaths reported (3).

Control of COVID-19 in Uganda has been mainly through the non-pharmacologic measures 68 adopted from the recommendations of the World Health Organization (WHO). These 69 measures include use of face masks, social distancing and hand washing or sanitization using 70 alcohol containing sanitizers (4) . With no vaccines for COVID-19 available, several 71 repurposed and new drugs have been reported in compassionate use and small trials with 72 mixed benefit (5).

Evidence is emerging to support the use of COVID-19 convalescent plasma (CCP) for 75 treatment of COVID-19 especially among patients with severe and critical forms of disease 76 (6-10). Administration of CCP has been found to be safe and associated with clinical, 77 radiological and laboratory improvements as well as reduction in mortality (6, (11) (12) (13) (14) .

However, some studies found no benefit of CCP with regard to reducing mortality and or length 79 of hospital stay, improving the day 15 disease free severity or shortening the time to clinical 80 improvement(15,16). One study by Li et al was terminated early due to inability to reach the 81 targeted sample size. Given the mixed and inconsistent nature of findings of CCP use , there 82 is need for more rigorous studies to assess the efficacy of CCP in treatment of COVID 19. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222067 doi: medRxiv preprint 6 a hemochromax machine. Up to 450mls of whole blood was collected in a quadruple bag using 140 an automated bio mixer and transported to the blood bank in a cool box at 2-10 o C within 8 hrs 141 of collection. Donors were requested to return to the donation centre for their blood grouping 142 results. At this visit, those that had TTIs were counselled and linked to care.

Plasma separation and storage 145

The LUXOmatic V2 blood separation device (19) Blood grouping and pretesting 158

The Immucor blood grouping Galileo system was used to perform ABO and Rh blood grouping is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222067 doi: medRxiv preprint 7

We collected blood samples, processed them and bio banked them for future use. Samples is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222067 doi: medRxiv preprint 11 241 

It may additionally be due to younger demographics in the present study.

Donor eligibility and recruitment are an integral part of a successful CCP collection program.

We instituted an eligibility criteria as has been recommended previously ( is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. ; https://doi.org/10.1101 https://doi.org/10. /2020 a trained psychologist administered a pre-screening questionnaire by telephone, asking for 263 obvious morbid conditions like HIV, Hepatitis, Hypertension, Diabetes, Syphilis among others.

In this study, 12.8% of the recovered individuals screened and found eligible to donate opted 266 out for various reasons including stigma. Stigma has previously been identified to affect 267 treatment seeking and also affect the recovered individuals (25-27). 

This study will inform an ongoing clinical trial assessing the safety and efficacy of CCP. To be 280 able to execute this, antibody titer levels will be key. Analysis on 72 donors revealed they all 281 had sufficient antibody titers in excess of 1:320, consistent with findings from a pilot program 

The 28 day period of convalescence has been associated with a high antibody level (29).

Specimen biobanking is critical in pandemic response, and biospecimen issues have long 289 been appreciated in emergency infectious disease control (30). In this feasibility study, we 290 . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222067 doi: medRxiv preprint 13 have been able to collect, process and store samples from recovered COVID 19 individuals 291 for future research. We shall be able to link this to clinical data and answer any other emerging 292 biomedical questions including monoclonal antibody manufacture.

Despite demonstrable feasibility of the collection and processing of CCP, the study had 296 limitations including inability to do apheresis as had originally been planned. This would have 297 allowed us to do more frequent donations from the same donors. We were unable to collect 298 all the needed data from the participants who didn't donate plasma. This would have given us 299 an opportunity to compare the successful donors and the those that were screened out. We 300 were also unable to do pathogen inactivation as is usually recommended for CCP. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. ; https://doi.org/10.1101/2020.10.29.20222067 doi: medRxiv preprint 372 . CC-BY-NC-ND 4.0 International license It is made available under a perpetuity.

is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprint

The copyright holder for this this version posted November 3, 2020. ; https://doi.org/10. 1101 

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is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted November 3, 2020. is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted November 3, 2020. ; https://doi.org/10.1101 https://doi.org/10. /2020 is the author/funder, who has granted medRxiv a license to display the preprint in (which was not certified by peer review) preprintThe copyright holder for this this version posted November 3, 2020. ; https://doi.org/10. 1101