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1.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.06.24.21259079

ABSTRACT

Background: One of the most questioned issues about SARS-CoV2 immunity is how long does it last. Whether lasting differences exist between infection and vaccination boosted immunity is yet to be known. The answer to this question will determine key issues such as the reliability of individual and herd immunity or the need of sanitary restrictions or periodical revaccination. The aim of this study was to determine how long total anti SARS-CoV2 antibodies due to past infection persist in peripheral blood and whether sex, age or haematological features can influence their lasting. Material and Methods: A total of 2432 donations SARS-CoV-2 from 662 repeat donors from April 2020 to February 2021 were analysed. Donors were 69.7% males and their average age was 46. An automated chemilumiscence immunoassay for total antibodies recognizing N protein of SARS-CoV-2 in human serum and plasma was performed. Results and discussion: In 97.6% donors with follow-up, anti SARS-CoV-2 protein N total antibodies remained positive up to 46 weeks after first positive determination. Blood group was not related to antibody waning. Lower lymphocyte counts and higher neutrophils and as well higher seric IgA would help predict future negativization of antibodies. The vast majority of donors keep their total immunoglobulins anti SARS-CoV-2 positive for longer than 10 months. Ageing might have a protective effect against antibody waning but, given the small number of cases that become negative, more studies, or larger cohorts would be needed to confirm these facts.

2.
medrxiv; 2021.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2021.04.28.21256242

ABSTRACT

Background and objectivesCOVID-19 can either cause death or go unnoticed but antibodies will remain protecting us of SARS-CoV-2 reinfection for an uncertain time and to an uncertain extent. Our aim was to describe seroprevalence evolution from summer 2019 to autumn 2020 in Spain and to describe its relationship with age, blood group and haematological parameters. Materials and methodsSera and plasma from historical donation archives excluding convalescent were randomized and a total of 12,313 donations tested by a Chemiluminiscent analysis for anti SARS-CoV-2 N protein total immunoglobulins. Blood donors were 60.9% males, average age 46+/-13. Sex, age, blood group, blood cell counts and percentages and immunoglobulin concentrations were extracted from electronic recordings. ResultsA seroprevalence of 6.7% in blood donors was found by the end of the first wave. No differences by sex, age or blood group were found regarding antibodies. Leukocyte count (p=0.026), haematocrit (p<0.001) and haemoglobin (p<0.001) were lower in positive donations than in negative ones. Sex differences were present in neutrophils, leukocytes, haemoglobin and haematocrit as related to SARS-CoV-2 antibodies. ConclusionsSeroprevalence due to asymptomatic cases would resemble that of global population. Sex and age would not affect COVID-19 susceptibility but its severity. Gender differences related to COVID-19 in leukocytes, haemoglobin and haematocrit would be present in asymptomatic individuals. Further studies are needed to confirm these gender differences as they can help better understand the immune response to COVID-19, its pathogenesis and prognosis.


Subject(s)
COVID-19
3.
medrxiv; 2020.
Preprint in English | medRxiv | ID: ppzbmed-10.1101.2020.08.26.20182444

ABSTRACT

Background: Passive immunotherapy with convalescent plasma (CP) is a potential treatment for COVID-19 for which evidence from controlled clinical trials is lacking. Methods: We conducted a multi-center, randomized clinical trial in patients hospitalized for COVID-19. All patients received standard of care treatment, including off-label use of marketed medicines, and were randomized 1:1 to receive one dose (250-300 mL) of CP from donors with IgG anti-SARS-CoV-2. The primary endpoint was the proportion of patients in categories 5, 6 or 7 of the COVID-19 ordinal scale at day 15. Results: The trial was stopped after first interim analysis due to the fall in recruitment related to pandemic control. With 81 patients randomized, there were no patients progressing to mechanical ventilation or death among the 38 patients assigned to receive plasma (0%) versus 6 out of 43 patients (14%) progressing in control arm. Mortality rates were 0% vs 9.3% at days 15 and 29 for the active and control groups, respectively (log-rank p=0.056). No significant differences were found in secondary endpoints. At inclusion, patients had a median time of 8 days (IQR, 6-9) of symptoms and 49,4% of them were positive for anti-SARS-CoV-2 IgG antibodies. Conclusions: Convalescent plasma could be superior to standard of care in avoiding progression to mechanical ventilation or death in hospitalized patients with COVID-19. The strong dependence of results on a limited number of events in the control group prevents drawing firm conclusions about CP efficacy from this trial. (Funded by Instituto de Salud Carlos III; NCT04345523).


Subject(s)
COVID-19 , Death
4.
biorxiv; 2020.
Preprint in English | bioRxiv | ID: ppzbmed-10.1101.2020.08.31.274704

ABSTRACT

SARS-CoV-2 enters cells via ACE-2, which binds the spike protein with moderate affinity. Despite a constant background mutational rate, the virus must retain binding with ACE2 for infectivity, providing a conserved constraint for SARS-CoV-2 inhibitors. To prevent mutational escape of SARS-CoV-2 and to prepare for future related coronavirus outbreaks, we engineered a de novo trimeric ACE2 (T-ACE2) protein scaffold that binds the trimeric spike protein with extremely high affinity (KD < 1 pM), while retaining ACE2 native sequence. T-ACE2 potently inhibits all tested pseudotyped viruses including SARS-CoV-2, SARS-CoV, eight naturally occurring SARS-CoV-2 mutants, two SARSr-CoVs as well as authentic SARS-CoV-2. The cryo-EM structure reveals that T-ACE2 can induce the transit of spike protein to "three-up" RBD conformation upon binding. T-ACE2 thus represents a promising class of broadly neutralizing proteins against SARS-CoVs and mutants.


Subject(s)
Severe Acute Respiratory Syndrome
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