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The BNT162b2 vaccine is highly effective against COVID-19 infection and was delivered with a 3-week time interval in registration studies1. However, many countries extended this interval to accelerate population coverage with a single vaccine. It is not known how immune responses are influenced by delaying the second dose. We provide the assessment of immune responses in the first 14 weeks after standard or extended-interval BNT162b2 vaccination and show that delaying the second dose strongly boosts the peak antibody response by 3.5-fold in older people. This enhanced antibody response may offer a longer period of clinical protection and delay the need for booster vaccination. In contrast, peak cellular-specific responses were the strongest in those vaccinated on a standard 3-week vaccine interval. As such, the timing of the second dose has a marked influence on the kinetics and magnitude of the adaptive immune response after mRNA vaccination in older people.

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Background Residents of long-term care facilities (LTCFs) have been prioritised for COVID-19 vaccination because of the high COVID-19 mortality in this population. Several countries have implemented an extended interval of up to 12 weeks between the first and second vaccine doses to increase population coverage of single-dose vaccination. We aimed to assess the magnitude and quality of adaptive immune responses following a single dose of COVID-19 vaccine in LTCF residents and staff. MethodsFrom the LTCFs participating in the ongoing VIVALDI study (ISRCTN14447421), staff and residents who had received a first dose of COVID-19 vaccine (BNT162b2 [tozinameran] or ChAdOx1 nCoV-19), had pre-vaccination and post-vaccination blood samples (collected between Dec 11, 2020, and Feb 16, 2021), and could be linked to a pseudoidentifier in the COVID-19 Data Store were included in our cohort. Past infection with SARS-CoV-2 was defined on the basis of nucleocapsid-specific IgG antibodies being detected through a semiquantitative immunoassay, and participants who tested positive on this assay after but not before vaccination were excluded from the study. Processed blood samples were assessed for spike-specific immune responses, including spike-specific IgG antibody titres, T-cell responses to spike protein peptide mixes, and inhibition of ACE2 binding by spike protein from four variants of SARS-CoV-2 (the original strain as well as the B.1.1.7, B.1.351, and P.1 variants). Responses before and after vaccination were compared on the basis of age, previous infection status, role (staff or resident), and time since vaccination. Findings Our cohort comprised 124 participants from 14 LTCFs: 89 (72%) staff (median age 48 years [IQR 35•5-56]) and 35 (28%) residents (87 years [77-90]). Blood samples were collected a median 40 days (IQR 25-47; range 6-52) after vaccination. 30 (24%) participants (18 [20%] staff and 12 [34%] residents) had serological evidence of previous SARS-CoV-2 infection. All participants with previous infection had high antibody titres following vaccination that were independent of age (r s =0•076, p=0•70). In participants without evidence of previous infection, titres were negatively correlated with age (r s =-0•434, p<0•0001) and were 8•2-times lower in residents than in staff. This effect appeared to result from a kinetic delay antibody generation in older infection-naive participants, with the negative age correlation disappearing only in samples taken more than 42 days post-vaccination (r s =-0•207, p=0•20; n=40), in contrast to samples taken after 0-21 days (r s =-0•774, p=0•0043; n=12) or 22-42 days (r s =-0•437, p=0•0034; n=43). Spike-specific cellular responses were similar between older and younger participants. In infection-naive participants, antibody inhibition of ACE2 binding by spike protein from the original SARS-CoV-2 strain was negatively correlated with age (r s =-0•439, p<0•0001), and was significantly lower against spike protein from the B.1.351 variant (median inhibition 31% [14-100], p=0•010) an...

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SUMMARYSickle trait is the commonest of the sickle haemoglo binopathies and affects approximately 9% of the Afro-Caribbean population of North America. ] Traditionally the condition was considered to be benign, important only for its genetic implications, 2 , 3 but some authors have challenged this viewpoint. Spontaneous vitreous haemorrhage, 3 , 4 proliferative retinopathr and other ocular lesions have been described, albeit in the presence of some precipitat ing factor.Factors known to enhance sickling of red blood cells, thereby increasing the risk of vascular throm bosis, include hypoxia, dehydration, acidosis, hyper viscosity and the percentage of abnormal haemoglobin.6 The combination of sickle trait and a significant degree of one or more of these factors may provoke sickle retinopathy. Three cases are reported to emphasise the importance of considering sickle trait as relevant to the management of eye disease in at-risk patients. presented to the eye casualty having been hit in the left eye by a paper pellet. On examination the vision was right 6/5 and left 6/18. On the left side a 5 mm hyphaema was present, the pupil was round and reactive and the intraocular pressure (lOP) was 18 mmHg. Dilated funduscopy was normal. The follow ing day the hyphaema had reduced in size but the lOP had risen to 38 mmHg, hence topical and oral ocular antihypertensive agents were introduced. Haemoglobin (Hb) electrophoresis revealed AS sickle trait with an HbS concentration of 38.3%. The next day the lOP had risen to 53 mmHg and oral glycerol was added to the regime. There was good response to this treatment, with the lOP returning to normal and gradual resolution of the hyphaema. Gonioscopy confirmed angle recession nasally.Six days after admission the patient was noted to have scattered preretinal and sub hyaloid haemor rhages in the temporal mid-periphery, but no retinal tears were identified. After 14 days the visual acuity was 6/6-3, the eye was quiet with no hyphaema and the rop was 13 mmHg. The haemorrhages in the mid-periphery remained and occluded vessels invol ving almost all of the peripheral retina were seen (Fig. 1). Six weeks after the incident the haemor rhages had resolved but there was no change in the appearance of the peripheral vasculature. A fluor escein angiogram (Fig. 2) showed extensive periph eral occlusion but no neovascularisation.The other fundus is normal and the lOP has remained at 12-15 mmHg on no treatment. Case 2A 59-year-old Jamaican woman was referred from the diabetic clinic because of reduced visual acuity and the finding of background diabetic retinopathy. She had been an insulin-dependent diabetic for 30 years, hypertension had been diagnosed 4 years previously and this was well controlled on nifedipine and a diuretic. She did not smoke. Visual acuity was Eye (1995) 9,589-593