SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3–11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

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...

A battery of drugs with antirheumatic properties was tested for effects on the progress of osteoarthritis induced by a lateral meniscectomy procedure in knee joint cartilage of rabbits. Oral administration of the potent glucocorticoids, paramethasone acetate or triamcinolone, resulted in dramatic inhibition of cartilage degeneration. Significant protection against development of osteoarthritic lesions was also observed in rabbits treated with pirprofen or CGS 5391B but not with 9 other nonsteroidal antiinflammatory drugs. A marked reduction in joint pathology was also observed in rabbits treated with tribenoside (a glucofuranoside derivative) and with tamoxifen (an anti‐estrogen). Slightly protective effects of borderline significance were observed with orgotein (a superoxide dismutase), gold sodium thiomalate, and D‐penicillamine. Chloroquine and calcitonin were without effect. Therapeutic effectiveness of drugs in this model of osteoarthritis cannot be explained on the basis of their antiinflammatory properties.

We have discussed previously the use of sequential measurements of serum C-reactive protein (CRP) and haptoglobin (Hp) and of the erythrocyte sedimentation rate (ESR) in the management of patients with rheumatoid arthritis (RA) and the desirability of developing drugs with the capacity for lowering values of these measurements (McConkey et al., 1972;McConkey et al., 1973;Constable et al., 1975;McConkey, 1976;Amos et al., 1977). The magnitude of the effect of a drug on serum CRP, Hp, and the ESR can be regarded as a measure of its efficacy in a particular sense. The information provides a guide to how well the disease rather than just symptoms is controlled. The purpose of the present investigation was to study and compare the effects of treatment with gold, dapsone, or prednisone. We describe a method of

A partial lateral meniscectomy procedure has been developed for the induction of a predictable and reproducible degenerative joint disease in knees of rabbits. The procedure adopted involves section of the fibular collateral and sesamoid ligaments and removal of 4-5 mm of the anterior lateral meniscus. In most experiments the animals are killed and tissues obtained for histologic examination at 6 weeks. Section of the ligaments alone (with or without penetration of the joint space) did not result in significant pathologic change. Significant degeneration was observed in tibia1 and femoral cartilage when the meniscus as well as the ligaments were cut, but the most extensive lesions were seen when a piece of the anterolateral meniscus was actually removed. These lesions included fibrillation, ulceration and erosion, "clone" and osteophyte formation, loss of chondrocytes, and loss of safraninophilic staining in the articular cartilage. The incidence and distribution of lesions with time following surgery were also investigated. Lesions were observed as early as 1-2 weeks post-surgery and increased in number and severity up to 12 weeks. A global scoring system has been devised to permit statistical comparisons of lesion incidence and severity in different groups of rabbits. This scoring system has enabled us to test drug efficacy in the rabbit lateral meniscectomy model of osteoarthritis.