Effectiveness of COVID-19 vaccines against SARS-CoV-2 infection with the Delta (B.1.617.2) variant: second interim results of a living systematic review and meta-analysis, 1 January to 25 August 2021

The Delta variant has become the dominant strain of SARS-CoV-2. We summarised the evidence on COVID-19 vaccine effectiveness (VE) identified in 17 studies that investigated VE against different endpoints. Pooled VE was 63.1% (95% confidence interval (CI): 40.9–76.9) against asymptomatic infection, 75.7% (95% CI: 69.3–80.8) against symptomatic infection and 90.9% (95% CI: 84.5–94.7) against hospitalisation. Compared with the Alpha variant, VE against mild outcomes was reduced by 10–20%, but fully maintained against severe COVID-19.     

Acute onset supraclavicular lymphadenopathy coinciding with intramuscular mRNA vaccination against COVID-19 may be related to vaccine injection technique,Spain, January and February 2021

Monitoring adverse reactions following immunisation is essential, particularly for new vaccines such as those against COVID-19. We describe 20 cases of acute onset of a single supraclavicular lymphadenopathy manifesting between 24 h and 9 days after ipsilateral intramuscular administration of an mRNA-based COVID-19 vaccine, referred to our WHO Collaborating Centre for Vaccine Safety. Our results indicate that the swelling of supraclavicular lymph nodes following immunisation may constitute a benign and self-limited condition, related to a higher than recommended injection site.     

mRNA vaccine effectiveness against COVID-19-related hospitalisations and deaths in older adults: a cohort study based on data linkage of national health registries in Portugal,February to August 2021

Through deterministic data linkage of health registries, mRNA vaccine effectiveness (VE) against COVID-19-related hospitalisations and deaths was measured in 1,880,351 older adults. VE against hospitalisations was 94% (95% confidence interval (CI): 88–97) and 82% (95% CI: 72–89) for those 65–79 and ≥ 80 years old, with no evidence of waning 98 days after dose two. VE against mortality was 96% (95% CI: 92–98) and 81% (95% CI: 74–87) in these two age groups.     

Vaccine effectiveness against infection with the Delta (B.1.617.2) variant,Norway, April to August 2021

Some variants of SARS-CoV-2 are associated with increased transmissibility, increased disease severity or decreased vaccine effectiveness (VE). In this population-based cohort study (n = 4,204,859), the Delta variant was identified in 5,430 (0.13%) individuals, of whom 84 were admitted to hospital. VE against laboratory confirmed infection with the Delta variant was 22.4% among partly vaccinated (95% confidence interval (CI): 17.0−27.4) and 64.6% (95% CI: 60.6−68.2) among fully vaccinated individuals, compared with 54.5% (95% CI: 50.4−58.3) and 84.4% (95%CI: 81.8−86.5) against the Alpha variant.     

Assessing the effect of non-pharmaceutical interventions on COVID-19 transmission in Spain, 30 August 2020 to 31 January 2021

BackgroundAfter a national lockdown during the first wave of the COVID-19 pandemic in Spain, regional governments implemented different non-pharmaceutical interventions (NPIs) during the second wave.AimTo analyse which implemented NPIs significantly impacted effective reproduction number (R_t) in seven Spanish provinces during 30 August 2020–31 January 2021.MethodsWe coded each NPI and levels of stringency with a ‘severity index’ (SI) and computed a global SI (mean of SIs per six included interventions). We performed a Bayesian change point analysis on the R_t curve of each province to identify possible associations with global SI variations. We fitted and compared several generalised additive models using multimodel inference, to quantify the statistical effect on R_t of the global SI (stringency) and the individual SIs (separate effect of NPIs).ResultsThe global SI had a significant lowering effect on the R_t (mean: 0.16 ± 0.05 units for full stringency). Mandatory closing times for non-essential businesses, limited gatherings, and restricted outdoors seating capacities (negative) as well as curfews (positive) were the only NPIs with a significant effect. Regional mobility restrictions and limited indoors seating capacity showed no effect. Our results were consistent with a 1- to 3-week-delayed R_t as a response variable.ConclusionWhile response measures implemented during the second COVID-19 wave contributed substantially to a decreased reproduction number, the effectiveness of measures varied considerably. Our findings should be considered for future interventions, as social and economic consequences could be minimised by considering only measures proven effective.     

Nosocomial outbreak caused by the SARS-CoV-2 Delta variant in a highly vaccinated population,Israel, July 2021

A nosocomial outbreak of SARS-CoV-2 Delta variant infected 42 patients, staff and family members; 39 were fully vaccinated. The attack rate was 10.6% (16/151) among exposed staff and reached 23.7% (23/97) among exposed patients in a highly vaccinated population, 16–26 weeks after vaccination (median: 25 weeks). All cases were linked and traced to one patient. Several transmissions occurred between individuals wearing face masks. Fourteen of 23 patients became severely sick or died, raising a question about possible waning immunity.     

SARS-CoV-2 spike IgG titres up to 137 days following Comirnaty mRNA COVID-19 vaccination,Israel, February to May 2021

BackgroundData regarding the long-term protection afforded by vaccination for the SARS-CoV-2 infection are essential for allocation of scarce vaccination resources worldwide.MethodsWe conducted a retrospective cohort study aimed at studying the kinetics of IgG antibodies against SARS-CoV-2 in COVID-19-naïve patients fully vaccinated with two doses of Comirnaty mRNA COVID-19 vaccine. Geometric mean concentrations (GMCs) of antibody levels were reported. Linear models were used to assess antibody levels after full vaccination and their decline over time.ResultsThe study included 4,740 patients and 5,719 serological tests. Unadjusted GMCs peaked 28–41 days after the first dose at 10,174 AU/mL (95% CI: 9,211–11,237) and gradually decreased but remained well above the positivity cut-off. After adjusting for baseline characteristics and repeated measurements, the antibodies half-life time was 34.1 days (95% CI: 33.1–35.2), and females aged 16–39 years with no comorbidities had antibody levels of 20,613 AU/mL (95% CI: 18,526–22,934) on day 28 post-first-dose. Antibody levels were lower among males (0.736 of the level measured in females; 95% CI: 0.672–0.806), people aged 40–59 (0.729; 95% CI: 0.649–0.818) and ≥ 60 years (0.452; 95% CI: 0.398–0.513), and patients having haematological (0.241; 95% CI: 0.190–0.306) or solid malignancies (0.757; 95% CI: 0.650–0.881), chronic kidney disease with glomerular filtration rate (GFR) ≥ 30 (0.434; 95% CI: 0.354–0.532) or with GFR < 30 mL/min (0.176; 95% CI: 0.109–0.287), and immunosuppression (0.273; 95% CI: 0.235–0.317). Body mass index, cardiovascular disease, congestive heart failure, chronic obstructive pulmonary disease, diabetes and inflammatory bowel diseases were not associated with antibody levels.ConclusionsVaccination with two doses resulted in persistently high levels of antibodies (≥ cut-off of 50 AU/mL) up to 137 days post-first-dose. Risk factors for lower antibody levels were identified.     

Risk reduction of hospitalisation and severe disease in vaccinated COVID-19 cases during the SARS-CoV-2 variant Omicron BA.1-predominant period,Navarre, Spain,January to March 2022

BackgroundAs COVID-19 vaccine effectiveness against SARS-CoV-2 infection was lower for cases of the Omicron vs the Delta variant, understanding the effect of vaccination in reducing risk of hospitalisation and severe disease among COVID-19 cases is crucial.AimTo evaluate risk reduction of hospitalisation and severe disease in vaccinated COVID-19 cases during the Omicron BA.1-predominant period in Navarre, Spain.MethodsA case-to-case comparison included COVID-19 epidemiological surveillance data in adults ≥ 18 years from 3 January–20 March 2022. COVID-19 vaccination status was compared between hospitalised and non-hospitalised cases, and between severe (intensive care unit admission or death) and non-severe cases using logistic regression models.ResultsAmong 58,952 COVID-19 cases, 565 (1.0%) were hospitalised and 156 (0.3%) were severe. The risk of hospitalisation was reduced within the first 6 months after full COVID-19 vaccination (complete primary series) (adjusted odds ratio (aOR): 0.06; 95% CI: 0.04–0.09) and after 6 months (aOR: 0.16; 95% CI: 0.12–0.21; p_comparison < 0.001), as well as after a booster dose (aOR: 0.06: 95% CI: 0.04–0.07). Similarly, the risk of severe disease was reduced (aOR: 0.13, 0.18, and 0.06, respectively). Compared with cases fully vaccinated 6 months or more before a positive test, those who had received a booster dose had lower risk of hospitalisation (aOR: 0.38; 95% CI: 0.28–0.52) and severe disease (aOR: 0.38; 95% CI: 0.21–0.68).ConclusionsFull COVID-19 vaccination greatly reduced the risk of hospitalisation and severe outcomes in COVID-19 cases with the Omicron variant, and a booster dose improved this effect in people aged over 65 years.     

A 16-month-long experience of COVID-19 in allogeneic haematopoietic stem cell transplantation recipients: An SFGM-TC multicentre cohort study

This 16-month-long multicentre retrospective study of 225 allogeneic haematopoietic stem cell transplantation (alloHSCT) recipients with COVID-19 examines risk factors for severity and mortality, describing the successive waves of infections (from March to June 2020 and from August 2020 to June 2021). We confirm the negative role of low respiratory tract disease and immunosuppressive treatment. We highlight significantly lower percentages of severe forms and COVID-19-related mortality during the second wave. Monthly comparative evolution of cases in alloHSCT recipients and in the French population shows a higher number of cases in alloHSCT recipients during the first wave and a decrease from February 2021.     

Product-specific COVID-19 vaccine effectiveness against secondary infection in close contacts,Navarre, Spain,April to August 2021

COVID-19 vaccine effectiveness by product (two doses Comirnaty, Spikevax or Vaxzevria and one of Janssen), against infection ranged from 50% (95% CI: 42 to 57) for Janssen to 86% (70 to 93) for Vaxzevria-Comirnaty combination; among ≥ 60 year-olds, from 17% (−26 to 45) for Janssen to 68% (48 to 80) for Spikevax; and against hospitalisation from 74% (43 to 88) for Janssen to > 90% for other products. Two doses of vaccine were highly effective against hospitalisation, but suboptimal for infection control.     

Effectiveness of COVID-19 vaccines in preventing SARS-CoV-2 infection and hospitalisation,Navarre, Spain,January to April 2021

COVID-19 vaccine effectiveness was evaluated in close contacts of cases diagnosed during January–April 2021. Among 20,961 contacts, 7,240 SARS-CoV-2 infections were confirmed, with 5,467 being symptomatic and 559 leading to hospitalisations. Non-brand-specific one and two dose vaccine effectiveness were respectively, 35% (95% confidence interval (CI): 25 to 44) and 66% (95% CI: 57 to 74) against infections, 42% (95% CI: 31 to 52) and 82% (95% CI: 74 to 88) against symptomatic infection, and 72% (95% CI: 47 to 85) and 95% (95% CI: 62 to 99) against COVID-19 hospitalisation. The second dose significantly increased effectiveness. Findings support continuing complete vaccination.     

An outbreak caused by the SARS-CoV-2 Delta (B.1.617.2) variant in a care home after partial vaccination with a single dose of the COVID-19 vaccine Vaxzevria,London, England,April 2021

We investigated a COVID-19 outbreak of the SARS-CoV-2 Delta variant of concern in a London care home, where 8/21 residents and 14/21 staff had received a single dose of Vaxzevria (ChAdOx1-S; AstraZeneca) vaccine. We identified 24 SARS-CoV-2 infections (16 residents, 8 staff) among 40 individuals (19 residents, 21 staff); four (3 residents, 1 staff) were hospitalised, and none died. The attack rate after one vaccine dose was 35.7% (5/14) for staff and 81.3% (13/16) for residents.     

Impact of stringent non-pharmaceutical interventions applied during the second and third COVID-19 epidemic waves in Portugal, 9 November 2020 to 10 February 2021: an ecological study

BackgroundNon-pharmaceutical interventions (NPIs) were implemented worldwide to control the spread of SARS-CoV-2.AimTo evaluate the impact of tiered NPIs and a nationwide lockdown on reduction of COVID-19 incidence during the second and third epidemic waves in Portugal.MethodsSurveillance data on laboratory-confirmed COVID-19 cases were used to conduct an interrupted time series analysis to estimate changes in daily incidence during a second wave tiered NPI period (9 November–18 December 2020), and a third wave lockdown period without (15–21 January 2021) and with school closure (22 January–10 February 2021).ResultsSignificant changes in trends were observed for the overall incidence rate; declining trends were observed for tiered NPIs (−1.9% per day; incidence rate ratio (IRR): 0.981; 95% confidence interval (CI): 0.973–0.989) and a lockdown period without (−3.4% per day; IRR: 0.966; 95% CI: 0.935–0.998) and with school closure (−10.3% per day, IRR: 0.897; 95% CI: 0.846–0.951). Absolute effects associated with tiered NPIs and a lockdown on a subsequent 14-day period yielded 137 cases and 437 cases per 100,000 population potentially averted, respectively.ConclusionOur results indicate that tiered NPIs implemented during the second wave caused a decline in COVID-19 incidence, although modest. Moreover, a third wave lockdown without school closure was effective in reducing COVID-19 incidence, but the addition of school closure provided the strongest effect. These findings emphasise the importance of early and assertive decision-making to control the pandemic.     

COVID-19 vaccination in patients with diabetes mellitus: Current concepts,uncertainties and challenges

Background and aimsTo summarize the available evidence on the use COVID-19 vaccines in patients with diabetes mellitus.MethodsWe performed a thorough literature search with regard to COVID-19 vaccines in patients with type 1 and type 2 diabetes mellitus.ResultsThe novel coronavirus disease (COVID-19) tends to portend a poor prognosis in patients with diabetes mellitus (DM). Primary prevention remains the mainstay for mitigating the risks associated with COVID-19 in patients with DM. A significant step in primary prevention is timely vaccination. Routine vaccination against pneumococcal pneumonia, influenza, and hepatitis B is recommended in patients with DM with good efficacy and reasonable safety profile. With clinical data supporting a robust neutralizing antibody response in COVID-19 patients with DM, vaccination in individuals with DM is justified. In fact, as the burden of the disease is borne by people with DM, COVID-19 vaccination should be prioritized in individuals with DM. Multiple unresolved issues with regard to preferred vaccine type, vaccine efficacy and durability, frequency of administration, vaccination in children (<18 years) and pregnant/lactating women however remain, and need to be addressed through future research.ConclusionsPatients with type 1 and type 2 diabetes mellitus are at a high risk of poor prognosis with COVID-19 and vaccination should be prioritized in them. However, many unresolved issues with regard to COVID-19 vaccination need to be addressed through future research.     

Adverse events following first and second dose COVID-19 vaccination in England,October 2020 to September 2021: a national vaccine surveillance platform self-controlled case series study

BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3–7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91–0.94 and RI: 0.96; 95% CI: 0.94–0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95–0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00–1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28–1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97–1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.     

Evaluation of patients with antiphospholipid syndrome subsequently COVID-19 vaccinations: A retrospective cohort study

The aim of this study is to evaluate development of side effects, thrombotic or obstetric complications in our antiphospholipid syndrome (APS) patient group, after vaccination against coronavirus disease 2019 (COVID-19). A cohort was formed from patients who have previously been followed up with a diagnosis of APS. The patients of the cohort were evaluated retrospectively to find out if they were vaccinated with CoronaVac and/or BNT162b2 vaccines which are being used in our country. To evaluate the side effects seen after the vaccination, the information was collected by the patients in their outpatient appointments or making a phone call. Thirty-five APS patients who had received at least 1 dose of any of the COVID-19 vaccines were included in the study. Median (min–max) number of vaccine doses per patient was 2 (1–3). Eleven patients had a booster dose after primary vaccination. Twenty patients were ever vaccinated with BNT162b2 and 18 with CoronaVac. Among BNT162b2 recipients, 9 (45.0%) and among CoronaVac recipients 15 (42.9%) reported an adverse event after a vaccine administration. The most common adverse events were myalgia and malaise after any dose of both vaccines. No vaccine-related new thrombotic events or APS flares were observed. Our results were comparable with those reported in the literature. Comprehensive large-scale studies are needed for more accurate results on the evaluation of side effects after COVID-19 vaccination in APS patients.     

Increasing risk of breakthrough COVID-19 in outbreaks with high attack rates in European long-term care facilities,July to October 2021

We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July−October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8–52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.     

Relapse of cryoglobulinemic vasculitis with new-onset severe renal involvement in two patients following mRNA COVID-19 vaccination: A case report

Rationale:Since mass-scale severe acute respiratory syndrome coronavirus 2 vaccination, there have been case reports of several immune-mediated reactions, including new-onset and flares of glomerular disorders following immunization with mRNA coronavirus disease 2019 vaccines. Here, we report two cases, the first to our knowledge, of relapsing cryoglobulinemic vasculitis with new-onset severe renal involvement following mRNA coronavirus disease 2019 vaccination.Patient concerns:The relapse of the cutaneous and the new onset of severe renal involvement of cryoglobulinemic vasculitis occurred three weeks after the second dose of the mRNA Moderna coronavirus disease 2019 vaccination and two days after the first dose of mRNA Pfizer coronavirus disease 2019 vaccination in the first and second patient, respectively.Diagnosis:Kidney biopsies were performed. The first pacient''s kidney biopsy showed a membranoproliferative pattern of glomerular injury with extensive mesangial and endocapillary hypercellularity, while severe endothelial swelling, loss of fenestrations and widening of subendothelial space were identified by electron-microscopy. The second patient''s kidney biopsy was consistent with cryoglobulin associated membrano-proliferative pattern of glomerular injury.Interventions:Our patients were managed with a combination of immunosuppressants consisting of corticosteroids, Cyclophosphamide and Rituximab with a favourable outcome at the end of the induction period.Outcomes:Clinical and immunological response was achieved in both patients after four months of follow-up.Lessons:The temporal association of the relapse of the cryoglobulinemic vasculitis to mRNA coronavirus disease 2019 vaccination suggest that the vaccine might have been a trigger for the reactivation of the disease in our cases. This possible association should be acknowledged by physicians in order to provide optimal monitoring and treatment in case of reactivation of the disease post-immunization.