COVID-19 research news in brief

From the New England Journal of Medicine

Effectiveness of COVID-19 vaccines against the B.1.617.2 (delta) variant: “Effectiveness after one dose of vaccine (BNT162b2 or ChAdOx1 nCoV-19) was notably lower among persons with the delta variant (30.7%; 95% confidence interval [CI], 25.2 to 35.7) than among those with the alpha variant (48.7%; 95% CI, 45.5 to 51.7); the results were similar for both vaccines. With the BNT162b2 vaccine, the effectiveness of two doses was 93.7% (95% CI, 91.6 to 95.3) among persons with the alpha variant and 88.0% (95% CI, 85.3 to 90.1) among those with the delta variant. With the ChAdOx1 nCoV-19 vaccine, the effectiveness of two doses was 74.5% (95% CI, 68.4 to 79.4) among persons with the alpha variant and 67.0% (95% CI, 61.3 to 71.8) among those with the delta variant. Conclusions: Only modest differences in vaccine effectiveness were noted with the delta variant as compared with the alpha variant after the receipt of two vaccine doses. Absolute differences in vaccine effectiveness were more marked after the receipt of the first dose. This finding would support efforts to maximize vaccine uptake with two doses among vulnerable populations.”

Safety and efficacy of single-dose Ad26.COV2.S vaccine against COVID-19: “The per-protocol population included 19 630 SARS-CoV-2–negative participants who received Ad26.COV2.S and 19 691 who received placebo. Ad26.COV2.S protected against moderate to severe–critical COVID-19 with onset at least 14 days after administration (116 cases in the vaccine group vs. 348 in the placebo group; efficacy, 66.9%; adjusted 95% confidence interval [CI], 59.0 to 73.4) and at least 28 days after administration (66 vs. 193 cases; efficacy, 66.1%; adjusted 95% CI, 55.0 to 74.8). Vaccine efficacy was higher against severe–critical COVID-19 (76.7% [adjusted 95% CI, 54.6 to 89.1] for onset at ≥ 14 days and 85.4% [adjusted 95% CI, 54.2 to 96.9] for onset at ≥ 28 days). Despite 86 of 91 cases (94.5%) in South Africa with sequenced virus having the 20H/501Y.V2 variant, vaccine efficacy was 52.0% and 64.0% against moderate to severe–critical COVID-19 with onset at least 14 days and at least 28 days after administration, respectively, and efficacy against severe–critical COVID-19 was 73.1% and 81.7%, respectively. Reactogenicity was higher with Ad26.COV2.S than with placebo but was generally mild to moderate and transient. The incidence of serious adverse events was balanced between the two groups. Three deaths occurred in the vaccine group (none were COVID-19-related), and 16 in the placebo group (5 were COVID-19-related). Conclusions: A single dose of Ad26.COV2.S protected against symptomatic COVID-19 and asymptomatic SARS-CoV-2 infection and was effective against severe–critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of COVID-19 vaccines.”

Vaccine breakthrough infections with SARS-CoV-2 variants: “Emerging variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are of clinical concern. In a cohort of 417 persons who had received the second dose of BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) vaccine at least 2 weeks previously, we identified 2 women with vaccine breakthrough infection. Despite evidence of vaccine efficacy in both women, symptoms of coronavirus disease 2019 developed, and they tested positive for SARS-CoV-2 by polymerase-chain-reaction testing. Viral sequencing revealed variants of likely clinical importance, including E484K in 1 woman and three mutations (T95I, del142–144, and D614G) in both. These observations indicate a potential risk of illness after successful vaccination and subsequent infection with variant virus, and they provide support for continued efforts to prevent and diagnose infection and to characterize variants in vaccinated persons.”

From the BMJ

Risks of COVID-19 hospital admission and death for people with learning disability: population based cohort study using the OpenSAFELY platform: “For wave 1, 14 312 023 adults aged ≥ 16 years were included, and 90 307 (0.63%) were on the learning disability register. Among adults on the register, 538 (0.6%) had a COVID-19 related hospital admission; there were 222 (0.25%) COVID-19 related deaths and 602 (0.7%) non-COVID deaths. Among adults not on the register, 29 781 (0.2%) had a COVID-19 related hospital admission; there were 13 737 (0.1%) COVID-19 related deaths and 69 837 (0.5%) non-COVID deaths. Wave 1 hazard ratios for adults on the learning disability register (adjusted for age, sex, ethnicity, and geographical location) were 5.3 (95% confidence interval 4.9 to 5.8) for COVID-19 related hospital admission and 8.2 (7.2 to 9.4) for COVID-19 related death. Wave 2 produced similar estimates. Associations were stronger among those classified as having severe to profound learning disability, and among those in residential care. For both waves, Down’s syndrome and cerebral palsy were associated with increased hazards for both events; Down’s syndrome to a greater extent. Hazard ratios for non-COVID deaths followed similar patterns with weaker associations. Similar patterns of increased relative risk were seen for children, but COVID-19 related deaths and hospital admissions were rare, reflecting low event rates among children. Conclusions: People with learning disability have markedly increased risks of hospital admission and death from COVID-19, over and above the risks observed for non-COVID causes of death. Prompt access to COVID-19 testing and healthcare is warranted for this vulnerable group, and prioritisation for COVID-19 vaccination and other targeted preventive measures should be considered.”

Performance of the Innova SARS-CoV-2 antigen rapid lateral flow test in the Liverpool asymptomatic testing pilot: population based cohort study: “Of 5869 test results, 22 (0.4%) LFT results and 343 (5.8%) RT-qPCR results were void (that is, when the control line fails to appear within 30 minutes). Excluding the void results, the LFT versus RT-qPCR showed a sensitivity of 40.0% (95% confidence interval 28.5% to 52.4%; 28/70), specificity of 99.9% (99.8% to 99.99%; 5431/5434), positive predictive value of 90.3% (74.2% to 98.0%; 28/31), and negative predictive value of 99.2% (99.0% to 99.4%; 5431/5473). When the void samples were assumed to be negative, a sensitivity was observed for LFT of 37.8% (26.8% to 49.9%; 28/74), specificity of 99.6% (99.4% to 99.8%; 5431/5452), positive predictive value of 84.8% (68.1% to 94.9%; 28/33), and negative predictive value of 93.4% (92.7% to 94.0%; 5431/5814). The sensitivity in participants with an RT-qPCR cycle threshold (Ct) of < 18.3 (approximate viral loads > 10⁶ RNA copies/mL) was 90.9% (58.7% to 99.8%; 10/11), a Ct of < 24.4 (> 10⁴ RNA copies/mL) was 69.4% (51.9% to 83.7%; 25/36), and a Ct of > 24.4 (< 10⁴ RNA copies/mL) was 9.7% (1.9% to 23.7%; 3/34). LFT is likely to detect at least three fifths and at most 998 in every 1000 people with a positive RT-qPCR test result with high viral load. Conclusions: The Innova LFT can be useful for identifying infections among adults who report no symptoms of COVID-19, particularly those with high viral load who are more likely to infect others. The number of asymptomatic adults with lower Ct (indicating higher viral load) missed by LFT, although small, should be considered when using single LFT in high consequence settings. Clear and accurate communication with the public about how to interpret test results is important, given the chance of missing some cases, even at high viral loads. Further research is needed to understand how infectiousness is reflected in the viral antigen shedding detected by LFT versus the viral loads approximated by RT-qPCR.”

Coronary artery calcium score may be a novel predictor of COVID-19 prognosis: a retrospective study: “Multivariable logistic regression analysis of age, sex, smoking history, diabetes, hypertension, dyslipidaemia, number of days from symptom onset to hospitalisation and CACS of ≥ 180 was performed. It revealed that unlike CACS of < 180, CACS of ≥ 180 is associated with exacerbation of oxygenation or CT images of the chest during hospitalisation (OR: 12.879, 95% CI: 1.399 to 380.401). Furthermore, this model of eight variables showed good calibration (Hosmer–Lemeshow P = 0.119). Conclusion: CACS may be a prognosis marker of COVID-19 severity. Although coronary artery calcification is not typically assessed in pneumonia cases, it may provide a valuable clinical indicator for predicting severe COVID-19 outcomes.”

From JAMA

Effect of canakinumab vs placebo on survival without invasive mechanical ventilation in patients hospitalised with severe COVID-19: “Among 454 patients who were randomized (median age, 59 years; 187 women [41.2%]), 417 (91.9%) completed day 29 of the trial. Between days 3 and 29, 198 of 223 patients (88.8%) survived without requiring IMV in the canakinumab group and 191 of 223 (85.7%) in the placebo group, with a rate difference of 3.1% (95% CI, −3.1% to 9.3%) and an odds ratio of 1.39 (95% CI, 0.76 to 2.54; P = 0.29). COVID-19–related mortality occurred in 11 of 223 patients (4.9%) in the canakinumab group vs 16 of 222 (7.2%) in the placebo group, with a rate difference of −2.3% (95% CI, −6.7% to 2.2%) and an odds ratio of 0.67 (95% CI, 0.30 to 1.50). Serious adverse events were observed in 36 of 225 patients (16%) treated with canakinumab vs 46 of 223 (20.6%) who received placebo. Conclusions and relevance: Among patients hospitalized with severe COVID-19, treatment with canakinumab, compared with placebo, did not significantly increase the likelihood of survival without IMV at day 29.”

From the Lancet

Global minimum estimates of children affected by COVID-19-associated orphanhood and deaths of caregivers: a modelling study: “Globally, from March 1, 2020, to April 30, 2021, we estimate 1 134 000 children (95% credible interval 884 000–1 185 000) experienced the death of primary caregivers, including at least one parent or custodial grandparent. 1 562 000 children (1 299 000–1 683 000) experienced the death of at least one primary or secondary caregiver. Countries in our study set with primary caregiver death rates of at least one per 1000 children included Peru (10.2 per 1000 children), South Africa (5.1), Mexico (3.5), Brazil (2.4), Colombia (2.3), Iran (1.7), the USA (1.5), Argentina (1.1), and Russia (1.0). Numbers of children orphaned exceeded numbers of deaths among those aged 15–50 years. Between two and five times more children had deceased fathers than deceased mothers. Interpretation: Orphanhood and caregiver deaths are a hidden pandemic resulting from COVID-19-associated deaths. Accelerating equitable vaccine delivery is key to prevention. Psychosocial and economic support can help families to nurture children bereft of caregivers and help to ensure that institutionalisation is avoided. These data show the need for an additional pillar of our response: prevent, detect, respond, and care for children.”

Estimating global and regional disruptions to routine childhood vaccine coverage during the COVID-19 pandemic in 2020: a modelling study: “Globally, in 2020, estimated vaccine coverage was 76.7% (95% uncertainty interval 74.3–78.6) for [third-dose diphtheria-tetanus-pertussis (DTP3)] and 78.9% (74.8–81.9) for [first-dose measles-containing vaccine (MCV1)], representing relative reductions of 7.7% (6.0–10.1) for DTP3 and 7.9% (5.2–11.7) for MCV1, compared to expected doses delivered in the absence of the COVID-19 pandemic. From January to December, 2020, we estimated that 30.0 million (27.6–33.1) children missed doses of DTP3 and 27.2 million (23.4–32.5) children missed MCV1 doses. Compared to expected gaps in coverage for eligible children in 2020, these estimates represented an additional 8.5 million (6.5–11.6) children not routinely vaccinated with DTP3 and an additional 8.9 million (5.7–13.7) children not routinely vaccinated with MCV1 attributable to the COVID-19 pandemic. Globally, monthly disruptions were highest in April, 2020, across all GBD super-regions, with 4.6 million (4.0–5.4) children missing doses of DTP3 and 4.4 million (3.7–5.2) children missing doses of MCV1. Every GBD super-region saw reductions in vaccine coverage in March and April, with the most severe annual impacts in north Africa and the Middle East, south Asia, and Latin America and the Caribbean. We estimated the lowest annual reductions in vaccine delivery in sub-Saharan Africa, where disruptions remained minimal throughout the year. For some super-regions, including southeast Asia, east Asia, and Oceania for both DTP3 and MCV1, the high-income super-region for DTP3, and south Asia for MCV1, estimates suggest that monthly doses were delivered at or above expected levels during the second half of 2020. Interpretation: Routine immunisation services faced stark challenges in 2020, with the COVID-19 pandemic causing the most widespread and largest global disruption in recent history. Although the latest coverage trajectories point towards recovery in some regions, a combination of lagging catch-up immunisation services, continued SARS-CoV-2 transmission, and persistent gaps in vaccine coverage before the pandemic still left millions of children under-vaccinated or unvaccinated against preventable diseases at the end of 2020, and these gaps are likely to extend throughout 2021. Strengthening routine immunisation data systems and efforts to target resources and outreach will be essential to minimise the risk of vaccine-preventable disease outbreaks, reach children who missed routine vaccine doses during the pandemic, and accelerate progress towards higher and more equitable vaccination coverage over the next decade.”