Copy-editor: Rob Camp
Treatment
Paper of the Day
Horby PW, Campbell M, Staplin N, et al. for the RECOVERY Collaborative Group, and others. Tocilizumab in patients admitted to hospital with COVID-19 (RECOVERY): preliminary results of a randomised, controlled, open-label, platform trial. medRxiv 2021, posted 11 February. Full-text: https://www.medrxiv.org/content/10.1101/2021.02.11.21249258v1
In COVID patients with low oxygen and inflammation, tocilizumab saves lives, keeps you off a ventilator, and gets you out of hospital quicker. This is another result of the great RECOVERY trial. After randomizing more than 4000 patients (oxygen saturation < 92% on air or requiring oxygen therapy; and evidence of systemic 31 inflammation [C-reactive protein ≥ 75 mg/L]), treatment with tocilizumab reduced mortality (29% vs 33%), increased the chances of successful hospital discharge, and reduced the chances of requiring invasive mechanical ventilation (33% vs 38%). These benefits were on top of those previously reported for dexamethasone. Clinical guidelines need an update.
See also Tocilizumab reduces deaths in patients hospitalised with COVID-19, 11 February 2021. Link: https://www.recoverytrial.net/news/tocilizumab-reduces-deaths-in-patients-hospitalised-with-covid-19
Vaccines
(Another) Paper of the Day
Madhi A, Baillie VL, Cutland CL, et al. Safety and efficacy of the ChAdOx1 nCoV-19 (AZD1222) Covid-19 vaccine against the B.1.351 variant in South Africa. medRxiv 2021, posted 12 February. Full-text: https://www.medrxiv.org/content/10.1101/2021.02.10.21251247v1
Shabir Madhi et al. report a ChAdOx1-nCoV19 (AstraZeneca) trial in HIV-uninfected people in South Africa. 23/717 (3.2%) placebo and 19/750 (2.5%) vaccine recipients developed mild-moderate Covid-19. Of the primary endpoint cases, 39/42 (92.9%) were the B.1.351 variant – against which vaccine efficacy was 10.4%. The authors conclude that a two-dose regimen of ChAdOx1-nCoV19 did not show protection against mild-moderate Covid-19 due to B.1.351 variant.
Variants
Zhang W, Davis BD, Chen SS, Sincuir Martinez JM, Plummer JT, Vail E. Emergence of a Novel SARS-CoV-2 Variant in Southern California. JAMA. 2021 Feb 11. PubMed: https://pubmed.gov/33571356. Full-text: https://doi.org/10.1001/jama.2021.1612
In California, the proportion of SARS-CoV-2 cases associated with the CAL.20C variant rose from 3,8% to 25% between mid-November and late December. By then, it accounted for 24% of samples in one study, and 36,4% (66/181) of samples in a local Los Angeles cohort. The emerging predominance of this strain is temporally related to the time of onset of the current spike in SARS-CoV-2 infections in Southern California. CAL.20C is defined by mutations in the S protein (L452R, S13I, W152C) and in the ORF1a (I4205V) and ORF1b protein (D1183Y).
Transmission
Edwards DA, Ausiello D, Salzman J, et al. Exhaled aerosol increases with COVID-19 infection, age, and obesity. PNAS 2021, published 23 February. Full-text: https://www.pnas.org/content/118/8/e2021830118
David Edwards et al. report studies of exhaled aerosol suggesting that a critical factor in SARS-CoV-2 superspreading events is the propensity of certain individuals to exhale large numbers of small respiratory droplets. Their findings indicate that the capacity of airway lining mucus to resist breakup on breathing varies significantly between individuals, with a trend to increasing with the advance of COVID-19 infection and body mass index multiplied by age (i.e., BMI-years).
Immunology
Wang Z, Schmidt F, Weisblum Y, et al. mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. Nature 2021, published 10 February. Full-text: https://www.nature.com/articles/s41586-021-03324-6
Michel Nussenzweig and colleagues tested samples from 14 and 6 people who had received the Moderna or the Pfizer-BioNTech vaccine, respectively. Activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin.
Skelly DT, Harding AC, Gilbert Jaramillo J, et al. Vaccine-induced immunity provides more robust heterotypic immunity than natural infection to emerging SARS-CoV-2 variants of concern. Research Square 2021, posted 9 February, accessed 12 February. Full-text: https://www.researchsquare.com/article/rs-226857/v1?s=09
When testing antibody and T cell responses against B117, B1351 and a reference isolate (VIC001) representing the original circulating lineage B, Skelly et al. identified a reduction in antibody neutralization against the variants which was most evident in B1351. However, the majority of the T cell response was directed against epitopes conserved across all three strains. The reduction in antibody neutralization was less marked in post-boost vaccine-induced rather than in naturally-induced immune responses.
Severe COVID
Chamberlain SR, Grant JE, Trender W. Post-traumatic stress disorder symptoms in COVID-19 survivors: online population survey. BJPsych Open 2021, published 9 February. Full-text: https://www.cambridge.org/core/journals/bjpsych-open/article/posttraumatic-stress-disorder-symptoms-in-covid19-survivors-online-population-survey/66F00143472B15757736AE5E3E42E52C
Samuel R. Chamberlain et al. examined post-traumatic stress disorder (PTSD) symptoms in 13.049 survivors of suspected or confirmed COVID-19, from the UK general population. Up to a third of COVID-19 patients who required ventilator support experienced extensive PTSD symptoms. Intrusive images were the most prominent elevated symptom.
Beyond Corona
Sapoznik E, Chang BJ, Huh J, et al. A versatile oblique plane microscope for large-scale and high-resolution imaging of subcellular dynamics. Elife. 2020 Nov 12;9:e57681. PubMed: https://pubmed.gov/33179596. Full-text: https://doi.org/10.7554/eLife.57681
Using an oblique plane microscope (OPM), the authors image biological phenomena such as cell migration through confined spaces within a microfluidic device, subcellular photoactivation of Rac1, and large field of view imaging of neurons, developing embryos, and centimeter-scale tissue sections.