Copy-editor: Rob Camp
Paper of the Day
Zhou D, Dejnirattisai W, Supasa P, et al. Evidence of escape of SARS-CoV-2 variant B.1.351 from natural and vaccine induced sera. Cell February 23, 2021. Full-text: https://www.cell.com/action/showPdf?pii=S0092-8674%2821%2900226-9
The new variants have multiple changes in the immunodominant spike protein which facilitates viral cell entry via the ACE receptor. Mutations in the receptor recognition site on the spike are of great concern due to their potential for immune escape. Daming Zhou and colleagues from Oxford, UK describe a structure-function analysis of B.1.351 using a large cohort of convalescent and vaccinee serum samples. The receptor binding domain mutations provide tighter ACE2 binding and widespread escape from monoclonal antibody neutralization largely driven by E484K although K417N and N501Y act together against some important antibody classes. The neutralization titer for B.1.351 reduced 8 to 9-fold for both the Pfizer and AstraZeneca vaccinees. E484K, K417N and N501Y caused widespread escape from monoclonal antibodies. However, let‘s keep in mind that even if antibody responses to the new variants are not able to prevent infection, they may moderate severity. Moreover, T cell responses to spike may not be disrupted by the mutational changes described here.
Li Q, Nie J, Wu J. No higher infectivity but immune escape of SARS-CoV-2 501Y.V2 variants. Cell February 23, 2021. https://www.cell.com/action/showPdf?pii=S0092-8674%2821%2900231-2
More experiments on B.1.351 (also known as 501Y.V2). These variants DO NOT confer increased infectivity in multiple cell types except for murine (not human!) ACE2-overexpressing cells, where a substantial increase in infectivity was observed. As seen in the other paper, the susceptibility of the variants to neutralizing monoclonal antibodies was substantially diminished, and the neutralization ability of the sera from convalescent patients and immunized mice was also reduced. The neutralization resistance was mainly caused by E484K and N501Y mutations in the receptor-binding domain of Spike.
Vasques Nonaka CK, Franco MM, Gräf T, et al. Genomic evidence of SARS-CoV-2 reinfection involving E484K spike mutation, Brazil. Emerg Infect Dis. February 19, 2021. https://wwwnc.cdc.gov/eid/article/27/5/21-0191_article
A case of reinfection from distinct virus lineages in Brazil harboring the E484K mutation, a variant associated with escape from neutralizing antibodies (see above). Both episodes were considered to be mild.
Spinelli MA, Gliden DV, Gennatas ED. Importance of non-pharmaceutical interventions in lowering the viral inoculum to reduce susceptibility to infection by SARS-CoV-2 and potentially disease severity. Lancet Inf Dis February 22, 2021. Full-text: https://doi.org/10.1016/S1473-3099(20)30982-8
Matthew Spinelli and colleagues argue that even as safe and effective vaccines are being rolled out, non-pharmaceutical interventions (including social distancing, mask wearing, and improved ventilation) will continue to play an essential role in suppressing SARS-CoV-2 transmission until equitable and widespread vaccine administration has been completed. In this personal viewpoint, they review the influence of the viral inoculum on disease susceptibility for several human pathogens and the preliminary data available for SARS-CoV-2.
Toh ZQ, Higgings RA, Anderson J, et al. The use of dried blood spots for the serological evaluation of SARS-CoV-2 antibodies. Journal of Public Health, fdab011, 22 February 2021. https://doi.org/10.1093/pubmed/fdab011
Zheng Quan Toh and colleagues from Melbourne compared the SARS-CoV-2 IgG antibody response in paired serum and eluates from dried blood spot specimens. The IgG seropositivity rate was similar between serum and DBS specimens (18.9%, 18/95 versus 16.8%, 16/95), respectively. DBS would facilitate serosurveillance efforts particularly in hard-to-reach populations.
Markewitz R, Torge A, Wandinger KP. et al. Clinical correlates of anti-SARS-CoV-2 antibody profiles in Spanish COVID-19 patients from a high incidence region. Sci Rep 11, 4363 (2021). https://doi.org/10.1038/s41598-021-83969-5
No prognostic value of SARS-CoV-2 antibodies (assessed by the EUROIMMUN assay) in this cohort. Serum samples from 347 Spanish patients from a high-incidence region were collected at one point in time (ranging from 0 to 33 days since onset of symptoms). Neither the presence, nor the levels of antibodies served as prognostic markers. The presence and level of antibodies was not associated with age, sex, duration of hospitalization, treatment in the ICU or death. A subgroup of patients (IgG 4%) did not develop antibodies at the time of sample collection. Compared to the patients that did, no differences were found.
Zhao Y, Cunningham MH, Mediavilla JR, et al. Diagnosis, clinical characteristics, and outcomes of COVID-19 patients from a large healthcare system in northern New Jersey. Sci Rep 11, 4389 (2021). https://doi.org/10.1038/s41598-021-83959-7
In this large cohort of 722 patients from New Jersey, viral load, as indicated by the cycle of threshold (Ct) values from the RT-PCR test, was significantly higher in the oldest patient group (≥ 80), and inversely correlated with survival.
dos Santos LA, Germano de Góis Filho P, Fantini Silva AM, et al. Recurrent COVID-19 including evidence of reinfection and enhanced severity in thirty Brazilian healthcare workers. J Infection, February 12, 2021. DOI:https://doi.org/10.1016/j.jinf.2021.01.020
In 33 patients with recurrent COVID-19 and a positive PCR, recurrence was associated with working as a healthcare professional, blood-group A, and low IgG response to infection. All had recovered from first episode symptoms, returned to work and later suffered recurrent symptoms. Of note, recurrent episodes tended to be more severe, with one fatal infection.
Cross RW, Prasad AN, Borisevich V. Use of convalescent serum reduces severity of COVID-19 in nonhuman primates. Cell Rep February 23, 2021. Full-text: https://doi.org/10.1016/j.celrep.2021.108837
Several human clinical trials on the passive transfer of convalescent plama have yielded mixed results. In this animal experiment on 10 African green monkeys, sera with high SARS-CoV-2 neutralizing antibody titers showed the greatest benefit. Data suggested passive transfer as a therapy in humans in early stages of disease.
Xie C, Chen Y, Luo D, et al. Therapeutic potential of C1632 by inhibition of SARS-CoV-2 replication and viral-induced inflammation through upregulating let-7. Sig Transduct Target Ther 6, 84 (2021). https://doi.org/10.1038/s41392-021-00497-4
MicroRNAs (miRNAs) are small, non-coding RNAs that play regulatory roles in gene expression by targeting their mRNA. The authors report that let-7, an miRNA that is ubiquitously expressed in human cells, blocks SARS-CoV-2 replication by targeting S and M protein. In addition, let-7 suppresses the expression of multiple inflammatory factors. C1632, a small molecule serving as a let-7 stimulator, is capable of upregulating the expression of let-7, thus possibly reducing viral replication and secretion of inflammatory cytokines.