COVID-19 preprint round-up
Our AI summarises and provides extracts from the latest COVID-19 preprints published on medRxiv
The individual reports below - including each headline - were generated automatically by our machine-reading software from an RSS feed of recent COVID-19 preprints on 14 March 2021.
How does it work? Briefly, the technology comprises an ensemble of language models fine-tuned for extractive and abstractive summarisation built with spaCy, huggingface transformers and Scholarcy technology.
The headlines in italic are generated by our abstractive engine. The longer synopses use our extractive engine, and consist of automatically extracted highlights from the original texts, with some subclause truncation, transitional phrase removal, and rewriting in the third person.
There are few studies on the clinical characteristics of children and adolescents with COVID-19, and the diagnosis and control of the infection source is more challenging than that of adult patients.
L. Lou and colleagues (2021) studied clinical characteristics of COVID-19 in children and adolescents. An earlier study has found that COVID-19 in children below the age of 10 years constituted only 0.35% of cases. In this study, the authors conducted a systematic review and meta-analysis of the clinical characteristics of children and adolescents to better treat and control the current outbreak. The main clinical features in children and adolescents with COVID-19 were fever (56%), cough (45%), sneezing (14%), vomiting (14%). The most common laboratory abnormalities were elevated procalcitonin, elevated lactate dehydrogenase and increased lymphocyte count. Bilateral pneumonia was more common than unilateral pneumonia. The main manifestations were ground-glass opacities and patchy shadowing.
The review involved 49 studies. However, “There are also several limitations to our systematic review and meta-analysis. All reported cases were retrospective studies and there was a high degree of heterogeneity among the results. Subgroup analysis was not performed, which may also bias the results of the analysis. ,” admit the authors.
There is a growing body of evidence that children are less susceptible to SARS-CoV-2 infection compared to adults and if infected, children are more likely to develop an asymptomatic infection.
Y. Zhu et al. (2021) reported in ‘Pediatric nasal epithelial cells are less permissive to SARS-CoV-2 replication compared to adult cells’ that SARS-CoV-2 causes a broad range of clinical symptoms, ranging from asymptomatic infection to potentially fatal acute respiratory distress syndrome (ARDS) A low rate of pediatric SARS- cov-2 infections has been observed in multiple countries including China, Italy, Spain, the U.S.A. and Poland. Previous studies have suggested that the reduced susceptibility of children to SARS- CoV2 infection is due to reduced expression of ACE2 and TMPRSS2 mRNA. To contrast the infection dynamics, primary nasal epithelial cells from adults and children were used. Pediatric cells upregulated genes associated with pro-inflammatory pathways.
There were 10 donors included in the study. The findings claim to reinforce prior research in this field: “Specifically, the use of recombinant IFNs as a treatment in SARS has been identified as a promising therapeutic candidate. The data presented here support this notion,” Zhu claimed. However, “It is important to recognize the limitations of this study. Due to the difficulties associated with obtaining NECs from children only a limited number of NECs could be used. As donors were not selected on susceptibility to respiratory viral infection their responses should be broadly representative of other healthy children,” say the researchers.
A study of post-acute sequelae of SARS-CoV-2 (PASC).
M. Peluso et al. (2021) report that the public health ramifications of PASC and the need to uncover interventions to prevent or treat it are self-evident. From April 21 to December 31, 2020, they assembled a cohort of consecutive volunteers who had documented history of SARS-CoV-2 RNA-positivity. Participants underwent comprehensive questionnaire-based evaluation and biological specimen collection at their initial visit and at approximately 4month intervals thereafter. As coronavirus disease 2019 pandemic continues, attention has turned to characterizing post-acute sequelae of SARS-CoV-2 infection. The group found many with persistent physical symptoms through 8 months following onset of COVID-19 with an impact on self-rated overall health. Similar evaluations in a population-representative sample will be needed to estimate population-level prevalence.
There were 179 adults involved in the research. The researchers’ findings may deviate from prior work in this area: “It will only be through population-based probability samples that researchers can be confident that their study populations are representative of the relevant targets. The percentage of study participants with persistent symptoms that we and others calculate cannot be interpreted as meaningful population-level prevalence estimates.” Discussing potential shortcomings, “Our approach has extended upon earlier work about PASC and overcome several of the limitations of prior studies. We required documentation of SARS-CoV-2-RNA-positivity prior to enrollment. We included a large number of individuals who did not require hospitalization,” they concede.
Daily testing as an alternative to self-isolation may facilitate sharing contact details of close contacts among people who test positive for COVID-19, a pilot study in England suggests.
A. Martin et al. (2021) reported on engagement with daily testing instead of self-isolating in contacts of confirmed cases of SARS-CoV-2. In December 2020, Public Health England with NHS Test and Trace initiated a pilot study in which close contacts of people with confirmed COVID-19 were given the option to carryout lateral flow device antigen tests at home. The isolating of close contacts generates a wider impact on society and the economy. They carried out a survey to evaluate the acceptability of daily testing and assess levels of adherence to the rules relating to behaviour following a positive and negative test result. Most participants reported not engaging in any non-essential activities on days when they were trying to isolate. Risk factors for non-adherence to self-isolation include low income; inability to work from home; and being in jobs that do not provide pay for time off. Periods of lockdown may be particularly challenging for those from lowest income backgrounds
There were 1417 people included in the study. Discussing potential shortcomings, “In future studies, further explanation of the benefits and limitations of testing could be provided,” they concede. The team suggest that the behaviour following a negative test result of participants in the study is consistent with data generated as part of mass testing in Liverpool, where 17% of respondents reported being more likely to go to the shops.
There is a high seroprevalence of antibodies against SARS-CoV-2 among health care workers in Kenya, according to a survey conducted in 2020.
In ‘Seroprevalence of Antibodies to SARS-CoV-2 among Health Care Workers in Kenya’, A. Etyang and colleagues (2021) noted initial findings from SARS-CoV-2 antibody testing from Health Care Workers in three sites in Coastal, Central, and Western Kenya. They recruited 684 HCWs from Nairobi, Busia and Kilifi. There was a higher seroprevalence among HCWs in Nairobi compared with Kilifi and Busia. Serological surveys can estimate cumulative incidence of SARS-CoV-2 infection in key groups, such as HCWs, or the general population. Seroprevalence varied significantly by site: 43.8% (CI 35.8-52.2%), 12.6% in Busia, and 11.5% in Kilifi. The estimates are similar to those observed among HCWs in several high-income countries at the peak of the epidemic.
In Kilifi and Busia they aimed to recruit ≥ 50% of the 882 HCWs working in the healthcare facilities. The authors used a slightly different strategy at KNH, where the primary aim was to determine incidence and antibody kinetics among HCWs. The findings claim to back up prior research in this subject: “We conducted our study during and shortly after the first wave of the epidemic in Kenya. Our estimates are similar to those observed among HCWs in several high-income countries at the peak of their first wave,” Etyang claimed. However, “A household survey found 35% of the population in Nairobi had antibodies to SARS-CoV-229. The rural-urban difference in seroprevalence among HCWs that we observed was similar to what has been observed in other studies,” concede the researchers.
A genome-wide association study (GWAS) has found no evidence to support a link between vitamin D concentration and the risk of coronavirus disease, severity or hospitalization.
Z. Cui and Y. Tian (2021) described the causal effect of serum vitamin D concentration on COVID-19 susceptibility, severity and hospitalization traits. Vitamin D has many mechanisms to modulate immunity, such as physical barriers and innate and adaptive immunity. Vitamin D can reduce the production of proinflammatory T helper type 1 (Th1) cytokines. High-quality randomized controlled trials are necessary to explore and define the role of vitamin D supplementation in the prevention and treatment of COVID-19. Study did not provide evidence assessing the role of vitamin D supplementation during the COVID-19 pandemic. Found no evidence to support the causal associations between the serum 25(OH)D concentration. Sensitivity analyses did not reveal any sign of horizontal pleiotropy.
The study involved 417580 individuals. The researchers concede that “Small sample size and low follow-up of enrolled patients might limit the power of the study. Collider bias could arise when researchers restrict analyses on a collider variable in observational studies. Vitamin D binding protein was reported as a positive acute phase reactant after infections.” The authors suggest that future studies may be designed to comprehensively evaluate any nonlinear relationships between the vitamin D concentration and COVID-19 traits. The authors have provided data and code at: https://www.covid19hg.org/results.
Low vitamin D levels in patients with virus disease (COVID-19) may increase the risk of adverse outcomes.
P. Vanegas-Cedillo et al. (2021) described serum Vitamin D levels are associated with increased COVID-19 severity markers and mortality independent of visceral adiposity. Of the 551 patients included, low 25-OHD levels were present in 45.6% and severely low levels in 10.9%. Low 25-OHD levels were associated with mortality (HR 2.11, 95%CI 1.24-3.58, p=0.006) but not with critical COVID-19, adjusted for age, sex, body-mass index and epicardial fat. The increased risk of mortality was partly mediated by the effect of vitamin D on markers of disease severity, such as D-dimer and ultrasensitive cardiac troponins.
There were 551 patients in the research. However, “This study has certain strengths and limitations. It included a large number of patients with heterogenous risk profiles. A chemiluminescence immunoassay was used to assess vitamin D levels,” acknowledge the investigators. They advocate that obesity and ethnicity are important risk factors for severe disease, and are known to modulate vitamin D levels. This may be relevant in Mexico, where high rates of diabetes and obesity have been associated with an increased risk of severe disease. The researchers have provided data and code at: https://github.com/oyaxbell/covid_metabolism.
The death rate for COVID-19 among Native Americans is much higher than for other racial/ethnic groups, and varies enormously across states.
K. Leggat-Barr et al. (2021) reported on COVID-19 risk factors and mortality among Native Americans. Research has identified a diverse set of socioeconomic and health-related risk factors that increase the likelihood of viral infection, illness severity, hospitalization and mortality. The group estimate COVID-19 mortality for Native Americans relative to other racial/ethnic groups and explore how state-level mortality is associated with known risk factors. The national 2020 COVID-19 mortality level for Native Americans is almost three times that for Whites, an estimate considerably higher than the corresponding values for Blacks and Latinos. The risk factors are more prevalent among Native Americans who self-identify as a single-race.
Their results appear to challenge earlier work in the field: “Most frequently reported measures, such as the proportion of the group dying from COVID-19 in relation to the group’s representation in the population, fail to adjust for the large differences in underlying age distributions across racial and ethnic groups.” Discussing potential improvements, “An additional concern relates to inaccuracies in the data on deaths from COVID-19 due to misattribution of cause of death on death certificates. Misclassification of race and ethnicity is a particularly severe problem among Native Americans,” they concede.
A review of media reports on Sars-CoV-2 outbreaks in reception and accommodation centres for asylum seekers in Germany suggests that mass quarantine is a counter-productive containment measure in overcrowded camps.
R. Jahn et al. (2021) identified 101 COVID-19 outbreaks in 99 reception and accommodation centers across 14 of the 16 German federal states. 26 of these outbreaks occurred in Reception Centre and 75 in Accommodation Centre. Attack rates were higher under mass quarantine compared to conventional strategies. In Germany, the first Sars-CoV-2 cases in reception centres for refugees and asylum seekers were reported in March 2020. Pre-existing weaknesses in health information systems lead to a lack of reliable data on attack rates as well as effectiveness and consequences of containment measures. The estimates from this web-based systematic review show SARS-Cov-2 attack rates of 13% in German reception centers.
There were 99 reception and accommodation centers in the study. The results claim to substantiate prior research in this field: “Mass quarantine of reception centers may not only increase the risk of conflicts, stigma, or mental health disorders, but also associated with higher risk of transmission in camp contexts. This finding is consistent with modelling studies suggesting early evacuation is more effective to reduce transmission in confined contexts such as cruise ships,” Jahn said. Discussing potential improvements, “The results of this study are the first estimate of the attack rate of Sars-Cov-2 infection in refugee reception centers. The reason for a lack of studies lies in weak health information systems that do not have the capacity to generate timely and reliable health data in reception centers and refugee camps,” they concede. They propose that to better understand the dynamic of these local outbreaks, further research using individual-level data in respective outbreak sites is urgently needed. The significant heterogeneity between centers suggest relevant contextual factors in disease transmission.