Testing is the cornerstone of a successful public health response to coronavirus disease 2019 (COVID-19). Nasopharyngeal sampling for nucleic acid amplification testing (NAAT) is the current noninvasive criterion standard diagnostic test. However, nasopharyngeal testing requires trained personnel and handling of a specially designed swab, and the technique cannot be easily or reliably performed in all populations (eg, children and quarantined individuals).¹ A test that can be self-administered would greatly increase the options for case identification in the community. Consequently, alternative sampling sites are being explored to allow broader deployment of testing, increased access in remote regions, and testing among underserviced populations who may have limited access to highly qualified testing personnel. Of the currently available routes for testing, salivary testing likely represents the most practical option because it avoids the inconvenience, discomfort, and required technical expertise of nasopharyngeal sampling and could potentially be broadly deployed in the community. To date, the results of studies on the diagnostic performance of saliva NAAT are conflicting.^2,3 Furthermore, other studies have relied on the assumption that the sensitivity and specificity of the nasopharyngeal swab is perfect, which is not the case.⁴ To summarize the evidence on saliva NAAT performance, we conducted a systematic review of the operating characteristics of saliva NAAT for detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the diagnosis of COVID-19 using nasopharyngeal NAAT as the comparator. We performed a bayesian latent class meta-analysis that adjusts for the imperfect accuracy of the comparator.

Infectious diseases are causally related to a large array of noncommunicable diseases (NCDs). Identifying genetic determinants of infections and antibody-mediated immune responses may shed light on this relationship and provide therapeutic targets for drug and vaccine development. We used the UK biobank cohort of up to 10 000 serological measurements of infectious diseases and genome-wide genotyping. We used data on 13 pathogens to define 46 phenotypes: 15 seropositivity case–control phenotypes and 31 quantitative antibody measurement phenotypes. For each of these, we performed genome-wide association studies (GWAS) using the fastGWA linear mixed model package and human leukocyte antigen (HLA) classical allele and amino acid residue associations analyses using Lasso regression for variable selection. We included a total of 8735 individuals for case–control phenotypes, and an average (range) of 4286 (276–8555) samples per quantitative analysis. Fourteen of the GWAS yielded a genome-wide significant (P < 5 ×10^-8) locus at the major histocompatibility complex (MHC) on chromosome 6. Outside the MHC, we found a total of 60 loci, multiple associated with Epstein-Barr virus (EBV)–related NCDs (eg, RASA3, MED12L, and IRF4). FUT2 was also identified as an important gene for polyomaviridae. HLA analysis highlighted the importance of DRB1*09:01, DQB1*02:01, DQA1*01:02, and DQA1*03:01 in EBV serologies and of DRB1*15:01 in polyomaviridae. We have identified multiple genetic variants associated with antibody immune response to 13 infections, many of which are biologically plausible therapeutic or vaccine targets. This may help prioritize future research and drug development.

The OAS1/2/3 cluster has been identified as a risk locus for severe COVID-19 among individuals of European ancestry, with a protective haplotype of approximately 75 kilobases (kb) derived from Neanderthals in the chromosomal region 12q24.13. This haplotype contains a splice variant of OAS1, which occurs in people of African ancestry independently of gene flow from Neanderthals. Using trans-ancestry fine-mapping approaches in 20,779 hospitalized cases, we demonstrate that this splice variant is likely to be the SNP responsible for the association at this locus, thus strongly implicating OAS1 as an effector gene influencing COVID-19 severity.