Comparative transmissibility of SARS-CoV-2 variants Delta and Alpha in New England, USA.

The SARS-CoV-2 Delta variant rose to dominance in mid-2021, likely propelled by an estimated 40%-80% increased transmissibility over Alpha. To investigate if this ostensible difference in transmissibility is uniform across populations, we partner with public health programs from all six states in New England in the United States. We compare logistic growth rates during each variant's respective emergence period, finding that Delta emerged 1.37-2.63 times faster than Alpha (range across states). We compute variant-specific effective reproductive numbers, estimating that Delta is 63%-167% more transmissible than Alpha (range across states). Finally, we estimate that Delta infections generate on average 6.2 (95% CI 3.1-10.9) times more viral RNA copies per milliliter than Alpha infections during their respective emergence. Overall, our evidence suggests that Delta's enhanced transmissibility can be attributed to its innate ability to increase infectiousness, but its epidemiological dynamics may vary depending on underlying population attributes and sequencing data availability.

Viral Sequencing to Investigate Sources of SARS-CoV-2 Infection in US Healthcare Personnel.

BACKGROUND: Healthcare personnel (HCP) are at increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We posit that current infection control guidelines generally protect HCP from SARS-CoV-2 infection in a healthcare setting. METHODS: In this retrospective case series, we used viral genomics to investigate the likely source of SARS-CoV-2 infection in HCP at a major academic medical institution in the Upper Midwest of the United States between 25 March and 27 December 2020. We obtained limited epidemiological data through informal interviews and review of the electronic health record and combined this information with healthcare-associated viral sequences and viral sequences collected in the broader community to infer the most likely source of infection in HCP. RESULTS: We investigated SARS-CoV-2 infection clusters involving 95 HCP and 137 possible patient contact sequences. The majority of HCP infections could not be linked to a patient or coworker (55 of 95 [57.9%]) and were genetically similar to viruses circulating concurrently in the community. We found that 10.5% of HCP infections (10 of 95) could be traced to a coworker. Strikingly, only 4.2% (4 of 95) could be traced to a patient source. CONCLUSIONS: Infections among HCP add further strain to the healthcare system and put patients, HCP, and communities at risk. We found no evidence for healthcare-associated transmission in the majority of HCP infections evaluated. Although we cannot rule out the possibility of cryptic healthcare-associated transmission, it appears that HCP most commonly become infected with SARS-CoV-2 via community exposure. This emphasizes the ongoing importance of mask wearing, physical distancing, robust testing programs, and rapid distribution of vaccines.

High Prevalence of SARS-CoV-2 Genetic Variation and D614G Mutation in Pediatric Patients With COVID-19.

BACKGROUND: The full spectrum of the disease phenotype and viral genotype of coronavirus disease 2019 (COVID-19) have yet to be thoroughly explored in children. Here, we analyze the relationships between viral genetic variants and clinical characteristics in children. METHODS: Whole-genome sequencing was performed on respiratory specimens collected for all SARS-CoV-2-positive children (n = 141) between March 13 and June 16, 2020. Viral genetic variations across the SARS-CoV-2 genome were identified and investigated to evaluate genomic correlates of disease severity. RESULTS: Higher viral load was detected in symptomatic patients (P = .0007) and in children <5 years old (P = .0004). Genomic analysis revealed a mean pairwise difference of 10.8 single nucleotide variants (SNVs), and the majority (55.4%) of SNVs led to an amino acid change in the viral proteins. The D614G mutation in the spike protein was present in 99.3% of the isolates. The calculated viral mutational rate of 22.2 substitutions/year contrasts the 13.5 substitutions/year observed in California isolates without the D614G mutation. Phylogenetic clade 20C was associated with severe cases of COVID-19 (odds ratio, 6.95; P = .0467). Epidemiological investigation revealed major representation of 3 of 5 major Nextstrain clades (20A, 20B, and 20C) consistent with multiple introductions of SARS-CoV-2 in Southern California. CONCLUSIONS: Genomic evaluation demonstrated greater than expected genetic diversity, presence of the D614G mutation, increased mutation rate, and evidence of multiple introductions of SARS-CoV-2 into Southern California. Our findings suggest a possible association of phylogenetic clade 20C with severe disease, but small sample size precludes a definitive conclusion. Our study warrants larger and multi-institutional genomic evaluation and has implications for infection control practices.

Emergence of an early SARS-CoV-2 epidemic in the United States.

The emergence of the COVID-19 epidemic in the United States (U.S.) went largely undetected due to inadequate testing. New Orleans experienced one of the earliest and fastest accelerating outbreaks, coinciding with Mardi Gras. To gain insight into the emergence of SARS-CoV-2 in the U.S. and how large-scale events accelerate transmission, we sequenced SARS-CoV-2 genomes during the first wave of the COVID-19 epidemic in Louisiana. We show that SARS-CoV-2 in Louisiana had limited diversity compared to other U.S. states and that one introduction of SARS-CoV-2 led to almost all of the early transmission in Louisiana. By analyzing mobility and genomic data, we show that SARS-CoV-2 was already present in New Orleans before Mardi Gras, and the festival dramatically accelerated transmission. Our study provides an understanding of how superspreading during large-scale events played a key role during the early outbreak in the U.S. and can greatly accelerate epidemics.

Field and Molecular Epidemiology: How Viral Sequencing Changed Transmission Inferences in the First Portuguese SARS-CoV-2 Infection Cluster.

Field epidemiology and viral sequencing provide a comprehensive characterization of transmission chains and allow a better identification of superspreading events. However, very few examples have been presented to date during the COVID-19 pandemic. We studied the first COVID-19 cluster detected in Portugal (59 individuals involved amongst extended family and work environments), following the return of four related individuals from work trips to Italy. The first patient to introduce the virus would be misidentified following the traditional field inquiry alone, as shown by the viral sequencing in isolates from 23 individuals. The results also pointed out family, and not work environment, as the primary mode of transmission.

Molecular Detection of SARS-CoV-2 Infection in FFPE Samples and Histopathologic Findings in Fatal SARS-CoV-2 Cases.

OBJECTIVES: To report methods and findings of 2 autopsies with molecular evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals. METHODS: Postmortem examination was completed following Centers for Disease Control and Prevention public guidelines. Numerous formalin-fixed paraffin-embedded (FFPE) tissue types from each case were surveyed for SARS-CoV-2 RNA by quantitative reverse transcription polymerase chain reaction (qRT-PCR). SARS-CoV-2 viral genome was sequenced by next-generation sequencing (NGS) from FFPE lung tissue blocks. RESULTS: Postmortem examinations revealed diffuse alveolar damage, while no viral-associated hepatic, cardiac, or renal damage was observed. Viral RNA was detected in lungs, bronchi, lymph nodes, and spleen in both cases using qRT-PCR method. RNA sequencing using NGS in case 1 revealed mutations most consistent with Western European Clade A2a with ORF1a L3606F mutation. CONCLUSIONS: SARS-CoV-2 testing and viral sequencing can be performed from FFPE tissue. Detection and sequencing of SARS-CoV-2 in combination with morphological findings from postmortem tissue examination can aid in gaining a better understanding of the virus's pathophysiologic effects on human health.