Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation (preprint)

We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 remnant nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 or 20C/L452R, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an estimated 18.6-24% increase in transmissibility relative to wild-type circulating strains. This variant is characterized by three mutations in the spike protein, including a L452R substitution in the receptor-binding domain. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in SARS-CoV-2 variants of concern (B.1.1.7, B.1.351, and P.1 lineages). Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.

Genomic epidemiology identifies emergence and rapid transmission of SARS-CoV-2 B.1.1.7 in the United States (preprint)

As of January of 2021, the highly transmissible B.1.1.7 variant of SARS-CoV-2, which was first identified in the United Kingdom (U.K.), has gained a strong foothold across the world. Because of the sudden and rapid rise of B.1.1.7, we investigated the prevalence and growth dynamics of this variant in the United States (U.S.), tracking it back to its early emergence and onward local transmission. We found that the RT-qPCR testing anomaly of S gene target failure (SGTF), first observed in the U.K., was a reliable proxy for B.1.1.7 detection. We sequenced 212 B.1.1.7 SARS-CoV-2 genomes collected from testing facilities in the U.S. from December 2020 to January 2021. We found that while the fraction of B.1.1.7 among SGTF samples varied by state, detection of the variant increased at a logistic rate similar to those observed elsewhere, with a doubling rate of a little over a week and an increased transmission rate of 35-45%. By performing time-aware Bayesian phylodynamic analyses, we revealed several independent introductions of B.1.1.7 into the U.S. as early as late November 2020, with onward community transmission enabling the variant to spread to at least 30 states as of January 2021. Our study shows that the U.S. is on a similar trajectory as other countries where B.1.1.7 rapidly became the dominant SARS-CoV-2 variant, requiring immediate and decisive action to minimize COVID-19 morbidity and mortality.

Clinical features, diagnostics, and outcomes of patients presenting with acute respiratory illness: a comparison of patients with and without COVID-19 (preprint)

BackgroundEmerging data on the clinical presentation, diagnostics, and outcomes of patients with COVID-19 have largely been presented as case series. Few studies have compared these clinical features and outcomes of COVID-19 to other acute respiratory illnesses. MethodsWe examined all patients presenting to an emergency department in San Francisco, California between February 3 and March 31, 2020 with an acute respiratory illness who were tested for SARS-CoV-2. We determined COVID-19 status by PCR and metagenomic next generation sequencing (mNGS). We compared demographics, comorbidities, symptoms, vital signs, and laboratory results including viral diagnostics using PCR and mNGS. Among those hospitalized, we determined differences in treatment (antibiotics, antivirals, respiratory support) and outcomes (ICU admission, ICU interventions, acute respiratory distress syndrome, cardiac injury). FindingsIn a cohort of 316 patients, 33 (10%) tested positive for SARS-CoV-2; 31 patients, all without COVID-19, tested positive for another respiratory virus (16%). Among patients with additional viral testing, no co-infections with SARS-CoV-2 were identified by PCR or mNGS. Patients with COVID-19 reported longer symptoms duration (median 7 vs. 3 days) and were more likely to report fever (82% vs. 44%) fatigue (85% vs. 50%) and myalgias (61% vs 27%); p<0.001 for all comparisons. Lymphopenia (55% vs 34%, p=0.018) and bilateral opacities on initial chest radiograph (55% vs. 24%, p=0.001) were more common in patients with COVID-19. Patients with COVID-19 were more often hospitalized (79% vs. 56%, p=0.014). Of 186 hospitalized patients, patients with COVID-19 had longer hospitalizations (median 10.7d vs. 4.7d, p<0.001) and were more likely to develop ARDS (23% vs. 3%, p<0.001). Most comorbidities, home medications, signs and symptoms, vital signs, laboratory results, treatment, and outcomes did not differ by COVID-19 status. InterpretationWhile we found differences in clinical features of COVID-19 compared to other acute respiratory illnesses, there was significant overlap in presentation and comorbidities. Patients with COVID-19 were more likely to be admitted to the hospital, have longer hospitalizations and develop ARDS, and were unlikely to have co-existent viral infections. These findings enhance understanding of the clinical characteristics of COVID-19 in comparison to other acute respiratory illnesses.

Cryptic transmission of SARS-CoV-2 in Washington State (preprint)

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage (preprint)

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

Rapid Detection of 2019 Novel Coronavirus SARS-CoV-2 Using a CRISPR-based DETECTR Lateral Flow Assay (preprint)

An outbreak of novel betacoronavirus, SARS-CoV-2 (formerly named 2019-nCoV), began in Wuhan, China in December 2019 and the COVID-19 disease associated with infection has since spread rapidly to multiple countries. Here we report the development of SARS-CoV-2 DETECTR, a rapid (~30 min), low-cost, and accurate CRISPR-Cas12 based lateral flow assay for detection of SARS-CoV-2. We validated this method using contrived reference samples and clinical samples from infected US patients and demonstrated comparable performance to the US CDC SARS-CoV-2 real-time RT-PCR assay.