Severe Acute Respiratory Syndrome Coronavirus 2 and Respiratory Virus Sentinel Surveillance, California, USA, May 10, 2020-June 12, 2021.

State and local health departments established the California Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Respiratory Virus Sentinel Surveillance System to conduct enhanced surveillance for SARS-CoV-2 and other respiratory pathogens at sentinel outpatient testing sites in 10 counties throughout California, USA. We describe results obtained during May 10, 2020‒June 12, 2021, and compare persons with positive and negative SARS-CoV-2 PCR results by using Poisson regression. We detected SARS-CoV-2 in 1,696 (19.6%) of 8,662 specimens. Among 7,851 specimens tested by respiratory panel, rhinovirus/enterovirus was detected in 906 (11.5%) specimens and other respiratory pathogens in 136 (1.7%) specimens. We also detected 23 co-infections with SARS-CoV-2 and another pathogen. SARS-CoV-2 positivity was associated with male participants, an age of 35-49 years, Latino race/ethnicity, obesity, and work in transportation occupations. Sentinel surveillance can provide useful virologic and epidemiologic data to supplement other disease monitoring activities and might become increasingly useful as routine testing decreases.

A diagnostic host response biosignature for COVID-19 from RNA profiling of nasal swabs and blood.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease-19 (COVID-19), has emerged as the cause of a global pandemic. We used RNA sequencing to analyze 286 nasopharyngeal (NP) swab and 53 whole-blood (WB) samples from 333 patients with COVID-19 and controls. Overall, a muted immune response was observed in COVID-19 relative to other infections (influenza, other seasonal coronaviruses, and bacterial sepsis), with paradoxical down-regulation of several key differentially expressed genes. Hospitalized patients and outpatients exhibited up-regulation of interferon-associated pathways, although heightened and more robust inflammatory responses were observed in hospitalized patients with more clinically severe illness. Two-layer machine learning-based host classifiers consisting of complete (>1000 genes), medium (<100), and small (<20) gene biomarker panels identified COVID-19 disease with 85.1-86.5% accuracy when benchmarked using an independent test set. SARS-CoV-2 infection has a distinct biosignature that differs between NP swabs and WB and can be leveraged for COVID-19 diagnosis.

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

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 from respiratory swab RNA extracts. 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.

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

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.

Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, with >365,000 cases in California as of 17 July 2020. We investigated the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning nine counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least seven different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington state, with lack of a predominant lineage and limited transmission among communities. Lineages associated with outbreak clusters in two counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain the spread of SARS-CoV-2 in California and other states.

CRISPR-Cas12-based detection of SARS-CoV-2.

An outbreak of betacoronavirus severe acute respiratory syndrome (SARS)-CoV-2 began in Wuhan, China in December 2019. COVID-19, the disease associated with SARS-CoV-2 infection, rapidly spread to produce a global pandemic. We report development of a rapid (<40 min), easy-to-implement and accurate CRISPR-Cas12-based lateral flow assay for detection of SARS-CoV-2 from respiratory swab RNA extracts. We validated our method using contrived reference samples and clinical samples from patients in the United States, including 36 patients with COVID-19 infection and 42 patients with other viral respiratory infections. Our CRISPR-based DETECTR assay provides a visual and faster alternative to the US Centers for Disease Control and Prevention SARS-CoV-2 real-time RT-PCR assay, with 95% positive predictive agreement and 100% negative predictive agreement.

Treatment with neuraminidase inhibitors for critically ill patients with influenza A (H1N1)pdm09.

BACKGROUND: Neuraminidase inhibitor (NAI) antiviral drugs can shorten the duration of uncomplicated influenza when administered early (<48 hours after illness onset) to otherwise healthy outpatients, but the optimal timing of effective therapy for critically ill patients is not well established. METHODS: We analyzed California surveillance data to characterize the outcomes of patients in intensive care units (ICUs) treated with NAIs for influenza A(H1N1)pdm09 (pH1N1). Demographic and clinical data were abstracted from medical records, using standardized case report forms. RESULTS: From 3 April 2009 through 10 August 2010, 1950 pH1N1 cases hospitalized in ICUs were reported. Of 1859 (95%) with information available, 1676 (90%) received NAI treatment, and 183 (10%) did not. The median age was 37 years (range, 1 week-93 years), 1473 (79%) had ≥1 comorbidity, and 492 (26%) died. The median time from symptom onset to starting NAI treatment was 4 days (range, 0-52 days). NAI treatment was associated with survival: 107 of 183 untreated case patients (58%) survived, compared with 1260 of 1676 treated case patients (75%; P ≤ .0001). There was a trend toward improved survival for those treated earliest (P < .0001). Treatment initiated within 5 days after symptom onset was associated with improved survival compared to those never treated (P < .05). CONCLUSIONS: NAI treatment of critically ill pH1N1 patients improves survival. While earlier treatment conveyed the most benefit, patients who started treatment up to 5 days after symptom onset also were more likely to survive. Further research is needed about whether starting NAI treatment >5 days after symptom onset may also convey benefit.

Rapid influenza antigen test for diagnosis of pandemic (H1N1) 2009.

We compared the QuickVue Influenza test with PCR for diagnosing pandemic (H1N1) 2009 in 404 persons with influenza-like illness. Overall sensitivity, specificity, and positive and negative predictive values were 66%, 84%, 84%, and 64%, respectively. Rapid test results should be interpreted cautiously when pandemic (H1N1) 2009 virus is suspected.

Antigenic and genetic characteristics of swine-origin 2009 A(H1N1) influenza viruses circulating in humans.

Since its identification in April 2009, an A(H1N1) virus containing a unique combination of gene segments from both North American and Eurasian swine lineages has continued to circulate in humans. The lack of similarity between the 2009 A(H1N1) virus and its nearest relatives indicates that its gene segments have been circulating undetected for an extended period. Its low genetic diversity suggests that the introduction into humans was a single event or multiple events of similar viruses. Molecular markers predictive of adaptation to humans are not currently present in 2009 A(H1N1) viruses, suggesting that previously unrecognized molecular determinants could be responsible for the transmission among humans. Antigenically the viruses are homogeneous and similar to North American swine A(H1N1) viruses but distinct from seasonal human A(H1N1).

Creating a model program for influenza surveillance in California: results from the 2005-2006 influenza season.

BACKGROUND: Influenza surveillance is valuable for monitoring trends in influenza-related morbidity and mortality. Using the 2005-2006 influenza season as an example, this paper describes a comprehensive influenza surveillance program used by the California Department of Public Health (CDPH). METHODS: Data collected from patients evaluated for acute respiratory illness in a given week were reported and summarized the following week, including (1) electronic hospital pneumonia and influenza admission and antiviral usage records from Kaiser Permanente, (2) sentinel provider influenza-like illness (ILI) reports, (3) severe pediatric influenza case reports (e.g., children either hospitalized in intensive care or expired), (4) school clinic ILI evaluations, and (5) positive influenza test results from a network of academic, hospital, commercial, and public health laboratories and the state CDPH Viral and Rickettsial Disease Laboratory. RESULTS: Influenza activity in California in the 2005-2006 season was moderate in severity; all clinical and laboratory markers rose and fell consistently. Extensive laboratory characterization identified the predominant circulating virus strain as A/California/7/2004(H3N2), which was a component of the 2005-2006 influenza vaccine; 96% of samples tested showed adamantane resistance. CONCLUSIONS: By using multiple, complementary surveillance methods coupled with a strong laboratory component, the CDPH has developed a simple, flexible, stable, and widely accepted influenza surveillance system that can monitor trends in statewide influenza activity, ascertain the correlation between circulating strains with vaccine strains, and assist with detection of new strain variants. The methods described can serve as a model for influenza surveillance in other states.

Severe pediatric influenza in California, 2003-2005: implications for immunization recommendations.

OBJECTIVE: The 2003-2004 influenza season was marked by both the emergence of a new drift "Fujian" strain of influenza A virus and prominent reports of increased influenza-related deaths in children in the absence of baseline data for comparison. In December 2003, the California Department of Health Services initiated surveillance of children who were hospitalized in California with severe influenza in an attempt to measure its impact and to identify additional preventive measures. METHODS: From December 2003 to May 2005, surveillance of children who were hospitalized in PICUs or dying in the hospital with laboratory evidence of influenza was performed by hospital infection control practitioners and local public health departments using a standardized case definition and reporting form. RESULTS: In the 2003-2004 and 2004-2005 influenza seasons, 125 and 35 cases, respectively, of severe influenza in children were identified in California. The mean and median age of cases were 3.1 years and 1.5 years, with breakdown as follows: < 6 months, 39 (24%); 6 to 23 months, 53 (33%); 2 to 4 years, 40 (25%); 5 to 11 years, 15 (9%); and 12 to 17 years, 13 (8%). Fifty-three percent (85 of 160) had an underlying medical condition(s), including a neurologic disorder (n = 36), chronic pulmonary disease (n = 26), genetic disorder (n = 19), cardiac disease (n = 18), prematurity (n = 14), immunocompromised status (n = 12), endocrine/renal disease (n = 2), and other (n = 1). Only 16% (15 of 96) of all patients had received influenza vaccination. Thirty-seven patients had an underlying illness that met existing Advisory Committee on Immunization Practices (ACIP) or American Academy of Pediatrics (AAP) recommendations for immunization, but only 8 had been vaccinated. CONCLUSIONS: More than 3 times as many children were reported to be hospitalized in intensive care with influenza in California during the 2003-2004 season compared with the 2004-2005 season. Because children who are younger than 6 months remain at highest risk for severe influenza yet cannot currently be immunized, development and validation of preventive measures for them (eg, maternal immunization, breastfeeding, immunization of young infants and their close contacts) are urgently needed. ACIP's recent recommendation for influenza vaccination of children with conditions that can compromise respiratory function (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, other neuromuscular disorders) is further supported by the frequency of underlying neurologic disease in these cases of severe influenza. A significant proportion of children with severe influenza in California, including children who are aged 2 to 4 years or have underlying genetic syndromes or prematurity, would not have been routinely recommended for influenza vaccination in 2005-2006 ACIP and AAP recommendations, calling into question whether such guidelines should be expanded. Continued surveillance for severe influenza-related morbidity and mortality is important to measure the impact of influenza on children.

Maternal HIV-1 antibody and vertical transmission in subtype C virus infection.

The role of maternal humoral immune response and viral load was analyzed in relation to the incidence of mother-to-child transmission (MTCT) of infants born to HIV-1 subtype C infected mothers. High levels of viral RNA in the serum correlated with MTCT as did high titers of subtype C consensus V3 peptide binding antibodies (BA) and neutralizing antibody (NA) to subtype B HIV-1MN. Logistic regression analysis showed that maternal viral load and V3 peptide subtype C BA were independent predictors for MTCT, odds ratio (OR) = 2.22 and OR = 2.52, respectively. No correlation between NA to homologous HIV-1 subtype C virus and MTCT was found. BA to V3 peptides may provide a rapid inexpensive method that can be used to determine the risk of HIV-1 MTCT.