Implementation of California COVIDNet - a multi-sector collaboration for statewide SARS-CoV-2 genomic surveillance.

Introduction: The SARS-CoV-2 pandemic represented a formidable scientific and technological challenge to public health due to its rapid spread and evolution. To meet these challenges and to characterize the virus over time, the State of California established the California SARS-CoV-2 Whole Genome Sequencing (WGS) Initiative, or "California COVIDNet". This initiative constituted an unprecedented multi-sector collaborative effort to achieve large-scale genomic surveillance of SARS-CoV-2 across California to monitor the spread of variants within the state, to detect new and emerging variants, and to characterize outbreaks in congregate, workplace, and other settings. Methods: California COVIDNet consists of 50 laboratory partners that include public health laboratories, private clinical diagnostic laboratories, and academic sequencing facilities as well as expert advisors, scientists, consultants, and contractors. Data management, sample sourcing and processing, and computational infrastructure were major challenges that had to be resolved in the midst of the pandemic chaos in order to conduct SARS-CoV-2 genomic surveillance. Data management, storage, and analytics needs were addressed with both conventional database applications and newer cloud-based data solutions, which also fulfilled computational requirements. Results: Representative and randomly selected samples were sourced from state-sponsored community testing sites. Since March of 2021, California COVIDNet partners have contributed more than 450,000 SARS-CoV-2 genomes sequenced from remnant samples from both molecular and antigen tests. Combined with genomes from CDC-contracted WGS labs, there are currently nearly 800,000 genomes from all 61 local health jurisdictions (LHJs) in California in the COVIDNet sequence database. More than 5% of all reported positive tests in the state have been sequenced, with similar rates of sequencing across 5 major geographic regions in the state. Discussion: Implementation of California COVIDNet revealed challenges and limitations in the public health system. These were overcome by engaging in novel partnerships that established a successful genomic surveillance program which provided valuable data to inform the COVID-19 public health response in California. Significantly, California COVIDNet has provided a foundational data framework and computational infrastructure needed to respond to future public health crises.

A population-based study of neurologic manifestations of severe influenza A(H1N1)pdm09 in California.

BACKGROUND: Reported influenza-associated neurologic complications are generally limited to case series or case reports. We conducted a population-based study of neurologic manifestations associated with severe and fatal influenza A(H1N1)pdm09 (2009 H1N1) cases. METHODS: Medical records of patients with fatal or severe (hospitalized in intensive care unit) laboratory-confirmed 2009 H1N1 reported to the California Department of Public Health from 15 April 2009 through 31 December 2009 were reviewed to identify those with primary neurological manifestations. Cases with secondary neurologic manifestations (eg, hypoxia) were excluded. Primary influenza-associated neurologic complications (INCs) were classified into 4 groups: encephalopathy/encephalitis, seizures, meningitis, and other. Severe 2009 H1N1-associated neurologic incidence was calculated by using estimates of 2009 H1N1 illnesses in California. RESULTS: Of 2069 reported severe or fatal 2009 H1N1 cases, 419 (20%) had neurologic manifestations. Of these, 77 (18%) met our definition of INCs: encephalopathy/encephalitis (n = 29), seizures (n = 44), meningitis (n = 3), and other (Guillain-Barré Syndrome) (n = 1). The median age was 9 years (range, 4 months-92 years); the highest rate of disease was among pediatric Asian/Pacific Islanders (12.79 per 1,000,000) compared with pediatric white, non-Hispanics (3.09 per 1,000,000), Hispanics (4.58 per 1,000,000), and blacks (6.57 per 1,000,000). The median length of stay (LOS) was 4 days (range, 1-142), and there were 4 fatalities. The estimated incidence of INCs was 1.2 per 100,000 symptomatic 2009 H1N1 illnesses. CONCLUSIONS: Influenza-associated neurologic complications were observed in 4% of patients with fatal or severe 2009 H1N1. They were observed most often in pediatric patients, and Asian/Pacific Islanders appear to be overrepresented compared with the California population. Most patients with INCs had a relatively short LOS, and there were few fatalities.

In search of encephalitis etiologies: diagnostic challenges in the California Encephalitis Project, 1998-2000.

The California Encephalitis Project was initiated in June 1998 to identify the causes and characterize the clinical and epidemiologic features of encephalitis in California. Testing for >or=13 agents, including herpesviruses, enteroviruses, arboviruses, Bartonella species, Chlamydia species, and Mycoplasma pneumoniae, was performed at the Viral and Rickettsial Disease Laboratory (Richmond, California). Epidemiologic and clinical information collected for each case guided further testing. From June 1998 through December 2000, 334 patients who met our case definition of encephalitis were enrolled. A confirmed or probable viral agent of encephalitis was found in 31 cases (9%), a bacterial agent was found in 9 cases (3%), and a parasitic agent was found in 2 cases (1%). A possible etiology was identified in 41 cases (12%). A noninfectious etiology was identified in 32 cases (10%), and a nonencephalitis infection was identified in 11 (3%). Despite extensive testing and evaluation, the etiology of 208 cases (62%) remained unexplained.

Refractory status epilepticus in suspect encephalitis.

BACKGROUND: The California Encephalitis Project (CEP) is a program designed to determine causes of encephalitis. We sought to determine whether there are any distinguishing characteristics of patients with encephalitis who develop refractory status epilepticus from those who do not. METHODS: Data from all patients in the CEP were retrospectively reviewed and analyzed. Diagnostic testing was performed for a panel of infectious agents and medical information collected using a standardized form. Encephalitis patients were subdivided into three categories: (i) patients with status epilepticus unresponsive to standard antiepileptic therapy who required general anesthetic coma for management (Group I), (ii) patients with seizures or status epilepticus responsive to standard antiepileptic therapy (Group II), and (iii) patients without seizures (Group III). Supplementary information was requested on Group I patients. RESULTS: Of 1,151 patients; 43 (4%) were classified as Group I, 459 (40%) as Group II, and 649 (56%) as Group III. Compared to Groups II and III, Group I patients were younger (median age = 10.0 years), more likely to have fever (93%), prodromal respiratory (57%) or gastrointestinal illness (64%), and less likely to have CSF pleocytosis (47%) or abnormal neuroimaging (16%). A causative infectious agent was verified in three of the Group I patients; and a putative agent in nine others. Supplementary information on Group I revealed that 28% died within 2 years and 56% were neurologically impaired or undergoing rehabilitation. CONCLUSIONS: Encephalitis and refractory status epilepticus occur most commonly in the pediatric age group, an infectious etiology is usually not established, and outcomes are generally poor.

Medical care capacity for influenza outbreaks, Los Angeles.

In December 1997, media reported hospital overcrowding and "the worst [flu epidemic] in the past two decades" in Los Angeles County (LAC). We found that rates of pneumonia and influenza deaths, hospitalizations, and claims were substantially higher for the 1997-98 influenza season than the previous six seasons. Hours of emergency medical services (EMS) diversion (when emergency departments could not receive incoming patients) peaked during the influenza seasons studied; the number of EMS diversion hours per season also increased during the seasons 1993-94 to 1997-98, suggesting a decrease in medical care capacity during influenza seasons. Over the seven influenza seasons studied, the number of licensed beds decreased 12%, while the LAC population increased 5%. Our findings suggest that the capacity of health-care systems to handle patient visits during influenza seasons is diminishing.