This phase starts when global surveillance networks have identified, in Country X, a novel pathogen and/or an unusual cluster of disease that appears to be infectious and has a reasonable likelihood of being highly transmissible human-to-human. No cases of disease have yet been identified in the United States; however, an introduction into the United States should be considered highly probable.

In this phase, a novel pathogen has been detected in wastewater (which usually precedes the appearance of human cases) or has been reported in humans in the US in at least one location (e.g., a sick patient who presented at a hospital emergency department). The symptoms seen in patients fit the description of cases seen elsewhere in the world. Minimal information is currently available on pathogen characteristics, including modes of transmission, the period when an individual is infectious, and whether the disease can spread asymptomatically.

During this phase, the first available FDA-authorized test kit should be rapidly distributed to the PHLs and the LRN, and also to hospital laboratories and commercial laboratories in high-risk areas, unless there are severe limitations on the supply chain. It is likely that this first test will be a molecular (PCR-based) test as these are usually the most sensitive. It is conceivable that diagnosis of some emerging pathogens may require another methodology including serology or mass spectroscopy. Initially, the test will be needed for confirming a diagnosis in patients with symptoms, establishing surveillance to identify and track where and how the pathogen is circulating, and to guide efforts to slow or stop its spread. Knowledge of available laboratory supplies, including sample collection supplies, is key.

In this phase, speed and clear public communication of what is known and what is not known, as well as coordination of all activities, is critical. The White House testing lead should have regular updates on all available information, in coordination with CDC, the HHS Administration for Strategic Preparedness and Response (ASPR), the DHS Federal Emergency Management Agency (FEMA), and other relevant departments and agencies.

Health authorities have identified multiple clusters of cases in different US states, indicating that there has been more than one introduction and probable local transmission. Preliminary information is emerging that can be used to support public health action regarding the mode of transmission of the pathogen and incubation period. Diagnostics manufacturers are beginning to design and develop their own tests based on the available sequence. HHS has declared a national emergency.

The first-available FDA-authorized test has been deployed to PHL/LRN laboratories, which are actively testing. A surge process is in place to transfer samples if one regional LRN laboratory becomes overwhelmed and cannot maintain a 24-hour internal turnaround time (TAT), which is important to ensure test results support public health and medical decision-making. To do this, LRN laboratories will need to have interoperable test requisition and reporting systems. In the past, legal challenges have limited abilities to transfer specimens across state lines, which must be resolved. Plans have been executed for distribution of kits of the first available FDA-authorized test to hospital laboratories and potentially some commercial laboratories as a backup to the LRN laboratories. This is dependent on the state of the supply chain. Hospital laboratories and some commercial laboratories are also adapting the first available test to their own high throughput platforms and will pursue FDA-authorization. It appears likely that the need for testing will exceed the capacity of the LRN and hospital laboratories and the US government is actively engaging commercial laboratories. The FDA is reviewing the validation data from new tests with rapid turnaround for a decision – no more than 21 days. The CDC has confirmed enough of the early results by targeted sequencing of the amplicon, such that confirmation by a second method is no longer required.

Supply chains are holding but mechanisms are in place to ensure materials are being transported to areas of greatest need. Funds from federal reserves are needed to enable and support widespread testing. POC and home-use test platforms are being developed to detect the new pathogen but will not be available for some time.

The pathogen has been detected in many states and the caseloads indicate the US is in the rapidly rising part of the epidemic curve. Federal emergency funding mechanisms have been put in place. Public health laboratories are at capacity but, provided the supply line is stable, are able to provide testing with a turnaround time from specimen collection to provision of results of less than 48 hours, which is less than the disease incubation period. Since the need for testing has exceeded the capacity of the LRN and hospital laboratories, the US government has incentivized large commercial laboratories to develop and validate tests on high-throughput automated platforms; having received FDA authorization, commercial laboratories have rapidly increased capacity for testing. Diagnostic manufacturers are developing POC and home-use tests and these platforms are being tested in clinical trials and will soon be reviewed by the FDA. The FDA should be providing clear test development and validation guidance for manufacturers, including how many samples should be used in validation studies.

Genomic sequencing to detect variants as well as drug resistance mutations is widespread and a plan, with funding, for appropriate US coverage for viral and serological surveillance has been developed by the CDC. The knowledge about the pathogen has increased, including an understanding of which populations are most vulnerable, the route of transmission, which are the most effective specimen types and whether asymptomatic individuals can transmit the virus. It is not yet known whether natural infection produces any, or potentially long-lasting, protection. Vaccines and therapeutics are not available.

The plans and infrastructure are in place for surveillance and reporting of results of laboratory-based tests. Plans and infrastructure are being developed for surveillance and limited reporting of home-use tests and POC tests so that they can be put in place as soon as the devices are authorized. Appropriate ways of communicating a rapidly evolving situation to the public have been determined as well as designating the right officials to be the designated communicators.

The pathogen has shown a capacity for extensive genomic variability and the resulting ability to circumvent individual immunity or evade the therapeutic effect of drugs. Because of this, there have been successive, non-seasonal surges of cases. Hospitals are at capacity, and healthcare professionals are exhausted. Commercial laboratories, with US government financial support, continue to provide testing in the population, as do public health laboratories. Non-medical testing sites are being heavily used either as collection sites with specimens being processed with POC platforms or being delivered to laboratories. Home-use tests are also now widely available through government funding although data on their use is not readily available. Vaccines and therapeutic agents are not yet available. Maintaining capacity and capability for a high level of testing in the face of successive surges is critical.

The US is now on the downward slope of the epidemic curve, case numbers are steadily decreasing, and no new significant variants have been detected. Public health measures are being lifted all over the US and the population has psychologically moved beyond being in a pandemic state of mind. The population of health care workers and laboratory sciences has dramatically decreased with staff retiring or leaving the profession.

It is not well understood whether, or when, the current outbreak will be substantially over, whether the pathogen will become seasonal, or whether further variants will emerge. At this stage, it is understood that the pathogen cannot be easily eliminated, and that the disease will likely become endemic. There are no school, college, or business closures. Emergency status is likely to be lifted which will affect how data, important for determining public health action, are collected. For example, CDC and state health departments may no longer mandate case reporting.

Federal funding is being rolled back and non-medical testing sites are closing and most testing is provided by the standard procedures and reimbursements in a combination of commercial, hospital, and public health labs. Home testing is being promoted as an effective screening method that supports individual decision making. New home testing data collection systems have been implemented and a consensus has been reached on the appropriate non-identifying metadata to collect. Depending on the timeline to reach the deceleration phase, vaccines may or may not be available. If available, vaccine uptake is being measured and some level of population immunity has been achieved. The number of vaccinated persons has been estimated, as have estimates of what percentage of the population has been infected, and thus acquired some level of natural immunity.