COVID-19 Fundamentals

Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. From there, the DNA can be visualized with analysis techniques such as gel electrophoresis. The speed, inexpensiveness, ease of use, and high sensitivity and specificity make this technique highly useful for the basic and biomedical sciences, and it has become instrumental in many applications, including forensic analysis, diagnosis of infectious diseases, and diagnosis and screening of genetic abnormalities.

The molecule DNA is the repository of heritable genetic information. In humans, DNA is contained in 23 chromosome pairs within the nucleus. The molecule provides the basic template for replication of genetic information, RNA transcription, and protein biosynthesis to promote cellular function and survival.

Epidemiologists use specific measures of morbidity and mortality to characterize the degree to which illness and disease are present in a population and in how much this affects the population’s health and death rate.

Coronaviruses are a group of related viruses that contain positive-sense, single-stranded RNA. Coronavirus derives its name from "κορώνα" in Greek, which translates as “crown,” after the small club-shaped proteins visible as a ring around the viral envelope in electron micrographs. Coronaviruses have large genomes, a propensity for mutation, and frequent recombination events that have resulted in a diversity of species. These new species are capable of rapid adaptation to new hosts and ecologic environments. New coronavirus infections have appeared in both humans and animals. Coronaviruses are known to be the cause of some cases of the common cold, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19).

Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. A number of etiologies exist, including diseases of the lungs, cardiovascular, and nervous system. Patients with respiratory failure may present with dyspnea, tachypnea, and altered mentation. The diagnosis is made with arterial blood gas and supplemented with laboratory and imaging studies to elicit an etiology. Management involves treating the underlying cause, supplemental oxygen administration, and mechanical ventilation for severe cases.

Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. The replication cycle differs between viruses that infect bacteria (bacteriophages) and viruses that infect eukaryotic cells. Bacteriophages have either a lytic or lysogenic replication cycle, while eukaryotic viruses have a defined 6-step replication process.

The entire DNA of a cell is replicated during the S (synthesis) phase of the cell cycle. The principle of replication is based on complementary nucleotide base pairing: adenine forms hydrogen bonds with thymine (or uracil in RNA) and guanine forms hydrogen bonds with cytosine. Replication occurs prior to cell division in the S phase of the cell cycle in order to allow 2 sets of chromosomes to be present during the metaphase of mitosis, after which they are equally partitioned into 2 new cells during separation (anaphase).

Disease surveillance is an important and fundamental part of public health. Different epidemiologic measures are used to inform health care providers and policy-makers about the incidence rates, cumulative incidence, attack rates, prevalence, and person-time at risk of a disease or condition. Surveillance can help determine the cause of a disease as well as monitor the risks for developing that disease. Surveillance also follows changes in the levels of risk, thereby providing guidance for developing and implementing programs for disease prevention and control.

Epidemiological studies are designed to evaluate a hypothesized relationship between an exposure and an outcome; however, the existence and/or magnitude of these relationships may be erroneously affected by the design and execution of the study itself or by conscious or unconscious errors perpetrated by the investigators or the subjects. These systematic errors are called biases. If not avoided or accounted for, biases can completely invalidate the results of an otherwise well-thought-out study.