Image: Open Source Ventilator, Pakistan; Muhammad Umair

Epidemiology of COVID-19

The COVID-19 pandemic has exploded since the disease was first identified in China in December of 2019. As of October 28, 2022 more than 629 million cases of COVID-19 have been reported globally, including more than 6.5 million deaths [45]. The actual numbers are likely significantly higher. According to mathematical estimates, less than one in five COVID-19 cases that occurred in the first 29 months of the pandemic are accounted for in cases that have been officially registered [44].  Individuals of all ages are at risk for infection and severe disease. However, the probability of serious complications and fatal disease is highest in people over the age of 65 years and those living in long-term care facilities or nursing homes. Others at particularly high risk for COVID-19 are people of any age with existing underlying conditions, especially when not well-controlled [2,3].

Transmission of COVID-19

The onset and duration of viral shedding and period of infectiousness are not completely defined. Asymptomatic or pre-symptomatic individuals infected with COVID-19 may have viral RNA detected in upper respiratory specimens before the onset of symptoms [4]. Additionally, transmission from asymptomatic individuals has been described [5].

The time from exposure to onset of symptoms is typically around five days but may range from two to fourteen days [6]. The virus is primarily spread between people during close contact, [7] often via small droplets produced by coughing, sneezing, or talking [8]. Additionally, these droplets fall to the ground or onto surfaces where people may also become infected by touching a contaminated surface and then touching their face, nose, mouth, or eyes [9].

Smaller respiratory droplets, known as aerosols, have the ability to remain suspended in the air for a longer amount of time and can transmit the virus if they are inhaled by others. There have been reported outbreaks of COVID-19 in closed settings (such as restaurants, bars, and places of worship) where people were shouting, talking, or singing. These likely crowded and poorly ventilated spaces facilitated the spread of infectious aerosols [10].

It appears that the virus that causes COVID-19 can spread from people to animals in some situations. The USDA previously confirmed COVID-19 infection in one tiger at a zoo in New York after several large cats began to suffer from respiratory illness [11]. The CDC is aware of a small number of pets, including cats and dogs, reported to be infected with the virus that causes COVID-19. These infections occurred after the animals had close contact with people actively infected with COVID-19 [12]. Infected pets may show signs of illness or they may not have any symptoms. Of the pets that have been infected, most only had mild illness and fully recovered [13].

Clinical Presentation of COVID-19

The spectrum of illness from COVID-19 can range from asymptomatic infection to severe pneumonia with acute respiratory distress syndrome (ARDS) and death. In an early summary of 72,314 persons with COVID-19 in China, 81% of cases were reported to be mild, 14% were severe, and 5% were critical [14]. Symptoms may appear anywhere from 2-14 days after exposure to the virus. The most common symptoms of COVID-19 include: fever or chills, cough, shortness of breath or difficulty breathing, fatigue, body aches, headache, loss of taste or smell, sore throat, runny nose or congestion, nausea or vomiting, and diarrhea [15].

Using nasal or oral samples, viral testing determines the presence of an active infection with SARS-CoV-2, the virus responsible for COVID-19. The two most common forms of viral tests are antigen testing and nucleic acid amplification tests (NAATs). In certain circumstances, one test type may be preferred over another. All testing must be completed according to FDA guidelines.

Diagnosing COVID-19

PCR-based tests have become the gold-standard testing method and require processing in a laboratory. These tests are the most reliable diagnostics for symptomatic and asymptomatic patients alike. Following a positive test result, viral genetic material can stay in the body for up to 90 days, therefore it is not recommended that a PCR test be given within 90 days of a previous infection [41]. 

Rapid antigen tests provide results within fifteen to thirty minutes. They are less reliable than NAATs, particularly for those without symptoms. A single negative antigen test result cannot exclude the possibility of infection. For best infection identification, a negative antigen test must be repeated at least 48 hours apart (known as serial testing). To confirm the results of an antigen test, a follow-up NAAT is sometimes recommended.

Self-tests, also referred to as at-home tests, are generally antigen tests that may be done anywhere, without the need to attend a specialized testing facility. Follow the FDA and manufacturer’s instructions for testing frequency, if necessary. Multiple negative test results do not necessarily indicate the absence of a COVID-19 infection [40]. 

Abnormalities in chest X-ray vary, but typically reveal bilateral multifocal opacities. Chest x-rays obtained early during the course of infection may not reveal significant changes [18]. Abnormalities seen in computed tomography (CT) of the chest also vary, but typically reveal bilateral peripheral ground-glass opacities with the development of areas of consolidation later in the clinical course [19].

Treatment of COVID-19

Patients with a mild clinical presentation (without viral pneumonia and hypoxia) may not require hospitalization, and many patients will be able to manage their illness at home. The decision to monitor a patient in the inpatient or outpatient setting should be made on a case-by-case basis [27]. This decision will depend on the clinical presentation, requirement for supportive care, risk factors for complications, and if the patient is able to self-isolate at home. Patients with risk factors for severe illness should be monitored closely given the possible risk of progression to severe illness during the second week following symptom onset [28,29].

The global availability of targeted COVID-19 treatments varies widely. An antiviral medication may reduce the severity of symptoms by preventing the SARS-CoV-2 virus from replicating inside the body. Antiviral treatment may be given orally, as a pill (oral antivirals), or intravenously (intravenous antivirals) (IV antivirals). Oral antiviral treatment must be administered within five days of the onset of COVID-19 symptoms. Intravenous antivirals must be administered within seven days of the onset of symptoms [42]. 

Treatment with monoclonal antibodies (mAb) enhances the body’s ability to fight COVID-19. The mAb therapy can prevent the SARS-CoV-2 virus from entering cells, hence reducing the amount of virus in the body. These antibodies assist the immune system in recognizing the pathogen and responding more effectively. A mAb treatment may prevent symptoms from getting severe enough to require hospitalization. The medication must be administered within the first seven days of the onset of symptoms for individuals at high risk for developing severe COVID-19 symptoms. The mAb therapy may be administered via intravenous infusion or as a series of injections [43].

A patient may require hospitalization for severe symptoms or complications from a COVID-19 infection. The majority of inpatient management revolves around the supportive management of the most common complications of severe COVID-19: pneumonia, hypoxemic respiratory failure/ARDS, sepsis and septic shock, cardiomyopathy and arrhythmia, acute kidney injury, and complications from prolonged hospitalization including secondary bacterial infections, thromboembolism, gastrointestinal bleeding, and critical illness polyneuropathy/myopathy [35,36,37,38].

Clinical Resources

Information for Healthcare Professionals about Coronavirus (COVID-19)(CDC)

ADACoronavirus (COVID-19) Center for Dentists (ADA)

Q&A on coronaviruses (COVID-19) (WHO)

Coronavirus Disease 2019 (COVID-19) (FDA)

FEMA Releases Latest State-by-State COVID-19 Data (FEMA)

Visualization of Symptoms of COVID19 Over Time, ~5 Days After Exposure

Image: PUC Rio, Rio de Janeiro, Brazil; Marcelo Balisteri