COVID-19: The Pandemic Awaits a New Beginning

The coronavirus disease 2019 (COVID-19) pandemic is a nightmare that everyone is currently envisioning. It first emerged in December 2019 and continues to dwell within our existence to 2021. Many people wonder, “When can we attain normalcy again?” However, “normalcy” will no longer be considered returning to our “normal” routine because the pandemic caused so many people to endure herculean lifestyle changes. We can all agree that everyone awaits a “new beginning.” A time when we perhaps learned to coexist with the virus; however, this time, we are surviving.

It’s the start of a new year; however in reality, the effects of the pandemic continue to linger. In the United States, there are currently 23 million COVID-19 cases and 380,000 deaths, which continue to increase as we repeatedly draw the shorter end of the straw.1 The virus does not discriminate, for it infects anyone no matter the age, gender, race, or social status. Even the president, Donald Trump, who will soon meet the end of his presidency, could not shield himself from this virus in the same fashion as he protects his reputation by blaming others and lying. The Food and Drug Administration (FDA) granted emergency authorization through a compassionate-use program for Trump to receive doses of the experimental antibody cocktail (developed by Regeneron). He recovered quickly after receiving this magic bullet, which he inaccurately referred to as a “cure.”2

Etiology:

COVID-19 is caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It was first discovered when a group of patients was diagnosed with pneumonia in Wuhan, China. Coronaviruses do not solely infect humans; they are also found in ubiquitous animals such as dogs, cats, and birds.3

Transmission:

Coronaviruses are capable of cross-species transmission via genetic recombination. Bats are a natural reservoir for SARS-CoV-2, but recently it was reported that humans probably became infected with the virus through an intermediate host, such as the pangolin (scaly anteaters). 4 SARS-CoV-2 is a large, enveloped, single-stranded RNA virus that can hijack the machinery of human cells to initiate replication and produce many copies of itself. During the initial phase of the infection, SARS-CoV-2 targets nasal and bronchial epithelial cells by a binding interaction between the host angiotensin-converting enzyme 2 (ACE2) receptor and the spike (S) protein of the virus (Figure 1).5 The type 2 transmembrane serine protease (TMPRSS2) located on the host cell initiates viral uptake. The protease cleaves the ACE2 receptor and activates the S protein, mediating entry into host airway cells.5 Thereafter, the SARS-CoV-2 releases its RNA and utilizes the host cell machinery to replicate itself and assemble more virions (the complete form of a virus outside a host cell). The acceleration of viral replication promotes inflammation in the epithelial cells, activating the innate immune response, the first mechanism of the human defense system. In later stages of the infection, an influx of macrophages, T lymphocytes, and neutrophils (cells of the innate immune system) are recruited to the infection site.

Figure 1: The Mechanism of SARS-CoV-2 Entry into Host Cell

The primary mode of transmission to contract SARS-CoV-2 is via respiratory droplets from face-to-face exposure during talking, coughing, or sneezing. Prolonged exposure to an infected person (within 6 feet for at least 15 minutes) is associated with a higher risk for transmission.6 Individuals who contract the virus and do not present any symptoms related to the disease are asymptomatic. These individuals can also transmit the virus; however, brief exposures to asymptomatic contacts are considered a low risk for transmission. Alternative modes of transmission to a lesser degree include aerosols and contact surfaces. The virus survives longer on stainless steel and plastic (3-4 days) than cardboard and copper.7 The Centers for Disease Control and Prevention (CDC) established guidelines mandated to quarantine individuals infected with the virus. Individuals must quarantine for at least 10-14 days after exposure.8

Clinical Presentation9:

These mild symptoms may appear 2-14 days after exposure to the virus.

• Fever or chills

• Cough

• Shortness of breath or difficulty breathing

• Fatigue

• Muscle or body aches

• Headache

• New loss of taste or smell (ageusia or anosmia)

• Sore throat

• Congestion or runny nose

• Nausea or vomiting

• Diarrhea

COVID-19 also causes severe symptoms leading to an increase in hospitalizations:

• Trouble breathing

• Persistent pain or pressure in the chest

• New confusion

• Inability to wake or stay awake

• Bluish lips or face

Common laboratory abnormalities10:

• Profound lymphopenia (occurs when SARS-CoV-2 infects and kills T lymphocyte cells)

• Elevated liver enzymes: aspartate transaminase (AST) and alanine transaminase (ALT)

• Elevated inflammatory markers: C-reactive protein, erythrocyte sedimentation rate, and ferritin

Common complications11:

• Pneumonia

• Acute Respiratory Distress Syndrome (ARDS)

• Acute liver injury

• Acute myocarditis

• Deep vein thrombosis (blood clot formed in a deep vein, usually in the leg)

• Pulmonary embolism (blood clot formed in the arteries of the lungs)

• Acute kidney injury

• Sepsis (a life-threatening complication of an infection characterized by fever, difficulty breathing, low blood pressure, fast heart rate, and confusion)

• Intracranial hemorrhage

Diagnosis:

The primary diagnostic method is the reverse transcription polymerase chain reaction (RT-PCR) testing of a nasopharyngeal swab (Figure 2). Since there is a possibility of false-negative test results; clinical, laboratory, and imaging findings may also be used to make a plausible diagnosis. Factors contributing to false-negative test results include the adequacy of the specimen and time from exposure to the virus. The specimen source is also a factor since lower respiratory samples (sputum) are more sensitive than upper respiratory samples (nasopharyngeal swabs).3

Figure 2: Schematic of the diagnostic procedures used in the detection of SARS-CoV-2.

The PCR test is the current reference standard to detect SARS-CoV-2. Serologic testing has rapidly emerged and is also used to detect SARS-CoV-2 when RT-PCR may be falsely negative. Immunoassays identify antibodies to SARS-CoV-2 from clinical specimens. Compare to RT-PCR, serologic testing is easier to use with faster turn-around times. During the process of seroconversion (the time when antibodies develop and become detectable in the blood), IgM and IgG specific to SARS-CoV-2 spike or nucleocapsid proteins can be detected. Enzyme-linked immunosorbent assay (ELISA) is a common laboratory procedure that can measure antibody titers (IgM and IgG).

The ultimate goals to manage the COVID-19 pandemic are developing potent therapeutic agents to treat patients with the disease and providing immunity to the virus through vaccination. It is also crucial to practice preventive measures as we strive to determine “The Anticipated Resolution to the Memorable Pandemic.”

References:

1. World Health Organization. (2021, January 17). WHO COVID-19 Emergency Dashboard. Retrieved January 17, 2021, from https://covid19.who.int/region/amro/country/us

2. McGinley L and Johnson CY. (2020, November 21). Experimental Drug Given to Trump to Treat COVID-19 wins FDA clearance. The Washington Post. https://www.washingtonpost.com/health/2020/11/21/regeneron-fda-clearance/

3. Wiersinga WJ, Rhodes A, Cheng AC, et al. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19). JAMA. 2020;324(8):782-793.

4. Lam TT, Jia N, Zhang YW, et al. Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature. 2020.

5. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.

6. Chu DK, Akl EA, Duda S, et al; COVID-19 Systematic Urgent Review Group Effort (SURGE) study authors. Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19: a systematic review and meta-analysis. Lancet. 2020;395(10242):1973-1987.

7. van Doremalen N, Bushmaker T, Morris DH,et al. Aerosol and surface stability of SARS-CoV-2 as compared with SARS-CoV-1. N Engl J Med. 2020; 382(16):1564-1567.

8. Centers for Disease Control and Prevention. (2020, December 10). When to Quarantine. Your Health. Retrieved January 17, 2021, from https://www.cdc.gov/coronavirus/2019-ncov/if-you-are-sick/quarantine.html

9. Centers for Disease Control and Prevention. (2020, December 22). Symptoms of Coronavirus. Your Health. Retrieved January 17, 2021, from https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html

10. Levi M, Thachil J, Iba T, Levy JH. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020;7(6):e438-e440.

11. Cates J, Lucero-Obusan C and Dahl RM. (2020, October 23). Risk for In-Hospital Complications Associated with COVID-19 and Influenza. Morbidity and Mortality Weekly Report (MMWR). Retrieved January 16, 2021, from https://www.cdc.gov/mmwr/volumes/69/wr/mm6942e3.htm#T2_down

Cover Image created by Jessica Lewis

Figures 1 and 2 created with BioRender