The severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) infection leading to COVID-19 is a raging pandemic across the world at present. It has infected 13 million and killed 571,000 individuals around the world as of today. The infection was first reported in Wuhan, Hubei Province of China in late December 2019.
Now, a group of researchers from the Netherlands, United Kingdom, Australia, and the United States has collaborated in a review of what is currently known about the disease. Their study titled, “Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19) - A Review,” was published the JAMA Network on July 10, 2020.
Need for this review
There is a so-called “Tsunami” of scientific research and information as well as evidence regarding SARS-CoV-2 infection and COVID-19 disease. The virus and the course of the disease are new to the scientific world, as is its pathophysiology and course. The infection typically leads to severe respiratory and hematological complications in some individuals who require hospitalization. Due to this sudden rise in hospitalizations, there is a sudden overwhelming of the health care system leading to several public health problems. There is a rise in the number of patients with COVID-19 admitted with severe pneumonia, and some develop unexplained multi-organ failure, wrote the researchers. This review was undertaken to summarize the currently available evidence regarding the pathology, person-to-person transmission, diagnosis, and management of COVID-19.
How was the data gathered?
For this study, the team looked at all available evidence and scientific literature on the infection and the disease on various scientific databases such as PubMed, LitCovid, bioRxiv, medRxiv, ClinicalTrials.gov, the Chinese Clinical Trial Registry, and the International Clinical Trials Registry Platform. They searched for papers with keywords “coronavirus, severe acute respiratory syndrome coronavirus 2, 2019-nCoV, SARS-CoV-2, SARS-CoV, MERS-CoV, and COVID-19” for all studies that were published between January 1, 2002, and June 15, 2020.
What was found?
The following were the different observations from the available scientific literature. The team wrote:
The researchers wrote that the novel coronavirus is a single-stranded RNA virus, and the common viruses in this family include “229E, OC43, NL63, and HKU1”. They explained that this SARS-CoV-2 is the third coronavirus that has led to an outbreak of human disease over the past two decades. The first was severe acute respiratory syndrome (SARS) that originated in Foshan, China, in an outbreak in 2002-2003 SARS-CoV pandemic. The second outbreak was due to the Middle East respiratory syndrome (MERS) that began in the Arabian peninsula in 2012.
This new virus has a “diameter of 60 nm to 140 nm and distinctive spikes, ranging from 9 nm to 12 nm”. It looks like a solar corona wrote the researchers. They added that bats are found to the natural reservoir for SARS-CoV-2, and pangolins could be intermediate hosts before humans are infected.
How does the human host respond to COVID-19?
The infection with SARS-CoV-2 typically begins when the virus invades the epithelial cells of the nose and bronchi. The viral structural spike (S) protein binds to the angiotensin-converting enzyme 2 (ACE2) receptor. The host cell contains an enzyme called the type 2 transmembrane serine protease (TMPRSS2) that breaks down the ACE2 and activates the SARS-CoV-2 S protein that allows entry of the virus into the host cell. Both ACE2 and TMPRSS2 are found in the lung cells.
This infection leads to the lowering of the lymphocytes, especially T-lymphocytes, and there is a viral inflammatory response. ACE inhibitor and angiotensin receptor blocker medications use for hypertension have not found to raise the risk of infection and severe COVID-19 or deaths. As the infection progresses in the lungs, it leads to inflammation, and there is a rise in monocytes and neutrophils. This leads to inflammatory infiltration that manifests as “ground-glass opacities on computed tomographic imaging.” There is also overt lung edema leading to early-phase acute respiratory distress syndrome (ARDS).
As the disease progressively worsens, there is an activation of the coagulation factors and clotting factors that are rapidly consumed. Studies have shown that nearly 80 percent of those who died of COVID-19 develop diffuse intravascular coagulation. There are thrombocytopenia and development of clots and its complications such as “deep venous thrombosis, pulmonary embolism, and thrombotic arterial complications (e.g., limb ischemia, ischemic stroke, myocardial infarction),” the team wrote. Some of these patients develop sepsis and multi-organ failure.
Transmission of the infection
The available data suggests the SARS-CoV-2 infection spread via droplets generated when an infected person talks, coughs, or sneezes. The team wrote that exposure to a person who is infected for over 15 minutes within 6 feet distance and brief exposure to those patients who are coughing and have other symptoms is associated with a greater risk of transmission. The infection can also be transmitted via viruses left on surfaces. Small droplets containing the virus left suspended in air can also lead to transmission, they wrote. The risk of transmission of the virus from the mother to her unborn baby (vertical transmission) has not yet been reported. The infection is commonly seen in the third trimester, and there have been no deaths in the mothers, and the newborn babies of infected mothers have also fared well, they wrote.
The transmission of the infection can be prevented by wearing masks – especially N95 respirators and surgical masks and maintaining a distance of at least 6 feet. Repeated hand washing and the use of alcohol-based sanitizers are recommended.
Common symptoms and lab and imaging findings
The common symptoms among those who are hospitalized include fever, dry cough, shortness of breath, headache, weakness, runny nose, anosmia or loss of smell, loss of taste, etc. There is a lowering of lymphocyte count, raised inflammatory markers such as ESR and C reactive protein, ferritin, TNF-alfa, Interleukins 1 and 6. There is an abnormality in prothrombin time (prolonged), low platelet count, elevated D dimer, and low fibrinogen.
On radiographic images, there is infiltration on both lungs in the lower lobes that appears as ground-glass opacities on chest CT scan.
Diagnosis and management
Diagnosis of the infection is made by testing the samples from nasopharyngeal secretions using polymerase chain reaction (PCR).
At present, there is no specific drug that can effectively cure COVID-19. Treatment thus is primarily supportive and symptomatic. Remdesivir –a drug used against Ebola infection, has found to reduce the time for recovery significantly.
Other drugs that are being used wrote the researchers, include –
- “antivirals (e.g., remdesivir, favipiravir)
- antibodies (e.g., convalescent plasma, hyperimmune immunoglobulins)
- anti-inflammatory agents (dexamethasone, statins)
- targeted immunomodulatory therapies (eg, tocilizumab, sarilumab, anakinra, ruxolitinib)
- anticoagulants (eg, heparin)
- antifibrotics (eg, tyrosine kinase inhibitors)”
The team also found that evidence suggests the benefits of prophylactic treatment with subcutaneous low molecular weight heparin in all hospitalized patients with COVID-19.
The team wrote in conclusion, “Many aspects of transmission, infection, and treatment remain unclear. Advances in prevention and effective management of COVID-19 will require basic and clinical investigation and public health and clinical interventions.” They wrote that as of now, no vaccine is available to prevent SARS-CoV-2, but around 120 candidates are in development around the world.
- Wiersinga WJ, Rhodes A, Cheng AC, Peacock SJ, Prescott HC. Pathophysiology, Transmission, Diagnosis, and Treatment of Coronavirus Disease 2019 (COVID-19): A Review. JAMA. Published online July 10, 2020. doi:10.1001/jama.2020.12839, https://jamanetwork.com/journals/jama/fullarticle/2768391