COVID-19: Update on the Origin, Transmission, and Clinical Therapies

A summary of the current knowledge on the epidemiology, pathogenesis, and clinical characteristics of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), was published in Military Medical Research. The report indicated that while treatment with antiviral drugs has shown some effect, solid data from further clinical trials are needed, as are more studies regarding the transmission and pathogenicity mechanism of COVID-19.

In December 2019, an epidemic of acute respiratory tract infection first emerged in Wuhan, China, possibly related to a seafood market; however, there is no evidence so far that this was indeed the origin of SARS-CoV-2. Bats are the natural reservoir of a wide variety of coronaviruses, including those that caused SARS in 2002 and Middle East Respiratory Syndrome (MERS) in 2012. After virus genome sequencing, SARS-CoV-2 was shown to be 96.2% identical to a bat CoV RaTG13. Based on this finding, combined with evolutionary analysis, bats are suspected to be the natural host of origin of the virus.

Though COVID-19 exhibits strong infectivity compared with SARS and MERS, it has less virulence in terms of morbidity and mortality. Available data currently suggests that COVID-19 has a mortality of 3.4%, whereas the death rate of SARS was 9.6%, and that of MERS was approximately 35%. In terms of pathogenesis, SARS-CoV-2 binds to the angiotensin-converting enzyme 2, which is found in the lower respiratory tract of humans, with a high virus-receptor affinity to infection; however, the possible molecules facilitating membrane invagination for endocytosis remain unclear. The infection spreads primarily through the respiratory system via droplets, secretions, and direct contact; however, SARS-CoV-2 viron particles have been found in blood and fecal swabs, the possibility exists for other routes of transmission.

The COVID-19 incubation period is between 1 and 14 days, though clinically this has been evidenced to commonly occur over a period of 3 to 7 days, and is contagious during the latency period. It is highly transmissible in humans, with the most vulnerable populations being the elderly and individuals with underlying chronic diseases. The median age of COVID-19 patients is 47 to 59 years, and 41.9% to 45.7% of people affected by the infection are women. Patients present with similar symptoms, with the most common being fever (88.7%), cough (67.8%), fatigue (38.1%), sputum production (33.4%), shortness of breath (18.6%), sore throat (13.9%), and headache (13.6%), with a small proportion of patients experiencing gastrointestinal symptoms like diarrhea (3.8%) and vomiting (5.0%). Most patients manifest mild flu-like symptoms, and those who progress to critical condition can rapidly develop acute respiratory distress syndrome, multiple organ failure, and death.

In terms of laboratory examination results, most patients demonstrated normal or decreased white blood cell counts, and lymphocytopenia. However, patients with severe illness commonly demonstrate a significantly higher than normal neutrophil count, D-dimer, blood urea, and creatinine levels, as well as a further decrease in lymphocyte counts.

Computed tomography on the chest has demonstrated ground-glass opacity (56.4%) and bilateral patchy shadowing (51.8%), sometimes with a rounded morphology and a peripheral lung distribution. However, the researchers highlight that there are significant cases of people with SARS-CoV-2 infection and normal imaging results.

Given that no cure for COVID-19 currently exists, current treatments are focused on symptom relief and the prevention of respiratory failure. Treatment with potent antiviral drugs such as remdesivir, or lopinavir/ritonavir as well as the antimalarial medication chloroquine have shown early positive results in some patients with COVID-19, but further data from more clinical trials are urgently needed.

The researchers concluded that questions about SARS-CoV-2 “remain vague and more studies are urgent to explore the transmission and pathogenicity mechanism of the emerging coronavirus. To make clear the evolutionary path from the original host to cross-species transmission so as to potentially limit the transmission to naïve animals or humans. In addition, to uncover the mystery of the molecular mechanism of viral entry and replication, which provides the basis of future research on developing targeted antiviral drugs and vaccines.”

Reference

Guo YR, Cao QD, Hong ZS, et al. The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak – an update on the status. Mil Med Res. 2020;7(1):11.