Virology, transmission, and pathogenesis of SARS-CoV-2

Authors: Muge Cevik, clinical lecturer2,  Krutika Kuppalli, assistant professor3,  Jason Kindrachuk, assistant professor of virology4,  Malik Peiris, professor of virology5

What you need to know

  • SARS-CoV-2 is genetically similar to SARS-CoV-1, but characteristics of SARS-CoV-2—eg, structural differences in its surface proteins and viral load kinetics—may help explain its enhanced rate of transmission
  • In the respiratory tract, peak SARS-CoV-2 load is observed at the time of symptom onset or in the first week of illness, with subsequent decline thereafter, indicating the highest infectiousness potential just before or within the first five days of symptom onset
  • Reverse transcription polymerase chain reaction (RT-PCR) tests can detect viral SARS-CoV-2 RNA in the upper respiratory tract for a mean of 17 days; however, detection of viral RNA does not necessarily equate to infectiousness, and viral culture from PCR positive upper respiratory tract samples has been rarely positive beyond nine days of illness
  • Symptomatic and pre-symptomatic transmission (1-2 days before symptom onset), is likely to play a greater role in the spread of SARS-CoV-2 than asymptomatic transmission
  • A wide range of virus-neutralizing antibodies have been reported, and emerging evidence suggests that these may correlate with severity of illness but wane over time.

Since the emergence of SARS-CoV-2 in December 2019, there has been an unparalleled global effort to characterize the virus and the clinical course of disease. Coronavirus disease 2019 (covid-19), caused by SARS-CoV-2, follows a biphasic pattern of illness that likely results from the combination of an early viral response phase and an inflammatory second phase. Most clinical presentations are mild, and the typical pattern of covid-19 more resembles an influenza-like illness—which includes fever, cough, malaise, myalgia, headache, and taste and smell disturbance—rather than severe pneumonia (although emerging evidence about long term consequences is yet to be understood in detail).1 In this review, we provide a broad update on the emerging understanding of SARS-CoV-2 pathophysiology, including virology, transmission dynamics, and the immune response to the virus. Any of the mechanisms and assumptions discussed in the article and in our understanding of covid-19 may be revised as further evidence emerges.

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The Severe Acute Respiratory Syndrome

Authors: Joseph S.M. Peiris, M.D., D.Phil., Kwok Y. Yuen, M.D., Albert D.M.E. Osterhaus, Ph.D., and Klaus Stöhr, Ph.D.

The severe acute respiratory syndrome (SARS) is responsible for the first pandemic of the 21st century. Within months after its emergence in Guangdong Province in mainland China, it had affected more than 8000 patients and caused 774 deaths in 26 countries on five continents. It illustrated dramatically the potential of air travel and globalization for the dissemination of an emerging infectious disease and highlighted the need for a coordinated global response to contain such disease threats. We review the cause, epidemiology, and clinical features of the disease.


An unusual atypical pneumonia emerged in Foshan, Guangdong Province, mainland China, in November 2002.1,2 In February and March 2003, the disease spread to Hong Kong and then to Vietnam, Singapore, Canada, and elsewhere (Table 1).3,4 The new disease was named the severe acute respiratory syndrome (SARS), and a preliminary case definition was established.4 A novel coronavirus (SARS-CoV) was identified as the causative agent.5-10 Coronaviruses are a family of enveloped, single-stranded–RNA viruses causing disease in humans and animals, but the other known coronaviruses that affect humans cause only the common cold.

The presence of SARS-CoV has been demonstrated by reverse-trancriptase polymerase chain reaction (RT-PCR) and the isolation of the virus from respiratory secretions, feces, urine, and tissue specimens from lung biopsy,11,12 indicating that the infection is not confined to the respiratory tract. The experimental infection of cynomolgus macaques with SARS-CoV produced a pneumonia that was pathologically similar to SARS in humans.8,9 Other pathogens, including human metapneumovirus13,14 and chlamydia,7,15 have been detected together with SARS-CoV in some patients with SARS, but they have not been found consistently.5,9 The experimental infection of macaques with human metapneumovirus did not lead to a SARS-like disease, and coinfection of macaques with human metapneumovirus and SARS-CoV did not enhance the pathogenicity of the SARS-CoV in this animal model.8 Thus, all the information that is available to date suggests that SARS-CoV is necessary and sufficient for the causation of SARS in humans, but it remains to be determined whether microbial or other cofactors enhance the severity or transmissibility of the disease. The complete genetic sequence of the SARS-CoV genome was determined, and it provided confirmation that SARS-CoV belongs to a new group within the coronavirus family.

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