Pathogenesis

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This page collects observations, interpretations, and consequences for action about Pathogenesis of SARS-CoV2. Please observe the structure of the page, when you add your content. Please use references where possible. Remember to find the relevant page. For example, if your observation is about Sources, please use that page, instead of posting your content here.

What is already known

  • The evidence suggests an association of viral dose with the severity of the disease. However, the evidence of the relationship is limited by the poor quality of many of the studies, the retrospective nature of the studies, small sample sizes and the potential problem with selection bias. [1]
  • Katri Manninen made the following infographic on the natural history of #COVID19:

Natural History of #COVID19 - by Katri Manninen (C) 2020

Clinical characteristics

  • Viral illness that presents with the full spectrum of most respiratory virus. Some symptoms (and combinations) are more predictive for a positive COVID19-PCR: [2]
    • Cough + fever + shortness of breath: Triples the base chance of a positive PCR among patients with respiratory illness [3]
    • Anosmia has now been recognized as a typical clinical symptom of SARS-CoV2 infection.[4]
  • Predictors of severe outcome [2]
    • Shortness of breath, (or) fatigue, (or) headache, (or) abdominal pain
    • > 50 years of age
    • comorbidities (DM, CVD, active malignancies, renal disease, immune suppressants)
    • Oxygen saturation drop
    • Respiratory rate <20/min (lower risk); >24/min: worse
    • Being on a ventilator in ICU: 50% fatal outcome, according to American experience [2]
    • Neutrophil: Lymphocyte ratios
      • <3 - good prognosis
      • >6: worrisome
      • 10-20: ICU range
      • >20: few survivors
  • The virus has a nefrotoxic effect: this means to be extra careful with medication, such as ibuprofen [2]

Asymptomatic infections

Observations

  • for estimating the asymptomatic proportion of the natural history of coronavirus, data from a stable cohort of people with homogenous (in time and intensity) exposure may be most reliable. Cruise ship exposures may come close to such situation. A study of the COVID19 outbreak on the Pacific Princess cruise ship found proportions of asymptomatic infections up to 50% [5]

Analysis and interpretation

  • the Pacific Princess cruise ship population is not representative of any country or continent, however it suggests that we have to consider the possibility that the true number of coronavirus infections in a country may be twice as large as the number of confirmed, symptomatic cases.
    • This has consequences for the control strategy, and makes extensive contact tracing AND testing around confirmed cases even more important

Consequences for action

  • To follow the WHO advice to isolate each identified coronavirus infection followed by testing and monitoring of ALL contacts is critical to a successful COVID19 control strategy.
    • given the likely high proportion of asymptomatic cases, it seems imperative to apply testing widely among all contacts of confirmed infections, in order to isolate all positives.

References

  1. SARS-CoV-2 viral load and the severity of COVID-19. CEBM Oxford. March 26, 2020
  2. 2.0 2.1 2.2 2.3 TWIV This Week in Virology 29 March 2020: https://open.spotify.com/episode/7BEqdjQ8wp4CcG29Qd37LN?si=egc0im1eRqy7AMu3H8NKyQ
  3. Excerpt from TWIV 29 march: SWAB study, Washington state, USA, among 500+ patients with respiratory symptoms
  4. Hopkins, C., and N. Kumar. 2020. “Loss of Sense of Smell as Marker of COVID-19 Infection.” Retrieved from https://www.entuk.org/sites/default/files/files/Loss%20of%20sense%20of%20smell%20as%20marker%20of%20COVID.pdf
  5. Mizumoto, Kenji, et al. "Estimating the asymptomatic ratio of 2019 novel coronavirus onboard the princess cruises ship, 2020." medRxiv (2020).