The Med Book
COVID: Uncertainties in Clinical Presentation and Investigations
Reading time: 10 minutes
Knowledge of the virus is constantly changing and I will update this as and when significant new information with clinical implications becomes available.
Uncertainties with SARS-COV-2
The information below, gives us an idea of the uncertainties we are facing with this virus.
The following was the breakdown of 72,314 cases reported in China with the COVID outbreak (1):
- 62% – confirmed cases (+ve rt-PCR tests from throat swabs)
- 22% suspected cases based on clinical features and exposures only, not tested
- 15% clinically diagnosed based on clinical features and imaging only
- 1% asymptomatic based on +ve rt-PCR but no symptoms
It is difficult to interpret the asymptomatic proportion, in that symptomatic individuals are more likely to be tested at the start of an outbreak. The overall case fatality rate was 2.3% but this depends on the denominator (how many people were tested?) and the demographics of the population since older people with co-morbidities have higher mortality.
Figure 1
The Diamond Princess Cruise ship (Figure 1) served as an unfortunate Petri dish giving us great insight into the transmissibility and quantum of asymptomatic cases with SARS-COV-2 (2,3). Out of 3711 passengers and crew members, a total of 705 people tested positive and seven died (4). This gives a case fatality rate of 0.99% that is lesser than that of SARS-COV (9.5%) and MERS (34.4%) but more than that of influenza (0.1%). It is worth bearing in mind the following points which put things into perspective:
- The close confines of a cruise ship make it really difficult to isolate cases (people still had to have room-mates).
- A higher proportion of older people were on board (more vulnerable) making the number of confirmed positives an interesting case study.
- Nearly all the people had been tested and some of them re-tested before being allowed to disembark.
Asymptomatic individuals
17.9% were identified as asymptomatic cases (3). There were several limitations in this study. Only symptomatic individuals were initially tested and therefore the asymptomatic cases might be under-estimated. Secondly, most individuals on board were > 60 years of age who are often symptomatic owing to co-morbidities which also under-estimates the asymptomatic proportion.
It is important to highlight that we do not know if asymptomatic individuals are infective since, shedding viral RNA in your secretions does not equate to infectivity.
The problem of false negatives
Combine this with the poor sensitivity of rt-PCR tests reported in China at the start of the outbreak. Nasal swabs had a 63% positive rate and pharyngeal swabs 32% (5). The use of different PCR test reagents in other countries will have different accuracies but it shows that basic medical concepts of sensitivity and specificity of tests are still at play. As always in medicine, tests do not make the diagnosis, clinicians do! For now, this would be a good dictum to follow. We simply do not yet have the data to give us the sensitivity and specificity of the test we are using as the test is not standardised. False negatives in this scenario will however have significant public health implications.
To summarise, we are still grappling with the test accuracy, impact of asymptomatic individuals and the case fatality rate (Figure 2).
Figure 2
Clinical features
Unfortunately no symptom is specific to COVID. Symptoms commonly seen in other viral respiratory infections/ pneumonia are found in COVID, like fever, cough, myalgias, anorexia and breathlessness. Taste and smell alterations have been reported but this can also occur with other viral infections like common cold (6). Other symptoms like sore throat, rhinorrhea, gastrointestinal (GI) symptoms and headache are uncommon in COVID. GI symptoms have been reported to be the only symptoms in some patients.
Severity of illness
The Chinese CDC released a report outlining the severity of illness among 72,314 cases as follows (1):
- Mild 81% (no or mild pneumonia)
- Severe 14% (defined as dyspnea, hypoxia or >50% lung involvement on imaging within 24 to 48 hours from presentation)
- Critical 5% (Respiratory failure, shock, multi-organ failure)
In general, presence of medical co-morbidities increases the risk of severe illness and mortality. These include hypertension, cardiovascular disease, diabetes mellitus, chronic lung disease, cancer, chronic kidney disease and cerebrovascular disease.
Increasing age increases the risk of hospitalisation and mortality. In the same report, the case fatality rate for people between 70-79 years old was 8% and > 80 years was 15% respectively. 80% of the deaths occurred in people aged > 60 or ≥ 65 in China and US respectively (1,7).
Mortality in patients needing critical care is the same as in ARDS which is 50%.
Complications (similar to other infections)
- Respiratory – ARDS (Acute Respiratory Distress Syndrome) can develop shortly after the onset of breathlessness
- Cardiac – cardiac injury, arrhythmias, shock, cardiomyopathy
- Coagulopathy and thromboembolism (8)
- Cytokine storm (9)
- Secondary bacterial infection (not very common)
Laboratory findings
As with medicine in general, systemic inflammation presents with multi-organ laboratory abnormalities and indirectly points to severe illness in COVID. As a general rule, greater deviation from the norm correlates with severity.
Systemic markers of inflammation – CRP > 100mg/L, D-Dimer > 1 µg/ml and elevations in LDH, Troponin, ferritin and Creatine phosphokinase all point to severity. Although procalcitonin helps in distinguishing viral from bacterial infections, it has a limited role in COVID since severe illness in later stages is associated with a high procalcitonin.
Haematological: lymphopenia < 0.8 × 109/L
Unsurprisingly, a combination of rising D-dimer with a falling lymphocyte count is seen in non-survivors which might help highlight deterioration (10).
It is interesting to note that asymptomatic individuals can actually have laboratory abnormalities including ground glass changes of viral pneumonia on the CT scan.
Disclaimer: Views expressed are personal.
References
- Wu Z, McGoogan JM. Characteristics of and Important Lessons from the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72314 Cases from the Chinese Center for Disease Control and Prevention. JAMA – J Am Med Assoc. 2020;
- Field Briefing: Diamond Princess COVID-19 Cases, 20 Feb Update [Internet]. [cited 2020 Apr 11]. Available from: https://www.niid.go.jp/niid/en/2019-ncov-e/9417-covid-dp-fe-02.html
- Mizumoto K, Kagaya K, Zarebski A, Chowell G. Estimating the asymptomatic proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond Princess cruise ship, Yokohama, Japan, 2020. Eurosurveillance. 2020 Mar 12;25(10):2000180.
- Rajgor DD, Lee MH, Archuleta S, Bagdasarian N, Quek SC. The many estimates of the COVID-19 case fatality rate. Lancet Infect Dis. 2020 Mar;0(0).
- Wang W, Xu Y, Gao R, Lu R, Han K, Wu G, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA – Journal of the American Medical Association. American Medical Association; 2020.
- Giacomelli A, Pezzati L, Conti F, Bernacchia D, Siano M, Oreni L, et al. Self-reported olfactory and taste disorders in SARS-CoV-2 patients: a cross-sectional study. Clin Infect Dis. 2020 Mar 26;
- (CDC) C for DC and P. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) – United States, February 12-March 16, 2020. MMWR Morb Mortal Wkly Rep. 2020 Mar 27;69(12):343–6.
- Brady L. Stein MM. Coagulopathy Associated with COVID-19. NEJM J Watch. 2020 Apr 6;2020.
- Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet (London, England). 2020 Mar 28;395(10229):1033–4.
- Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical Characteristics of 138 Hospitalized Patients with 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA – J Am Med Assoc. 2020 Mar 17;323(11):1061–9.
Subscribe to Blog via Email
Join 56 other subscribers
Facebook
Twitter
LinkedIn
medbookprof
I'm a Consultant Pulmonologist having experienced medicine first-hand across two continents stretching from the South Indian peninsula to the British Isles, the emerald nation of Ireland, to the Mediterranean climes of Italy and to the happiest country on earth, Denmark. Along the way, I have served as an honorary Associate Clinical Teacher and Royal College Associate tutor at University Hospital of Wales, collected a Masters in Medical Education and a passion for teaching. My enthusiasm is matched only by my thirst for simplifying clinical knowledge for medical students and making it accessible on a global scale.