The initial dose of virus and the amount of virus an individual has at any one time might worsen the severity of COVID-19 disease, finds the Oxford COVID-19 Evidence Service Team of the Centre for Evidence-based Medicine.
Viral load is a measure of the number of viral particles present in an individual. Higher SARS-CoV-2 viral loads might worsen outcomes, and data from China suggests the viral load is higher in patients with more severe disease. The amount of virus exposure at the start of infection – the infectious dose – may increase the severity of the illness and is also linked to a higher viral load.
Healthcare workers can be exposed more often due to numerous infected individuals’ exposures. In the early stages of an outbreak, initial contacts might not be recognized, particularly contacts with those with mild symptoms, or when the use of protective measures is suboptimal. Reducing the frequency and intensity of exposure to SARs-CoV-2 might reduce the infectious dose and result in less severe cases.
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.
An analysis of the nasopharyngeal viral load of 79 SARs patients in Amoy Gardens, Hong Kong, in the 2003 outbreak. reported that while patients admitted to hospital had initially similar illness severity regardless of proximity to the initial case. During the SARS outbreak, Amoy Gardens was placed under active surveillance, and residents underwent frequent examinations including nasopharyngeal specimens collected at an early stage.
The SARS pandemic in 2002-2003 affected 8,098 people with 774 deaths. An analysis of 142 patients with SARs reported that Viral load in Nasal Pharyngeal Aspirates between days 10 and 15 after the onset of symptoms was associated with:
· Oxygen desaturation, OR=3.1 (95% CI, 1.6- 6.2),
· Mechanical ventilation, OR =11.3 (95% CI, 3.6-35.1)
· Diarrhea, OR=2.5 (95% CI, 1.3-5),
· Hepatic dysfunction, OR =2.5 (95% CI, 1.2-5.2) and
· Mortality (OR=54; 95% CI, 7-415).
Compared with other common viral respiratory diseases, the onset of peak viral load appeared to be delayed. Only those who sent the specimen on day 10 were included, which further limits firm conclusions to be drawn.
SARs-Co-2:
A retrospective, multicenter cohort study, of 191 adult inpatients (median age 56.0) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) discharged or died by Jan 31, 2020.
· The median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors,
· The longest observed duration of viral shedding in survivors was 37 days.
· SARS-CoV-2 was detectable until death in non-survivors.
· Severe lymphopenia was observed until death in non-survivors.
A preprint of the temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and analysis of a separate sample of 77 infector-infectee transmission pairs modelled the following:
· Infectiousness started from 2.5 days before symptom onset and reached its peak at 0.6 days before symptom onset.
· The proportion of transmission before symptom onset (area under the curve) was 44%.
· Infectiousness was estimated to decline relatively quickly within 7 days of illness onset
Influenza:
The link to the initial dose and subsequent severity of the disease is linked with the 1918-19 Spanish Flu pandemic. Simulation models showed that the infectious dose was related to the number of simultaneous contacts a susceptible person has with infectious ones; that severe cases of influenza result from higher infectious doses of the virus; and over-crowded places are the ideal environment for a susceptible person to be exposed to very high infectious doses of influenza.
· High infectious dose and influenza disease progression have been shown in experimental animals;
· The high infectious dose is associated with a higher viral load; and
· The high infectious dose is associated with a smaller period of time to maximum viral load.
· Influenza Infectious Dose May Explain the High Mortality of the Second and Third Wave of 1918–1919 Influenza Pandemic.
· An analysis of 147 inpatients with influenza A (H3N2) infection (mean age, 72±16 years) reported major comorbidities and systemic corticosteroid were associated with slower viral clearance. Severe cases of influenza have more active and prolonged viral replication.
