MicrobiologyBytes

Acute respiratory viruses cause substantial morbidity and mortality worldwide. Lower respiratory-tract infections are the leading cause of communicable disease death and among the top five contributors to disability-adjusted life years. Viruses are the primary cause of lower respiratory-tract infections in children and a substantial cause of such infections in all age-groups. The incubation period of an infectious disease is the time between infection and symptom onset. This period is widely reported because it is useful in infectious disease surveillance and control, in which the time of symptom onset may be the only indication of the time of infection. The incubation period plays an essential part in surveillance for healthcare-associated infections, and may aid in diagnosis if laboratory facilities are unavailable. The incubation period is clinically relevant in the administration of antiviral medications, many of which are most effective when given before or immediately after symptom onset. Epidemiological studies depend on the incubation period to identify potential sources of infection. Predictive models designed to inform policy decisions use the incubation period to evaluate the potential of surveillance programmes and interventions to confront emerging epidemics.

The length of the incubation period by comparison with the latent period (the time between infection and becoming infectious) determines the potential effectiveness of control measures that target symptomatic individuals. “4–5 days” may refer to the most common range, the highest and lowest incubation periods in a study, or some other interval. Without knowing which summary measure is being stated, it is hard to use this information to make clinical or infection control decisions. Estimates given without attribution or based on few observations do not meet the standards of evidence we demand for modern medical information. A recent paper reviews the literature on nine respiratory viruses selected for their clinical or public-health importance: adenovirus, human coronavirus, SARS-associated coronavirus, influenza, measles, human metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), and rhinovirus. By systematic review and analysis of published estimates and data, the authors aimed to capture the consensus in the medical literature on these incubation periods, characterise the evidence underlying this consensus, and provide improved estimates of incubation periods for these infections.

Incubation periods of acute respiratory viral infections: a systematic review. Lancet Infect Dis 2009;
9: 291–300
Knowledge of the incubation period is essential in the investigation and control of infectious disease, but statements of incubation period are often poorly referenced, inconsistent, or based on limited data. In a systematic review of the literature on nine respiratory viral infections of public-health importance, we identified 436 articles with statements of incubation period and 38 with data for pooled analysis. We fitted a log-normal distribution to pooled data and found the median incubation period to be 5·6 days (95% CI 4·8–6·3) for adenovirus, 3·2 days (95% CI 2·8–3·7) for human coronavirus, 4·0 days (95% CI 3·6–4·4) for severe acute respiratory syndrome coronavirus, 1·4 days (95% CI 1·3–1·5) for influenza A, 0·6 days (95% CI 0·5–0·6) for influenza B, 12·5 days (95% CI 11·8–13·3) for measles, 2·6 days (95% CI 2·1–3·1) for parainfluenza, 4·4 days (95% CI 3·9–4·9) for respiratory syncytial virus, and 1·9 days (95% CI 1·4–2·4) for rhinovirus. When using the incubation period, it is important to consider its full distribution: the right tail for quarantine policy, the central regions for likely times and sources of infection, and the full distribution for models used in pandemic planning. Our estimates combine published data to give the detail necessary for these and other applications.

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Previous studies have demonstrated that IgG and neutralizing antibodies against coronavirus associated with the severe acute respiratory syndrome (SARS) may persist, in spite of a decline in titer, for two years in patients who have recovered from SARS. For 3 years, we followed patients who had recovered from infection with SARS-associated coronavirus, to measure the longevity of specific antibodies. Fifty-six patients who were positive for serum IgG and neutralizing antibodies against SARS-associated coronavirus at the time of recovery from acute SARS infection were included in this study. The titers of IgG and neutralizing antibodies were significantly correlated during the 3-year follow-up period. The titers peaked at month 4 and diminished thereafter. IgG and neutralizing antibodies were undetectable in 19.4% and 11.1% of serum samples, respectively, at month 30, and in 25.8% and 16.1%, respectively, at month 36. For the IgG antibody, the mean titers dropped from 244 at month 4 to 34 at month 30 and 28 at month 36. For the neutralizing antibody, the mean titers dropped from 1232 at month 4 to 32 at month 30 and remained at that value through month 36. There were no significant differences in the kinetics of specific antibodies according to disease severity, duration of hospitalization, type and number of coexisting conditions, or use or nonuse of corticosteroids.
Experiments in animals indicate that IgG and neutralizing antibodies, along with T-cell mediated immunity, are essential for protection against live-virus challenge. These data suggest that immune protection may wane over time, as demonstrated in patients infected with human coronavirus 229E. How this waning humoral immunity may affect future SARS-associated disease in the context of re-exposure to SARS is unknown. In the absence of another SARS outbreak, we do not know whether lower or even undetectable levels of specific antibodies would be adequate to protect a person from reinfection due to a potential anamnestic response, as seen with other viral infections such as measles and hepatitis A. The implications of the lower neutralizing antibody levels in patients with aseptic femoral neck necrosis are unclear.

Disappearance of Antibodies to SARS-Associated Coronavirus after Recovery
NEJM 2007 357: 1162-1163