SARS-CoV-2 has evolved an incubation time more like seasonal coronaviruses

The incubation period for COVID-19—the time between when SARS-CoV-2 first infects a person and when resulting COVID-19 symptoms first appear—has gradually shortened as the pandemic has stretched on and the virus has mutated. That's according to a new meta-analysis published this week in JAMA Network Open by researchers in Beijing, who harvested data on over 8,000 patients from 142 COVID-19 studies.

When the original version of the novel virus mushroomed out of Wuhan, China, the mean incubation period was 6.65 days, according to pooled data from 119 studies. But then, the incubation period got shorter as the variants evolved. The alpha variant had a mean incubation of 5 days, according to one study; beta, 4.5 days, according to another; delta had a mean of 4.41 days, according to pooled data from six studies; and now with omicron, the incubation period has shrunk to 3.42 days, according to data from five studies.

The current shortened incubation period now puts SARS-CoV-2 more in line with commonplace respiratory viruses, including the four human coronaviruses that circulate seasonally and cause mild infections similar to the common cold. Their incubation period is 3.2 days. Rhinovirus, the most common cause of the common cold, has a mean incubation period of 1.4 days. For influenza, it can range from 1.43 to 1.64 days, and parainfluenza has a mean of 2.6 days.

Better or worse

In terms of disease severity, the significance of a shorter incubation period isn't entirely clear—which was demonstrated by studies included in the meta-analysis that broke out specific groups of people, including older adults, children, and people who developed severe COVID-19.

For instance, pooled data from eight studies that estimated the incubation period just in people over the age of 60—people who are at relatively high risk of severe COVID-19—found that they tended to have slightly longer incubation periods, with a mean of 7.43 days. This fit with earlier data, which found that older adults also had longer incubation periods in the original SARS virus outbreak in the early 2000s. Researchers then and now speculate that a longer incubation period in older adults reflects slower immune responses to the virus.

But children, who are at relatively low risk of severe COVID-19, also tended to have relatively longer incubation periods with SARS-CoV-2. Their mean incubation period was 8.82 days, according to pooled data from eight studies. The authors speculate that this may be because symptoms in children are so mild that detection of COVID-19 symptoms can be delayed.

Further muddling the picture is pooled data from six studies that looked specifically at incubation periods in people who developed severe disease and those who developed non-severe disease. In this comparison, the patients with severe COVID-19 tended to have shorter incubation periods (6.69 days) than those with non-severe cases (6.99 days). The authors of the meta-analysis speculate that this could be related to people with severe disease starting off with more cells initially infected with the virus than those who only have mild illness.

“Great significance”

Overall, the complex relationship between incubation time and COVID-19 severity highlights that the disease is dependent on a variety of factors, particularly virus-related factors (i.e., virulence of the virus and infectious dose) and human host-specific factors (i.e., immune system function and prior immunity from infection or vaccination). Omicron, the most recent variant and the one with the shortest incubation period so far, is considered to cause relatively mild disease. But it also came along after widespread vaccination and prior infections, which are generally protective against severe disease.

Still, despite the complexity, the incubation period is "one of the most important epidemiological parameters of infectious diseases," the authors write. "Knowledge of the disease’s incubation period is of great significance for case definition, management of emerging threats, estimation of the duration of follow-up for contact tracing and secondary case detection, and the establishment of public health programs aimed at reducing local transmission," such as social distancing, isolation, face mask mandates, and quarantining. This is particularly key for SARS-CoV-2, which has proven highly effective at pre-symptomatic transmission.

The meta-analysis has several limitations. Like all meta-analyses, it harvested data from diverse data sets from studies conducted in many different countries, creating the potential for confounding variables. Some of the data also relied on people's recall of exposure dates. Last, the majority of the studies included in the analysis were during the initial version of SARS-CoV-2. Thus, estimates of the incubation periods for the more recent variants relied on less data. However, the meta-analysis's general finding has been echoed by others that found that the incubation period has shortened over the pandemic and, in the era of omicron, is now in the range of three to four days.