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SARS-Cov-2 incubation period according to vaccination status during the fifth COVID-19 wave in a tertiary-care center in Spain: a cohort study

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Jordi Cortés Martínez, Daewoo Pak, Gabriela Abelenda-Alonso, Klaus Langohr, Jing Ning, Alexander Rombauts, Mireia Colom, Yu Shen, Guadalupe Gómez Melis

Vaccination clearly changes many COVID-19 outcomes, but does it change the time from exposure to symptoms? This study finds a short Delta-variant incubation period, with no statistically significant difference between vaccination statuses.

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Vaccination clearly changes many COVID-19 outcomes, but does it change the time from exposure to symptoms? This study finds a short Delta-variant incubation period, with no statistically significant difference between vaccination statuses. The incubation period is the elapsed time between exposure to the pathogen and the onset of symptoms.

Both mRNA-based and adenoviral vector-based vaccines have shown to be effective, but concerns remained about possible decreases in vaccine effectiveness for new variants and variations in the incubation period. Earlier studies had analyzed incubation periods for the original Wuhan strain and several variants, mainly Alpha or Delta, but no studies had been specifically designed to estimate incubation according to vaccination status and vaccine type.

The study aimed to determine whether the SARS-CoV-2 Delta variant’s incubation period differs between vaccinated and unvaccinated patients, and to analyze incubation according to the type of vaccine administered. This was an observational unicentric study at Hospital Universitari de Bellvitge in Barcelona, using a structured telephone survey performed by trained interviewers to estimate the COVID-19 incubation period.

Because no test determined the SARS-CoV-2 variant in admitted patients, the Delta variant was assumed because of its high prevalence during the hospitalization period. Between July sixth and December thirteenth, twenty twenty-one, the study assessed subjects older than eighteen admitted with PCR-proven first-episode SARS-CoV-2 infection.

All included patients gave informed consent to participate in the study. The telephone survey used pre-designed questions to determine the moment of exposure and minimize variability. A case report form was specifically designed for the study and implemented in the Redcap tool.

The main variables were the exposure period and symptom-onset dates; other variables included age, gender, vaccination status, and vaccine type. The COVID-19 incubation-period distribution was estimated with generalized odds-rate regression models, including the log-logistic proportional-odds model and the Weibull proportional-hazards model as special cases.

The covariate vector included patient age, sex, and vaccination-related variables, while the model described the probability that incubation time is larger than a given time. The estimated median incubation time was obtained by solving the survival probability equation at one-half for a specific set of covariates.

Figure one traces how the study cohort was narrowed from four hundred seventy-eight phone calls to four hundred six confirmed cases, excluding nonresponse, language barriers, deaths, duplicates, missing dates, and previous COVID-19. A further one hundred sixty-four cases with unknown exposure periods were excluded, leaving two hundred forty-two patients with complete information.

These patients were then divided into one hundred seventeen unvaccinated and one hundred twenty-five vaccinated participants, with the vaccinated group further classified by vaccine and dose history. Table One compares the one hundred sixty-four excluded patients with the two hundred forty-two included in the analysis across age, sex, and vaccination characteristics.

Among included patients, mean age was fifty-eight point zero with a standard deviation of nineteen point nine, fifty-nine point five percent were men, and fifty-one point seven percent had received vaccination. The table also reports a median of fifteen days from exposure to survey date, with an interquartile range of four to fifty-one days, clarifying the composition and timing of the analyzed sample.

The unadjusted estimated median incubation period was two point eight days, with a ninety-five percent confidence interval from two point five to three point one days. The estimated ninety-fifth percentile was eight days, meaning that the probability a patient had an incubation period of less than eight days was zero point ninety-five.

No statistically significant differences in incubation periods were found when stratifying by vaccination status, age, or sex, although slight differences appeared by vaccine type. Figure two compares median incubation time across three vaccine-status groups, with confidence intervals shown as horizontal bars.

This matters because the study text says the analysis found no statistically significant differences in incubation periods by vaccination status, so the visual helps place the group-specific estimates and their uncertainty in context. The best model included only vaccine type as the explanatory variable.

The estimated median was two point one days for patients who received an adenovirus-based vaccine, compared with two point nine days for patients not fully vaccinated and three point one days for patients vaccinated with mRNA. These differences did not reach statistical significance in the best model, which was adjusted only by vaccine type.

The overall median incubation time with the Delta variant was almost three days, with a ninety-fifth percentile of about eight days. The incubation times found in this study were shorter than those observed with earlier variants; one meta-analysis reported a range from five point six to six point seven days, depending on the chosen model.

For more recent variants, other studies reported estimated medians of three point four days for Delta and three point one days for Omicron, while a systematic review estimated four point four and three point four days for those variants. The cohort consisted exclusively of patients hospitalized for COVID-19 and did not include outpatient cases.

This could cause selection bias because hospitalized patients with more severe symptoms could have a higher viral load and therefore shorter incubation times. The study also lacked some patient information that might be relevant for incubation time, such as severity of symptoms.

In this hospitalized cohort, Delta’s median incubation period was 2.8 days, and vaccination status did not significantly change it. That matters because quarantine and exposure-monitoring decisions depend on how quickly symptoms appear.

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