Secondary Attack Rates, Transmission, Incubation and Serial Interval Periods of first SARS-CoV-2 Omicron variant cases in a northern region of Spain.

doi:10.21203/rs.3.rs-1279005/v1

SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) quickly spread during December 2021 in Cantabria, a northern region of Spain. In total 622 cases were studied, and 1.420 close contacted were individually contact-traced and followed up. Secondary Attack Rates (SAR) and Transmission, Incubation and Serial Interval periods were estimated and compared with Delta cases. Greater transmission was found (Omicron SAR 39% vs 26%) with an increased tendency to asymptomatic or early infectiousness.

COVID-19

Incubation period

Surveillance

Omicron variant

Secondary Attack Rate

622 cases of SARS-CoV-2 infection compatible with the Omicron variant (BA.1/B.1.1.529) [1], were studied by Contact Tracing Program in Cantabria (North Spain) during December 2021. 1.420 close contacts (household, social and occupational) were identified with 455 secondary cases among them. The aim of this article is to report the main epidemiological characteristics: Secondary Attack Rates (SARs), Transmission period, Incubation period and Serial Intervals of these cases compared with the Delta variant compatible cases.

The Omicron cases were detected by real-time polymerase chain reaction (qPCR) using TaqMan SARS-CoV-2 mutation panel (Thermofisher) for single nucleotide polymorphism (SNP) genotyping focused on K417N and L452R mutation. Cases that were positive to K417N mutation and negative to L452R were considered compatible with Omicron. The analysis method was validated through confirmation via whole genome sequencing of 63 samples. Libraries were constructed using Ion AmpliSeq™ SARS-CoV-2 Insight Research Assay (Thermofisher) and were sequenced with Ion GeneStudio S5 system. NGS data were analysed using Torret suite software and were assembled by IRMA [2]. Lineage assignment was done by Pangolin [3] using consensus fasta.

Sociodemographic characteristics (age, age group), vaccination status (dichotomized to either non vaccinated or fully vaccinated as per each vaccine´s protocol) and presence or absence of symptoms, as well as symptom onset date (SOD) or diagnosis date (DD) for the asymptomatic cases were obtained from the contact tracing program of Cantabria. The same information was obtained from the 1.708 COVID-19 cases of November 2021, when the delta variant of SARS-CoV-2 dominated among 1.299/1.299 (100%) of the samples. 12.587 close contacts with 2.201 secondary cases were identified for them.

Secondary attack rates.

In Spain, close contacts were tested up to 3 and 9 days after the date of last contact (DLC) [4]. SAR was defined as the proportion of secondary cases among close contacts (less than 2 meters 15 minutes) identified through contact tracing (-2 to +10 days after index case symptoms onset or diagnosis, otherwise). Each relationship was classified by the setting where it took place (household, social or occupational), and school settings were excluded from all analyses. Global SAR was defined as the average of secondary cases among all the relationships [5]. All SAR are presented as per index case´s vaccination status, with their sample CI 95%. Delta-Omicron SARs difference was tested by a Pearson´s chi-squared test, as well as differences between vaccinated-unvaccinated SARs within variant and setting (Table 1).

Global SAR was 39% (36.5 - 42.2%) for Omicron cases and 26% (25.3 - 27.4%) for Delta, a 13% increase (9.9 - 16.1%; p < 0.000) (table 1). A higher SAR was also registered in social (30.5% vs 16.2%) and occupational (31% vs 10.5%) field, but not between household contacts (49.4% vs 48%).

Among Delta variant cases, the unvaccinated showed an overall increased SAR of 7.8% (5.6 - 10; p < 0.000), household SAR of 9.9% (5.8 - 14%; p < 0.000 ), and occupational SAR of 9.5% (0.8 - 18.1; p = 0.01) compared to the vaccinated. In contrast, for the Omicron variant, no differences were found between vaccinated and unvaccinated in any of them.

Transmission, Incubation and Serial Interval periods.

Symptomatic index cases relationships were selected to calculate the days between the index case SOD and Day of Last Contact (DLC) were individually obtained. Transmission period was therefore defined as the distribution of days from index case SOD to DLC for close contacts that became secondary cases. For incubation and serial interval periods, it was required that the index and secondary case were symptomatic. The incubation period was defined as the days between DLC and secondary case SOD and Serial Interval as the days between the index case SOD and the secondary case SOD [6].

For the three periods, mean (standard deviation, sd) and median (q1, q3) were reported. Omicron-Delta means differences and Student´s T test, CI 95% and p value were performed. Histogram, density plot, boxplot and cumulative distribution functions for Omicron variant are depicted in figure 1. Delta´s figures can be found in Fig S2A-C.

Compared with Delta (mean = 0.8, median = 1), omicron variant cases transmission period was shorter (median = 0, mean = 0.5) (Fig. 1A) and grouped around day 0 after symptom onset. Mean differences between both variants were statistically significant (-0.3; IC95% -0.56 - -0.02) and IQR (q1, q3) remained equal. Figure 2 depicts transmission periods for Omicron and Delta, stratified by vaccine and symptomatic status.

Incubation period had a median of 3 days for both variants and IQR was shorter for Omicron (Fig. 1B). No mean differences in incubation period were found. Finally, the mean serial interval was significantly shorter for Omicron (4.8 vs 5.4 days, IC95% -0.6 - -0.15; p = 0.008)(Fig. 1C) with a median of 4 vs 5 days. No differences within variants were found between vaccine status for any of the periods. Results can be found in Table 2.

Omicron variant has spread quickly around the world since its first notification in South Africa on 11th November of 2021[7]. These results show a significant increase of SAR for Omicron cases in North Spain (Cantabria) compared with Delta in a similar period and with high vaccine coverage (> 80% of target population). Global SAR showed a 50% increase (from 26.3–39.3%), as in social events SAR (from 16.2–30.5%), but didn’t show significant differences in household SAR.

In this case, once infected, index vaccinated cases seem to have the same transmission capacity that non-vaccinated people. This did not happen with Delta, where significant SARs differences were observed in global, household and occupational settings (Table 1) within groups.

Omicron´s increased transmissibility (SARs) is consistent with the registered tendency of asymptomatic or early-symptomatic transmission. SARS-CoV-2 transmission took place between days -1 to +3 of SOD, when most secondary cases contacts happen. Median day of transmission was reduced from +1 after symptom onset in Delta to day 0 (SOD) (Table 1). Even though the incubation period did not statistically differ, serial interval was significantly decreased in Omicron (mean = 4.8 vs 5.3, median = 4 vs 5) and was again more grouped to the left (IQR 3 vs 5). 90% of secondary cases had an incubation period of 6 and 7 days for Omicron and Delta, respectively.

It’s hypothesized that Omicron´s increased SAR is derived by a concentration of contagion events towards the pre- or pauci- symptomatic period, when people may not be aware of infection and public health containment measures such as contact-tracing, isolation and quick testing are not possible. Half of Omicron contagion events happened before symptom onset. This could imply that the effectiveness of non pharmaceutical measures targeting symptomatic cases (such a contact tracing, quick testing and isolating) would be significantly decreased in the absence of preventive measures such a social distancing, limiting massive gatherings or social meetings.

Recent debate regarding isolation periods of cases and quarantine periods of contacts, due to their social and economical impact in daily life, has arised [8–10], especially due to possible changes in disease dynamics caused by omicron variant [11–13]. Transmission periods for both Omicron and Delta cases, show that transmission after the 5th day of SOD is very rare, 8/356 (2%) secondary cases in Omicron and 79/1642 (5%) in Delta (Figure 2) This could potentially contribute to decrease the burden of the control measures against COVID-19.

Author´s contributions

JAM performed the analyses and wrote the first draft; AAL supervised analyses, wrote manuscript and is the senior author; RW and TV designed the COVID-19 information system; JCM and JRL lead the microbiology team which performs SARS-CoV-2 genome sequencing. All authors revised, proofread and contributed to the manuscript. AAL, RW, TV, JCM and JRL managed the alert of the first Omicron cases in Cantabria.

None of the authors declare any conflict of interest

1. Classification of Omicron (B.1.1.529): SARS-CoV-2 Variant of Concern [Internet]. [cited 2022 Jan 12]. Available from: https://www.who.int/news/item/26-11-2021-classification-of-omicron-(b.1.1.529)-sars-cov-2-variant-of-concern

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3. O’Toole Á, Scher E, Underwood A, Jackson B, Hill V, McCrone JT, et al. Assignment of Epidemiological Lineages in an Emerging Pandemic Using the Pangolin Tool. Virus Evolution. 2021 Jul 5;veab064.

4. Dirección General de Salud Pública. Consejería de Sanidad de Cantabria. Protocolo de detección y manejo de casos y contactos de covid-19. Versión 8 [Internet]. Available from: https://www.scsalud.es/documents/2162705/9256837/PROTOCOLO_MANEJO+CASOS+Y+CONTACTOS_V8_221221.pdf/1f7542f9-eca4-5460-1a96-1a121bbca4f5?t=1640176144144

5. Fung HF, Martinez L, Alarid-Escudero F, Salomon JA, Studdert DM, Andrews JR, et al. The Household Secondary Attack Rate of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Rapid Review. Clinical Infectious Diseases. 2021 Jul 30;73(Supplement_2):S138–45.

6. Alene M, Yismaw L, Assemie MA, Ketema DB, Gietaneh W, Birhan TY. Serial interval and incubation period of COVID-19: a systematic review and meta-analysis. BMC Infect Dis. 2021 Dec;21(1):257.

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10. Ministerio de Sanidad. Evaluación rápida de riesgo. Variantes de SARS-CoV-2 en España: Ómicron. 8a actualización, 21 de diciembre de 2021 [Internet]. Available from: https://www.sanidad.gob.es/profesionales/saludPublica/ccayes/alertasActual/nCov/documentos/20211221-ERR.pdf

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Table 1. Secondary Attack Rates by setting and vaccine status of the index case.

	Omicron				Delta				Prop. difference (IC-95%)
Settings	Index cases	Close contacts	Second. Cases	SAR (CI 95)	Index cases	Close contacts	Second. Cases	SAR (CI 95)	Prop. difference (IC-95%)
Global	333	1126	443	39.3% (36.5 - 42.2)	1403	7013	1846	26.3% (25.3 - 27.4)	13* (9.9 - 16.1)
Unvaccinated index	210	655	269	41.1% (37.4 - 44.9)	535	2876	895	31.1%** (29.5 - 32.8)	10* (5.7 - 14.2)
Vaccinated index	111	436	159	36.5% (32.1 - 41.1)	829	3904	910	23.3%** (22 - 24.7)	13.2* (8.3 - 18)
Household	287	533	263	49.4% (54- 53.6)	1095	2350	1129	48% (46 - 50)	1.3 (-3.4 - 6)
Unvaccinated index	187	354	171	49.4% (44.2 - 54.7)	450	1118	595	53.2%** (50.3 - 56)	-3.8 (-9.8 - 2.2)
Vaccinated index	91	171	85	49.7% (42.3 - 57)	622	1198	519	43%** (40.5 - 46)	6.4 (-1.6 - 14.4)
Social	143	524	160	30.5% (26.8 - 34.6)	836	4153	672	16.2% (15.1 - 17.3)	14.4* (10.3 - 18.5)
Unvaccinated index	76	283	88	31.1% (26 - 36.7)	315	1640	284	17.3% (15.6 - 19.2)	13.8* (7.9 - 19.7)
Vaccinated index	61	224	64	28.6% (23.1 - 34)	495	2351	368	15.7% (14.2 - 17.2)	12.9* (6.6 - 19.3)
Occupational	29	58	18	31% (20.6 - 43.8)	148	411	43	10.5% (7.93 -13.8)	20.6* (7.3 - 33.8)
Unvaccinated index	14	22	8	36.4% (19.7 - 57)	39	97	16	16.5%** (10.4 -25.1)	20.1 (-0.04 - 44.1)
Vaccinated index	14	34	10	29.4% (16.8 - 46.1)	105	298	21	7%** (4.7 - 10.5)	22.4* (5.1 - 40)

*p < 0.000; ** differences vaccinated-unvaccinated within same-variant context

Table 2. Comparison of Omicron and Delta Transmission, Incubation and Serial interval periods (mean and median) by index case vaccination status.

	Mean (sd)				Median (q1, q3)
	Ómicron	Delta	Diff (IC 95%) *	p	Ómicron	Delta
Transmision period	0.5 (2.3)	0.8 (2.6)	-0.3 (-0.56 - -0.02)	0.04	0 (-1, 2)	1 (-1, 2)
Unvaccinated index	0.5 (2.3)	0.7 (2.5)	-0.2 (-0.6 - 0.14)	0.22	1 (-1, 2)
Vaccinated index	0.6 (2.3)	0.9 (2.7)	-0.3 (-0.7 - 0.14)	0.89	0 (-1, 2)
Incubation period	3.1 (2.6)	3.3 (2.7)	-0.2 (-0.6 - 0.16)	0.29	3 (1, 4)	3 (1, 5)
Unvaccinated index	3.1 (2.7)	3.3 (2.6)	-0.2 (-0.7 - 0.3)	0.46	3 (1, 4)
Vaccinated index	3 (2.2)	3.4 (2.9)	-0.4 (-0.9 - 0.14)	0.16	3 (2, 4)
Serial Interval	4.8 (3)	5.4 (3.1)	-0.6 (-1 - -0.15)	0.008	4 (3, 6)	5 (3, 8)
Unvaccinated index	4.7 (3.1)	5.4 (3.1)	-0.7 (-1.3 - -0.06)	0.02		5 (3, 8)
Vaccinated index	4.9 (3.1)	5.3 (3.1)	-0.4 (-1 - 0.28)	0.26		5 (3, 7)

*Student´s T test for difference in Delta and Omicron period means

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Secondary Attack Rates, Transmission, Incubation and Serial Interval Periods of first SARS-CoV-2 Omicron variant cases in a northern region of Spain. Supplementary Materials

Secondary Attack Rates, Transmission, Incubation and Serial Interval Periods of first SARS-CoV-2 Omicron variant cases in a northern region of Spain.

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