COVID-19 Update: Variant of Concern Disease Severity and Persistence of Antibodies Following Infection

Reviewed by: Dr. Michael Payne, MD; London Health Sciences Centre

The emergence of variants of concern (VOC), in particularly the Delta variant, has complicated pandemic response in terms of the needed herd immunity to limit transmission as well as anticipated demands on health care resources, in particular ICU capacity, based on rates of disease severity. Three recent studies shed light on VOC disease severity and persistence of antibodies after infection.

A large retrospective cohort study performed in Ontario, Canada, shows the stepwise increase in disease severity risk with N501Y-positive VOCs (Alpha/Beta/Gamma) and again with Delta VOC. However, vaccination was still strongly protective against severe disease for VOCs. This study evaluated the relative virulence of variants of concern (VOC), as compared to non-VOC SARS-CoV-2 strains, using risk of hospitalization, intensive care admission and death. Patients testing positive for SARS-CoV-2, with VOC screening test results available, were included between February 7th to June 27th, 2021. The cohort included 212,326 patients. Compared to non-VOC strains, the increased risk associated with N501Y-positive variants was 52% for hospitalization, 89% for ICU admission and 51% for death. Increased risk with the Delta variant was more pronounced at 108% for hospitalization, 235% for ICU admission and 133% for death. However, vaccination was protective, with a decreased risk of ICU admission and death (approximately 80-90%).

Another large retrospective review utilized the CDC COVID-19–Associated Hospitalization Surveillance Network (COVID-NET), analyzing COVID-19 hospital admission data from 14 States. Trends in severe disease for non-pregnant adults were compared for periods before (January–June 2021) and after Delta variant predominance (July–August 2021). Overall, the rate of hospitalizations decreased pre-Delta, and subsequently increased during the Delta variant period. However, the proportion of patients requiring ICU admission or died during their hospitalization did not significantly change. There was a significant increase in the proportion of hospitalized patients 18-49 years old, from 24.7% to 35.8%. This is potentially attributable to lower vaccination rates within this age cohort. Amongst those ≥50 years old, there was a general trend towards increasing severe outcomes (ICU admission and death) during the Delta variant period, however, it was not statistically significant. The Delta VOC is more transmissible than previous strains, however, there is conflicting evidence regarding disease severity/outcomes and further study is needed to inform planning for potential impacts on the health care system.

In order to assess antibody persistence from primary infection, a second study followed a cohort of patients from Italy with COVID-19 infection, from early in the pandemic. It included the severity of illness information, including asymptomatic individuals. A prospective longitudinal study was conducted with monthly serological follow-up during the first 4 months, and then at 6, 8, and 10 months after the disease onset of all recovered adult patients with COVID-19 during the first wave (from March to May 2020). A total of 546 individuals were included (289 female, mean age 53.1 years), most patients had mild COVID-19 illness (370, 68.3%). The median duration of follow-up was 302 days. The seroconversion rate at 2 months was 32% for IgM and 90% for IgG. Seroreversion was found in 90% of patients for IgM at 4 months and in 47% for IgG at 10 months. Older age, number of symptoms at acute onset, and severity of acute COVID-19 were all independent predictors of increased persistence of both IgM and IgG. This study shows that serologic response for COVID-19 is more closely related to observations of antibody persistence after infection with common seasonal human coronaviruses (HCoVs), which decline between 6 and 12 months after infection. This study did not measure neutralizing antibodies or cell-mediated immunity, which is a limitation. However, it does help inform the potential risk of re-infection following COVID-19 infection. 


David N. Fisman and Ashleigh R. Tuite. Evaluation of the relative virulence of novel SARS-CoV-2 variants: a retrospective cohort study in Ontario, Canada. CMAJ October 25, 2021 193 (42) E1619-E1625; DOI:

Taylor CA, et al. COVID-NET Surveillance Team. Severity of Disease Among Adults Hospitalized with Laboratory-Confirmed COVID-19 Before and During the Period of SARS-CoV-2 B.1.617.2 (Delta) Predominance – COVID-NET, 14 States, January-August 2021. MMWR Morb Mortal Wkly Rep. 2021 Oct 29;70(43):1513-1519. DOI:

Peghin M, De Martino M, Fabris M, Palese A, Visintini E, Graziano E, Gerussi V, Bontempo G, D’Aurizio F, Biasotto A, Sartor A, Pipan C, Marzinotto S, Curcio F, Bouza E, Isola M, Tascini C. 2021. The fall in antibody response to SARS-CoV-2: a longitudinal study of asymptomatic to critically ill patients up to 10 months after recovery. J Clin Microbiol 59: e01138-21.

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