Immune responses and immunity to SARS-CoV-2

Immune responses

Immune response to SARS-CoV-2 involves both cell-mediated immunity and antibody production.

Cell-mediated immune response

T-cell responses against the SARS-CoV-2 spike protein have been characterised and correlate well with IgG and IgA antibody titres in COVID-19 patients, which has important implications for vaccine design and long-term immune response [233-235] It is currently unknown whether antibody responses or T-cell responses in infected people confer protective immunity, and if so, how strong response is needed for this to occur. CD8+ T cells are the main inflammatory cells and play a vital role in virus clearance. Total lymphocytes, CD4+ T cells, CD8+ T cells, B cells, and natural killer cells showed a significant association with inflammatory status in COVID-19, especially CD8+ T cells and CD4+/CD8+ ratio  [236]. Decreased absolute numbers of T lymphocytes, CD4+ T cells, and CD8+ T cells were observed in both mild cases and severe cases, but accentuated in the severe cases. In multivariate analysis, post-treatment decrease in CD8+ T cells and B cells and increase in CD4+/CD8+ ratio were indicated as independent predictors of poor treatment outcome [237]. The expression of IFN-γ by CD4+ T cells also tends to be lower in severe cases than in moderate cases [238].

Antibody-mediated immune response and protective immunity

The detection of antibodies to SARS-CoV-2 does not indicate directly protective immunity and correlates of protection for COVID-19 have not yet been established.

Most persons infected with SARS-CoV-2 display an antibody response between day 10 and day 21 after infection. Detection in mild cases can take longer time (four weeks or more) and in a small number of cases antibodies (i.e., IgM, IgG) are not detected at all (at least during the studies’ time scale). Based on the currently available data, the IgM and IgG antibodies to SARS-CoV-2 develop between 6–15 days post disease onset [239-244]. The median seroconversion time for total antibodies, IgM and then IgG were day-11, day-12 and day-14 post symptom onset, respectively. The presence of antibodies was detected in <40% among patients within 1 week from onset, and rapidly increased to 100% (total antibodies), 94.3% (IgM) and 79.8% (IgG) from day-15 after onset [245].  

The longevity of the antibody response is still unknown, but it is known that antibodies to other coronaviruses wane over time (range: 12 – 52 weeks from the onset of symptoms) and homologous re-infections have been shown [246]. SARS-CoV-2 IgM and IgG antibody levels may remain over the course of seven weeks [247] or at least in 80% of the cases until day 49 [69]. In comparison, 90% and 50% of SARS-CoV-1 infected patients have been shown to maintain IgG antibodies for two and three years respectively [248]. In addition, it could be important to detect nasal IgA antibodies, as the serum IgA antibodies were not raised, but IgA persisted in the nasal mucosa one year post-infection for seasonal coronavirus 229E [249].

Longitudinal serological studies that follow patients’ immunity over an extended period of time would be required to study the duration of immunity [250].

Reinfections with all seasonal coronaviruses occur in nature, usually within three years [251]. However, the elapsed time between infections does not mean that the protective immunity lasted for the same period of time, because the reinfection was also dependent on re-exposure. Based on the minimum infection intervals and the observed dynamics of antibody waning, the study showed that the duration of protective immunity may last 6 to 12 months. These results were in line with a model of the protective immunity and reinfection dynamics of HCoV-OC43 and HCoV-HKU1 in which the estimated period of protective immunity was 45 weeks [6]. Primary infection with SARS-CoV-2 was shown to protect rhesus macaques from subsequent challenge and casts doubts on reports that the re-positivity observed in discharged patients is due to re-infection [252].

Population immunity

Population immunity

The updated overview of the findings of population-based (from random sampling, residual clinical samples or blood donor samples) seroepidemiological studies in EU/EEA Member States are shown in Table. All EU/EEA Member States have low levels of seropositivity, even without adjusting for test sensitivity and specificity, and it is unlikely that population immunity levels reached by winter 2020/2021 with current transmission patterns will be sufficient for indirect protection.

Table: Preliminary results of first seroepidemiological population studies in EU/EEA Member States and the UK from public sources, as of 8 June 2020

Country

Number (n) and

Source of samples

Time of sampling

Laboratory method

Proportion of positive samples (%)

Austria

[253]

269

General population

Week 18

n/a

4.7

Belgium [254]

3 397

Residual sera

Mid- April

EUROIMMUN IgG

6.0

Czechia [255]

26 549

General population

week 18

Wantai rapid test

0.0-4.0

Denmark [256]

5 422

Blood donors

week 18

EUROIMMUN Elisa

2.4

Finland [257]

2800

General population

Weeks 16-23

Fluorescence-based multiplex

1.0-4.3*

Luxembourg [258]

1862

General population

Weeks 17-19

EUROIMMUN IgG

1.97

Netherlands [259]

7 361

Blood donors

Weeks 15-16

Wantai Elisa

2.7

Spain [80]

60 983

General population

Weeks 18-19

Orient Gene IgM/IgG

5.0

Sweden [260]

1 104

Residual sera

Week 18

n/a

3.7-7.3

UK (England) [261]

7 694

Blood donors

Weeks 13-21

EUROIMMUN

8.5**

UK (Scotland) [262]

500

Blood donors

Week 13

pseudotyped microneutralisation assay

1.0

*confirmation with microneutralisation test 0.25-0.83%.

**adjusted for test sensitivity, specificity and age.

 

References