CME INDIA Presentation by Admin.

COVIDOLOGY Burning Issues – What to do?

After vaccination, get the anti-spike antibody and not nucleocapsid or Total Antibody.

Covidology Burning Issues Now

• Which components of the immune system are most important in fighting SARS-CoV-2, if antibodies, what titers are required to maintain immunity?
• Will past infection by SARS-CoV-2 have future vaccine selection?
• How long do neutralizing antibodies last?
• Is a single infection sufficient to induce memory B and T cell development?

See these 2 tests reports of the same person from 2 labs post Vaccination

After 21st day:

So, what you think of it?

2nd Lab report follows, same day, same person:

Dr Manoj Chawla, Mumbai:

• This is not the spike protein one, I think.
• Check with the lab again. This <1 and >1 is the regular igG. The other report mentions antibodies to the spike protein and is reported differently.

Dr Sanjeev R Pathak, Ahmedabad:

• After vaccination, Get the anti-spike antibodies and not nucleocapsid or total.

Lab Post Vaccination Antibody test has been not standardised so far. Following 2 labs have mentioned in a better way:

Enabling the body to produce a viral antigen (the spike protein) stimulating an immune response

• All three vaccines—two mRNA vaccines (Pfizer-BioNTech and Moderna) and a DNA vaccine (Oxford-AstraZeneca)—encode genetic information, enabling the body to produce a viral antigen (the spike protein) that stimulates an immune response.

Viral antigens have been used to detect antibodies for SARS-CoV-2

Corona virus genome encodes 4 structural protein

1. Spike (S) — The S protein is very large trans membrane protein. It assembles into trimers to form the distinctive SURFACE SPIKES of corona virus.
2. Envelop(E).
3. Membrane(M).
4. Nucleocapsid(N).

IMPORTANT: After infection with SARS CoV2, the host mounts an immune response against the virus, typically including production of SPECIFIC Antibodies against viral antigen.

Anti SARS CoV2 assay: It uses a recombinant protein representing the RBD of the S antigen in a double antigen sandwich assay format – This favours the QUANTITAIVE determination of high affinity antibody against SARS CoV2.

If you quantify the antibody response can help to determine the specific antibody titer.

Available vaccines induced neutralising antibodies to the spike protein and also cellular immune responses

• IgA and IgM levels decline after 60 days post–symptom onset, though IgG levels remain significant.
• IgG antibodies have been shown to persist up to 90 days, even in mild cases.
• Patients with severe COVID-19 appear to have higher levels of antibodies than those with mild/asymptomatic cases, but the kinetics of antibody levels are similar across all cases. 
• Titers of neutralizing antibodies in patients with severe COVID-19 are up to seven times higher than in those with mild disease.
• Importantly, mild and asymptomatic cases of COVID-19 also appear to have SARS-CoV-2–specific T cell responses.
• These responsive T cell titers appear to correlate with antispike, anti-RBD, and anti-nucleoprotein (NP) antibody levels.
• Importantly, even without seroconversion, contact cases still had active T cell responses. 

Accurate interpretation of serology testing depends on antigen specificity, but also on the type of antibody being detected

• IgM is one of the first antibodies produced during infection. It can be expressed in monomeric form on the surface of B lymphocytes or found circulating in the blood and lymphatic fluid in pentameric form.
• IgG typically appears later in infection when mature B cells receive signals to switch from production of IgM to IgG. 

How can we determine if the antibodies being detected by common serology assays are capable of neutralizing SARS-CoV-2?

• Neutralizing antibodies (NAb) are a subset of antibodies produced against a virus that independently block viral entry into host cells and are primarily of the IgG isotype.
• Neutralizing antibodies are classically detected using Plaque Reduction Neutralization Tests (PRNTs).
• BSL2 neutralization tests have been developed using Pseudo typed Vesicular Stomatitis Virus (VSV) expressing SARS-CoV-2 spike (S) protein.

CME INDIA Learning Points

(By Dr Awadhesh Kumar Singh, DM, Endo, Kolkata)

1. Types of antibodies produced after natural Covid infection could be different – it could be either – Spike (S), Membrane (M), Envelope E) and Nucleocapsid (N) and therefore total IgG antibody titre would be high.
2. These antibodies are different from antibody produced by different vaccines. Antibody produced by different vaccines could be different depending upon the types of vaccine used.
3. While Moderna Pfizer and Oxford AZ vaccine are directed towards spike antigen it would produce anti spike antibody, live attenuated full virus vaccine such as Covaxin should produce all antibodies. Therefore physicians should be alert when testing for antibody titre following two different vaccine 💉

• At present, no standard protocol having validated laboratory test to detect neutralising post vaccination antibody exists.
• Lab results must mention COVID IgG against spike protein.

CME INDIA Tail Piece

[1]

T cells that stop people from dying

These are findings from a small but important study (1):

• Early induction of functional SARS-CoV2-specific T cells was observed in patients with mild disease and rapid viral clearance. This supports the prognostic value of detecting SARS-CoV-2-specific T cells.
• Virus-specific humoral and cellular immunity act synergistically to protect the host from viral infection.
• SARS-CoV-2 viral RNA in the respiratory tract in parallel with antibodies and circulating T cells specific for various structural (nucleoprotein [NP], membrane [M], ORF3a, and spike) and non-structural (ORF7/8, NSP7, and NSP13) proteins.
• Although rapid induction and quantity of humoral responses associate with an increase in disease severity, early induction of interferon (IFN)-g-secreting SARS-CoV-2-specific T cells are present in patients with mild disease and accelerated viral clearance.
• These findings provide support for the prognostic value of early functional SARS-CoV-2-specific T cells with important implications in vaccine design and immune monitoring.
• This longitudinal analysis of the dynamics of virological and virus-specific immunological parameters during the acute phase of SARS-CoV-2 infection revealed a positive relation between early detection of IFN-g-secreting SARS-CoV-2-specific T cells and early control of infection.

[2]

Dr Santosh Malpani, Nanded shares:

Vaccination at Nanded (Maharashtra)

1. Walk in for doctors.
2. Take vaccine on Saturday.
3. Take PCM thrice a day for 3 days after vaccine.
4. Take vitamin D if deficient.
5. Plenty of fluids after vaccine.
6. Usually body and joint pain starts after 10 hrs of vaccination, on peak after 18 hrs and wanes off after 36 hrs.
7. May feel like increased appetite on second day.

Reference

1. Early induction of functional SARS-CoV-2-specific T cells associates with rapid viral clearance and mild disease in COVID-19 patients

Tan et al., 2021, Cell Reports 34, 108728 February 9, 2021 ª 2021 The Author(s). https://doi.org/10.1016/j.celrep.2021.108728

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