HUMORAL IMMUNITY IN PATIENTS WITH SARS-COV-2 INFECTION: A REVIEW

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H.D. Ogundipe

Department of Surgery, University College Hospital, Ibadan, Oyo State, Nigeria

Abstract

The COVID-19 pandemic caused by SARS-CoV-2 started in China in December, 2019 and has spread across several continents. As at 5th December, 2020, there have been 65,257,767 confirmed cases of COVID-19 worldwide with 1,513,179 deaths (2.31% mortality) Humoral immune responses are highly specific and they provide long-lasting protection against reinfection and the titre of antibodies that persist is directly related to the extent of protection afforded. As research towards generating effective vaccines against SARS-CoV-2 are in advanced stages, there is need for continued robust review of the available data from various studies on the antibody response from natural SARS-COV-2 infection as regards the potential for immunity against re-infection following exposure to the antigens of this virus. Antibodies against RBD of the spike protein of SARS-CoV-2 were detected in majority of patients, appearing within the first week, peaking by 3rd week. IgG antibodies was observed to last beyond 120days and it is predicted seroreversion would happen at about 42.72 months. Antibody response to SARS-CoV-2 correlates with the severity of COVID-19. It was also higher amongst males, hospitalized patients, older people and patients with higher BMI and was lower among smokers, immunosuppressed individuals and patients using anti-inflammatory medications. Persistence of high levels of antiSARS-CoV-2 neutralizing antibodies (IgG) following natural infection is thus likely to be associated with conferment of long term protection against re-infection or attenuate disease severity if reinfection occurs. There is a good potential for development of immunity against SARS-CoV-2 infection in vaccinated individuals.

Keywords: SARS-CoV-2, Antibody response, AntiSARS-CoV-2 antibody

Introduction

The COVID-19 pandemic caused by SARS-CoV-2 started in Hubei province, China in December, 2019 and has spread across all continents except the Antarctica. Globally, as of 5 December 2020, there have been 65,257,767 confirmed cases of COVID19, including 1,513,179 deaths. (2.31 %).¹

Adaptive immune response involves T cells, which seek out and destroy cells that have been infected by the invading pathogen (cell mediated immunity) and B cells the produce antibodies targeted against particular disease causing organisms (humoral).

IgM antibodies are produced first and disappear after a few weeks and their presence as such suggest recent infection. IgG antibodies are produced at the same time or 2-3 days later, and titres (levels) usually remain for months or years, their co-existence with IgM antibody suggest recent infection and when they occur alone, it denotes prior infection² and their persistence suggests development of immunity.³

Humoral immune responses are highly specific and they provide long-lasting protection against reinfection. The quantity of antibodies that persist is directly related to the extent of protection afforded against the virus that induced them.⁴

Antibodies act by either prevention infection of cells by binding to the virus and preventing its interaction with its receptor (neutralizing antibodies) or by causing destruction of infected cells and virus bound to them and marking them for demolition through cell mediated immune response (binding antibodies)

Neutralizing antibodies play a major role in viral clearance and prevention of re-infection and their continued presence in the apparent absence of the inducing pathogen backed up by memory cells provides a first line of defense against re-infection.^3,5 Consequently, they are central to reducing transmission of infection as well as limiting morbidity and mortality from infections. Thus in epidemics and pandemics, like COVID-19, ability to generate adequate and lasting neutralizing antibodies against viral infection is essential for its limiting viral spread.⁶

Researches towards generating effective vaccines that protect against SARS-CoV-2 infection are in advanced stages, however, there is limited understanding of the antibody response from natural SARS-COV-2 infection. There are concerns that SARS-CoV-2 infection may induce transient antibody response⁴ raising apprehension about risk of re-infection and the uncertainty about the duration of vaccine protection.⁷ A proper understanding of antibody response to SARS-CoV-2 will help guide development of modalities and strategies for vaccination.^7,8

OBJECTIVES
This review aims to:

1. Profile the antibody response among individuals who are infected with or have recovered from SARS-CoV-2 infection, viz a viz: · the occurrence of antiSARS-COV-2 antibodies
   · longevity of antiSARS-COV-2 antibodies
   · factors that determine the magnitude of the
   antibody response
2. Find possible evidence of protection against SARS-CoV-2 infection/re-infection from the immune response to natural exposure to the virus/ viral antigen.

METHOD OF THE REVIEW
Google, Google scholar, Pubmed, Ajol were searched over a 2 week period (between 23rd of November 2020 and 6^th December 2020) for articles with data of studies on the antibody response to SARS-CoV-2 using the following search terms: immune response against SARS-CoV-2, antibody response to SARS-CoV-2, antiSARS-CoV-2 antibodies, antibodies against SARS-CoV2 Spike/S protein, anti-SARS-CoV-2 RBD antibodies, immunity against SARS-CoV-2 re-infection, anti-SARSCoV-2 neutralizing antibodies.

From the result of the searches done above, a total of 30 studies were selected for this review. Information as to the presence of anti-SARS-Cov-2 antibodies, the time of appearance of these antibodies, the time of peaking of antibody titre, time of commencement of antibody decay, time to seroreversion were abstracted from these papers where available.

Information about the group of patients with the highest and lowest antibody titres as well as reports of re-infection following recovery were also obtained where available.

RESULTS OF THE REVIEW
CoronaVirus Antigen and Antibody Response
Neutralizing antibodies are usually generated against antigens on the membrane of the infective agent. Antibodies to SARS-CoV-2 can target any of its antigens, the receptor binding domain (RBD) on the spike protein on the membrane of SARS-CoV-2 is the commonest target for antibody assays.⁹

The spike protein on SARS-CoV-2 is a glycoprotein that contains the receptor binding domain (RBD), this is used by the virus to attach to the receptor (angiotensin converting enzyme 2 (ACE2) receptor) on the surface of the mucosa of the host cell.^9,10,11

Neutralization antibody titers which play a key role in viral clearance and protection against infection have been found to significantly correlate with anti-spike titres (titers against RBD),^{5,9, 12} especially IgG titres.⁶ This was also observed by Lou et al. who noted decline in viral load with increasing antibody levels. ¹³ Furthermore, levels of neutralizing antibody titres have also being found to correlate to numbers of virusspecific T cells.¹⁴

This suggests that IgG antibody titres could be used to speculate the overall adaptive immune response against SARS-CoV-2 infection and the attendant protection from infection/re-infection.

TIME OF APPEARANCE OF ANTI-SARSCoV-2 ANTIBODIES
IgM antibodies against SARS-CoV-2 can be present within the first few days (by day 3 after infection), with IgG counterparts appearing a few days later.^15,16 seroconversion for all (IgM, IgG, NAb) antibodies was observed for most patients to have occurred by second to third week post infection^7,8,15,16,17

Expectedly, IgM antibodies appeared earlier and peaked faster than IgG anti SARS-CoV-2 antibodies.17,18 However, the time to seroconversion in asymptomatic and mild COVID-19 cases was longer.⁹ Anti-SARSCoV-2 S-specific, IgM antibodies peaked at days 20- 25days from onset of symptoms.^7,18,19,20

Anti-SARS-CoV-2 S-specific IgG antibodies were identifiable from day 7 onwards and peaked in the 4^th -5^th week (day 25-35).^7,18,19,20 Some studies also found that all patients develop IgG antibodies by 19- 20 days after infection.^5,21