Marble Surface

27 May, 2021

The Battle Isn't Over Yet

Dr. Barbara Passaia, University of Sao Paulo

Close up of scientist in lab coat workin

The SARs-CoV-2 virus infects human cells through recognition and binding to its ACE2 receptor. This mechanism allows it to enter the cells and start to replicate its genetic material in few hours. Within days, the virus production is extremely high and transmissible. The SARs-CoV-2 binding mechanism to its receptor is so efficient that some scientists are studying its peculiarities to improve nanoparticles for cancer treatment as a target therapy with few side effects. Besides that, each person responds to infection in different ways. Some people have no symptoms, others have mild symptoms and a small percentage of people have severe and life-threatening condition, requiring intensive care, for weeks to months. There is also a group of people who remain with symptoms, such as ageusia and fatigue, for more than two months after healing (called “long Covid”).

The way our immune system fights SARs-CoV-2 virus has been studied since the beginning of Covid-19 pandemic and now we know more about that. Researchers identified immune response profile at different stages of the disease analyzing proteins present in the urine of patients who had Covid-19. The immune system of patients in early stage was suppressed because there was reduced levels of tartrate-resistant acid phosphatase type 5, protein tyrosine phosphatase receptor type C and leptin. However, patients with severe symptoms, in the final stage of Covid-19, have exaggerated response and excess of cytokines. This lack of control of the immune system and excessive signaling caused by cytokines make the patient's immune response as damaging as the virus infection.

Meantime, we observed there are people who respond well to infection, even though they are considered to be in a vulnerable group (elderly and comorbid people). While others, young and healthy, can have complications from Covid-19. An explanation for that may be previous exposure to other types of coronaviruses. It was observed that people who had not been exposed to SARS-CoV-2 had reactive T cells and specific IgG for the SARS-CoV-2 spike protein. Some children and adolescents who had this previous immunity had mild symptoms, demonstrating that this may be a mechanism that leads to a good response to SARS-CoV-2 infection. 

By the way, children usually have no severe symptoms. Interestingly, it is not an expected pattern for viruses affecting respiratory system in this age. This leads to the belief that differences in the immune system of children and elderly people may be fundamental to the body's response to SARS-CoV-2 infection. T cells from T helper type 2 are more abundant in children, for example. However, although children are usually asymptomatic and do not have severe breathing problems, they can develop multisystem inflammatory syndrome (MIS-C). Despite of being rare, it is serious and has a severe inflammatory condition and heart damage. Some differences were observed: Adults generate anti-nucleocapsid IgG antibody and anti-spike IgG, IgA and IgM antibodies. Pediatric patients mainly have just anti-spike IgG antibodies. There are no significant differences between the immune response profile of children with or without MIS-C, so immunity is not related to that. Therefore, children generally respond well to SARS-CoV-2, even if antibody production appears to be reduced.

Antibodies. Such important agents to guarantee the defense of our organism against an invader. It was recently discovered that levels of anti-spike IgA and mainly anti-spike IgG and IgM antibodies decrease considerably months after infection, but memory B cells levels remain the same for six months. That is, the number of antibodies may decrease, but the cells responsible for remembering SARS-CoV-2 will still be there. Then our body would be able to fight a new infection. Nevertheless, there are data suggesting that the acquired immune response can vary depending on the severity of the disease. Thus, individuals who had a severe Coivd-19 would be less likely to be reinfected.

In 2020 the world followed pandemic evolution. Several countries went through peak of cases and took necessary measures for control, but what we see now is that pandemic is not yet controlled around the world. Many countries are struggling to control virus spreading. Thanks to science, we have vaccine. There is hope. But we cannot consider that the game is won.

At this time, some countries are experiencing the second wave of infection. Perhaps, worse than the first. The UK has tightened restrictions to contain the spread of a new virus strain (501Y Variant 2 / B.1.1.7 Variant), with high transmission rate. Studies had shown that this new variant acquired greater efficiency in binding to ACE2 receptor and thus, greater capacity to invade human cells. Two recent studies, not yet reviewed, showed that antibodies obtained from plasma from individuals who had Covid-19 were unable to neutralize the variant 501Y.V2 observed in South Africa. However, another study found that Modern and Pfizer-BioNTech vaccines were still efficient in neutralizing viruses with the new variants. Another new lineage was detected in December in Manaus, Amazonas State (Brazil), called P.1 (descendent of B.1.1.28 variant). In the beginning of 2021, the state of Amazonas experienced days of profound sadness: with high number of cases, overcrowded hospitals, people died because there was not enough oxygen for medical care. Amazonas is experiencing second wave of high virus spreading, even if at first it was thought that Amazonas population would achieve herd immunity. Some months will still be needed for further studies, but emergence of new variants can be worrying.

Vaccine is hope. Prevention is our reality.

We need, as individuals and society, to have responsibility. Do not spread the virus, avoid reinfection and protect the most vulnerable. Together we will win.

References

Brodin, Petter. “Immune determinants of COVID-19 disease presentation and severity.” Nature medicine vol. 27,1 (2021): 28-33. doi:10.1038/s41591-020-01202-8

 

Faria, Nuno R et al. “Genomic characterisation of an emergent SARS-CoV-2 lineage in Manaus: preliminary findings.” Accessed in: https://virological.org/t/586. 12 Jan. 2021,

 

Gaebler, Christian et al. “Evolution of antibody immunity to SARS-CoV-2.” Nature, 10.1038/s41586-021-03207-w. 18 Jan. 2021, doi:10.1038/s41586-021-03207-w

 

Guthmiller, Jenna J et al. “SARS-CoV-2 Infection Severity Is Linked to Superior Humoral Immunity against the Spike.” mBio vol. 12,1 e02940-20. 19 Jan. 2021, doi:10.1128/mBio.02940-20

Leung, Kathy et al. “Early transmissibility assessment of the N501Y mutant strains of SARS-CoV-2 in the United Kingdom, October to November 2020.” Euro surveillance vol. 26,1 (2021): 2002106. doi:10.2807/1560-7917.ES.2020.26.1.2002106

 

Ribeiro, I R S et al. “Nano-targeting lessons from the SARS-CoV-2.” Nano today vol. 36 (2021): 101012. doi:10.1016/j.nantod.2020.101012

Tian, Wenmin et al. “Immune suppression in the early stage of COVID-19 disease.” Nature communications vol. 11,1 5859. 17 Nov. 2020, doi:10.1038/s41467-020-19706-9 

 

Wang, Zijun et al. "Mrna Vaccine-Elicited Antibodies to Sars-Cov-2 and Circulating Variants." bioRxiv 19 Jan. 2021, doi:10.1101/2021.01.15.426911

Weisberg, Stuart P et al. “Distinct antibody responses to SARS-CoV-2 in children and adults across the COVID-19 clinical spectrum.” Nature immunology vol. 22,1 (2021): 25-31. doi:10.1038/s41590-020-00826-9 

 

Wibmer, Constantinos K et al. "Sars-Cov-2 501y.V2 Escapes Neutralization by South African Covid-19 Donor Plasma." bioRxiv 19 Jan. 2021, doi:10.1101/2021.01.18.427166