The latest guidance from the U.S. Centers for Disease Control and Prevention says people who are fully vaccinated should get tested three to five days after a potential exposure, even if they don’t have symptoms.
That change comes two months after the agency eased its initial testing guidance. In May, the CDC said vaccinated people face very little risk of serious illness and don’t need to be tested in most cases, even if exposed to someone who was sick. The thinking was that vaccinated people also weren’t likely to spread it to others.
But the agency says it’s reversing that guidance because of the more contagious delta variant, which now accounts for most COVID-19 infections.
The COVID-19 vaccines are still very good at protecting people from getting seriously ill, but the CDC says new data shows vaccinated people infected with the delta variant could spread it to others.
Doctors, nurses and other health care workers should consult with their employers, some of whom may require routine testing for their staff. People working in prisons and homeless shelters are also generally subject to stepped-up testing requirements.
U.S. citizens returning from abroad still have to present a negative COVID-19 test before boarding their flights home, regardless of their vaccination status. Anyone who tests positive for COVID-19 should still isolate for 10 days, the CDC says.
THE CRITICAL QUESTIONS
The challenge for modern vaccinology is to be able to provoke all the requisite steps leading to immune system activation in vivo, and to provide a non-virulent, harmless type of a given agent capable of generating a strong and adequate immune response tailored against specific viral attack (Moser and Leo, 2010). Thus, some questions arise regarding the development of the vaccine (see Table 1 for current development state of COVID-19 vaccines) that will be administered to billions of people at risk of COVID-19 infection.
WILL VACCINE STIMULATE THE IMMUNE RESPONSE?
As mentioned earlier, ACE2 is the route of SARS-CoV-2 infection. However, this receptor plays a vital role in both innate and adaptive immune responses by modulating the antigen present antigen cells that interact with T cells to initiate defense initiatives (Bernstein et al., 2018). This receptor of transmembrane protease acts in the conversion of angiotensin 1-8 (Ang II) to angiotensin 1-7 (Ang 1-7), prompting diuresis/natriuresis, preserving renal function, and attenuating cardiac and vascular reformation (Vickers et al., 2002; Santos et al., 2008; Zhang et al., 2010).
ACE2 also has an important role in the nervous system, and disruption of this receptor can trigger neurological disorders (Kabbani and Olds, 2020). However, a study reported that innate T cells, a heterogeneous class of T lymphocytes (MAIT, γδT and iNKT cells), are also altered by SARS-CoV-2 (Jouan et al., 2020). Besides, a study cohort of 38 patients found that a decline in T cells, B cells, and NK cells was linked to SARS due to coronavirus (Cui et al., 2003).
On the other hand, a study conducted on bronchoalveolar lavage fluid of eight COVID-19 patients exhibited chemokine-dominant hypercytokinemia, often called a ‘cytokine storm,’ which robustly promotes expression of numerous IFN-stimulated genes that lead to multi-organ failure (Zhou et al., 2020). Therefore, SARS-CoV-2, directly and indirectly, triggers the impairment and hyper-stimulation of the immune system (Jamilloux et al., 2020; Yazdanpanah et al., 2020).
But, cellular immunogenicity, humoral, and cell-mediated immune responses are crucial for vaccine-derived immunity and rapid cytotoxic response against viral infection (Morris et al., 2016; Ewer et al., 2017). Thus, should vaccines stimulate or suppress the immune response system of the host against COVID-19 infections?
WILL A VACCINE PROVIDE SUSTAINABLE IMMUNE ENDURANCE?
Another major concern about immunity against coronaviruses is the endurance of the immune response system. For effective immunization, vaccine-induced long-term regulation of the immune system, especially humoral and cell-mediated arms of the adaptive system, functions through producing the effector cells for the current infection and memory cells for future infections with the pathogenic agent (Clem, 2011).
However, a number of studies showed that immune responses against COVID-19 do not last long-term. A study conducted on 285 SARS-CoV-2-infected persons reported that antiviral immunoglobulin-G (IgG) and IgM were increased during the first 3 weeks after symptom onset, and then began to decrease (Long et al., 2020a).
A case report of 34 hospitalized patients (admitted from Feb 1 to Feb 29, 2020) with confirmed SARS-CoV-2 revealed that IgM levels reached their peak of after three weeks and then continued to decline up to the end of 7 weeks of observation, whereas IgG values remained more or less the same (Xiao et al., 2020).
In another case report, both IgM and the IgG declined after the peak period; this study was conducted on 60 convalescent patients where the value of those two antibodies reached their summit 6-7 weeks after onset, and a decline was observed in the following week (Du et al., 2020). A report from the National COVID Scientific Advisory Panel of the UK mentioned that IgG titers increased within three weeks of the onset of symptoms and started to drop by eight weeks in plasma samples collected from 40 confirmed COVID-infected persons (Adams et al., 2020).
Another study noted that the most plasma samples obtained from eight convalescent COVID-19 patients recovering from COVID-19 without hospitalization did not contain high neutralizing activity levels (Robbiani et al., 2020). In cases of asymptomatic infection, a study conducted on 37 individuals reported that they had a weaker immune response, i.e., a greater reduction of IgG and neutralizing antibody levels (Long et al., 2020b).
These phenomena are not new to the scientific world. Exactly 30 years ago, in 1990, a study reported a similar result. From an investigation of circulating lymphocyte populations in 15 volunteers infected with a CoV 229-E strain, the researchers observed that the concentration of antibodies began to rise one week after inoculation and then reached their peak another week later. After that, titers of the antibody began to decline.
They also claimed that despite the slightly high concentration after one year, this did not always prevent the volunteer from being reinfected with homologous virus (Callow et al., 1990). Thus, how long will a vaccine-mediated immune response be sustained and at what magnitude?
HOW WILL SARS-COV-2 MUTATE?
The genome of coronavirus is highly susceptible to mutations that result in genetic drift and evade immune recognition. Several studies have described this phenomenon. The genetic analysis of 86 complete or near-complete genomes of SARS-CoV-2 disclosed many mutations and deletions in coding and non-coding regions (Phan, 2020). High-resolution mapping of the SARS-CoV-2 transcriptome and epitranscriptome found at least 41 potential RNA modification sites with an AAGAA motif (Kim et al., 2020).
A study of 95 complete genome sequences found 116 mutations including the three most common mutations, i.e., 8782C>T in ORF1ab, 28144T>C in ORF8, and 29095C>T in the N gene (Khailany et al., 2020).
Mutations are also found in the S protein region, the crucial part for binding to human receptor ACE2. Another study reported that five of the six receptor binding domain residues of the S protein of SARS-CoV-2 differ from SARS-CoV (Andersen et al., 2020). However, this transformation does not stop there.
A study identified 13 mutations in the S protein especially in spike D614G, which began to spread in Europe in early February 2020. This study also showed the evidence of recombination between the locally circulated strains indicating the multiple strain infections. (Korber et al., 2020).
Twelve distinct variants were identified within the B-cell epitopes of the S protein, N protein, and M protein, and 21 distinct variants within T-cell epitopes. Of the 12 variants in the B-cell epitopes, 23403A>G Variant (p. D614 G) in an S-protein epitope has frequently been found in European countries such as the Netherlands, Switzerland and France, but rarely seen in China (Koyama et al., 2020). However, SARS-CoV-19 might not be evolving as rapidly as other RNA viruses, but we still need much more scientific evidence.
Nevertheless, rapidly evolving viruses such as influenza need to be monitored to recommend new vaccine formulations twice each year (Gerdil, 2003). Similarly, no human immunodeficiency virus vaccines exist yet (Andrews and Rowland-Jones, 2017). In these circumstances, will the genetic stability of the SARS-CoV-19 remain such an extent that let the scientists develop a safe and effective vaccine?
reference link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771841/