Vaccine or monoclonal therapy: which is the winning weapon against COVID-19?

The COVID-19 (coronavirus disease 2019) pandemic is causing thousands of deaths and blocking activities of the global community. All hopes are now placed on vaccines, such as BioNTech/Pfizer, Oxford/AstraZeneca, Moderna, Sinovac, CanSino, Sinopharm, Novavax, etc. However, a new problem is emerging: the possibility of reinfection for recovered subjects. Recent reports have outlined cases of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) reinfection from different countries including the USA, Ecuador, Hong Kong and Belgium [1]. It is necessary to verify whether all of these cases are truly reinfection because the possibility of reinfection could drastically reduce the effectiveness of the vaccination campaign in progress and affect government and public-health policy decisions in the coming months. Protective, sustainable and long-lasting immunity following SARS-CoV-2 infection is uncertain, but it is essential for the efficacy of the vaccine strategy. For some viruses, the first infection can provide lifelong immunity, whereas for seasonal coronaviruses protective immunity is short-lived. How long does coronavirus immunity last after testing positive? This is the question that all experts have been asking themselves since the beginning of the pandemic and that several studies are now trying to answer. A recent report studied the immunological memory in 188 patients affected by SARS-CoV-2 [2]. While antibodies and T-lymphocytes tended to decrease slightly over time, B-lymphocytes were observed to increase in number [2]. In people affected by SARS-CoV-2, the immune response modulated by IgM and IgG antibodies shows an activation starting from the seventh day following infection, up to a very rapid increase in the number of total antibodies between the second and third week, even close to 100% [2]. A small percentage of patients do not have immune protection, probably due to the low amount of virus to which they are exposed [2]. B-lymphocytes or memory cells ‘remember’ the viral infection and, if re-exposed to the virus, are able to trigger a protective immune response through the rapid production of antibodies [3]. A recent study reported that all patients continued to have memory B-cells that recognised one of the viral components up to 8 months after infection [3]. These results give hope for the effectiveness of any coronavirus vaccine and also explain why there have been very few cases of reinfection among the millions of those who were positive worldwide [3]. Another problem is due to virus mutations with new variants. The UK identified a variant called B.1.1.7 with a large number of mutations in from a sample taken in September 2020. This variant is able to spread more easily and quickly than other variants. In January 2021, UK experts reported that this variant may be associated with an increased risk of death compared with other variant viruses, but more studies are needed to confirm this finding. In South Africa, another variant called B.1.351 emerged independently of B.1.1.7. Originally detected in early October 2020, B.1.351 shares some mutations with B.1.1.7. Preliminary evidence from non-peer-reviewed publications suggests that the Moderna mRNA-1273 vaccine currently used in the USA may be less effective against this variant [4], but additional studies are needed. In Brazil, a variant called P.1 emerged and contains a set of additional mutations that may affect the ability of antibodies (from natural infection or vaccination) to recognise and neutralise the virus [5], but again additional studies are required. All of these variants appear to be more contagious. For this reason, it may be necessary to organise new strategies to use together with vaccines in the fight against SARS-CoV-2. Indeed, in November 2020 the US Food and Drug Administration (FDA) issued an emergency use authorisation (EUA) for bamlanivimab and for the cocktail of casirivimab and imdevimab. They are monoclonal antibodies specifically directed against the viral spike protein and able to block virus attachment and entry into human cells. They appear to be effective in treating patients with mild or moderate COVID-19 with a reduction in hospitalisations. On the other hand, other monoclonal antibodies are in the clinical trial phase, such as: AZD7442 directed to the SARS-CoV-2 spike protein; VIR-7831, selected on the basis of its potential to neutralise the virus; and anakinra, able to block the so-called cytokine storm typical of the disease, specifically inhibiting the proinflammatory cytokines interleukin (IL)-1α and IL-1β. On 21 January 2021, Eli Lilly pointed out that its neutralising antibody bamlanivimab prevented COVID-19 at nursing homes in the BLAZE-2 trial, reducing risk of COVID-19 illness by up to 80% for residents [6]. Only four COVID-19-related deaths occurred in the study, and all were in nursing home residents in the placebo group [6]. In conclusion, recent studies have indicated that a small percentage of patients do not have immune protection after SARS-CoV-2 infection, probably due to the low amount of virus to which they are exposed, so can a patient recovered from COVID-19 get sick again? Could this also happen with vaccination? Reinfection cases with SARS-CoV-2 proved that levels of immunity are not 100% for all individuals. Although several vaccines are ready, the presence of more than 80 genotypic variants of the virus, the possibility of reinfection and the short duration of seropositivity for neutralising antibodies raise the concern that vaccination may not result in effective and long-term immunity against SARS-CoV-2. Furthermore, immunoglobulin levels may not correlate with viral shedding and the risk of transmissibility of SARS-CoV-2. Some considerations arise from all of these data. First, several studies reinforce the possibility that vaccines will work for a long time with a very optimistic result. Second, it is necessary to vaccinate even those who have already had COVID-19, although later than all others. Third, for many months it will be necessary to continue to observe all of the prescriptions adopted in order to limit the spread of the virus and any new variants. Fourth, all of these factors raise concerns that eliminating SARS-CoV-2 and the COVID-19 pandemic may not be as feasible as once assumed and that we must rely more on prevention of transmission until more aspects of the virus and its pathogenicity are discovered. If we want to win the war against SARS-CoV-2, is necessary to identify possible innovative treatment alternatives such as monoclonal antibodies [7], nanotechnology applications such as viral inactivators, including cellular nanosponges in order to reduce viral adhesion [8], or the treatment of personal protective equipment (PPE) with charged metallic (such as Cu, Ag, Fe and Zn among others) nanoparticles, which seems to result in the release of antiviral agents (i.e. reactive oxygen species) able to inhibit viral entry into host cells by means of interactions with cell receptors [9].