**4.5 Neoplasia (cancer)**

Cancer patients are regarded as more vulnerable to severe COVID-19, due to the direct immunosuppression caused by the tumor or indirectly by the antitumor treatment [127, 128]. Patients with hematological malignancies, such as leukemia and lymphoma, have an exacerbated cellular proliferation with a reduction in the immune response, increasing the susceptibility to infections [129].

Location and cancer stage can also impact COVID-19 development. A recent report among patients with cancer identified that lung cancer, gastrointestinal cancer, and breast cancer are the most common [130]. Patients with stage IV cancer also account for a high number of COVID-19-infected patients [130, 131]. Cancer patients with COVID-19 also have an increase in hospitalization duration and severity [130, 131].

In addition to immune suppression, hospitalized cancer patients or patients undergoing frequent hospital visits may be at great risk for SARS-CoV-2 infection, increasing the necessity for precautionary measures [132, 133].

## **4.6 Immunodeficiencies**

Immunodeficiencies are uncommon and chronic disorders of the immune system, that hinders the ability to develop an appropriate immune response, leading to deficient, exacerbated, or absent response to an infection or disease [134]. The immunodeficiency can be localized in any cell or structure of the immune system, compromising barrier immunity, innate immunity, or adaptive immune.

Immunodeficiency disorders can be divided into primary and secondary immunodeficiencies. Primary immunodeficiencies are a consequence of genetic defects, and secondary immunodeficiencies are caused by external or environmental factors, such as nutritional disorders or HIV [135].

The most common primary immunodeficiency is the common variable immunodeficiency that affects the patients' ability to mount an appropriate humoral response during infection [136]. These patients are commonly treated with immunoglobulin replacement [137]. A recent case report identified a patient with common variable immunodeficiency and severe COVID-19, that was successfully treated with COVID-19 convalescent plasma [138]. Although it is important to highlight that convalescent plasma treatment has controversial results, even when applied at the beginning of the infection and with high titers of neutralizing antibodies [139–141].

Reports of patients with primary and secondary immunodeficiencies identified an increase in severity and mortality due to COVID-19 in these patients in comparison with available data on COVID-19 [142, 143]. Also, patients with immunodeficiencies can present other comorbidities, further increasing the death risk by COVID-19 and increased risk for the development of secondary infections during hospitalization [142, 143]. Certain immunodeficiencies compromise specific anti-viral immune responses, for example, TLR7 gene defect, with compromised type I and II interferon production, are linked to severe COVID-19 in young individuals [144].

A common secondary immunodeficiency AIDS, the one caused by HIV, can compromise the anti-viral immune response during COVID-19. Patients with low CD4+ count have a higher severity and mortality risk compared with patients with normal CD4+ count [145]. In patients with HIV viral suppression, other comorbidities may increase patients' death risk during COVID-19 [30, 145].

#### **4.7 Co-infections**

Bacteria and viral co-infections and secondary infection in COVID-19 patients are important factors in the patients' treatment and outcome [146]. Co-pathogens included bacteria, fungi, parasites and viruses can modulate patients' immunity and also curb the anti-SARS-CoV-2 immune response [146]. Patients with invasive mechanical ventilation are at greater risk for bacterial coinfections [17, 147], also several patients report diarrhea without gastrointestinal SARS-CoV-2 infection, which could be a secondary gastrointestinal infection or microbiota dysbiosis [108].

Co-infections can increase the susceptibility to severe COVID-19, by an increase in the hyper inflammation or hypercoagulation status [74, 148]. Few reports have investigated the impact of parasites on COVID-19, such as leishmaniasis, toxoplasmosis, malaria, and Chagas disease [148–151]. Clinical manifestations of those diseases are usually associated with an increased and unregulated type 1 pro-inflammatory response, similar to COVID-19 [151]. In fact, a few case reports identified that chagasic patients with COVID-19 present an exacerbated inflammatory response, with a high lethality [74, 148]. This represents a further difficulty in the treatment of COVID-19, since the combination of drugs for the treatment of COVID-19 and the co-infections, the immune response to the co-infections and possible comorbidities need to be equated.

#### **5. COVID-19 vaccines**

COVID-19 vaccines are currently the only prophylactic/curative treatment for COVID-19, since drug repurposing and monoclonal antibodies trials had limited success, and investigations with convalescent plasma have conflicting results [87, 139–141, 152, 153]. Several vaccines are currently developed and in developing. Due to the high demand for a COVID-19 vaccine, significant advances in vaccine technologies have been made in the last year. Currently, 3 types of vaccines are being administered worldwide: inactivated virus vaccines (IVV) [154], vaccines that use mRNA with lipid nanoparticle (LNP) delivery systems [155], and vaccines containing DNA delivered within non-replicating recombinant adenovirus (AdV) vector systems [156]. AdV and mRNA vaccines aim to induce the production of SARS-CoV-2 S protein and induces the production of neutralizing antibodies [139, 141, 153].

All vaccines can induce the recognition of the viral antigen (immunogen) and also serve as an adjuvant to boost the immune response, the immunogen is recognized by innate immunity receptors such as toll-like receptors 3 and 7, RIG-I, and NOD2 inducing cellular activation and the production of interferons. This process will also induce the migration of DCs to secondary lymphoid organs and prime SARS-CoV-2-specific T cells [139, 141, 153]. Further questions regarding the effectiveness of vaccines are still going to be investigated, especially the long-term immunity and efficacy against new variants.

#### **6. Conclusions**

COVID-19 is a hyperinflammatory and hypercoagulation syndrome, with a hallmark increase in inflammatory mediators such as C-reactive protein, creatinine, urea, cytokines, and chemokines in the blood, with an increase in the neutrophil count and reduction in lymphocyte and platelet count. These processes lead to a

#### *Immune Response to COVID-19 DOI: http://dx.doi.org/10.5772/intechopen.98964*

dysregulated immune response that can be lethal. The overall mortality ratio is still unknown but is higher in patients with comorbidities. Patients with common and rare comorbidities may present differences in the immune response in comparison to healthy individuals.

The COVID-19 pandemic is a hallmark of world history, this systemic disease killed millions, raised ethical dilemmas, and put science and immunology on the daily lives of millions worldwide. Immunological investigations have helped the development of treatments and vaccines for this disease, but many questions are still left to be answered. The current knowledge is limited, but never in the previous history so many researchers around the world were focused on investigations on one disease. Several technologies developed and tested during this pandemic may bring light to other diseases, such as the new technologies in vaccine development and treatments.
