In December 2019, a pneumonia cluster of unknown etiology appeared in the city of Wuhan (China’s Hubei). Virus isolation and molecular analysis allowed a novel coronavirus (CoV) to be identified, named SARS-CoV-2, by the International Committee on Virus Taxonomy, representing the seventh member of the Coronaviridae family to infect humans. Initial investigations suggested that it could be originally transmitted by bats, as SARS CoV-2 had a nucleotide identity that was a 96% match with bat coronavirus, although the real origin of the infection is still debated [1].

The main clinical features of SARS CoV-2 disease (COVID-19) are fever, cough, muscle pain, and dyspnea, while atypical symptoms include diarrhea and vomiting. The clinical severity of COVID-19 was graded as follows: asymptomatic disease (positive SARS CoV-2 PCR test without clinical signs of infection), mild disease (symptoms of acute upper respiratory tract infection without pneumonia), moderate disease (radiological evidence of pneumonia), severe disease (pneumonia with dyspnea and hypoxemia), and critical disease (pneumonia with acute respiratory distress syndrome, respiratory failure, shock, and multiple organ dysfunction) [2]. More than 80% of COVID-19 cases in adults were classified as mild/moderate, while the majority of infections in children are asymptomatic [2]. Conversely, patients with comorbidities (age ≥ 65 years, smoking habits, chronic cardiovascular and pulmonary diseases, renal insufficiency, sickle cell disease, diabetes, obesity, pregnancy, and cancer) have been associated with a higher risk of progressing to the severe/critical disease stages [3].

The known routes of COVID-19 transmission were droplets as well as direct physical contact, while the possibility of fecal transmission has not been confirmed yet [4]. Vertical transmission has been described only in a small subgroup of cases and has been mainly related to the third trimester of pregnancy [5]. Infected individuals may be contagious before the onset of symptoms [6]. The estimated incubation period is up to 14 days from the time of exposure, with a median incubation ranging from four to five days [6]. Asymptomatic infection, particularly in children, is an important source of disease for the community, as these asymptomatic patients can easily cause familial clusters.

Considering the dramatic increase of the number of COVID-19 confirmed cases, the World Health Organization initially declared this epidemic a public health emergency of international concern on the 30 January 2020, while the COVID-19 disease was definitively declared a pandemic on the 11 March 2020.

The SARS-CoV-2 vaccine has recently emerged as the main weapon to fight the COVID-19 pandemic.

The various candidate anti-SARS-CoV-2 vaccines can be grouped according to the technological platform used to their development in order to elicit a protective immune response [57]. Two vaccines based on SARS-CoV-2 attenuated viruses have reached the clinical trial phase [58]. Vaccines based on inactivated SARS-CoV-2 viruses are more stable than live attenuated ones but their limitation is mainly linked to the short duration of elicited immune memory [57]. Vaccines based on SARS-CoV-2 proteins are mostly produced in vitro using recombinant DNA technology. Some of them are currently in phase II clinical trials. No vaccines based on naked DNA have been registered for human use yet. There are different vaccines based on mRNA carried by liposomes and some of these have recently completed phase III studies. The antigen encoded by the mRNA is represented by the Spike protein, its variants, or its fragments, while the DNA encoding for the Spike protein can be transported into cells by viral vectors [57]. The majority of vaccines based on viral vectors technology are currently under investigation in phase III trials [58].

Following the recommendation of the European Medicines Agency (EMA), on 21 December 2020, the European Commission authorized the first vaccine against COVID-19, mRNA BNT162b2 (Comirnaty), manufactured by Pfizer and BioNTech. There are limited data on the efficacy of vaccination in cancer patients, with most of the available information relating to the influenza vaccine [59]. Observational clinical studies have shown lower influenza mortality and morbidity in vaccinated cancer patients, suggesting an effective immune response, even during systemic chemotherapy [60,61,62]. Data on the efficacy and safety of SARS-CoV-2 vaccines in cancer patients are still limited, as these patients were largely excluded from pivotal trials. Only two studies enrolled cancer patients (4% and 0.5% of the total population, respectively), but no dedicated analysis was performed [63,64].

Recent published data suggested a satisfactory serological status following the second dose of vaccine in cancer patients [65,66,67,68,69].

An observational, prospective cohort study analyzed the humoral immune response to SARS-CoV-2 vaccination in 232 cancer patients compared to 100 healthy volunteers [70]. Two weeks after the second dose of vaccination, 90.5% of cancer patients were seropositive compared to 98% of healthy controls (p = 0.015). The majority of seronegative patients were male, older than 70 years, with comorbidities that were on active anticancer treatment. The median antibody titers of cancer patients were significantly lower than controls. An interesting finding concerning the role of cigarette smoking in the immunological response of cancer patients showed a significant association between antibody titer and smoking status, with significantly higher values found in the non-smoker compared with the smoker cohort (p = 0.006) [70]. Similarly, an Israeli prospective study showed a 90% seroconversion rate in 102 cancer patients undergoing active anticancer treatment compared to 100% in 78 healthy controls following the second dose of BNT162b2 vaccine [65]. Lung cancer patients had a 92% seroconversion rate [65]. A follow-up analysis found that 5.5 weeks after the second dose, 100% of healthy controls (78/78) vs 90% of cancer patients (90/102) were seropositive, with a significantly lower median IgG titer than controls [71]. In a larger study including a total of 200 cancer patients who received full dosing with one of the Food and Drug Administration-approved vaccines, relatively lower IgG titers were observed after vaccination with adenoviral (Ad26.COV2.S) compared to mRNA-based vaccines (mRNA-1273, BNT162b2) [72]. Chemotherapy has been associated with lower seropositivity rates than both targeted and immunotherapy treatments [73].

Vaccines could potentially be less effective in lung cancer patients than healthy controls. In the Israeli study, patients with thoracic malignancies had lower antibody titers (1334 AU/mL) than both healthy subjects (7160 AU/mL) and the overall cancer cohort (1931 AU/mL) [65]. Recently, Gounant and colleagues reported the results of the prospective observational COVIDVAC-OH study investigating the efficacy of vaccination against SARS-CoV-2 in patients with thoracic malignancies [74]. Only seven cases of COVID-19 were observed among 306 vaccinated subjects (2.3%), confirming the efficacy of COVID-19 mRNA vaccines in lung cancer patients. Of 269 serological tests available 2 weeks after the second vaccine dose, 6.3% were still negative (<50 AU/mL). Lack of immunization was associated with age and chronic corticosteroid treatment. Thirty patients with persistent low antibody titers achieved an immunization rate of 88% after receiving a third vaccine dose [74].

To date, February 2022, more than 9 billion doses of vaccine have been administered worldwide, with the rate of administration varying greatly between different areas of the world. Month after month the rate of positivity, hospitalizations and mortality from SARS-CoV-2 significantly decreases over the time, allowing the reopening of major services and borders.