ABSTRACT
The coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread throughout the world. This disease has a spectrum of different clinical pictures with different outcomes. Herein, we report all the data from three paucisymptomatic patients during a hospital stay that might represent a paradigmatic example of the method by which SARS-CoV-2 is shed. We demonstrated the lack of an adequate qualitative and quantitative immune response by multiparametric flow cytometry analysis. Our data can provide a new perspective about the method by which SARS-CoV-2 is shed and the clinical weight of viral persistence. In all three cases, the long persistence of the virus and the consistent reduction in both innate and adaptative immune cells are not associated with greater disease severity. These patients might represent at least part of the population. In particular, one patient oscillated between positive and negative swab tests several times without presenting any immune response. In all three cases, the immune response failure was not associated with a clinically significant involvement, indicating that it is not the virus's ability to impair the immune system, as well as its presence and persistence the fundamental mechanism that might causally lead to death. Finally, this kind of immune response in paucisymptomatic patients could pose a considerable danger to public health that questions the quarantine period. It is urgent to quantify the phenomenon with a large sample study.
ABSTRACT
The outbreak of coronavirus disease 2019 (COVID-19) is posing a threat to global health. This disease has different clinical manifestations and different outcomes. The immune response to the novel 2019 coronavirus is complex and involves both innate and adaptive immunity. In this context, cell-mediated immunity plays a vital role in effective immunity against SARS-CoV-2. Significant differences have been observed when comparing severe and non-severe patients. Since these immunological characteristics have not been fully elucidated, we aimed to use cluster analysis to investigate the immune cell patterns in patients with COVID-19 who required hospitalization but not intensive care. We identified four clusters of different immunological patterns, the worst being characterized by total lymphocytes, T helper lymphocytes CD4+ (CD4+), T cytotoxic lymphocytes CD8+ (CD8+) and natural killer (NK) cells below the normal range, together with natural killer lymphocyte granzyme < 50% (NK granzyme+) and antibody-secreting plasma cells (ASCs) equal to 0 with fatal outcomes. In the worst group, 50% of patients died in the intensive care unit. Moreover, a negative trend was found among four groups regarding total lymphocytes, CD4+, CD8+ and B lymphocytes (p < 0.001, p < 0.005, p < 0.000, p < 0.044, respectively). This detailed analysis of immune changes may have prognostic value. It may provide a new perspective for identifying subsets of COVID-19 patients and selecting novel prospective treatment strategies. Notwithstanding these results, this is a preliminary report with a small sample size, and our data may not be generalizable. Further cohort studies with larger samples are necessary to quantify the prognostic value's weight, according to immunological changes in COVID-19 patients, for predicting prognoses and realizing improvements in clinical conditions.