Recent pathological examination revealed that SARS-CoV-2 remained in pneumocytes and virus-caused lung lesions by postmortem pathologic study in a ready-for-discharge COVID-19 patient who succumbed to a sudden cardiovascular accident. These results suggest that the SARS-CoV-2 in discharged patients has not been completely cleared. The effective antiviral responses of the host both in cell-mediated and humoral immunity are essential for controlling viral replication, limiting the spread of virus, inflammation and cleaning the infected cells[6-8]. It is well known that T cell immunity plays an important role in SARS-CoV-2 infection. The lower the absolute value of T lymphocytes before treatment, especially CD4+ T lymphocytes, the longer the duration of virus clearance[9, 10]. Since serum-specific antibodies against SARS-CoV-2 could be detected, the more significant role that B cells play was revealed in COVID-19 infection. The serologic antibody test is helpful for the diagnosis of SARS-CoV-2 infection[11, 12]. The present study shows that compared to the score-matched group, the levels of serum-specific IgM antibody against SARS-CoV-2, first produced by B cells in primary humoral immunity, were significantly lower in the PCR-positive group. There was no obvious difference in the levels of serum-specific IgG antibody between the PCR-positive group and the score-matched group. These findings suggest that serum-specific IgM antibody, the most crucial serum immunoglobulin in primary humoral immunity, plays a critical role in the clearance of virus in the early phase of COVID-19 infection. The immune role of B lymphocytes in clearing virus was also demonstrated by the observation that children appeared to be more resistant to SARS-CoV-2 in the early phase of infection, possibly because their B lymphocytes are able to generate natural antibodies in a timely manner upon encountering novel pathogens when compared to B cells from adults. Nevertheless, some published case reports showed that treatment with a B-cell depleting monoclonal antibody played a protective role in COVID-19. Additionally, COVID-19 patients with primary antibody deficiency had mild symptoms and fewer complications. The possible cause for these results was the proinflammatory factors produced by B cells, especially IL-6, which is involved in cytokine storm syndrome (CSS). The proinflammatory role of B cells, rather than the immune function of B cells in COVID-19 infection, was emphasized.
More importantly, we found that the levels of procalcitonin in the PCR-positive-again group were markedly reduced compared to those in the score-matched group. The findings suggest that COVID-19 patients combined with slight bacterial infection probably enhance the primary humoral immune response and promote the production of serum-specific IgM antibody in the early stage, which plays an important role in the clearance of SARS-CoV-2. Procalcitonin is a 13 kDa glycoprotein that is produced by parathyroid cells under normal physiological conditions. It is also called thyrocalcitonin. However, in bacterial infection, liver macrophages and monocytes, lymphocytes and endocrine cells of lung and intestinal tissues can also secrete procalcitonin under the action of endotoxin, tumor necrosis factors and interleukin-6, and the serum procalcitonin level was significantly increased. Compared with other markers of infection, procalcitonin has a better specificity for bacterial infection. The increase in procalcitonin levels occurs earlier than that of other markers of infection, which can be used for the early diagnosis of infection.
Procalcitonin is a type of acute phase reaction protein that has levels that reflect the activity of infectious diseases. Viral infection and nonspecific inflammation do not lead to elevated procalcitonin levels, but bacterial infection, severe shock, and multiple organ dysfunction syndrome (MODS) can all lead to significantly elevated procalcitonin levels. When systemic infection, severe inflammation or sepsis occurs, the level of procalcitonin in the patient's peripheral blood will increase rapidly. According to the expert consensus of emergency clinical application of procalcitonin (PCT) in China, the levels of procalcitonin in patients with systemic inflammatory response syndrome (sirs), sepsis and septic shock increased in turn and were positively correlated with the severity of the disease.
The increase in PCT concentration was not affected by the immunosuppression state of the body. In the sepsis model, the high inflammatory reaction was often accompanied by the immunosuppression stage, which was more likely to be accompanied by MODS and secondary infection. Clinical outcome is often determined by the balance of inflammatory response and immunosuppressive status. In a succinct meta-analysis of COVID-19 and PCT from Italy, the small amount of data available thus far indicates that continuous measurement of procalcitonin may play a role in predicting the progression of the disease to a more severe form, since production and release of parathyroid-derived calcitonin are greatly amplified during bacterial infection, and interleukin and elevated levels of tumor necrosis factor-α (TNF-α) and IL-6 actively maintain calcitonin. However, synthesis of the biomarker is inhibited by interferon, whose concentration increases during viral infection. Therefore, in patients with COVID-19, procalcitonin levels may return to normal. Inflammation can activate the body's immune response, and from our data, it is possible to confirm, precisely because of a slight increase in PCT, on the basis of ruling out coinfection with bacteria, that the autoimmune response can help the body clear the new coronavirus.