Natural killer cells associated with SARS-CoV-2 viral RNA shedding, antibody response and mortality in COVID-19 patients.

Coronavirus disease 2019 (COVID-19) is a novel infectious viral disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two consecutively negative SARS-CoV-2 viral RNA test ( interval ≥ 24 hours), improved respiratory symptoms and obvious absorption of inflammation in pulmonary imaging are the discharge criteria for COVID-19 patients. The clearance profile of viral RNA in the upper respiratory tract specimens, including nasopharyngeal swab and/or oropharyngeal swabs, is related to innate immune cells such as Natural Killer cells. A total of 168 patients were included for the study. In this cohort, non-severe and severe groups showed significant differences in white blood cells, neutrophils, lymphocytes, basophils and platelets counts, as well as in infection related parameters such as CRP and serum cytokine IL-6. For lymphocyte subsets tests at admission, the severe group displayed significantly lower cell counts than the non-severe group. Higher counts of total T cells, CD4 + T cells, CD8 + T cells, and NK cells in peripheral blood showed a significant correlation with the shorter time taken to obtain the first negative viral RNA test and first positive IgM/ IgG antibody test. The number of B cells was only correlated with time to achieve the first positive IgM/IgG test. The count of NK cells was also correlated with a higher level of IgG antibody (p = 0.025). The lymphocytopenia group had a significantly worse survival rate (p = 0.022) and a longer duration (p = 0.023) of viral shedding than the normal lymphocyte count group. A lower NK cell count correlates the most with the worse survival rate (p<0.001) and a longer duration (p<0.001) of viral shedding. This study suggests the potential value of allo-Natural Killer cell therapy as an universal COVID-19 treatment strategy.

SARS-CoV-2 induced thrombocytopenia as an important biomarker significantly correlated with abnormal coagulation function, increased intravascular blood clot risk and mortality in COVID-19 patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a novel infectious viral disease, which lacks well-established diagnostic laboratory parameters that could be used to evaluate disease severity, thromboembolism or cardiovascular events and to predict clinical prognosis. Coagulation cascade and platelet functions have not been well studied in the COVID-19 patients. METHODS: A total of 178 patients enrolled in Wuhan Huoshenshan Hospital were included for the study. Blood platelets and coagulation functions were analyzed in COVID-19 patients with non-severe and severe subgroups. Other biochemical laboratory parameters were also analyzed. RESULTS: Forty-nine (27.5%) out of 178 patients were diagnosed with severe disease in this study, and 129 patients with non-severe disease. Severe disease group had significant lower platelet count 186.00 (103.50-249.00) ×109/L than 251.00 (202.00-317.00) ×109/L of non-severe group, p = 0.000. Severe group also had significantly abnormal coagulation parameters than non-severe group: prothrombin time (PT) 14.55 (13.40-16.53) s vs. 12.70 (12.15-13.59) s, p = 0.000; international normalized ratio (INR) 1.21 (1.13-1.36) vs. 1.06 (1.01-1.13), p = 0.000; thrombin time (TT) 16.35 (15.69-17.47) s vs. 15.68 (14.79-16.69) s, p = 0.011; D-Dimer 1.05 (0.68-5.90) mg/L vs. 0.42 (0.28-0.79) mg/L, p = 0.000; While the liver function parameter alanine aminotransferase (ALT) and aspartate aminotransferase (AST) didn't show significance between two groups, ALT 30.80 (19.00-58.30) IU/L vs. 28.80 (15.75-50.15) IU/L, p = 0.487; AST 27.80 (19.30-40.55) IU/L vs. 22.6 (16.7-32.03) IU/L, p = 0.102. Disseminated intravascular coagulation (DIC) rate was 6.1% in severe group while 0% in non-severe group. Survival rate of severe disease group was worse than non-severe group, 85.7% vs. 100%, p = 0.000. Thrombocytopenia correlated with coagulation function, DIC rate and survival. Six out of 7 death case had thrombocytopenia during hospitalization, and platelet count decreased subsequently until death. Thrombocytopenia occurred within 1 week after admission in 6 recovered patients. And increased platelet levels followed by positive SARS-CoV-2 IgM/IgG and negative coronavirus nucleic acid tested in 8 recovered patients. CONCLUSIONS: Low platelet count is associated with abnormal coagulation function and increased risk of DIC, severe disease manifestation and increased mortality in patients with COVID-19.