Table 1.

Current available studies on HLA-G expression in patients with COVID-19.

Study method, subjects and size	Results and Implication for HLA-G expression	Reference
A 50s male patient had a positive for SARS-CoV-2 4 days after the start of symptoms. After 4-week-negative, he was admitted due to stomach pain, and a histologic examination was performed after colonoscopy.	HLA-G expression was found in intestinal mucosa epithelial cells and in some lymphocytes, in correspondence with SARS-CoV-2–positive sites. In submucosa, HLA-G expression was detectable only in few lymphocytes. Induction of HLA-G expression at the site of SARS-CoV-2 infection might be a cause of the COVID-19-dependent bleeding.	(72)
A 55-year-old female patient with critical COVID-19 admitted seven days after the onset of symptoms. Dynamics of HLA-G and its receptors ILT2, ILT4 and KIR2DL4 expression in peripheral immune cells with flow cytometry, and the outcomes of the patient during the 23-day ICU treatment.	The percentage of HLA-G+ T cells (median: 6.29%; range: 1.18-11.2%), B cells (median: 5.93%; range: 2.38-10.50%) and monocytes (median: 9.73%; range: 5.51-12.20%) is of a high (at admission)–low (during hospitalization)–high ( convalescence) pattern, while the percentage of receptors ILT2-, ILT4- and KIR2DL4-expressing cells remained more stable.	(73)
103 COVID-19 patients and 105 healthy controls were included in the case-control study.	sHLA-G were significantly increased in COVID-19 patients compared to controls (19.3 vs. 12.7 ng/mL; p <0.001). No statistical difference was observed between sHLA-G and gender, BMI, chronic disease, or ABO and Rh blood groups. Patients in the quartiles >50–75% and >75% of sHLA-G level were more likely to have COVID-19.	(74)
An investigator-initiated, prospective, single-center study. Fifty-four COVID-19 (moderate-to-severe) patients, 11 control patients that presented respiratory failure without SARS-CoV-2 infection), and 100 healthy control subjects. Serum sHLA-G were analyzed after enrollment (T1; Baseline), and every 7 ± 2 days for an additional 2 consecutive visits (T2 and T3). Correlation between sHLA-G and clinical outcomes was evaluated.	Higher sHLA-G in COVID-19 patients compared to controls with respiratory failure (165.87 vs. 49.54ng/mL; p < 0.01) and healthy controls ( 165.8 vs. 20.51ng/mL; p < 0.001) at T1. sHLA-G at T1 did not differ between COVID-19survivors and non survivors, but significantly decreased over time in non-survivors (p = 0.036 at T2; p = 0.04 at T3). In control patients, sHLA-G levels decreased in both survivors and non-survivors over time with no statistical differences. Increased severity of COVID-19 from T1 to T2 (but not T2 to T3) was associated with a significantly decreased sHLA-G (p = 0.012). Improved clinical conditions were associated with an increased sHLA-G between T1 and T2 (p = 0.01). Increased sHLA-G reduced neutrophil adhesion to the endothelial cells.	(75)