tetano
Editor, Senior Moderator
MedComm (2020)
. 2025 Nov 2;6(11):e70469.
doi: 10.1002/mco2.70469. eCollection 2025 Nov. SARS-CoV-2 Spike Protein as a Target of the COVID-19 Vaccine Disrupts Insulin Signaling in Type 2 Diabetes
Lixiang Zhai[SUP] 1 2 [/SUP], Min Zhuang[SUP] 1 2 [/SUP], Hoi Ki Wong[SUP] 2 [/SUP], Chengyuan Lin[SUP] 1 [/SUP], Haoran Ying[SUP] 1 [/SUP], Jialing Zhang[SUP] 1 2 [/SUP], Gengyu Bao[SUP] 1 [/SUP], Yijing Zhang[SUP] 2 [/SUP], Shujun Xu[SUP] 1 2 [/SUP], Jingyuan Luo[SUP] 1 2 [/SUP], Shuofeng Yuan[SUP] 3 [/SUP], Hoi Leong Xavier Wong[SUP] 2 [/SUP], Zhao-Xiang Bian[SUP] 1 2 [/SUP]
Affiliations
Diabetes is associated with an increased risk of coronavirus disease 2019 (COVID-19)-associated morbidity and mortality. COVID-19 vaccines substantially reduce the risk of serious COVID-19 outcomes, making them important for individuals with diabetes. However, the effects of the COVID-19 vaccines on glucose control in patients with diabetes remain unclear. Here, we demonstrate that COVID-19 vaccine boosters impair insulin sensitivity in both mice and patients with type 2 diabetes (T2D). In mice, the administration of four vaccine doses elevated the levels of SARS-CoV-2 spike protein and impaired glucose tolerance and insulin sensitivity. Mechanistically, we showed that the SARS-CoV-2 spike protein, guided by the mRNA COVID-19 vaccine, interferes with insulin signaling by binding to angiotensin-converting enzyme 2, TLR4, and ER. We found that 66% of T2D patients exhibited aggravated insulin resistance to booster shots of the mRNA COVID-19 vaccine. Furthermore, treatment with metformin improved insulin signaling variations induced by COVID-19 vaccine boosters in mice. These findings indicate that COVID-19 vaccine boosters impair insulin sensitivity in T2D and that metformin may mitigate these effects. These results maintain the risk-benefit ratio in favor of COVID-19 vaccination for the prevention of severe clinical outcomes, yet highlight the need for close glycemic monitoring of patients with diabetes after receiving mRNA COVID-19.
Keywords: COVID‐19; SARS‐CoV‐2; diabetes; insulin sensitivity; vaccine.
. 2025 Nov 2;6(11):e70469.
doi: 10.1002/mco2.70469. eCollection 2025 Nov. SARS-CoV-2 Spike Protein as a Target of the COVID-19 Vaccine Disrupts Insulin Signaling in Type 2 Diabetes
Lixiang Zhai[SUP] 1 2 [/SUP], Min Zhuang[SUP] 1 2 [/SUP], Hoi Ki Wong[SUP] 2 [/SUP], Chengyuan Lin[SUP] 1 [/SUP], Haoran Ying[SUP] 1 [/SUP], Jialing Zhang[SUP] 1 2 [/SUP], Gengyu Bao[SUP] 1 [/SUP], Yijing Zhang[SUP] 2 [/SUP], Shujun Xu[SUP] 1 2 [/SUP], Jingyuan Luo[SUP] 1 2 [/SUP], Shuofeng Yuan[SUP] 3 [/SUP], Hoi Leong Xavier Wong[SUP] 2 [/SUP], Zhao-Xiang Bian[SUP] 1 2 [/SUP]
Affiliations
- PMID: 41190280
- PMCID: PMC12580406
- DOI: 10.1002/mco2.70469
Diabetes is associated with an increased risk of coronavirus disease 2019 (COVID-19)-associated morbidity and mortality. COVID-19 vaccines substantially reduce the risk of serious COVID-19 outcomes, making them important for individuals with diabetes. However, the effects of the COVID-19 vaccines on glucose control in patients with diabetes remain unclear. Here, we demonstrate that COVID-19 vaccine boosters impair insulin sensitivity in both mice and patients with type 2 diabetes (T2D). In mice, the administration of four vaccine doses elevated the levels of SARS-CoV-2 spike protein and impaired glucose tolerance and insulin sensitivity. Mechanistically, we showed that the SARS-CoV-2 spike protein, guided by the mRNA COVID-19 vaccine, interferes with insulin signaling by binding to angiotensin-converting enzyme 2, TLR4, and ER. We found that 66% of T2D patients exhibited aggravated insulin resistance to booster shots of the mRNA COVID-19 vaccine. Furthermore, treatment with metformin improved insulin signaling variations induced by COVID-19 vaccine boosters in mice. These findings indicate that COVID-19 vaccine boosters impair insulin sensitivity in T2D and that metformin may mitigate these effects. These results maintain the risk-benefit ratio in favor of COVID-19 vaccination for the prevention of severe clinical outcomes, yet highlight the need for close glycemic monitoring of patients with diabetes after receiving mRNA COVID-19.
Keywords: COVID‐19; SARS‐CoV‐2; diabetes; insulin sensitivity; vaccine.