Since the beginning of 2020, the entire global health care system has been severely challenged by the outbreak of coronavirus 2019 disease (COVID-19). Robust evidence has demonstrated a more severe course of COVID-19 in the presence of several comorbidities, such as cardiovascular diseases, diabetes mellitus, and obesity. Here, we critically appraise the recent research discoveries linking periodontitis to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to severe COVID-19, with a special focus on the associated biological mechanisms and the available epidemiological evidence. SARS-CoV-2 main receptors and coreceptors (ACE2, TMPRSS2, furin, CD147) are overexpressed in periodontal tissues of periodontitis patients, with inflammation, periodontal pathogens, and damage-induced pyroptosis triggering a positive feedback loop. However, meta-analyses of epidemiological studies only indicated a nonstatistically significant tendency for an increased risk of SARS-CoV-2 infection in subjects with periodontitis (odds ratio [OR] = 1.69; 95% CI, 0.91–3.13, P = 0.09). Furthermore, periodontitis may worsen clinical COVID-19 courses through multiple direct and indirect pathways, including damage to lower airways due to aspiration of periodontal pathogens, exacerbation of the cytokine storm via the low-grade chronic systemic inflammation, and SARS-CoV-2 dissemination through the ulcerated gingival epithelium with consequent induced pulmonary vessels vasculopathy. Indeed, meta-analyses of epidemiological studies indicated that periodontitis subjects are more likely to experience a more severe course of COVID-19. Specifically, periodontitis was associated with a 4-fold increased odds of hospitalization (OR = 4.72; 95% CI, 1.11–20.03, P = 0.04), 6-fold of requiring assisted ventilation (OR = 6.24; 95% CI, 2.78–14.02, P = 0.00), and more than 7-fold of death due to COVID-19 complications (OR = 7.51; 95% CI, 2.16–26.10, P = 0.00). The breakthrough analyzed here emphasizes the relevance of the mouth-systemic connection as a target to mitigate the current COVID-19 emergency and the future predicted coronavirus pandemics.

自 2020 年初以来，整个全球医疗保健系统都受到了 2019 年冠状病毒病 (COVID-19) 爆发的严峻挑战。强有力的证据表明，在存在多种合并症（如心血管疾病、糖尿病和肥胖）的情况下，COVID-19 的病程更为严重。在这里，我们批判性地评估了最近将牙周炎与严重急性呼吸综合征冠状病毒 2 (SARS-CoV-2) 感染和严重 COVID-19 联系起来的研究发现，特别关注相关的生物学机制和可用的流行病学证据。SARS-CoV-2 主要受体和辅助受体（ACE2、TMPRSS2、弗林蛋白酶、CD147）在牙周炎患者的牙周组织中过度表达，炎症、牙周病原体和损伤诱导的细胞焦亡触发正反馈循环。P  = 0.09）。此外，牙周炎可能通过多种直接和间接途径使临床 COVID-19 病程恶化，包括由于吸入牙周病原体对下气道的损害、通过低度慢性全身炎症加剧细胞因子风暴以及 SARS-CoV-2 传播通过溃疡的牙龈上皮和随后诱发的肺血管血管病变。事实上，流行病学研究的荟萃分析表明，牙周炎患者更有可能经历更严重的 COVID-19 病程。具体而言，牙周炎与住院几率增加 4 倍相关（OR = 4.72；95% CI，1.11–20.03，P  = 0.04），需要辅助通气的几率增加 6 倍（OR = 6.24；95% CI，2.78– 14.02,磷 = 0.00），以及因 COVID-19 并发症导致的死亡人数超过 7 倍（OR = 7.51；95% CI，2.16–26.10，P  = 0.00）。这里分析的突破强调了口腔系统连接作为缓解当前 COVID-19 紧急情况和未来预测的冠状病毒大流行的目标的相关性。