PDF(Pubmed)
Abstract：
BACKGROUND: The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has lasted for three years. Coinfection with seasonal influenza may occur resulting in more severe diseases. The interaction between these two viruses for infection and the effect of antiviral treatment remains unclear.
METHODS: A SARS-CoV-2 and influenza H1N1 coinfection model on Calu-3 cell line was established, upon which the simultaneous and sequential coinfection was evaluated by comparing the viral load. The efficacy of molnupiravir and baloxavir against individual virus and coinfection were also studied.
RESULTS: The replication of SARS-CoV-2 was significantly interfered when the influenza virus was infected simultaneously or in advance (p < 0.05). On the contrary, the replication of the influenza virus was not affected by the SARS-CoV-2. Molnupiravir monotherapy had significant inhibitory effect on SARS-CoV-2 when the concentration reached to 6.25 μM but did not show any significant anti-influenza activity. Baloxavir was effective against influenza within the dosage range and showed significant effect of anti-SARS-CoV-2 at 16 μM. In the treatment of coinfection, molnupiravir had significant effect for SARS-CoV-2 from 6.25 μM to 100 μM and inhibited H1N1 at 100 μM (p < 0.05). The tested dosage range of baloxavir can inhibit H1N1 significantly (p < 0.05), while at the highest concentration of baloxavir did not further inhibit SARS-CoV-2, and the replication of SARS-CoV-2 significantly increased in lower concentrations. Combination treatment can effectively inhibit influenza H1N1 and SARS-CoV-2 replication during coinfection. Compared with molnupiravir or baloxavir monotherapy, combination therapy was more effective in less dosage to inhibit the replication of both viruses.
CONCLUSIONS: In coinfection, the replication of SARS-CoV-2 would be interfered by influenza H1N1. Compared with molnupiravir or baloxavir monotherapy, treatment with a combination of molnupiravir and baloxavir should be considered for early treatment in patients with SARS-CoV-2 and influenza coinfection.
METHODS: A SARS-CoV-2 and influenza H1N1 coinfection model on Calu-3 cell line was established, upon which the simultaneous and sequential coinfection was evaluated by comparing the viral load. The efficacy of molnupiravir and baloxavir against individual virus and coinfection were also studied.
RESULTS: The replication of SARS-CoV-2 was significantly interfered when the influenza virus was infected simultaneously or in advance (p < 0.05). On the contrary, the replication of the influenza virus was not affected by the SARS-CoV-2. Molnupiravir monotherapy had significant inhibitory effect on SARS-CoV-2 when the concentration reached to 6.25 μM but did not show any significant anti-influenza activity. Baloxavir was effective against influenza within the dosage range and showed significant effect of anti-SARS-CoV-2 at 16 μM. In the treatment of coinfection, molnupiravir had significant effect for SARS-CoV-2 from 6.25 μM to 100 μM and inhibited H1N1 at 100 μM (p < 0.05). The tested dosage range of baloxavir can inhibit H1N1 significantly (p < 0.05), while at the highest concentration of baloxavir did not further inhibit SARS-CoV-2, and the replication of SARS-CoV-2 significantly increased in lower concentrations. Combination treatment can effectively inhibit influenza H1N1 and SARS-CoV-2 replication during coinfection. Compared with molnupiravir or baloxavir monotherapy, combination therapy was more effective in less dosage to inhibit the replication of both viruses.
CONCLUSIONS: In coinfection, the replication of SARS-CoV-2 would be interfered by influenza H1N1. Compared with molnupiravir or baloxavir monotherapy, treatment with a combination of molnupiravir and baloxavir should be considered for early treatment in patients with SARS-CoV-2 and influenza coinfection.
摘要：
背景：由严重急性呼吸道综合症冠状病毒2（SARS-CoV-2）引起的大流行已经持续了三年。与季节性流感共感染可能会导致更严重的疾病。这两种病毒感染和抗病毒治疗效果之间的相互作用尚不清楚。
方法：建立SARS-CoV-2和H1N1流感在Calu-3细胞系上的共感染模型，通过比较病毒载量来评估同时和顺序合并感染。还研究了molnupiravir和baloxavir对单个病毒和合并感染的功效。
结果：当同时或提前感染流感病毒时，SARS-CoV-2的复制受到明显干扰（p<0.05）。相反,流感病毒的复制不受SARS-CoV-2的影响。当浓度达到6.25μM时，Molnupiravir单药对SARS-CoV-2具有显着的抑制作用，但未显示任何显着的抗流感活性。Baloxavir在该剂量范围内对流感有效，并在16μM时显示出抗SARS-CoV-2的显着作用。在合并感染的治疗中，从6.25μM到100μM，莫那普拉韦对SARS-CoV-2有明显的抑制作用，在100μM时对H1N1具有抑制作用（p<0.05）。巴洛沙韦的剂量范围可以明显抑制H1N1（p<0.05），而在最高浓度的巴洛沙韦并没有进一步抑制SARS-CoV-2，并且在较低浓度下SARS-CoV-2的复制显着增加。联合治疗可有效抑制合并感染期间甲型H1N1流感和SARS-CoV-2的复制。与莫努比拉韦或巴洛沙韦单药治疗相比，联合治疗在较少的剂量下更有效地抑制两种病毒的复制.
结论：在共感染中，SARS-CoV-2的复制会受到H1N1流感的干扰。与莫努比拉韦或巴洛沙韦单药治疗相比，对于SARS-CoV-2和流感合并感染的患者,早期治疗应考虑使用莫诺比拉韦和巴洛沙韦联合治疗.
方法：建立SARS-CoV-2和H1N1流感在Calu-3细胞系上的共感染模型，通过比较病毒载量来评估同时和顺序合并感染。还研究了molnupiravir和baloxavir对单个病毒和合并感染的功效。
结果：当同时或提前感染流感病毒时，SARS-CoV-2的复制受到明显干扰（p<0.05）。相反,流感病毒的复制不受SARS-CoV-2的影响。当浓度达到6.25μM时，Molnupiravir单药对SARS-CoV-2具有显着的抑制作用，但未显示任何显着的抗流感活性。Baloxavir在该剂量范围内对流感有效，并在16μM时显示出抗SARS-CoV-2的显着作用。在合并感染的治疗中，从6.25μM到100μM，莫那普拉韦对SARS-CoV-2有明显的抑制作用，在100μM时对H1N1具有抑制作用（p<0.05）。巴洛沙韦的剂量范围可以明显抑制H1N1（p<0.05），而在最高浓度的巴洛沙韦并没有进一步抑制SARS-CoV-2，并且在较低浓度下SARS-CoV-2的复制显着增加。联合治疗可有效抑制合并感染期间甲型H1N1流感和SARS-CoV-2的复制。与莫努比拉韦或巴洛沙韦单药治疗相比，联合治疗在较少的剂量下更有效地抑制两种病毒的复制.
结论：在共感染中，SARS-CoV-2的复制会受到H1N1流感的干扰。与莫努比拉韦或巴洛沙韦单药治疗相比，对于SARS-CoV-2和流感合并感染的患者,早期治疗应考虑使用莫诺比拉韦和巴洛沙韦联合治疗.
