influenza A subtype H1N1 infection

Patients are not islands, nor does medicine exist outside of society. Alliances of family, friends, community partners, caregivers, and clinicians accompany us through even the most acute health care experiences. Recognizing and building on these coalitions promotes people-centered care by activating relationships, supporting people through equity, and overcoming dehumanizing environments with solidarity — I am in this for you because I know that you are in it for me; we are in this together. How might such people-centered care impact health outcomes? Let’s reflect on this question through the story of Diego Naranjo. Diego’s story Diego Naranjo rose with great difficulty early on the morning of May 14, 2018, having tried to sleep off a combination cold and fever over the weekend, and drove to a client meeting in Medellín, Colombia, that he felt he could not miss. He exited the meeting unable to stop coughing and hardly able to breathe and called his wife Claudia to say that he needed to go to the emergency room and would pick her up on the way. Diego was quickly diagnosed with pneumonia and hospitalized, then taken to the intensive care unit (ICU) to be intubated as his condition deteriorated. The next thing he knew, he struggled to open his eyes, sensed Claudia’s presence, and told her that he loved her. She caressed his face and responded with great emotion that he was in the Clínica Cardio VID of Medellín, had been in a coma induced by the H1N1 influenza for 75 days, and should be careful not to move because he was connected to a machine (ECMO) that was keeping him alive. Diego had received exceptionally high-quality care throughout his coma, which continued through his recovery. A key ingredient, perhaps the key ingredient, was the bond established between his family and the team of health care providers and caregivers. Family and community members arrived from day one to support him and Claudia in any way possible, and they were permitted significant access. They established relationships with doctors, nurses, assistants, even the cafeteria staff, and their contagious love for Diego gelled with the positivity and warmth of his care team, even in the most difficult moments. The medical team communicated frequently and openly with Claudia and others, engaging them in important decisions, and took up Diego’s cause as their own, showing genuine enthusiasm for every glimmer of hope and sign of progress. This solidarity humanized Diego’s difficult treatment (one grandson counted 18 tubes and hoses coming in and out of his body) in the face of multiple near-death experiences, fostering trust that enabled the medical team and family to make effective and rapid decisions at critical moments, such as deciding to take him off the ECMO. “It was all or nothing!” Claudia wrote in her diary. “I told them yes, let’s go for it, and we jumped into the water.” The unity of support from loved ones, clinicians, and caregivers — when combined with his faith — kept Diego committed to life through the most difficult moments of his recovery. When he first opened his eyes, when he came off the ECMO, when he took his first steps, when he was finally cleared to go home weeks later, they all celebrated moments of mutual victory. Solidarity in people-centered care Since the groundbreaking 2001 Institute of Medicine report Crossing the Quality Chasm proposed the patient-centered care model, efforts to improve health care have emphasized health promotion as much as disease prevention. Many health and allied professionals in the United States now use the phrase person-centered care as they seek to address the “whole person.” Diego’s story indicates the potential in following the World Health Organization (WHO) and others in taking an additional step to speak of people-centered care. In a 2021 report by the National Academies of Sciences, Engineering, and Medicine on high-quality primary care, the authors write that “… relationships with the people, their families, and the communities being served; and equity, which acknowledges and empowers those people, families, and communities … represent an important transition in how primary care needs to move forward in the twenty-first century.” I would add solidarity as the critical galvanizing force necessary to overcome the institutional legacy of dehumanizing health care systems. Imbuing people-centered coalitions with solidarity for our health — the sense that we’re in it together — requires mutual trust and commitment and even, as Diego would say, love. How do we realize such solidarity? Whether in Colombia or the U.S. or elsewhere, this calls for strong social ties, equitable access to care, and providers enabled to bring their whole selves to work. Four modest system improvements in the U.S. are assisting with valuing and activating people’s families and support networks in health care today: What would it take for all patients’ supporters to feel as welcome as Diego’s did in the ICU, accompanying their loved ones and participating with medical teams in caregiving and decision-making? The adoption of flexible hospital visitation policies has shown progress in this regard, of course with dramatic setbacks during the Covid-19 pandemic. Medical respite, in which a professional “subs in” for an individual’s primary caregiver, usually a family member or close companion, for a meaningful number of days per year also supports family involvement. In California, 336 hours annually of medical respite are now a covered benefit offered through the state’s Medicaid program, enabling people to remain at home who otherwise might be institutionalized. A third positive development is the increasing adoption of policies and technology platforms that give trusted family and companions access to the medical record and empower them to collaborate with medical staff and other service providers as participants on the care team. In linguistically diverse environments, the uptake of AI and machine translation tools for communication between caregivers and families can address key gaps in translation services. Health care providers are just scratching the surface in learning how — and how not — to use such methods to establish solidarity with their patients and patients’ support networks. Conclusion Diego writes in his book that a much younger man was admitted around the same time as him to the same high-quality medical facility with the same condition, H1N1, and was also connected to an ECMO. This young man did not have any visitors, he was intolerant with the nurses and other staff, and could be heard shouting at them. Tragically, he died within a week. We don’t know anything about his circumstances except that he did not receive support from family or community in the ICU, as Diego did, nor did he feel solidarity with the medical team — and he suffered a dramatically different outcome. Dr. John Rowe, a professor of health policy and aging at Columbia University, tells his medical students, “One of the best indicators of how well an elderly patient will be faring in six months is to ask him ‘how many friends or family he’s seen in the last week.’” In reflecting on his own experience relative to that of others such as this man, Diego writes, “I am certain that science is fundamental… I simultaneously have the certainty and am a living witness that love and solidarity have an enormous curative effect beyond giving the patient an irreplaceable incentive to seek improvement.” Linking arms with individuals, their families, and their communities enables health care stakeholders to harness this power of love and solidarity, enriching today’s whole-person approaches with people-centered care at the heart of health.

近期，国内多家疫苗上市企业陆续披露了公司2023年业绩预告或业绩快报，本文统计了康泰生物、万泰生物、华兰生物、沃森生物、百克生物、康希诺、金迪克生物及康乐卫士这8家企业的业绩情况。其中，仅有3家业绩预告增长，其余5家业绩均下滑。详情如下。1、康泰生物1月9日，康泰生物发布了2023年度业绩预告：公司预计实现归母净利润8.5-9.5亿元，同比增长740.50%-815.86%；扣非净利润7-8.3亿元，同比增长483.04%-554.17%。即公司扭亏为盈。图表1：康泰生物2023年度业绩预告公司表示业绩变动的原因可归结于以下2点：（1）常规疫苗的持续增长。公司按照年度经营计划积极开展各项工作，以市场为导向，持续优化营销网络布局，加强市场推广及销售工作，公司常规疫苗（不考虑新冠疫苗）总体销售收入较上年同比增长不低于16%。（2）公司上年同期计提资产减值准备金额较大，致使本期净利润较上年同期增长幅度较大。本报告期预计非经常性损益对净利润的影响金额约为12,000万元-15,000万元，去年同期非经常性损益的金额为5,004.13万元。从已上市常规疫苗产品看，13价肺炎球菌多糖结合疫苗、四联疫苗和乙肝疫苗合计占公司收入比重颇高，另外，2023年获批上市的冻干人用狂犬病疫苗（人二倍体细胞）有望成为公司新的业绩增长点。从在研产品布局看，公司目前布局了30余项研发项目，进度较快的如水痘减毒活疫苗已提交上市申请，Sabin株脊髓灰质炎灭活疫苗（Vero细胞）、ACYW135群脑膜炎球菌结合疫苗、甲型肝炎灭活疫苗均已开展Ⅲ期临床，四价流感疫苗有望在今年读出III期数据或申报上市，因此预计公司未来两年有4-5个新品种获批上市。图表2：康泰生物在研管线2、万泰生物1月24日，万泰生物发布了2023年年度业绩预减公告：预计实现归母净利润12-13.5亿元，同比减少74.66%-71.49%；扣非净利润10.5-12亿元，同比减少76.74%-73.42%。公司表示业绩暴跌的主要原因是2价HPV疫苗产品及新冠诊断相关收入等不及预期：（1）公司的二价HPV疫苗受九价HPV疫苗扩龄影响以及市场竞争等因素影响，收入及利润出现大幅下降，其中二价HPV疫苗收入较上年同期下降约42亿元。（2）2023年国内外新冠肺炎检测市场需求断崖式减少，致使公司体外诊断业务及原料相关收入及利润出现大幅下降，其中新冠诊断相关收入较上年同期下降约12亿元。（3）公司与新冠疫苗相关研发投入、专用原料及成品、生产专用设备等资产减值事项对公司整体利润下滑影响金额约4亿元以上。相关阅读：业绩暴跌！万泰生物2023年业绩预告发布，2价HPV疫苗营收减少42亿元万泰生物目前在研疫苗管线包括20价肺炎疫苗、重组带状疱疹病毒疫苗、重组三价轮状疫苗亚单位疫苗、第三代HPV疫苗等新型基因工程疫苗，以及冻干水痘减毒活疫苗、新型冻干水痘减毒活疫苗（VZV-7D）、四价肠道病毒灭活疫苗和鼻喷三价新冠-三价流感病毒疫苗等。3、华兰生物1月24日，华兰生物发布了2023年度业绩预告：预计实现归母净利润7.5-9.5亿元，同比增长44.33%-82.82%；扣非净利润6.5-8.5亿元，同比增长43.91%-88.19%。图表3：华兰生物2023年度业绩预告公司表示业绩变动的原因一方面是流感疫苗市场需求旺盛，公司流感疫苗销量较上年明显增加；另一方面，公司预计2023年度非经常性损益对当期净利润的影响约为10,000万元，上年同期为6,795万元。华兰生物的业务包括血液制品、疫苗制品、创新药和生物类似药研发生产三类业务。其中，疫苗板块收入约占四成左右。目前，公司已上市的疫苗品种包括流感病毒裂解疫苗、甲型H1N1流感病毒裂解疫苗、四价流感病毒裂解疫苗、 四价流感病毒裂解疫苗（儿童剂型）、A 群 C 群脑膜炎球菌多糖疫苗、ACYW135 群脑膜炎球菌多糖疫苗、重组乙型肝炎疫苗（汉逊酵母）。另外，其他疫苗如狂犬疫苗和破伤风疫苗也都进展不错。图表4：华兰疫苗在研疫苗4、沃森生物1月26日，沃森生物发布了2023年度业绩预告：公司预计营收约41亿元；归属于上市公司股东的净利润4-4.6亿元，同比下降37%-45%；扣非净利润5.34-5.98亿元，同比下降30%-38%。图表5：沃森生物2023年度业绩预告公司表示业绩变动的原因可归结于以下4点：（1）公司持有的港股嘉和生物及圣诺医药股价大幅下跌，以及其他非上市金融资产期末估值下降，导致报告期内公允价值变动损失约2.3亿元。（2）受市场竞争等影响，公司上市疫苗销售情况不佳——13价肺炎球菌多糖结合疫苗产品销售量较上年同期下降，双价人乳头瘤病毒疫苗（毕赤酵母）销售量未达预期。（3）公司结合疫苗市场竞争环境变化和销售预测等综合因素对资产进行减值测试，预计对双价人乳头瘤病毒疫苗（毕赤酵母）及其他疫苗产品的存货、应收款项等相关资产计提减值准备约2.4亿元。 （4）公司预计2023年非经常性损益金额约为-1.3,600万元，去年同期为-13,047.25万元。沃森生物现有已上市的产品包括13价肺炎结合疫苗、2价HPV疫苗、23价多糖/4价脑膜炎多糖疫苗等；进展较快的在研产品包括四价流脑多糖结合疫苗（预计2024年年底）、四联苗（预计2025-2026）、9价HPV（预计2027-2028），此外，其他在研产品还包括24价多糖结合疫苗、B群脑膜炎疫苗、GBS疫苗等管线。5、百克生物2月24日，百克生物发布了2023年度业绩快报：实现营收182,468.88万元，同比增长70.30%；归母净利润50,100.92万元，同比增长175.98%；归母扣非净利润49,335.83万元，同比增长195.86%。图表6：百克生物2023年度业绩快报公司表示促进业绩增长的主要因素为带状疱疹减毒活疫苗的销售放量： （1）受国内新生儿出生率下降等因素的影响，水痘减毒活疫苗内销下降，公司积极推进出口工作，外销有所增加；（2）冻干鼻喷流感减毒活疫苗销量与上年基本持平；（3）公司于2023年初取得带状疱疹减毒活疫苗《药品注册证书》，于2023年4月获得《生物制品批签发证明》，并陆续实现销售，丰富了公司疫苗种类，使公司总体收入规模及净利润同比上升。相关阅读：百克生物发布2023年业绩预告：带疱疫苗放量，净利润有望实现翻倍百克生物目前有16项产品在研，产品布局覆盖多种疾病。如公司百白破疫苗正在进行Ⅲ期临床样品的准备工作；在狂犬病领域，公司已布局了三代狂苗、狂犬单抗多款产品；另外，公司的重组带状疱疹疫苗、HSV-2 mRNA疫苗以及Hib疫苗计划于2024年开展临床试验申报工作；组分百白破成人疫苗、RSV 疫苗及抗体、阿尔茨海默病治疗性疫苗等多个项目的临床前研究工作也在积极推进中。图表7：百克生物在售产品及部分在研产品情况6、康希诺2月24日，康希诺发布了2023 年度业绩快报：2023年公司实现营收3.57亿元，同比下降65.49%；净利润亏损14.47亿元，同比亏损增加59.14%；扣非净利润亏损15.63亿元，亏损幅度均比去年有所扩大。图表8：康希诺2023年度业绩快报公司表示亏损原因如下：（1）新冠疫苗相关产品。公司新冠疫苗相关收入较同期大幅下降；基于预期，公司对已经发生的及未来可能发生的新冠疫苗产品退回金额进行核算及合理估计，并于报告期内冲减疫苗产品收入；考虑新冠疫苗相关存货和长期资产的未来使用计划，公司对存在减值迹象的存货、应收退货成本、预付账款和长期资产进行了减值测试，并根据测试结果计提减值损失。（2)流脑疫苗产品。公司为持续推广流脑疫苗产品增加营销活动推广，销售费用较同期增长。相关阅读：康希诺13价肺炎结合疫苗申报上市，一款补位新产品即将到来？目前，康希诺现有产品管线有上十种在研疫苗，涵盖了脑膜炎、肺炎、结核病、埃博拉、百白破等12个疾病领域。图表9：康希诺在研管线7、金迪克生物2月24日，金迪克生物发布了2023年度业绩快报：实现营收13,996.59万元，同比下降56.05%；归母净利润-6,577.96万元，同比下降258.34%；归母扣非净利润-7,451.00万元，同比下降429.42%。图表10：金迪克生物2023年度业绩快报公司表示影响经营业绩的主要因素包括以下2点： （1）2023年7月因泰州地区突发特大暴雨导致公司流感疫苗车间临时停产，直到2023年12月18日，公司才恢复流感疫苗销售。（2）公司对预计无法销售的产成品和在产品进行报废处理，全年共计提资产减值准备5,515.11万元，其中包含前三季度已计提的资产减值准备3,196.69万元，造成全年净利润亏损。实际上，多年以来，金迪克一直存在单品依赖问题。而为了缓解该状况，金迪克除了四价流感疫苗系列产品外，也拓展布局了其他品类产品管线，目前，金迪克主要管线已实现了对流行性感冒、狂犬病、水痘、带状疱疹和肺炎5种重要传染性疾病预防的覆盖，在研主要产品共有9个。其中，进展较快的有冻干人用狂犬病疫苗（Vero细胞），已完成III期临床试验；四价流感病毒裂解疫苗（儿童）完成了I期临床试验；剩余管线多处于临床前研究阶段。8、康乐卫士2月26日，康乐卫士发布了2023年度业绩快报：预计实现营收1,779,663.64元，同比下降6.36%；净亏损301,265,684.43元，同比增长2.89%；扣非净亏损314,030,201.46元，同比增长6.79%；基本每股亏损为1.11元，同比下降51.53 %。公司表示业绩变动的主要原因为公开发行及权益分派等所致。图表11：康乐卫士2023年度业绩快报康乐卫士的在研管线包括三价HPV疫苗、九价HPV疫苗、十五价HPV疫苗、七价诺如病毒疫苗、RSV疫苗、带状疱疹疫苗、多价手足口病疫苗和脊髓灰质炎疫苗等多种重组人用疫苗。在管线进展方面，预计公司的核心产品三价HPV疫苗将于2024年年底前在国内递交上市申请，相较于现有二价和四价HPV疫苗，该疫苗能将东亚女性宫颈癌的预防率从70%提高到78%；九价HPV疫苗预计于2025年同步在中国及印尼递交BLA，该疫苗有望成为首批获批使用的国产九价HPV疫苗之一；十五价HPV疫苗将于2024年启动一期临床；其他品类疫苗如RSV疫苗、带疱疫苗预计于2024年底前递交IND申请。图表12：康乐卫士在研管线相关阅读：康乐卫士递表港交所，首家“北+H”企业或将诞生！参考资料：[1]暴大雷！千亿医药大白马估值暴跌80%，业绩大幅缩水，外资减持，彻底崩了！.飞鲸投研.2024-02-22.[2]业绩暴涨816%的「疫苗龙头」.药智网.2024-01-21.[3]康泰生物2023年净利润超8.5亿元，在研疫苗近30项！.Vaccine之家.2024-01-11.[4]市值缩水三分之二后，万泰生物能否抓住九价HPV这根“救命稻草”？.同写意.2023-12-29.[5]华兰生物——2023年股价在血制品行业中吊车尾，2024年呢？.跳着踢踏舞去上班.2024-01-15.[6]华兰生物未来增长路径.胡涂投研.2023-11-27.[7]股市分析：沃森生物（浅析）！.财豹.2023-12-16.[8]流感疫苗车间正式复产 金迪克单品依赖何时解？.中经医健资本圈.2023-11-20.[9]康泰生物、万泰生物、华兰生物、沃森生物、百克生物、康希诺、金迪克生物及康乐卫士官网，业绩预告或快报公告.识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

The prospect of the worrisome triple threat of COVID, RSV and flu was assuaged last year by the effectiveness of flu vaccines. Two recent studies from the Centers for Disease Control and Prevention's VISION Network have found that flu vaccines were effective for all ages against both moderate and severe flu in the U.S. during the 2022-2023 flu season. The prospect of the worrisome triple threat of COVID, RSV and flu was assuaged last year by the effectiveness of flu vaccines. Two recent studies from the Centers for Disease Control and Prevention's VISION Network have found that flu vaccines were effective for all ages against both moderate and severe flu in the U.S. during the 2022-2023 flu season. Both the pediatric and adult VISION Network studies analyzed flu-associated emergency department (E.D.)/urgent care visits (indicative of moderate disease) and hospitalization (indicative of severe disease) from October 2022 through March 2023, a flu season in which far fewer individuals were social distancing or wearing masks than during the two previous flu seasons. Vaccination reduced the risk of flu-related E.D./urgent care visits and hospitalization for those 6 months to 17 years by almost half. For adults, regardless of age, vaccination reduced the risk of E.D. urgent care visits by almost half and reduced the risk of hospitalization by slightly more than a third. These results led the authors of both studies to conclude that flu vaccination is likely to substantially reduce illness, death and strain on healthcare resources. "We study the effectiveness of flu and other vaccines to ensure that our processes for forecasting the most effective vaccines are working well and therefore might potentially also be translatable to other diseases as well," said Shaun Grannis, M.D., M.S., a co-author of both the pediatric and adult VISION Network studies, Regenstrief Institute vice president for data and analytics and a family practice physician. "Given influenza's significant disease burden -- for example the H1N1 (swine) flu killed over a quarter of a million people worldwide in 2009-2010 -- we want to make sure that we understand virus trends as well as other factors and that we're continuing to do as well as and as much as we can to reduce the flu disease burden." Both the pediatric and adult studies evaluated electronic health record (EHR) data from sites across three healthcare systems in California, Utah, Minnesota and Wisconsin. Flu vaccine effectiveness: 2022-2023 flu season for ages 6 months to 17 years Vaccination reduced the risk of flu-related E.D./urgent care visits (moderate disease) by 48 percent and hospitalization (severe disease) by 40 percent overall across ages 6 months to 17 years. Broken down by age, risk reduction was greater for those age 6 months to 4 years than older children and adolescents. Ages 6 months to four years Ages 5 to 17 years Approximately 30 percent of E.D./critical care visits for acute respiratory illness in children and adolescents were positive for flu, as were 14 percent of hospitalizations. "Vaccine Effectiveness Against Pediatric Influenza-A-Associated Urgent Care, Emergency Department, and Hospital Encounters During the 2022-2023 Season, VISION Network" is published in Clinical Infectious Diseases. Flu vaccine effectiveness: 2022-2023 flu season for ages 18-64 Vaccine effectiveness was 45 percent against E.D./critical care visits(moderate disease) for adults under age 65. Effectiveness against hospitalization (severe disease) was 23 percent. Adults younger than 65 typically received standard-dose inactivated vaccines. Flu vaccine effectiveness: 2022-2023 flu season for ages 65 and older Vaccine effectiveness was 41 percent against both flu-associated E.D./urgent care visits (moderate disease) and hospitalization (serious disease) for this age group. Adults age 65 and older typically received enhanced vaccine products. "Influenza vaccine effectiveness against influenza-A-associated emergency department, urgent care, and hospitalization encounters among U.S. adults, 2022-2023" is published in the Journal of Infectious Diseases. "As with COVID, the dynamics of flu differs between children and adults. But we found that for both children and adults, vaccination significantly reduced the need for trips to the E.D, or critical care center and for hospitalization for flu-related illnesses last flu season and this is encouraging," said Dr. Grannis. "I'm hopeful that we will see similar or even better vaccine effectiveness during the current flu season. Even if they do experience symptoms, people who are vaccinated typically tend to have milder, shorter cases of the flu, a viral illness which can carry a severe disease burden. "The vaccine effectiveness we saw in last year's flu season is encouraging. As both a research scientist and a primary care physician, I urge everyone to be vaccinated for flu this year and every year -- it's good for each person's health and the health of your community." About Shaun Grannis, M.D., M.S. In addition to his role as the vice president for data and analytics at Regenstrief Institute, Shaun Grannis, M.D., M.S., holds the Regenstrief Chair in Medical Informatics and is a professor of family medicine at Indiana University School of Medicine.