COVID-19 大流行期間的死亡率：統計中的盲點

資料來源：剌胳針傳染病期刊，2022年4月22卷

                               圖片：Flickr/Ramakrishna Math 

線上發布 2021 年 12 月 22 日 https://doi.org/10.1016/S1473-3099(21)00767-2

在高收入國家以及低、中等收入國家 [LMICs] 中，漏報 COVID-19 相關死亡很常見。此外，僅使用致死率（或稱個案死亡率，Case fatality ratio）會導致低估 SARS-CoV-2 感染引起的死亡率。因此，美國疾病控制和預防中心等全球機構採用了特定時間範圍內超額全因死亡率 (all-cause mortality) 的計算來評估情況的嚴重性。

    Joseph A Lewnard 及其同事在工作中付出的艱苦努力值得稱讚，他們對《刺胳針傳染病》中報告的數據進行了詳細分析。在一項觀察性研究中，作者透過計算 2020 年 3 月 24 日至 2021 年 6 月 30 日期間，在印度欽奈之觀察死亡率與預期死亡率之間的差異，評估了 COVID-19 大流行期間的超額死亡率。為了估計預期死亡率，Lewnard 及其同事使用回歸模型，按年齡和性別進行分層。此外，作者測量了預期壽命的變化，並評估了全因死亡率的變化如何在不同社會經濟背景的社區中發生變化。在研究期間，Lewnard 及其同事估計每 1,000 名居民中有 5·18 人額外死亡（95% 的信賴區間為 5·11-5·25；與大流行前時期相比增加了 41%），在第二波疫情高峰期更有4·75 倍更高的死亡率。

COVID-19 大流行主要是一場後勤危機，而不是一場純粹的醫療危機，其中發病率和死亡率主要是由於缺乏及時診斷和治療，而不是適當治療失敗。全球的醫療照護系統沒有為應對這場危機做好充分準備，尤其是在印度等中、低收入國家。 Lewnard 及其同事發現，政府關於 COVID-19 死亡率的統計數據與他們根據欽奈民事登記系統 (CRS) 數據計算的超額全因死亡率之間存在巨大差異。然而，我們認為，欽奈這種超額的全因死亡率不僅代表了 COVID-19 本身的死亡率，還包括因後勤危機導致的管理不理想或缺乏管理而導致的 COVID-19 死亡。正如在這次後勤危機期間所預期的那樣，這種超額死亡率的很大一部分還可能包括由於非 COVID-19 原因導致的超額死亡。

在處理大量患者時，COVID-19 大流行期間的建檔是一項艱鉅的任務。儘管印度政府可能已經為測試、認證等制定了適當的規則和規範，但在大流行期間，這些規則的實施極具挑戰性。在此期間，需要密切關注當地醫生如何在政府特定登記處去填寫死亡表格並證明 COVID-19 是死因的做法。患者可能在到達醫療機構或在醫療機構登記後發生死亡但並其未接受 COVID-19 檢測或治療，甚至在到達醫療機構之前死亡的患者，可能導致 COVID-19 的漏診以及將死亡錯誤報告為與 COVID-19 無關。在確認之前需要查明是否對所有此類死亡進行了 PCR 檢測（儘管在現行的強制性死後 RT-PCR 檢測規則情況下）。

我們還必須記住我們用來診斷這種快速傳播病毒的 RT-PCR 測試的缺點。單次常規 RT-PCR 測試可能會漏掉多達三分之一的 COVID-19 感染，即使進行第二次測試，敏感度也僅達 79%。

值得注意的是，COVID-19 後的後遺症，例如由於 COVID-19 相關的血栓前狀態導致的危及生命的真菌感染和缺血性事件（如中風、心肌梗塞等），也可能增加了過多的延遲死亡率。在民事登記系統 (CRS) 數據中的這些死亡也不太可能被記錄為COVID-19。危及生命的血栓併發症可能是一小部分 COVID-19 病例的初始表現，照顧的醫護人員可能會錯過這些併發症。

在 COVID-19 中被詳細描述的所謂快樂低氧血症的發生，在某些個案也可能會進一步延遲就醫，直到患者明顯病重，即使經過適當的治療，死亡人數也會進一步增加。一小部分人最初可能從其他替代醫療系統拜訪了當地從業者，這也再次可能導致診斷和治療的遺漏或延遲，最終增加死亡率。

此外，由於與感染 COVID-19 相關的恐懼或污名，不願將患有呼吸道症狀的老年人（尤其是那些獨居且生活品質相對較差的老年人）轉移到醫療機構等社會問題，亦可能還會增加死亡率統計。此外，封鎖可能會在一定程度上阻止許多人尋求醫療救助，直到他們變得明顯生病。最後，存在一種未經證實的看法，即人為和政治因素可能在一定程度上影響了某些國家的檔案資料。

總之，第二波死亡人數的增加，可能不僅是由於 delta 病毒株 (B.1.617.2) 更高的 R0 值和毒力以及 COVID-19 適當行為的鬆懈（大眾感覺疫情已結束），但也肇因於這種對衛生保健機構和需要被照護個人上的衛生系統預期不足和後勤障礙所造成的。

Ajith Kumar A K, Neha Mishra 

ajithkumaraxk@hotmail.com

Manipal 醫院重症監護科 (AKAK) 和傳染病科 (NM) ，印度班加羅爾 17 號 

剌胳針傳染病期刊，2022年4月22卷

Mortality during the COVID-19 pandemic: the blind spots in statistics 

Flickr/Ramakrishna Math 

Published Online December 22, 2021 https://doi.org/10.1016/ S1473-3099(21)00767-2 

    Underreporting of COVID-19 associated death is common in both high-income countries and lowincome and middle-income countries [LMICs]. Additionally, the use of case-fatality ratio alone has led to underestimation of mortality due to SARS-CoV-2 infection. Hence, global bodies such as the US Centers for Disease Control and Prevention have adopted a calculation of excess all-cause mortality during a particular time frame to assess the gravity of the situation.

    Joseph A Lewnard and colleagues deserve an accolade for the strenuous effort put into their work, with a detailed analysis of data reported in The Lancet Infectious Diseases. In an observational study, the authors assessed the excess mortality during the COVID-19 pandemic by calculating the difference between observed and expected mortality during the period between March 24, 2020, and June 30, 2021, in Chennai, India. To estimate expected mortality, Lewnard and colleagues used regression models, with stratification by age and sex. Additionally, the authors measured changes in life expectancy and assessed how changes in all-cause mortality varied across communities with different socioeconomic contexts. During the study period, Lewnard and colleagues estimated 5·18 excess deaths per 1000 residents (95% uncertainty interval 5·11–5·25; a 41% increase compared with pre-pandemic period mortality), with a 4·75-times higher mortality during the peak of the second wave.

The COVID-19 pandemic has predominantly been a logistical crisis rather than a pure medical crisis wherein morbidity and mortality result mainly from lack of timely diagnosis and treatment, rather than failure of appropriate treatment. Health-care systems across the globe were inadequately prepared to handle the crisis, especially in LMICs such as India. Lewnard and colleagues found a gross disparity between the government statistics on COVID-19 mortality versus the excess all cause mortality they calculated on the basis of Chennai Civil Registration System (CRS) data. However, we argue that this excess all-cause mortality in Chennai not only represents the mortality attributable to COVID-19 per se, but also includes the COVID-19 deaths resulting from the logistical crisis resulting in suboptimal or absent management. A good proportion of this excess mortality could also include the excess deaths due to non-COVID-19 causes, as expected during this logistical crisis.

Documentation during the COVID-19 pandemic, when dealing with vast numbers of patients, is a daunting task. Although the Indian Government might have framed appropriate rules and regulations for testing, certifying, and so on, the implementation of such rules was extremely challenging during the pandemic. One needs to look closely at the local practice of how medical practitioners were filling death forms and certifying COVID-19 as the cause of death in the given government registry during this period. Deaths might have occurred after patients reached or registered at a health-care facility without being able to get tested or treated for COVID-19, and the patients dying even before reaching the health-care facility might have led to missed diagnoses of COVID-19 and erroneous reporting of the deaths as non-COVID-19- related. Whether the PCR testing was done in all such deaths (despite existing rules for a mandatory post death RT-PCR test) before certification needs to be ascertained. 

We must also remember the shortcomings of the RT-PCR test on which we depend for diagnosing this rapidly spreading virus. Up to a third of COVID-19 infections could be missed by single conventional RT-PCR test, and even with a second test, the sensitivity is only up to 79%. 

Notably, post-COVID-19 sequelae, such as life threatening fungal infections and ischaemic events (stroke, myocardial infarction, and so on) due to the COVID-19-related prothrombotic state, might have also added to excess delayed mortalities. These deaths are unlikely to have been documented as due to COVID-19 in CRS data. Life-threatening thrombotic complications could be the initial presentation in a small percentage of COVID-19 cases, which could be missed by the attending health-care staff. 

The occurrence of so-called happy hypoxemia, well described in COVID-19, might have further delayed the seeking of medical attention in some cases, until the patient was overtly sick, further increasing the death count even with appropriate treatment. A small proportion of the population might have initially visited local practitioners from alternative systems of medicine, which again could have contributed to a missed or delayed diagnosis and treatment, ultimately adding to the increased mortality.

Moreover, social issues such as reluctance to transfer older people (especially those who are staying alone with relatively poor quality of life) with respiratory symptoms to a health-care facility due to the fear or stigma associated with contracting COVID-19 might have additionally increased the mortality tally. Furthermore, lockdowns might have discouraged many people from seeking medical attention to some extent until they became overtly sick. Finally, there is an unsubstantiated perception that human and political factors might have influenced the documentation to some extent in certain countries. 

In conclusion, the increased deaths in the second wave might have occurred not only due to the higher R0 and virulence of the delta strain (B.1.617.2) and laxity in COVID-19-appropriate behaviour (the public feeling that the game is over), but also due to the inadequate anticipation of the health systems and the logistical obstacles this creates both for health-care facilities and individuals in need of care. 

*Ajith Kumar A K, Neha Mishra ajithkumaraxk@hotmail.com 

Department of Critical Care (AKAK) and Department of Infectious Diseases (NM), Manipal Hospitals, Bangalore-17, India

www.thelancet.com/infection Vol 22 April 2022