[轉載]404文件：張文宏2022年6月上海新冠病例學術研究報告(英文，長，不喜勿入)

(註1：張文宏的這份研究報告指出，上海超過95%非高危人群的重症率=0，那麼上海人這三個月被嚴厲封控的意義到底為何？)
(這報告雖然和國外研究其他國家的情況一致，可是等於打臉動態清零政策，所以被刪，不過牆內還可搜到相關報導。)
(註2：中國CDC已經刪除了文件的描述網頁，但目前PDF還能下載，之後會不會連PDF也刪?我不知道)
(註3：原文件是PDF，所以圖表全被我跳過了，有興趣查圖表的朋友請下載PDF)
(註4：我直接複製PDF文字貼上，所以排版很亂，請見諒。)
https://weekly.chinacdc. cn/fileCCDCW/journal/article/ccdcw/newcreate/CCDCW220132.pdf

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China CDC Weekly

Preplanned Studies

Dynamic Disease Manifestations Among Non-Severe COVID-19

Patients Without Unstable Medical Conditions: A Follow-Up
Study — Shanghai Municipality, China, March 22–May 03, 2022
Xin Ma1,&,#; Jingwen Ai1,2,&; Jianpeng Cai2,&; Shu Chen1,2,&; Sen Wang1,2,3,&; Haocheng Zhang1,2,&; Ke Lin2,&; Wei
Zhang4
; Hongyu Wang2
; Yi Zhang2
; Feng Sun1,2; Yang Li1,2; Shu Zhang1,2; Leer Shen5
;
Shunjie Chen6
; Guanzhu Lu7
; Jie Xu7
; Xiaohua Chen5
; Wenhong Zhang1,2,3,8,#

Summary
What is already known about this topic?
High transmissibility of the Omicron variant has placed a huge burden on healthcare resources. The vast majority of Omicron infections are non-severe among the cases with less high risk factors.
What is added by this report?
In the Shanghai Omicron wave, the risk of developing severe illness was very low (0.065%, 22/33,816) in initially non-severe patients without unstable conditions. Older age, presence of comorbidities, initial symptoms, vaccination status, and several laboratory indicators were associated with prolonged viral shedding time, development of severe illness, and
coronavirus disease 2019 (COVID-19) pneumonia.

What are the implications for public health

practice?
This study provides evidence for refining COVID-19 public health strategies to minimize the risk of overwhelming of regional medical resources.

Since identification of Omicron in November 2021,Omicron variant infections have increased exponentially in multiple countries, and Omicron has become the main epidemic severe acute respiratorysyndrome coronavirus 2 (SARS-CoV-2) strain in the world. Transmission of Omicron BA.2 is nearly 30% higher than Omicron BA.1 transmission and is significantly higher than transmission of the earlier non-Omicron variants.

Affected by the global spread of Omicron, Shanghai Municipality reported 626,863 Omicron infections between March 1 and June 4, 2022 (1). Preliminar data suggest that Omicron generally causes less severe symptoms than previous SARS-CoV-2 variants (2), but progression to severe cases occurs and is influenced by vaccination status, age, underlying medical conditions,and other factors (3). Given the high transmissibility of Omicron, the overall clinical profile and prognosis of
the huge number of non-severe Omicron infections should strongly influence public health policies,including hospitalization and treatment strategies during the coronavirus disease 2019 (COVID-19) pandemic. For example, due to its high transmissibility and high force of infection, regions that previously admitted all SARS-CoV-2-infected individuals may not have sufficient hospital resources to admit nonsevere Omicron patients (4). Therefore, reliable data on the spectrum of clinical features, risk factors for development of COVID-19 pneumonia, and viral shedding time (VST) of non-severe Omicron patients is critically important.

In this study, under the policy of “all those in need have been tested, and if positive, have been quarantined, hospitalized, or treated” in China, we conducted a large cohort study to describe the spectrum of clinical features, risk factors for
progression, and dynamic changes in viral load among initially non-severe Omicron-infected patients in four Shanghai hospitals during the Omicron outbreak.Our study was conducted between March 22, 2022 and May 03, 2022 at Huashan Hospital, Shanghai Sixth People’s Hospital, Shanghai Ninth People’s Hospital, and Shanghai Fourth People’s Hospital. All
admission, discharge, diagnostic, and therapeutic decisions were made based on the latest version of the national COVID-19 protocol (5). The study protocol was approved by the ethics committee of Huashan Hospital, receiving the ethics code number KY2000-596.

Patients were eligible for the study if they were diagnosed with non-severe COVID-19 upon hospital
admission. Patients with unstable medical conditions were excluded. The definition of unstable medical
conditions, complete exclusion criteria and research details were in the Supplementary Material (available
in https://weekly.chinacdc. cn/). Informed consents were gathered from eligible patients. Upon enrollment,
physicians obtained baseline demographic and health information. Non-severe infections were defined as
asymptomatic, mild, or moderate according to the latest version of the national COVID-19 protocol (5).

We used baseline information, VST, laboratory results, computer tomography (CT) scan results, and
clinical prognosis for risk analyses. Measures of clinical prognosis included progression from infection to
pneumonia and from infection to critical illness. Risk group were: patients ≥60 years old; patients who had
stable underlying medical conditions (including cardiovascular disease, diabetes mellitus, lung disease,
hepatic disease, cerebrovascular disease, and kidney disease) or who had an immunodeficiency [e.g., human
immunodeficiency virus infection, chronic use of corticosteroids, or use of other immunosuppressivedrugs] (5).

Statistical significance of comparisons of baseline clinical characteristics and demographics were tested
with Mann-Whitney U, χ² test, or Fisher’s exact test, as appropriate. Due to overlap of age and
comorbidities with risk group, we developed two multivariable Cox regression models to estimate
adjusted hazards ratios (aHR) for factors influencing VST. VST was defined as the difference in days
between the first positive test and the first of two consecutively-negative tests. We adjusted for age, sex,
comorbidities, vaccination status, final diagnose, and initial symptoms in model 1. We adjusted for risk
group, sex, vaccination status, final diagnosis, and initial symptoms in model 2. We used logistic
regression to estimate adjusted odds ratios (aOR) of risk factors for developing COVID-19 pneumonia. We
adjusted for age, sex, comorbidities, vaccination status,and initial symptoms in the logistic model. All tests
were two-sided; P<0.05 was considered statistically significant. Statistical analyses were performed with
SPSS (version 20.0, IBM, Armonk, NY, USA), Stata (MP version 16.0, StataCrop, College Station, TX,
USA), or GraphPad Prism 8 (GraphPad Software Inc.,San Diego, CA,USA).

We enrolled 33,816 SARS-CoV-2 positive participants (Supplementary Figure S1, available in https://weekly.chinacdc. cn/) 21,619 (63.9%) patients were male, the median age of patients was 44.5 years,
1,273 (3.7%) patients aged <18, 26,948 (76.7%) patients aged 18–59, and 5,595 (16.5%) patients aged
≥60. 9,260 (27.4%) patients had risk factors, and6,333 (18.7%) of whom had comorbidities. Among
patients with comorbidities, hypertension was the most common comorbidity (4,902/6,333, 77.4%), followed
by diabetes mellitus (1,641/6,333, 25.9%) and lung disease (329/6,333, 5.2%) (Figure1A). Among all
participants, most (32,688/33,816, 96.7%) had fewer than two comorbidities. Most of the participants had
received full or booster vaccination: 73.1% in riskgroup subjects and 80.6% in non-risk group subjects
(Figure 1B); 76.2% and 78.6% of participants were ultimately diagnosed with asymptomatic infection in
the risk group and the non-risk group, respectively (Figure 1C). Cough and sputum production were the
most common symptoms (19.0%), followed by fatigue (5.2%) and fever (4.0%). VST was longer in the risk
group [6 days, interquartile range (IQR): 4–9 days] than in the non-risk group (6 days, IQR: 3–8 days)
(P<0.001) (Figure 1D). VST was shorter in vaccinated subjects (6 days, IQR: 3–8 days) than in nonvaccinated subjects (6 days, IQR: 3–8.25 days) (P<0.001). The median duration of symptom
persistence was 7 days. Dynamic changes in viral load are shown in Supplementary Figure S2 (available in
https://weekly.chinacdc. cn/).

Compared to patients under 40 years old, patients 40–59 years old [aHR: 0.90; 95% confidence interval
(CI), 0.88–0.92], 60–79 years old (aHR: 0.85; 95% CI, 0.82–0.88) and ≥80 years old (aHR: 0.73; 95%
CI, 0.65–0.84) had longer VSTs in the Cox proportional hazards model (Table 1). In model 1,
presence of comorbidities (aHR: 0.96; 95% CI, 0.93–0.98) and being initially symptomatic (aHR:
0.95; 95% CI, 0.93–0.98) were also associated with increased VST; being fully vaccinated (aHR: 1.06;
95% CI, 1.03–1.10) and booster vaccinated (aHR: 1.07; 95% CI, 1.03–1.10) were associated with
decreased VST. In model 2, VST was longer in the risk group than in the non-risk group (aHR: 0.89; 95% CI,
0.87–0.92) (Figure 1E).

In the entire study cohort, 22 patients developed severe/critical infection; all were in the risk group.
Severity rates among all subjects and risk-group subjects were 0.065% and 0.238%, respectively.
Hypertension (31.8%) was the most common comorbidity, followed by diabetes (13.6%) and lung
disease (13.6%). Patients in the risk group who developed severe/critical infection were older
(75.8±10.7 vs. 60.0±11.3, P<0.001) and were more likely to be unvaccinated (54.5% vs. 24.2%; P=0.002).
(Table 2)

Seven hundred and eight patients suspected to haveCOVID-19 pneumonia received chest CT scans; 14.0% (99/708) had manifestations of COVID-19 pneumonia on CT. The incidence of pneumonia in the risk group was 19.8% (72/363), which was higher than in the non-risk group (7.8%, 27/345, P<0.001). Multivariable logistic regression analysis (Table 3),
showed that compared to patients under the age of 40, being 60–79 years old (aOR: 3.09; 95% CI, 1.41–6.80) or ≥80 years old (aOR: 3.68; 95% CI, 1.32–10.32) was associated with increased risk of COVID-19 pneumonia. Being male (aOR: 1.85; 95% CI, 1.16–2.94) was also associated with increased risk of pneumonia. Some patients (n=203) received
laboratory examinations, and we found thatlymphopenia (aOR: 6.56; 95% CI, 2.27–19.02), elevated C-reactive protein (CRP) (aOR: 4.64; 95% CI, 2.13–10.13), and prolonged prothrombin time (PT) (aOR: 24.30; 95% CI, 1.73–286.80) were associated with increased risk of COVID-19 pneumonia in multivariable logistic regression.

DISCUSSION

Analyzing dynamic changes of clinical characteristics and risk factors for illness progression among initially non-severe Omicron patients is essential to the construction of public health strategies that can minimize the risk of overwhelming regional medicalresources. Our study was restricted to infected patients with non-severe illness upon hospital admission. No
subjects had organ failure but upper respiratory symptoms were prevalent among the symptomatic patients in our study. Among those with symptoms in our study, the median duration of symptoms was 7 days, similar to the 5-day median duration of symptoms for Omicron infections in other studies (6). This suggests that despite the higher percentage of
asymptomatic Omicron infections in Shanghai,specific symptoms persisted in some patients. Debilitating symptoms, such as fever, dizziness, and headaches were uncommon, which is also consistent with previous research (6).

VST is an important factor for assessing risk of transmission and for guiding decisions regarding nonpharmaceutical intervention application. According to previous research, the median VST was 6 days (interquartile range 4–8 days) in symptomatic Omicron infected outpatients (7). However, until now, no studies have reported VST among non-severe
patients. In our study, the median VST in non-severe patients was 6 days (IQR 3–8 days). Other studies have
shown that older age and hypertension are associated with longer VSTs (8), which is consistent with our
research. We also found that the presence of other comorbidities and initial symptoms was also associated
with increased VST, and that full vaccination and booster vaccination was associated with decreased VST.
These findings have important implications for future COVID-19 public health strategic planning.

Twenty-two patients (0.065% of the total study cohort) developed severe or critical infections. These patients all had risk factors and were older on average and more likely to be unvaccinated — findings that are consistence with previous research (9–10). Compared to the initail wave of COVID-19 outbreak in Wuhan, 2020 (11), Omicron infected individuals in our study had a much lower rate of developing severe/critical infection (0.065%). There are several possible reasons for this large difference. First, previous studies showedOmicron infections were more likely to cause weaker attacks on the lungs, suggesting that Omicron may lead to a smaller percent of severe cases (12). Second, the enrolled patients in our study were all non-severe upon admission, and all without unstable conditions. Most of them had no more than two comorbidities. Our study therefore reflected the clinical manifestations and outcomes of relatively healthy
Omicron-infected patients. However, considering the relatively high transmissibility of Omicron, the total
number of severe infections can still rise rapidly during an epidemic.

Compared with Delta, Omicron’s relative inability to colonize or damage the lungs may result in fewer
cases of dangerous pneumonia and respiratory distress.However, we showed that some initially non-severe
Omicron patients could still develop pneumonia. Our study found that patients with COVID-19 pneumonia
were older and more likely to have comorbidities. However, young Omicron patients can also develop COVID-19 pneumonia. Recently, a case of COVID19 pneumonia caused by the Omicron variant was reported in a 19-year-old woman who had no obvious risk factors (13). In our research, 11.1% of the COVID-19 pneumonia patients were younger than 40
years, and the youngest was 22 years old. Among young COVID-19 pneumonia patients above, 72.7%
had no underlying medical conditions, and only 1 was unvaccinated. Although being younger, vaccinated,
having no underlying diseases can serve as protective factors for progression to severe disease, these factorsdo not provide 100% protection from pneumonia. We further analyzed laboratory indicators for pneumonia.
Lymphopenia, elevated CRP, and prolonged PT were associated with development of pneumonia, as other studies have reported (14–15). Our finding can encourage clinicians to conduct CT screening among certain Omicron infected populations. Early identification and treatment of pneumonia may further reduce the risk of severe COVID-19 disease progression.

Our study had at least three limitations. First, we only enrolled non-severe, stabilized Omicron patients
and therefore could not describe the overall clinical spectrum of Omicron infections, especially severe Omicron infections. Second, not all patients received CT scan and laboratory tests. Third, all symptoms were self-reported, potentially introducing bias.

Our study demonstrated the dynamic clinical manifestation, symptoms duration, and VST patterns among initially non-severe Omicron patients. Median symptom persistence was 7 days. Older age, having comorbidities, and being initially symptomatic were associated with longer VST, while vaccination was associated with shorter VST. The overall severity
progression rate was very low in these initially nonsevere patients without unstable conditions. Older age and lack of vaccination increased risk of progression to severe/critical illness. Male sex, older age, lymphopenia, elevated CRP, and prolonged PT were associated with higher risk of developing pneumonia.

Conflicts of interest: No conflicts of interest.

Acknowledgements: All study participants.

Funding: Supported by Research Grants from Shanghai Municipal Science and Technology Major Project (HS2021SHZX001), the Shanghai Science and Technology Committee (20dz2260100, 20Z119
01100, 20dz2210403).
doi: 10.46234/ccdcw2022.115
# Corresponding authors: Xin Ma, [email protected]; Wenhong Zhang, [email protected]. cn.

1 National Medical Center for Infectious Diseases, Huashan Hospital,Fudan University, Shanghai, China; 2 Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Huashan Hospital, Fudan University, Shanghai, China; 3 Huashen Institute of Microbes and Infections, Shanghai,
China; 4 Society of clinical epidemiology and evidence-based medicine, Shanghai Medical Association, Shanghai, China; 5 Department of Infectious Diseases, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China; 6
Shanghai Fouth People’s Hospital, School of Medicine, Tongji University, Shanghai, China; 7 Shanghai Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; 8 National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China.

&Joint first authors.
Submitted: June 05, 2022; Accepted: June 16, 2022

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SUPPLEMENTARY MATERIAL

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