Virology: RNA viruses  病毒學：RNA 病毒

RNA enveloped virus: INFLUENZA VIRUSES - Major outbreaks
RNA 包膜病毒：流感病毒 - 主要疫情

• In 1997, an outbreak of human influenza (avian influenza, bird flu) caused by an H5N1 strain of influenza A virus began.
  1997 年，由甲型流感病毒 H5N1 毒株引起的人流感（禽流感、禽流感）暴發。
• In 2009, there was an outbreak of human influenza caused by an H1N1 influenza A virus of swine origin (swine-origin influenza virus, S- OIV).
  2009 年，由豬源性甲型 H1N1 流感病毒（豬源性流感病毒，S-OIV）引發了人類流感疫情。
• In 2013, an outbreak of influenza caused by an H7N9 strain of influenza virus occurred.
  2013 年，發生了由 H7N9 流感病毒株引起的流感疫情。

Human Influenza Virus  人類流感病毒

- Influenza A&B cause most human illness and the flu season
- 甲型和乙型流感是大多數人類疾病和流感季節的原因

Human Influenza Virus  人類流感病毒

• Influenza A viruses are divided into subtypes based on two proteins on the surface of the envelope: hemagglutinin ( H ) and neuraminidase ( N )
  甲型流感病毒根據包膜表面的兩種蛋白質分為亞型：血凝素 （H） 和神經氨酸酶 （N）
• influenza A can change antigenicity of their hemagglutinin and neuraminidase proteins.
  甲型流感可以改變其血凝素和神經氨酸酶蛋白的抗原性。
• Influenza B viruses are classified into two lineages: B/Yamagata and B/Victoria
  乙型流感病毒分為兩個譜系：B/Yamagata 和 B/Victoria
• Two peak periods:  兩個高峰期：
• winter, Dec to Feb in the Northern hemisphere, causing a significant number of deaths, especially in elderly. Morbidity of influenza in children <2 yrs old is also very high.
  冬季，北半球的 12 月至 2 月，造成大量死亡，尤其是老年人。兒童 <2 歲流感的發病率也非常高。
• winter, June to Aug in the Southern hemisphere (e.g., in Australia and New Zealand)
  冬季，南半球為 6 月至 8 月（例如，澳大利亞和紐西蘭）
• In the tropics, influenza occurs year round with little seasonal variation.
  在熱帶地區，流感全年發生，季節性變化很小。

Naming of influenza:  影響命名：

Human Influenza Virus  人類流感病毒

• Disease: influenza/flu  疾病：流感/流感
• Transmission: airborne droplets
  傳播：空氣中的飛沫
• attaches to and penetrates epithelial cells in trachea and bronchi $\to$$\to$rarr\rightarrow Viral replication $\to$$\to$rarr\rightarrow destruction of the host cells.
  附著並穿透氣管和支氣管 $\to$$\to$rarr\rightarrow 中的上皮細胞 病毒複製 $\to$$\to$rarr\rightarrow 破壞宿主細胞。
• Regeneration of epithelium takes ~3-4 wks. Viremia (virus in the blood) is rare.
  上皮再生需要 ~3-4 周。病毒血症（血液中的病毒）很少見。
• Virus is shed in respiratory secretions for 5 to 10 days, with a peak of 1 to 3 days following illness onset.
  病毒在呼吸道分泌物中排出 5 至 10 天，發病後 1 至 3 天達到高峰。
• Presentation: Fever, muscle ache, headache, sore throat, cough.
  表現： 發燒、肌肉酸痛、頭痛、喉嚨痛、咳嗽。
• influenzal or bacterial pneumonia (eg. Staphylococcus aureus) may complicate the course
  流感或細菌性肺炎（例如。金黃色葡萄球菌）可能會使病程複雜化

Human Influenza Virus  人類流感病毒

• Diagnosis: clinical diagnosis of flu; Immunoassay
  診斷：流感的臨床診斷;免疫
• Treatment: rest, symptomatic drugs, flu antiviral drugs
  治療：休息、對症藥物、流感抗病毒藥物
• Prevention:  預防：
• vaccine  疫苗

• hand washing, wear masks  洗手、戴口罩

Table 1. 2024-2025 Influenza Vaccine Composition ${}^1$${}^1$^(1){ }^{1}
表 1.2024-2025 年流感疫苗成分 ${}^1$${}^1$^(1){ }^{1}

1. All influenza vaccines available in the US for the 2024-2025 influenza season are trivalent. $B/$$B/$B//B / Yamagata lineage viruses, the second influenza $B$$B$BB virus strain included in quadrivalent vaccines in recent years, have not circulated since March 2020.
   美國 2024-2025 年流感季節的所有流感疫苗都是三價疫苗。 $B/$$B/$B//B / 山形譜系病毒是近年來四價疫苗中包含的第二種流感 $B$$B$BB 病毒株，自 2020 年 3 月以來一直沒有傳播。
   

   

RNA enveloped virus： PARAMYXOVIRUSES

MUMPS VIRUS  流行性腮腺炎病毒

Mumps  腮腺炎

MUMPS VIRUS  流行性腮腺炎病毒

• Two Complications  兩種併發症
• Orchitis:  睾丸炎：
  if happen in postpubertal males, and if bilateral, can result in sterility
  如果發生在青春期后的男性中，並且是雙側的，則可能導致不育
  (Postpubertal males have a fibrous tunica albuginea, which resists expansion, thereby causing pressure necrosis of the testis)
  （青春期后男性有纖維狀白膜，抵抗擴張，從而導致睾丸壓力壞死）
• Meningitis: usually benign, selflimited, and without sequelae
  腦膜炎：通常為良性、自限性，無後遺症
  

  

Red, Swollen Testes  睾丸紅腫

MUMPS VIRUS  流行性腮腺炎病毒

• Diagnosis: clinically diagnose, cell culture from saliva, spinal fluid, or urine, immunoassay
  診斷：臨床診斷，唾液、脊髓液或尿液細胞培養，免疫測定
• Treatment: symptomatic, supportive
  治療：對症治療、支援
• Prevention: Vaccine  預防：疫苗
• MMR (measles, mumps, rubella) vaccine at 1 and 6 years old.
  在 1 歲和 6 歲時接種 MMR（麻疹、腮腺炎、風疹）疫苗。
  

  

RNA Enveloped Viruses: CORONAVIRUSES
RNA 包膜病毒：冠狀病毒

• may cause mild illness like common cold as well as severe illness in humans.
  可能導致普通感冒等輕微疾病以及人類嚴重疾病。
• in 2002, a new atypical pneumonia called severe acute respiratory syndrome (SARS), emerged.
  2002 年，出現了一種新的非典型肺炎，稱為嚴重急性呼吸系統綜合症 （SARS）。
  $\to 8300$$\to 8300$rarr8300\rightarrow 8300 cases and 785 deaths. Mortality rate ~ 9%.
  $\to 8300$$\to 8300$rarr8300\rightarrow 8300 病例和 785 例死亡。死亡率 ~ 9%。
• In 2012, another severe pneumonia called Middle East respiratory syndrome(MERS) emerged.
  2012 年，出現了另一種稱為中東呼吸綜合征 （MERS） 的嚴重肺炎。
  $\to 2613$$\to 2613$rarr2613\rightarrow 2613 laboratory-confirmed cases of MERS were reported globally, with 943 associated deaths. Mortality rate $36\mathrm{\%}$$36\mathrm{\%}$36%36 \%.
  $\to 2613$$\to 2613$rarr2613\rightarrow 2613 全球報告了 MERS 實驗室確診病例，其中 943 例相關死亡。死亡率 $36\mathrm{\%}$$36\mathrm{\%}$36%36 \% .

RNA Enveloped Viruses: CORONAVIRUSES
RNA 包膜病毒：冠狀病毒

• In 2019, worldwide pandemic of COVID19 virus.
  2019 年，COVID19 病毒的全球大流行。
• WHO reported $>400$$>400$> 400>400 million cases with 5.8 million death by Feb, 2022 (death rate $\sim 1.45\mathrm{\%}$$\sim 1.45\mathrm{\%}$∼1.45%\sim 1.45 \% )
  截至 2022 年 2 月，世衛組織報告 $>400$$>400$> 400>400 了 100 萬例病例，其中 580 萬人死亡（死亡率 $\sim 1.45\mathrm{\%}$$\sim 1.45\mathrm{\%}$∼1.45%\sim 1.45 \% ）
• locally in HK, 1660515 RAT confirmed cases, and 13825 deaths recorded. Mortality rate 0.833%
  在香港本地，1660515 例快速抗原測試確診病例，並記錄了 13825 例死亡病例。死亡率 0.833%

Coronavirus Structure  冠狀病毒結構

CORONAVIRUSES  冠狀病毒

• Transmission : droplets / airborne
  傳播 ： 飛沫 / 空氣傳播
• Presentation: runny nose, sore throat, cough, fever; some have bronchitis, viral or secondary bacterial pneumonia may complicate.
  表現：流鼻涕、喉嚨痛、咳嗽、發熱;有些人有支氣管炎，病毒性或繼發性細菌性肺炎可能會複雜化。
• Diagnosis: clinical diagnose;
  診斷：臨床診斷;
• if suspect SARS or MERS: serology, immunoassay
  如果懷疑 SARS 或 MERS：血清學、免疫測定
• if suspect COVID-19: immunoassay
  如果懷疑 COVID-19：免疫測定
• Treatment : symptomatic, supportive
  Treatment ： 對症治療， 支援
• Prevention:  預防：
• vaccine for COVID 19  COVID 19 疫苗
• wear surgical masks, hand washing
  戴外科口罩，洗手
• good ventilation  良好的通風
• good environmental hygiene
  良好的環境衛生

2002 : SARS  2002 年：SARS

• severe acute respiratory syndrome (SARS)
  嚴重急性呼吸系統綜合症 （SARS）
• originated in China  起源於中國
• flu-like symptoms  流感樣癥狀
• many develop severe atypical pneumonia, and ARDS, requiring mechanical ventilation.
  許多人發展為嚴重的非典型肺炎和 ARDS，需要機械通氣。
• Chest X-ray reveals interstitial “ground-glass” infiltrates
  胸部 X 線檢查顯示間質性「毛玻璃樣」浸潤
• Leukopenia and thrombocytopenia
  白細胞減少症和血小板減少症
• Death often due to respiratory failure.
  死亡常因呼吸衰竭。
• Other possible complications include heart and liver failure.
  其他可能的併發症包括心力衰竭和肝衰竭。

2002 : SARS  2002 年：SARS

• Treatment:  治療：
• supportive  支援
• A combination of ribavirin and steroids has been tried in treating severe SARS cases, but their efficacy is uncertain
  利巴韋林和類固醇的組合已被嘗試用於治療嚴重的 SARS 病例，但其療效尚不確定

2012 : MERS  2012 ： MERS （中東呼吸綜合征）

• Middle East respiratory syndrome(MERS)
  中東呼吸綜合征 （MERS）
• originated in Saudi Arabia
  起源於沙烏地阿拉伯
• exact route of transmission is still unclear.
  確切的傳播途徑尚不清楚。

• cause severe respiratory illnesses.
  導致嚴重的呼吸系統疾病。
• Severe complications such as pneumonia and kidney failure.
  嚴重的併發症，如肺炎和腎衰竭。
• Some also have gastrointestinal symptoms including diarrhoea and nausea/ vomiting.
  有些患者還會出現胃腸道癥狀，包括腹瀉和噁心/嘔吐。
• Treatment: supportive  治療：支援
  

  

2019 : COVID19  2019 年：COVID19

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
  嚴重急性呼吸系統綜合症冠狀病毒 2 （SARS-CoV-2）
• first discovered in bronchoalveolar lavage samples taken from clusters of patients with pneumonia of unknown cause in Wuhan City, Hubei Province, China, in December 2019
  2019年12月在中國湖北省武漢市不明原因肺炎患者集群採集的支氣管肺泡灌洗液樣本中首次發現
• transmission: aerosol, droplets, fecal-oral transmission also possible.
  傳播：氣溶膠、飛沫、糞口傳播也是可能的。
• flu-like symptoms, loss of smell/taste, vomiting and diarrhea.
  流感樣癥狀、嗅覺/味覺喪失、嘔吐和腹瀉。
• Complications: respiratory failure, acute respiratory distress syndrome (ARDS), sepsis and septic shock, thromboembolism, and/or multi-organ failure including injury of the heart, liver or kidneys.
  併發症：呼吸衰竭、急性呼吸窘迫綜合征 （ARDS）、敗血症和感染性休克、血栓栓塞和/或多器官衰竭，包括心臟、肝臟或腎臟損傷。

COVID19

• The spikes (glycoprotein) on the virus connect to the ACE2 receptor of host cells.
  病毒上的刺突（糖蛋白）連接到宿主細胞的 ACE2 受體。
• ACE2 receptor are most abundant in upper respiratory tract cells and lung cells. Gut cells are also rich in ACE2 receptors.
  ACE2 受體在上呼吸道細胞和肺細胞中最為豐富。腸道細胞還富含 ACE2 受體。
• loss of smell is due to the infection of olfactory epithelial cells, with subsequent damage to the olfactory neurons.
  嗅覺喪失是由於嗅覺上皮細胞感染，隨後對嗅覺神經元造成損害。
• Kidney and myocardial injuries may also be related to ACE2 receptors and the mechanism of CNS damage is not yet clear.
  腎臟和心肌損傷也可能與 ACE2 受體有關，CNS 損傷的機制尚不清楚。

COVID19

• release of excess inflammatory cytokines(cytokines storm) $\to$$\to$rarr\rightarrow causes acute respiratory distress syndrome, blood clotting events such as strokes, myocardial infarction, encephalitis, acute kidney injury, and vasculitis.
  過量的炎性細胞因數（細胞因數風暴） $\to$$\to$rarr\rightarrow 的釋放會導致急性呼吸窘迫綜合征、中風、心肌梗塞、腦炎、急性腎損傷和血管炎等凝血事件。

COVID19

• Diagnosis  診斷
• Antigen tests(RAT): immunoassay
  抗原檢測 （RAT）：免疫測定
• targets the capsid protein of the virus
  靶向病毒的衣殼蛋白
• immunoassay: Reverse transcription polymerase chain reaction (RT-PCR) test
  免疫測定：逆轉錄聚合酶鏈反應 （RT-PCR） 檢測
• reverse transcription of viral RNA to obtain DNA, followed by amplification for analysis
  病毒 RNA 逆轉錄以獲得 DNA，然後擴增進行分析

COVID19

• Antiviral drugs:  抗病毒藥物：
• Paxlovid is a combination of 2 medicines called nirmatrelvir and ritonavir.
  Paxlovid 是 2 種稱為 nirmatrelvir 和 ritonavir 的藥物的組合。
• Nirmatrelvir inhibit viral replication
  Nirmatrelvir 抑制病毒複製
• Ritonavir: slow down the metabolism of nirmatrelvir, thus increasing the concentration of nirmatrelvir to levels required for therapeutic effect.
  利托那韋：減慢奈馬曲韋的代謝，從而將奈馬曲韋的濃度增加到治療效果所需的水準。
• Molnupiravir: inhibits viral replication
  Molnupiravir：抑制病毒複製
  

  

RNA Nonenveloped Viruses PICORNAVIRUSES
RNA 無包膜病毒 小核糖核酸病毒

• Enteroviruses:  腸道病毒：
• poliovirus, Coxsackie viruses, echoviruses, and hepatitis A virus
  脊髓灰質炎病毒、柯薩奇病毒、埃可病毒和甲型肝炎病毒
• rhinoviruses  鼻病毒
  

  

RNA Nonenveloped Viruses  RNA 無包膜病毒

• 100 serologic types  100 種血清學類型

• infect limited to humans and chimpanzees.
  感染僅限於人類和黑猩猩。
• Disease: common cold.  疾病：普通感冒。
• Transmission: droplets, contact with contaminate surface
  傳播：飛沫，接觸污染表面
• Presentation: sneezing, nasal discharge, sore throat, cough, and headache; pneumonia in some cases.
  表現：打噴嚏、流鼻涕、咽痛、咳嗽和頭痛;肺炎。
• Diagnosis: Clinical diagnosis, cell culture
  診斷 ： 臨床診斷、細胞培養
• Treatment: symptomatic  治療：對症
  

  

Coxsackie virus  柯薩奇病毒

• Presentation:  介紹：
• Herpangina : fever, sore throat, and tender vesicles in the oropharynx.
  皰疹性咽峽炎 ： 發熱、喉嚨痛和口咽部水皰觸痛。
• Hand-foot-and-mouth disease: vesicular rash on the hands and feet, ulcerations in the mouth, mainly in children.
  手足口病：手足水皰疹，口腔潰瘍，主要見於兒童。
• Treatment: supportive/symptomatic
  治療：支援性/對症治療
• Watch out for dehydration in children due to poor intake
  注意兒童因攝入不足而導致的脫水
• Back to school until fever subsided and vesicles dried up completely.
  回到學校，直到發燒消退，水皰完全乾涸。