COVID-19-associated dermatologic manifestations

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Nuha Al-Howthi, MD[2] Ogechukwu Hannah Nnabude, MD; Aditya Ganti M.B.B.S. [3]

Overview

COVID-19 infections is caused by the novel coronavirus or also known as SARS-2 virus. The disease is believed to incline towards respiratory organs due to the high expression of ACE receptors. However, skin rashes have been uncommonly described in patients with COVID-19 infection. Dermatologic manifestations of COVID-19 though rare include an erythematous exanthem, livedo reticularis, vasculitis, urticaria, vesicles. Common clinical features of covid-19 infection includes fever, dry cough, shortness of breath, myalgia and fatigue.

Historical Perspective

  • In 1937, coronavirus was first isolated from chickens.
  • In 1965, Tyrrell and Bynoe used cultures of human ciliated embryonal trachea to propagate the first human coronavirus (HCoV) in vitro.
  • The etiological agent, a novel coronavirus, SARS-CoV-2, is a virus identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China.[1][2][3][4]
  • The outbreak was declared a Public Health Emergency of International Concern on 30 January 2020.
  • On March 12, 2020 the World Health Organization declared the COVID-19 outbreak a pandemic.

Pathophysiology

Immune Response

  • Immune complexes deposition stimulate T-helper cells to initiate cytokines cascade.
  • IL-1, IFN-γ, and TNF-α are produced to recruit eosinophils, CD8+ , B cells and natural killer cells resulting in lymphocytic thrombophilic arteritis.
  • Keratinocytes are destroyed by the cytotoxic lymphocytes which is secondary to langherhans cell activation resulting in vasodilation and spongiosis.
  • Microvascular injury occurs mediated by activation of complement pathways and an associated pro coagulant state.
  • The purpuric skin lesions showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d
  • In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature.

Microscopic pathology

  • Histopathological studies and PCR investigation on skin biopsies are necessary to clarify the close relationship between skin and SARS-CoV-2 infection. On microscopy features
    • Classic dyskeratotic cells
    • Ballooning multinucleated cells
    • Sparse necrotic keratinocytes
    • Lymphocytic satellitosis.
    • Punch biopsy of the upper dermis demonstrated
      • Diffuse telangiectatic small blood vessels
      • Nests of Langerhans cells within the epidermis
    • Perivascular spongiotic dermatitis with exocytosis al
    • Dense perivascular lymphocytic infiltration
    • Eosinophilic rich around the swollen blood vessels
    • Extravasated erythrocytes.
    • Lymphocytic vasculitis.

Differentiating COVID-19 Dermatologic manifestations with other Diseases

Disease Epidemiology Predisposing factors Clinical features[18][19][20] Lab abnormalities
Signs Symptoms
Toxic shock syndrome Occurs in both adults and children (9:1 female predominance)

(C. sordellii)[21][22][23][24][25]

Fever Hypotension Diffuse Rash Other signs
  • Diarrhea
  • Vomiting
  • Rash: Diffuse scarlantiform rash (red sunburn-like rash. It is flat and turns white if pressed)
  • Thick skin desquamation appears on the hands and feet at around 1-2 weeks of disease progression, and might be followed by hair desquamation or shedding of fingernails and toenails after 2-3 months[26]
+ + +
  • Nonpitting systemic edema
Meningococcemia Occurs in young adults living in close proximity (college dorms, military recruits)[30]
  • Close contact with a carrier
  • Intimate kissing and cigarette smoking are associated with increased risk of meningococcal carriage[31]
+ + +
  • Positive blood cultures (Neisseria meningitidis)
  • CSF findings typical of bacterial meningitis:[24]
    • Cells >300/uL
    • Predominantly granulocytes
    • Total protein 100-500mg/dl
    • Glucose ratio (CSF/plasma) <0.3
    • Lactate >2.1 mmol/L
    • CSF gram stain and culture may be positive
Stevens Johnson syndrome (SJS) HLA-B*1502 gene leads to increased susceptibility[35] Triggered by certain medications, most commonly: + + +
  • Histological work up of skin sections reveal wide spread necrotic epidermis involving all layers
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome + + +
  • Multi-organ dysfunction:[42]
    • Pneumonitis
    • Hepatitis
    • Renal failure
    • Encephalitis
    • Cardiac failure
Red man syndrome Patients in whom the offending drug infusion is given over less than 1 hour and who are not pre-treated with diphenhydramine[45] Hypersensitivity to:[46] + + +
  • Headache
  • Chills
  • Diziness
  • Chest pain
  • Dyspnea
  • Pruritis
No elevation in tryptase levels indicating that it is an anaphylactoid reaction[47]
Kawasaki

disease

Occurs in children, usually age 1-4 years

(autoimmune vasculitis)

+ + +
Scarlet fever Distributed equally among both genders. Most commonly affects children between five and fifteen years of age. Occurs after streptococcal pharyngitis/tonsillitis + +/- + Rash:
  • Characteristic sandpaper-like rash which appears days after the illness begins (although the rash can appear before illness or up to 7 days later), rash may first appear on the neck, underarm, and groin

Epidemiology and Demographics

  • The incidence of dermatologic manifestations with COVID-19 infections increases with age; the median age at diagnosis is 53 years.
  • Males are more commonly affected than females.
  • Most of the patients were children (median 13 years) and young adults (median 31, average 36, range 18–91 years old).

Risk Factors

There are no established risk factors to determine what conditions or diseases predispose Covid-19 infection to manifest as cutaneous complications. However, similar to all viral illnesses, exposure is considered the most significant risk factor for infection with Coronavirus disease 2019 (COVID-19).

History and Symptoms

  • The timing of skin lesions depends on various factors and not really known but 3 days before diagnosis to 13 days after diagnosis.
  • The most common cutaneous manifestation of COVID-19 is a maculopapular exanthem (morbilliform).
  • Majority of lesions were localized on the trunk, however, some patients experienced cutaneous manifestations in the hands and feet.
  • Skin lesion development occurred before the onset of respiratory symptoms or COVID-19 diagnosis in some of the patients , and lesions spontaneously healed in all patients within 10 days
  • The other cutaneous manifestations included:

Physical Examination

    • Acral eruption of erythemato‐violaceous papules and macules, with possible bullous evolution, or digital swelling.
    • Acute acro-ischemia in the child
      • Presentations of acro-ischemia including finger/toe cyanosis, skin bulla and dry gangrene..
      • Expression of secondary microthrombosis due to endothelial damage and vascular disorders..
    • Erythema multiforme-like lesions that might be another pattern of exanthem associated with COVID-19 infection.
    • Further studies are needed to evaluate whether these lesions are associated with the virus, the drug intake or any other conditions.
    • COVID-19 Toes.
      • Similar to the type of cold related changes we have seen in the feet of people for many years, but often occurring in places where the conditions are not cold and damp.
      • These seem to happen more commonly in younger patients.
    • Chilblain‐like lesions
      • The pseudo‐chilblain pattern frequently appears late in the evolution of the COVID‐19 disease.
      • The lesion was red–purple papules on the dorsal aspect of the fingers on both hands and diffused erythema in the subungual area of thumb.

Laboratory Findings

Diagnostic studies

  • Diagnosis of COVID-19 infection was successfully confirmed by RT-PCR.
  • Histopathological studies and PCR investigation on skin biopsies are necessary to confirm infection of skin with SARS-CoV-2 infection.

Prognosis

  • The skin lesions are initially reddish and papular resembling chilblains.
  • Subsequently, in the span of approximately 1 week they become more purpuric and flattened.
  • Finally, they seem to resolve by themselves without requiring any treatment.
  • Aggravation of previous skin diseases, such as rosacea, eczema, atopic dermatitis and neurodermatitis, was also observed in some Covid‐19 patients.

Treatment

  • Supportive care for patients is typically the standard protocol because no specific effective antiviral therapies have been identified.
  • Currently, infection prevention and control are considered urgent and critical due to the lack of specific treatment and heightened risk of spreading during the incubation period.



References

  1. https://www.cdc.gov/coronavirus/2019-ncov/about/index.html. Missing or empty |title= (help)
  2. Lu, Jian; Cui, Jie; Qian, Zhaohui; Wang, Yirong; Zhang, Hong; Duan, Yuange; Wu, Xinkai; Yao, Xinmin; Song, Yuhe; Li, Xiang; Wu, Changcheng; Tang, Xiaolu (2020). "On the origin and continuing evolution of SARS-CoV-2". National Science Review. doi:10.1093/nsr/nwaa036. ISSN 2095-5138.
  3. Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". The Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. ISSN 0140-6736.
  4. https://www.cdc.gov/coronavirus/2019-ncov/about/transmission.html. Missing or empty |title= (help)
  5. Heymann, David L; Shindo, Nahoko (2020). "COVID-19: what is next for public health?". The Lancet. 395 (10224): 542–545. doi:10.1016/S0140-6736(20)30374-3. ISSN 0140-6736.
  6. Rothe, Camilla; Schunk, Mirjam; Sothmann, Peter; Bretzel, Gisela; Froeschl, Guenter; Wallrauch, Claudia; Zimmer, Thorbjörn; Thiel, Verena; Janke, Christian; Guggemos, Wolfgang; Seilmaier, Michael; Drosten, Christian; Vollmar, Patrick; Zwirglmaier, Katrin; Zange, Sabine; Wölfel, Roman; Hoelscher, Michael (2020). "Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany". New England Journal of Medicine. 382 (10): 970–971. doi:10.1056/NEJMc2001468. ISSN 0028-4793.
  7. Zhou, Peng; Yang, Xing-Lou; Wang, Xian-Guang; Hu, Ben; Zhang, Lei; Zhang, Wei; Si, Hao-Rui; Zhu, Yan; Li, Bei; Huang, Chao-Lin; Chen, Hui-Dong; Chen, Jing; Luo, Yun; Guo, Hua; Jiang, Ren-Di; Liu, Mei-Qin; Chen, Ying; Shen, Xu-Rui; Wang, Xi; Zheng, Xiao-Shuang; Zhao, Kai; Chen, Quan-Jiao; Deng, Fei; Liu, Lin-Lin; Yan, Bing; Zhan, Fa-Xian; Wang, Yan-Yi; Xiao, Geng-Fu; Shi, Zheng-Li (2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. doi:10.1038/s41586-020-2012-7. ISSN 0028-0836.
  8. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F, Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L, Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu WJ, Wang D, Xu W, Holmes EC, Gao GF, Wu G, Chen W, Shi W, Tan W (February 2020). "Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding". Lancet. 395 (10224): 565–574. doi:10.1016/S0140-6736(20)30251-8. PMID 32007145 Check |pmid= value (help).
  9. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL (February 2020). "A pneumonia outbreak associated with a new coronavirus of probable bat origin". Nature. doi:10.1038/s41586-020-2012-7. PMID 32015507 Check |pmid= value (help).
  10. Crackower, Michael A.; Sarao, Renu; Oudit, Gavin Y.; Yagil, Chana; Kozieradzki, Ivona; Scanga, Sam E.; Oliveira-dos-Santos, Antonio J.; da Costa, Joan; Zhang, Liyong; Pei, York; Scholey, James; Ferrario, Carlos M.; Manoukian, Armen S.; Chappell, Mark C.; Backx, Peter H.; Yagil, Yoram; Penninger, Josef M. (2002). "Angiotensin-converting enzyme 2 is an essential regulator of heart function". Nature. 417 (6891): 822–828. doi:10.1038/nature00786. ISSN 0028-0836.
  11. Danilczyk, Ursula; Sarao, Renu; Remy, Christine; Benabbas, Chahira; Stange, Gerti; Richter, Andreas; Arya, Sudha; Pospisilik, J. Andrew; Singer, Dustin; Camargo, Simone M. R.; Makrides, Victoria; Ramadan, Tamara; Verrey, Francois; Wagner, Carsten A.; Penninger, Josef M. (2006). "Essential role for collectrin in renal amino acid transport". Nature. 444 (7122): 1088–1091. doi:10.1038/nature05475. ISSN 0028-0836.
  12. Gu, Jiang; Gong, Encong; Zhang, Bo; Zheng, Jie; Gao, Zifen; Zhong, Yanfeng; Zou, Wanzhong; Zhan, Jun; Wang, Shenglan; Xie, Zhigang; Zhuang, Hui; Wu, Bingquan; Zhong, Haohao; Shao, Hongquan; Fang, Weigang; Gao, Dongshia; Pei, Fei; Li, Xingwang; He, Zhongpin; Xu, Danzhen; Shi, Xeying; Anderson, Virginia M.; Leong, Anthony S.-Y. (2005). "Multiple organ infection and the pathogenesis of SARS". The Journal of Experimental Medicine. 202 (3): 415–424. doi:10.1084/jem.20050828. ISSN 1540-9538.
  13. Ding, Yanqing; He, Li; Zhang, Qingling; Huang, Zhongxi; Che, Xiaoyan; Hou, Jinlin; Wang, Huijun; Shen, Hong; Qiu, Liwen; Li, Zhuguo; Geng, Jian; Cai, Junjie; Han, Huixia; Li, Xin; Kang, Wei; Weng, Desheng; Liang, Ping; Jiang, Shibo (2004). "Organ distribution of severe acute respiratory syndrome(SARS) associated coronavirus(SARS-CoV) in SARS patients: implications for pathogenesis and virus transmission pathways". The Journal of Pathology. 203 (2): 622–630. doi:10.1002/path.1560. ISSN 0022-3417.
  14. Hamming, I; Timens, W; Bulthuis, MLC; Lely, AT; Navis, GJ; van Goor, H (2004). "Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis". The Journal of Pathology. 203 (2): 631–637. doi:10.1002/path.1570. ISSN 0022-3417.
  15. Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong (2020). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China". JAMA. doi:10.1001/jama.2020.1585. ISSN 0098-7484.
  16. Huang, Chaolin; Wang, Yeming; Li, Xingwang; Ren, Lili; Zhao, Jianping; Hu, Yi; Zhang, Li; Fan, Guohui; Xu, Jiuyang; Gu, Xiaoying; Cheng, Zhenshun; Yu, Ting; Xia, Jiaan; Wei, Yuan; Wu, Wenjuan; Xie, Xuelei; Yin, Wen; Li, Hui; Liu, Min; Xiao, Yan; Gao, Hong; Guo, Li; Xie, Jungang; Wang, Guangfa; Jiang, Rongmeng; Gao, Zhancheng; Jin, Qi; Wang, Jianwei; Cao, Bin (2020). "Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China". The Lancet. 395 (10223): 497–506. doi:10.1016/S0140-6736(20)30183-5. ISSN 0140-6736.
  17. Guan, Wei-jie; Ni, Zheng-yi; Hu, Yu; Liang, Wen-hua; Ou, Chun-quan; He, Jian-xing; Liu, Lei; Shan, Hong; Lei, Chun-liang; Hui, David SC; Du, Bin; Li, Lan-juan; Zeng, Guang; Yuen, Kowk-Yung; Chen, Ru-chong; Tang, Chun-li; Wang, Tao; Chen, Ping-yan; Xiang, Jie; Li, Shi-yue; Wang, Jin-lin; Liang, Zi-jing; Peng, Yi-xiang; Wei, Li; Liu, Yong; Hu, Ya-hua; Peng, Peng; Wang, Jian-ming; Liu, Ji-yang; Chen, Zhong; Li, Gang; Zheng, Zhi-jian; Qiu, Shao-qin; Luo, Jie; Ye, Chang-jiang; Zhu, Shao-yong; Zhong, Nan-shan (2020). doi:10.1101/2020.02.06.20020974. Missing or empty |title= (help)
  18. Todd JK (1988). "Toxic shock syndrome". Clin. Microbiol. Rev. 1 (4): 432–46. PMC 358064. PMID 3069202.
  19. Kang JH (2015). "Febrile Illness with Skin Rashes". Infect Chemother. 47 (3): 155–66. doi:10.3947/ic.2015.47.3.155. PMC 4607768. PMID 26483989.
  20. Sivagnanam S, Deleu D (2003). "Red man syndrome". Crit Care. 7 (2): 119–20. PMC 270616. PMID 12720556.
  21. McGregor JA, Soper DE, Lovell G, Todd JK (1989). "Maternal deaths associated with Clostridium sordellii infection". Am. J. Obstet. Gynecol. 161 (4): 987–95. PMID 2801850.
  22. "Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol--United States and Canada, 2001-2005". MMWR Morb. Mortal. Wkly. Rep. 54 (29): 724. 2005. PMID 16049422.
  23. Fischer M, Bhatnagar J, Guarner J, Reagan S, Hacker JK, Van Meter SH, Poukens V, Whiteman DB, Iton A, Cheung M, Dassey DE, Shieh WJ, Zaki SR (2005). "Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion". N. Engl. J. Med. 353 (22): 2352–60. doi:10.1056/NEJMoa051620. PMID 16319384.
  24. Sinave C, Le Templier G, Blouin D, Léveillé F, Deland E (2002). "Toxic shock syndrome due to Clostridium sordellii: a dramatic postpartum and postabortion disease". Clin. Infect. Dis. 35 (11): 1441–3. doi:10.1086/344464. PMID 12439811.
  25. Ho CS, Bhatnagar J, Cohen AL, Hacker JK, Zane SB, Reagan S, Fischer M, Shieh WJ, Guarner J, Ahmad S, Zaki SR, McDonald LC (2009). "Undiagnosed cases of fatal Clostridium-associated toxic shock in Californian women of childbearing age". Am. J. Obstet. Gynecol. 201 (5): 459.e1–7. doi:10.1016/j.ajog.2009.05.023. PMID 19628200.
  26. Kang JH (2015). "Febrile Illness with Skin Rashes". Infect Chemother. 47 (3): 155–66. doi:10.3947/ic.2015.47.3.155. PMC 4607768. PMID 26483989.
  27. Brook MG, Bannister BA (1988). "Scarlet fever can mimic toxic shock syndrome". Postgrad Med J. 64 (758): 965–7. PMC 2429080. PMID 3256819.
  28. Minemura M, Tajiri K, Shimizu Y (2014). "Liver involvement in systemic infection". World J Hepatol. 6 (9): 632–42. doi:10.4254/wjh.v6.i9.632. PMC 4179142. PMID 25276279.
  29. Chesney RW, Chesney PJ, Davis JP, Segar WE (1981). "Renal manifestations of the staphylococcal toxic-shock syndrome". Am. J. Med. 71 (4): 583–8. PMID 7282746.
  30. Harrison LH (2010). "Epidemiological profile of meningococcal disease in the United States". Clin. Infect. Dis. 50 Suppl 2: S37–44. doi:10.1086/648963. PMC 2820831. PMID 20144015.
  31. MacLennan J, Kafatos G, Neal K, Andrews N, Cameron JC, Roberts R, Evans MR, Cann K, Baxter DN, Maiden MC, Stuart JM (2006). "Social behavior and meningococcal carriage in British teenagers". Emerging Infect. Dis. 12 (6): 950–7. PMC 3373034. PMID 16707051.
  32. WARTENBERG R (1950). "The signs of Brudzinski and of Kernig". J. Pediatr. 37 (4): 679–84. PMID 14779273.
  33. Bush LM (2014). "Case 28-2014: A man with a rash, headache, fever, nausea, and photophobia". N. Engl. J. Med. 371 (23): 2238–9. doi:10.1056/NEJMc1412237#SA2. PMID 25470712.
  34. "Meningitis Symptoms - Meningitis Research Foundation".
  35. Chung WH, Hung SI, Hong HS, Hsih MS, Yang LC, Ho HC, Wu JY, Chen YT (2004). "Medical genetics: a marker for Stevens-Johnson syndrome". Nature. 428 (6982): 486. doi:10.1038/428486a. PMID 15057820.
  36. Techasatian L, Panombualert S, Uppala R, Jetsrisuparb C (2016). "Drug-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in children: 20 years study in a tertiary care hospital". World J Pediatr. doi:10.1007/s12519-016-0057-3. PMID 27650525.
  37. Harr T, French LE (2010). "Toxic epidermal necrolysis and Stevens-Johnson syndrome". Orphanet J Rare Dis. 5: 39. doi:10.1186/1750-1172-5-39. PMC 3018455. PMID 21162721.
  38. Harr T, French LE (2010). "Toxic epidermal necrolysis and Stevens-Johnson syndrome". Orphanet J Rare Dis. 5: 39. doi:10.1186/1750-1172-5-39. PMC 3018455. PMID 21162721.
  39. Chang YS, Huang FC, Tseng SH, Hsu CK, Ho CL, Sheu HM (2007). "Erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis: acute ocular manifestations, causes, and management". Cornea. 26 (2): 123–9. doi:10.1097/ICO.0b013e31802eb264. PMID 17251797.
  40. Harr T, French LE (2010). "Toxic epidermal necrolysis and Stevens-Johnson syndrome". Orphanet J Rare Dis. 5: 39. doi:10.1186/1750-1172-5-39. PMC 3018455. PMID 21162721.
  41. Choudhary S, McLeod M, Torchia D, Romanelli P (2013). "Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) Syndrome". J Clin Aesthet Dermatol. 6 (6): 31–7. PMC 3718748. PMID 23882307.
  42. Eshki M, Allanore L, Musette P, Milpied B, Grange A, Guillaume JC, Chosidow O, Guillot I, Paradis V, Joly P, Crickx B, Ranger-Rogez S, Descamps V (2009). "Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan failure". Arch Dermatol. 145 (1): 67–72. doi:10.1001/archderm.145.1.67. PMID 19153346.
  43. Peyrière H, Dereure O, Breton H, Demoly P, Cociglio M, Blayac JP, Hillaire-Buys D (2006). "Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist?". Br. J. Dermatol. 155 (2): 422–8. doi:10.1111/j.1365-2133.2006.07284.x. PMID 16882184.
  44. Eshki M, Allanore L, Musette P, Milpied B, Grange A, Guillaume JC, Chosidow O, Guillot I, Paradis V, Joly P, Crickx B, Ranger-Rogez S, Descamps V (2009). "Twelve-year analysis of severe cases of drug reaction with eosinophilia and systemic symptoms: a cause of unpredictable multiorgan failure". Arch Dermatol. 145 (1): 67–72. doi:10.1001/archderm.145.1.67. PMID 19153346.
  45. Wallace MR, Mascola JR, Oldfield EC (1991). "Red man syndrome: incidence, etiology, and prophylaxis". J. Infect. Dis. 164 (6): 1180–5. PMID 1955716.
  46. Sivagnanam S, Deleu D (2003). "Red man syndrome". Crit Care. 7 (2): 119–20. PMC 270616. PMID 12720556.
  47. Renz CL, Laroche D, Thurn JD, Finn HA, Lynch JP, Thisted R, Moss J (1998). "Tryptase levels are not increased during vancomycin-induced anaphylactoid reactions". Anesthesiology. 89 (3): 620–5. PMID 9743397.
  48. Lin YJ, Cheng MC, Lo MH, Chien SJ (2015). "Early Differentiation of Kawasaki Disease Shock Syndrome and Toxic Shock Syndrome in a Pediatric Intensive Care Unit". Pediatr. Infect. Dis. J. 34 (11): 1163–7. doi:10.1097/INF.0000000000000852. PMID 26222065.
  49. http://weekly.chinacdc.cn/en/article/id/e53946e2-c6c4-41e9-9a9b-fea8db1a8f51. Missing or empty |title= (help)
  50. Li, Qun; Guan, Xuhua; Wu, Peng; Wang, Xiaoye; Zhou, Lei; Tong, Yeqing; Ren, Ruiqi; Leung, Kathy S.M.; Lau, Eric H.Y.; Wong, Jessica Y.; Xing, Xuesen; Xiang, Nijuan; Wu, Yang; Li, Chao; Chen, Qi; Li, Dan; Liu, Tian; Zhao, Jing; Liu, Man; Tu, Wenxiao; Chen, Chuding; Jin, Lianmei; Yang, Rui; Wang, Qi; Zhou, Suhua; Wang, Rui; Liu, Hui; Luo, Yinbo; Liu, Yuan; Shao, Ge; Li, Huan; Tao, Zhongfa; Yang, Yang; Deng, Zhiqiang; Liu, Boxi; Ma, Zhitao; Zhang, Yanping; Shi, Guoqing; Lam, Tommy T.Y.; Wu, Joseph T.; Gao, George F.; Cowling, Benjamin J.; Yang, Bo; Leung, Gabriel M.; Feng, Zijian (2020). "Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia". New England Journal of Medicine. doi:10.1056/NEJMoa2001316. ISSN 0028-4793.
  51. Heymann, David L; Shindo, Nahoko (2020). "COVID-19: what is next for public health?". The Lancet. 395 (10224): 542–545. doi:10.1016/S0140-6736(20)30374-3. ISSN 0140-6736.
  52. https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/high-risk-complications.html. Missing or empty |title= (help)
  53. Hu, Zhiliang; Song, Ci; Xu, Chuanjun; Jin, Guangfu; Chen, Yaling; Xu, Xin; Ma, Hongxia; Chen, Wei; Lin, Yuan; Zheng, Yishan; Wang, Jianming; Hu, Zhibin; Yi, Yongxiang; Shen, Hongbing (2020). "Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China". Science China Life Sciences. doi:10.1007/s11427-020-1661-4. ISSN 1674-7305.
  54. Porcheddu, Rossella; Serra, Caterina; Kelvin, David; Kelvin, Nikki; Rubino, Salvatore (2020). "Similarity in Case Fatality Rates (CFR) of COVID-19/SARS-COV-2 in Italy and China". The Journal of Infection in Developing Countries. 14 (02): 125–128. doi:10.3855/jidc.12600. ISSN 1972-2680.
  55. Wilder-Smith, Annelies; Chiew, Calvin J; Lee, Vernon J (2020). "Can we contain the COVID-19 outbreak with the same measures as for SARS?". The Lancet Infectious Diseases. doi:10.1016/S1473-3099(20)30129-8. ISSN 1473-3099.
  56. (PDF) https://www.cdc.gov/coronavirus/2019-ncov/downloads/community-mitigation-strategy.pdf. Missing or empty |title= (help)