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Virology, transmission, and pathogenesis of SARS-CoV-2

BMJ 2020; 371 doi: https://doi.org/10.1136/bmj.m3862 (Published 23 October 2020) Cite this as: BMJ 2020;371:m3862

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Re: Virology, transmission, and pathogenesis of SARS-CoV-2 ; comparison of post viral symptoms in previous outbreaks.

Dear Editor
It is interesting to compare post viral symptoms in hree conditions, Covid 19 pandemic (2019) , SARS CoV corona virus outbreak (2003) and Myalgic Encephalomyelitis Chronic Fatigue Syndrome(ME CFS)
The SARS outbreak in 2003 in North America initially involved 364 cases centered in Toronto, Canada , 273 (75%) were confirmed with the virus, 80% were healthcare workers, and 17% lived in the household of a previously diagnosed patient. Fever was the prime symptom in 97% of patients. Respiratory findings including cough (59%) , dyspnea (37%), pulmonary infiltrates (68%). Lymphopenia (57%) and thrombocytopenia (36% ). Rhinorrhea, sore throat, and an elevated neutrophil count were common .
The 2020 Covid 19 pandemic had overlap in symptoms . Fever accompanied dyspnea, cough, loss of taste and smell, decreased oxygen tension, accumulation of fluid in the lungs, muscle aching, generalized pain and massive debilitating fatigue. Oxygen administration was required in a large number of cases .Ventilators were initially used to combat the respiratory problems but failed to reverse the anoxia in a large number of cases. The Death rate climbed . Surviving Patients suffered from continued massive fatigue and "brain fog" . The brain fog decreased the patients cognitive ability and short term memory.
In 1955, Myalgic Encephalomyelitis first described by Melvin Ramsay a consultant physician in the Royal Free Hospital, London. A cohort of young doctors and nurses developed massive fatigue and brain fog. The general opinion was that they were lazy or suffering from a psychosomatic condition or hysteria. Ramsey thought otherwise and considered that a virus was involved. He initially used the term Post Viral Fatigue, and thought the problem might be due to a Coxsackie virus . Other patients appeared without exposure to coxsackie virus, the diagnostic term was changed to Myalgic Encephalomyelitis, relating to the effect on muscles, peripheral nerves and the brain. His diagnostic ability was remarkable considering that diagnostic imaging was not as yet developed. There were no CAT, MRI or PET scans just plain medical acumen. Diagnostic criteria were later published (xx) The unfortunate term Chronic Fatigue Syndrome (CFS) was used a decade so later partly through the media terming the condition Yuppie disease and denigrating the condition to imagination. Over the years a number of patients consider their massive debilitating fatigue to be related to a 'flu like episode early in the disease.
Fatigue and brain fog after exposure to a virus is common to the three conditions as are other symptoms (figure 1).
POTS a cardio vascular symptom is seen in ME CFS and Covid 19. Post Exertion malaise (PEM) is also seen in ME CFS and Covid 19.
Up-regulation of the immune system has been observed in ME CFS , SARS , and the cytokine storm seen in Covid 19.
The cytokines IL2, IL7, and IL 10 have shown abnormality in ME CFS, Covid 19 and SARS . Abnormalities have been seen in other immune mechanisms; Toll-like receptors (TLRs), chemokine receptors (CCRs) and death receptor ligands in Dendrytic cells have been seen in all three conditions.
The etiology of ME CFS is not apparent consideration of viral exposure due to Epstein Barr Virus (EBV), Human Herpes Virus 6 (HHV6), Cytomegalovirus (CMV), Parvo virus B19, and coxsackie B virus have been researched.
It is now obvious that prolonged Massive fatigue can follow viral exposure and previous skepticism should be allayed.

Figure 1 Positive findings in the conditions

Symptom SARS 2003 Covid 19 ME CFS
————————————————————————————
Fever + + +*
Dyspnea + + +/-
Fatigue + + +
Muscle pain , body ache + + +
sore throat + + +
lymphadenopathy + + +
loss of taste/ smell +
abnormal lymphpocyte + + +
abnormal cytokines + + +
abnormal immune resp + + +
Brain Fog + + +
POTS + + +

* patients with ME CFS feel "hot" but when temperature is taken the temperature is within normal range
POTS Postural Orthostatic Tachycardia Syndrome

refs.  
1 Muge Cevik, Krutika Kuppalli, Jason Kindrachuk,
Virology, transmission, and pathogenesis of SARS-CoV-2
BMJ 371 doi: https://doi.org/10.1136/bmj.m3862 , 23 October 2020);371:m3862
2 Francesco Sardanelli, Andrea Cozzi,Lorenzo Monfardini, Claudio Bnà, Riccardo Alessandro Foà, Angelo Spinazzola,Silvia Tresoldi, Maurizio Cariati,Francesco Secchi,and Simone Schiaffinoa Association of mediastinal lymphadenopathy with COVID-19 prognosis BMC Immunol Lancet Infect Dis. 2020 Nov; 20(11): 1230–1231
3 Sana Salehi , Aidin Abedi , Sudheer Balakrishnan , Ali Gholamrezanezhad
Coronavirus Disease 2019 (COVID-19): A Systematic Review of Imaging Findings in 919 Patients  AJR Am J Roentgenol 2020 Jul;215(1):87-93.
4 Ramsey, Melvin An Outbreak of Encephalomyelitis in the Royal Free Hospital , London, in 1955 Br Med J. 1957 Oct 19; 2(5050): 895–904.
5 Fukuda, K.; Straus, S. E.; Hickie, I.; Sharpe, M. C.; Dobbins, J. G.; Komaroff, A. et al (Dec 1994). ME criteria Annals of Internal Medicine. 121 (12): 953–959.
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7 Klimas NG, Broderick G, Fletcher MA. Biomarkers for Chronic Fatigue Brain Behav Immun. 2012 Nov;26(8):1202-10.
8 Chung Y. Cheung, Leo L. M. Poon, Iris H. Y. Ng, Winsie Luk, Sin-Fun Sia, Mavis H. S. Wu, Kwok-Hung Chan, Kwok-Yung Yuen, Siamon Gordon, Yi Guan, and Joseph S. M. Peiris Cytokine Responses in Severe Acute Respiratory Syndrome Coronavirus-Infected Macrophages In Vitro: Possible Relevance to Pathogenesis J Virol. 2005 Jun; 79(12): 7819–7826.
9 Broderick, G., Katz, B.Z., Fernandes, H., Fletcher, M.A., Klimas, N., Smith, F.A., O'Gorman, M.R., Vernon, S.D., Taylor, R. J Cytokine Expression Profiles of Immune Imbalance in Post-Mononucleosis Chronic Fatigue Transl Med. 2012 Sep 13;10:191.

Muge Cevik, Krutika Kuppalli, Jason Kindrachuk,
Virology, transmission, and pathogenesis of SARS-CoV-2
BMJ 371 doi: https://doi.org/10.1136/bmj.m3862 , 23 October 2020);371:m3862

Competing interests: No competing interests

30 October 2020
Derek Enlander
Physician
Mount Sinai Medical Center ,. New York
1035 Fifth Avenue New York 10028