As of 7th April, in a small city with approximately 160,000 citizens, the confirmed COVID-19 + cases are 50. The mortality rate is 0.
The patients in my clinic were mainly those with respiratory diseases. There have been no confirmed COVID-19 cases.
Some patients had fevers. With the therapeutic strategy in line with several previous posts, there have been no confirmed cases of COVID-19 yet. Even several patients with fevers and bronchitis who dropped out of screening hospitals concerning COVID-19 without testing recovered without the aggravation of respiratory diseases. About the reason why they were dropped out of COVID-19 test even with fevers, has not it known.
The therapeutic drugs administered did NOT include hydroxychloroquine and azithromycin.
The taken home message is that primary care in the early phase of respiratory diseases amid COVID-19 contagion is a key factor to a key factor to prevent the patients from being vulnerable to COVID-19.
Early diagnosis, Early treatment!
P.S.
In some patients with neurologic signs, including headache, alteration of smell and taste and oral mucosa, acyclovir was prescribed simultaneously as I posted.
Casanova et al demonstrated fecally contaminated liquid droplets of SARS cases are a potential vehicle for contagion besides respiratory droplets. This study reported that SARS coronaviruses remained infectious in water and sewage for days to weeks.[1]
For this reason, waterborne infection of COVID-19 coronaviruses should be checked meticulously to prevent further spread of COVID-19.
In addition to facial masks for blocking respiratory droplets, drinking water should be sterilized. At home, we must boil water or mix bitter herbs or lemons with water before drinking.
The government should pay attention to sterilize water supply source.
REFERENCE:
Casanova L, Rutala WA, Weber DJ, Sobsey MD. Survival of surrogate coronaviruses in water. Water Res. 2009 Apr;43(7):1893-8.
Conventional coronavirus is known as an ss(single-stranded) RNA virus. Its incubation period is 2 ~ 5 days, whereas novel coronavirus is 4 ~ 14 days and SARS one is 2 ~ 7 days.
As supportive evidence of the incubation period of novel coronavirus longer than that of SARS coronavirus, there was a report three persons recovered from COVID-19 still had positive RT-PCR results for novel coronaviruses, even without symptoms and contagion into nearby family members.[1]
Its clinical implication has not been solved.
Despite novel coronaviruses are similar to SARS ones, why is the incubation period of novel coronaviruses longer than SARS ones?
What are the factors to explain the above phenomena?
In SARS, viral shedding is the nonlytic release of the vast majority of mature virions into the extracellular space via the Golgi apparatus from the ER.[2]. If novel coronavirus behaves in this way, the incubation period may be similar to that of SARS coronavirus.
If so, there must be the other pathway for viral shedding and replication to be continued except for the extracellular space, namely the intracellular space.
Which compartment of the intracellular space is probably suitable for viral shedding and replication?
The author supposes that the isolated hidden place for introverted viral shedding into the cell may be an intranuclear space, for the vast majority of viral release happens on the extracellular cytoplasmic border, as aforementioned.
The author infers the answer from the point that the main target cell organelle by novel coronavirus is endoplasmic-reticulum(ER).
Among four main proteins in coronaviruses, N protein forms a complex by binding to genomic RNA and M protein triggers the formation of interacting virions in this endoplasmic reticulum-Golgi apparatus intermediate compartment(ERGIC) with this complex.[3][4]
The characteristic electron microscopic findings of the alveolar epithelial cells in SARS cases are markedly dilated rough endoplasmic reticulum(RER) and smooth endoplasmic reticulum(SER).[5]
Uniquely, there was a comment on the membranous inclusion bodies in some nuclei.[5]
Considering the genetic & electron microscopic similarity of novel coronavirus to SARS coronavirus, the chance for nuclear inclusions to occur is high.
About the structure of nuclear inclusions, the reference journal did not include the related figure, and we can not clearly describe the electron microscopic feature to explain viral shedding into the intra-nuclear space.
Instead, the electron microscopic finding of nuclear inclusions in the cells may be an alternative tool to explain why nuclear inclusions in novel coronaviral infected cells can be a hidden reservoir for persistent viral replication.
About the detailed structure of nuclear inclusion, that in pituitary adenoma may be appropriate for a comparable explanation.
The nuclear inclusion in pituitary adenoma is composed of the ER-rich cytoplasm within the cell nucleus.
Yang et al(2003) analyzed the genesis of nuclear inclusion as the result of intracytoplasmic invagination into the nucleus. [6]
A part of the outline of the nuclear inclusion is composed of a double-layered membrane at the locus between the nucleus and the cytoplasm. Its origin can not be proved to be from whether ER or nuclear membrane.
The point is that nuclear inclusion includes ER-rich cytoplasmic components, which is continuous with the ER on the cytoplasmic side.
The author thinks that this nuclear inclusion with ER-rich cytoplasmic component can be a reservoir for persistent viral replication even during viral release into the extracellular space and cell division.
Despite the detrimental cytolytic cytotoxicity in COVID-19 cases, the presence of the long incubation period of novel coronaviruses can be explained by this hypothesis.
Hence, further research for novel coronaviruses should be performed to investigate the presence of nuclear inclusions in COVID-19 cases.
P.S.
If nuclear inclusions in COVID-19 cases will be found, please correspond to me about the next step for therapeutic strategy.
REFERENCE:
[1] Lan L, Xu D, Ye G, et al. Positive RT-PCR Test Results in Patients Recovered From COVID-19. JAMA. Published online February 27, 2020.
[2] Denison MR. CORONAVIRUS RESEARCH: KEYS TO DIAGNOSIS, TREATMENT, AND PREVENTION OF SARS. In: Institute of Medicine (US) Forum on Microbial Threats; Knobler S, Mahmoud A, Lemon S, et al., editors. Learning from SARS: Preparing for the Next Disease Outbreak: Workshop Summary. Washington (DC): National Academies Press (US); 2004.
[3] de Haan CA, Masters PS, Lili Kuo, Harry Vennema, Peter JM, Rottier. Coronavirus particle assembly: primary structure requirements of the membrane protein. J Virol. 1998; 72: 6838-6850.
[4] Escors D, Ortego J, Enjuanes L. The membrane M protein of the transmissible gastroenteritis coronavirus binds to the internal core through the carboxy-terminus. Adv Exp Med Biol. 2001; 494: 589-593.
[5] Ding Y, Wang H, Shen H, Li Z, Geng J, Han H, Cai J, Li X, Kang W, Weng D, Lu Y, Wu D, He L, Yao K. The clinical pathology of severe acute respiratory syndrome (SARS): a report from China. J Pathol. 2003 Jul;200(3):282-9.(PDF free download)
[6] Yang SW, Yang KM, Kang Hy, Kim TS. Intranuclear cytoplasmic pseudoinclusions in pituitary adenomas. Yonsei Med J. 2003 Oct 30;44(5):816-20.(PDF free download)
Chapter 12 of Exodus in Bible reports on Passover day. Here God ordered the Israelite to avoid disaster on Passover day.
Chapter 12: verse 12th and 13th of Exodus, Bible says, "12on that same night I will pass through Egypt and strike down every firstborn - both men and animals - and I will bring judgment on all the gods of Egypt. I am the LORD.13The blood will be a sign for you on the houses where you are; and when I see the blood, I will pass over you. No destructive plague will touch you when I strike Egypt" (Figure 1).
The Passover means the disaster skipped the Israelite who kept the orders of God.
God orders the Israelite to paint the blood of lamb or goat on the sides and tops of the doorframe.
Why did God order this?
I interpreted this question medically. In terms of pathology, my opinion on these two problems is as follows;
Blood color varies from red to dark purple according to oxygen saturation. The main component of blood hue is caused by RBC (Red Blood Cell). When oxygen is rich in blood, blood color is red by binding O2to iron in hemoglobin. Conversely, when oxygen is deficient, blood hue is dark purple. When we have cut wound in the skin, the blood coagulates slightly sticky. This occurs mainly by the fibrin component. The fibrin particles are interlocked and form chains of fibrin, a structure of meshwork (Fig.2.). This meshwork structure filters blood cells, especially platelets and RBCs. All this process leads to blood coagulation. The characteristics of the fibrin component endow the blood glutinous.
Sticking nature of blood by fibrin and blood other components, namely viscous force, makes blood to acquire the filtering power to capture fine dust of air including microorganisms (bacteria and virus particles).
This may dilute the density of microbial pathogen particles.
As a principle of vaccine, the diluted amount of microbial pathogens may work as an immune-boosting effect rather than causing disease.
In this situation, I infer the people who did not paint blood on the doorframe may inhale contaminated air and be exposed to the infectious state. In contrast, people, namely the Israelites who paint blood on the doorframe, may inhale the air of diluted infectious microbial particles, which worked as a vaccine effect.
Furthermore, God designates that doorframe painting with blood should be done at night (Exodus, chapter 12; verse 6th:Take care of them until the fourteenth day of the month, when all the people of the community of Israel must slaughter them at twilight). To keep the viscosity of blood, the blood should preserve the liquidness. The liquid state may most be maintained at the cool state. The cool state in a day may be kept at the night time after sunset.
For the above reason, I infer God ordered blood paint on the doorframe at night in a day.
Copyright (C-2013-017025)PASSOVER DAY – Medical Interpretation by a Pathologist – (English)
Facial Mask in the year 2020:
As of March. 2020, novel coronavirus infection is pandemic. As a primary preventive method, the importance of the facial mask is raised. The author thinks that the facial mask may play a role in decreasing the number of viral droplets in inflowing air like the doorframe painted with blood in Passover.
