Laboratory abnormalities in patients with COVID-2019 infection.
(NOTE The Hemoglobin)!!!
March 2020
Clinical Chemistry and Laboratory Medicine
DOI:
10.1515/cclm-2020-0198
Lab:
Mario Plebaniâs Lab
The currently available data suggests that many laboratory parameters are deranged in patients with COVID-19, and some of these may also be considered significant predictors of adverse clinical outcomes. The most frequent abnormalities were lymphopenia (35â75% of cases), increased values of CRP (75â93% of cases), LDH (27â92% of cases), ESR (up to 85% of cases) and D-dimer (36â43% of cases), as well as low concentrations of serum albumin (50â98% of cases) and hemoglobin (41â50%). Many laboratory abnormalities were instead predictive of adverse outcome, including increased white blood cell count, increased neutrophil count, decreased lymphocyte count, decreased albumin, increased LDH, ALT, AST, bilirubin, creatinine, cardiac troponins, D-dimer, prothrombin time, procalcitonin and CRP values.
My personal approach for home sanitization of masks. Microwave Sterilizer Bag for Steam âNewKleeAreâ zapping masks. At 60ml water. Reuse up to 30 times. 1.5 to 3 minutes for 800 to 110 Watt Microwaves. Several brands available. See prior posts for CDC and related references for encapsulated virus sterilization recommendations.
Will try zapping one with strip when sweetie is out in the garden in case it arcs over.
Preprint not peer reviewed
COVID-19: Attacks the 1-Beta Chain of Hemoglobin and
Captures the Porphyrin to Inhibit Human Heme Metabolism
Wenzhong Liu
1,2,*, Hualan Li2
1 School of Computer Science and Engineering, Sichuan University of Science & Engineering, Zigong, 643002, China; 2 School of Life Science and Food Engineering, Yibin University, Yibin,644000, China; * Correspondence: liuwz@suse.edu.cn;
Abstract
"The novel coronavirus pneumonia (COVID-19) is an infectious acute respiratory infection caused
by the novel coronavirus. The virus is a positive-strand RNA virus with high homology to bat
coronavirus.
In this study, conserved domain analysis, homology modeling, and molecular docking were used to compare the biological roles of certain proteins of the novel coronavirus. The results showed the ORF8 and surface glycoprotein could bind to the porphyrin, respectively.
At the same time, orf1ab, ORF10, and ORF3a proteins could coordinate attack the heme on the 1-beta chain of hemoglobin to dissociate the iron to form the porphyrin. The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide.
The lung cells have extremely intense poisoning and inflammatory due to the inability to exchange carbon dioxide and oxygen frequently, which eventually results in ground-glass-like lung images.
The mechanism also interfered with the normal heme anabolic pathway of the human body, is expected to result in human disease.
According to the validation analysis of these finds, chloroquine could prevent orf1ab, ORF3a, and ORF10 to attack the heme to form the porphyrin, and inhibit the binding of ORF8 and surface glycoproteins to porphyrins to a certain extent, effectively relieve the symptoms of respiratory distress. Favipiravir could inhibit the envelope protein and ORF7a protein bind to porphyrin, prevent the virus from entering host cells, and catching free porphyrins.
Because the novel coronavirus is dependent on porphyrins, it may originate from an ancient virus. Therefore, this research is of high value to contemporary biological experiments, disease prevention, and clinical treatment. "
Keywords: Novel Coronavirus; Respiratory distress; Ground-glass-Like Lung; E2 glycoprotein; ORF8; orf1ab; chloroquine; Blood; Diabetic; Fluorescence resonance energy transfer; Ancient virus; Cytokine Storm
https://s3-eu-west-1.amazonaws.com/pstorage-chemrxiv-899408398289/22129965/covid19202000328EN1.pdf
Hmmm. High volume O2 vs low pressure intubation. hemoglobinopathy??
"The thinking at that time, which was just a few weeks ago but feels like a different era, was that COVID-19 patients who required more than low-flow oxygen were going to progress to mechanical ventilation anyway, so you might as well skip the intervening steps. Furthermore, there was a lot of concern that high-flow nasal cannula and noninvasive ventilation would propel the patientâs virus-rich aerosols into the room, potentially infecting other patients and healthcare providers.
So, like everyone else, we adopted the âintubate earlyâ paradigm, and sent this first round of sick coronavirus patients to the ICU on a ventilator. But the sick patients started arriving in bigger numbersâin one shift we intubated six patientsâand it became clear that if we kept this up, we were going to run out of ventilators and ICU beds by the end of the week. On top of this, we were starting to get early studies out of China and Italy that showed alarmingly poor outcomes of patients on ventilators. Was intubate-early the right strategy?
Around this time, many of us started to notice an unusual phenomenon in people with COVID-19 lung disease. Every patient seen in the emergency department has their oxygen saturationâa marker of how completely blood is carrying oxygen to the tissuesâmeasured at triage, using a device that fits over the finger, a pulse oximeter. A normal saturation is above 95 percent. Some COVID-19 patients, however had the kind of very low saturations that we associate with cyanosis and respiratory distressâbut they were comfortably speaking to us or texting on their phones.
Nobody knows what to make of this, and this observation is so new that we donât yet know how patients who are âhappily desaturatedâ will fare. But it is very disorienting, because we rely heavily on oxygen saturation to determine how sick our patients are. Some have speculated that the virus causes a change in the molecule that carries oxygen (a hemoglobinopathy) that could confound pulse oximetry. Others suggest that COVID-19 mimics physiology seen at high altitudes, or pulmonary decompression sickness, when a diver ascends to the surface too rapidly.
Once a few of these anecdotes circulated, social media was flooded with them, and this has added another layer to the quandary: not only are we uncertain about when to intubate COVID-19 patients; one of the most important parameters we use to decide when to intubate seems in this disease to be deceiving us, for reasons no one yet understands."
Why Hydroxychloroquine may have a beneficial effect. Apparently on of the viral impact is attack of poryphin and the hemoglobin model as evidenced by low hemoglobin levels and O2 saturation on non respiratory distressed patients. The HQC attaches to the hemoglobin molecule and inhibits the virus from attaching and destroying the cage around the Fe2+ and Fe3+ molecules that transport the O2 and Co2 in and out of the lungs.
Trans Am Clin Climatol Assoc. 1998; 109: 97â106.
PMCID: PMC2194336
PMID: 9601131
Involvement of heme in the antimalarial action of chloroquine.
C. D. Fitch
When malaria parasites digest hemoglobin, they release FP intracellularly. FP is an oxidized form of heme which is toxic for biological membranes. The parasites are not poisoned when they digest hemoglobin, however, because they sequester FP in hemozoin. In fact, the refractile, dark brown substance in hemozoin is sequestered FP. Chloroquine binds tightly to nonhemozoin FP and, under certain circumstances, enhances its toxicity. In addition, chloroquine interferes with FP sequestration and causes toxic nonhemozoin FP to accumulate to lethal levels in erythrocytes parasitized with malaria parasites. Evidently, this is how chloroquine kills malaria parasites. It is desirable, therefore, to know more about FP sequestration and how it is affected by chloroquine. Malaria parasites possess a catalyst for FP sequestration which is modulated by treatment with quinoline antimalarial drugs such as chloroquine and quinine. Chloroquine treatment causes the activity of the catalyst to decrease by 80 to 90 percent. Quinine treatment has no obvious direct effect on the catalyst for FP sequestration. Nevertheless, quinine treatment antagonizes and reverses the chloroquine-induced loss of ability to sequester FP. The effect of chloroquine treatment also is antagonized by various metabolic inhibitors, including inhibitors of protein biosynthesis such as cycloheximide. These findings indicate that chloroquine, like quinine, does not interact directly with the catalyst for FP sequestration. Instead, they are evidence that chloroquine acts by increasing the amount, accessibility, or reactivity of a regulator of the catalyst for FP sequestration. I propose that chloroquine increases the amount of the regulator, which inactivates the catalyst for FP sequestration, which leads to accumulation of nonhemozoin FP, which binds with high-affinity to chloroquine and which ultimately kills the malaria parasite.
Trans Am Clin Climatol Assoc. 1998; 109: 97â106.
PMCID: PMC2194336
PMID: 9601131
Involvement of heme in the antimalarial action of chloroquine.
C. D. Fitch
Iâve posted some papers and blogs on hemoglobin issues with many Covid patients and seeming contradictions in high volume O2 vice intubation. Theory going around in EM doc circuits about why Sat. O2 is so low but still good pulmonary compliance and not in distress. May explain why HCQ and other VIT D etc may have an positive effect on viral damage to hemoglobin molecules. Science is engaged, truth will out! Please stand by.
When youâre making a grocery run and someone on the next aisle coughsâ:face_with_hand_over_mouth:
Cleaning and Disinfection for Households
Interim Recommendations for U.S. Households with Suspected or Confirmed Coronavirus Disease 2019 (COVID-19)
Linens, clothing, and other items that go in the laundry
Wear disposable gloves when handling dirty laundry from an ill person and then discard after each use. If using reusable gloves, those gloves should be dedicated for cleaning and disinfection of surfaces for COVID-19 and should not be used for other household purposes. Clean hands immediately after gloves are removed.
If no gloves are used when handling dirty laundry, be sure to wash hands afterwards.
If possible, do not shake dirty laundry. This will minimize the possibility of dispersing virus through the air.
Launder items as appropriate in accordance with the manufacturerâs instructions. If possible, launder items using the warmest appropriate water setting for the items and dry items completely. Dirty laundry from an ill person can be washed with other peopleâs items.
Clean and disinfect clothes hampers according to guidance above for surfaces. If possible, consider placing a bag liner that is either disposable (can be thrown away) or can be laundered.
https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/cleaning-disinfection.html
Presymptomatic Transmission of SARS-CoV-2
Stephen G. Baum, MD reviewing Wei WE et al. MMWR Morb Mortal Wkly Rep 2020 Apr 1
Transmission of the novel coronavirus SARS-CoV-2 can occur before symptom onset in the infector and is a confounding phenomenon in efforts to contain spread.
Transmission of respiratory pathogens from asymptomatic persons to recipients no doubt occurs in many types of infection. For example, chickenpox is highly contagious several days before the classic rash erupts and is likely spread by varicella virus from the respiratory tract (although this has rarely been documented). As part of the current multifaceted exploration of the pathogenesis of the novel coronavirus SARS-CoV-2, researchers attempted to document whether this virus could be spread in the asymptomatic phase of infection. The subset of asymptomatic transmitters of infection they chose were patients who ultimately became symptomatic. Therefore, transmission from these patients was dubbed presymptomatic.
Investigation of all 243 cases of COVID-19 reported in Singapore from January 23 through March 16, 2020, revealed seven clusters of cases in which presymptomatic transmission seemed the most likely mode of spread. Detailed epidemiologic histories ruled out contact of the cluster members with any other source other than the person who was presymptomatic at the time of contact. Clusters contained from 2 to 5 patients each and involved such contact as churchgoing with common or proximate seating, common singing class, and transmission to a spouse or home partner after contact with a traveler. In 4 of the 7 clusters, exposure occurred 1 to 3 days before the source patient developed symptoms. In 157 of the 243 cases, local acquisition in Singapore was the cause.
SARS-CoV-2 persists in stool after respiratory samples test negative
Reuters Health News | March 25, 2020
SARS-CoV-2 viral RNA can persist in stool samples long after respiratory samples have tested negative for the virus that causes COVID-19, researchers report.
Dr. Xi Huang from Fifth Affiliated Hospital, Sun Yat-sen University, Zhuhai, Guangdong Province, China and colleagues collected respiratory and fecal samples from 74 patients with COVID-19 diagnosed by two sequential respiratory tract samples that tested positive for SARS-CoV-2 by RT-PCR.
Fecal samples from 33 patients (45%) were negative for SARS-CoV-2 RNA, while their respiratory swabs remained positive for a mean 15.4 days from first symptom onset.
Among the 41 patients (55%) with positive fecal and respiratory samples, respiratory samples remained positive for SARS-CoV-2 RNA for a mean 16.7 days and fecal samples remained positive for a mean 27.9 days after first symptom onset, according to the online report in The Lancet Gastroenterology and Hepatology.
One patient had positive fecal samples for 33 days continuously after the respiratory samples became negative, and another patient tested positive for SARS-CoV-2 RNA in their fecal samples for 47 days after first symptom onset.
Fecal sample viral positivity was not associated with the presence of gastrointestinal symptoms or with COVID-19 disease severity, but antiviral treatment was positively associated with the presence of viral RNA in fecal samples.
âAlthough knowledge about the viability of SARS-CoV-2 is limited, the virus could remain viable in the environment for days, which could lead to fecal-oral transmission, as seen with severe acute respiratory virus CoV and Middle East respiratory syndrome CoV,â the researchers note. âTherefore, routine stool sample testing with real-time RT-PCR is highly recommended after the clearance of viral RNA in a patientâs respiratory samples. Strict precautions to prevent transmission should be taken for patients who are in hospital or self-quarantined if their fecal samples test positive.â
SEE ALSO: FDA-approved drugs could help fight COVID-19
âDetermining whether a virus is viable using nucleic acid detection is difficult; further research using fresh stool samples at later timepoints in patients with extended duration of fecal sample positivity is required to define transmission potential,â they add.
Dr. Danson Xue Wei Yeo from Tan Tock Seng Hospital, Singapore, who recently reviewed the possibility of fecal-oral transmission of SARS-CoV-2, told Reuters Health by email, âIt is not surprising that the fecal viral RNA shedding pattern of SARS-CoV-2 is similar to that of SARS-COV. The surprising thing is that most of these patients do not have GI symptoms even though they have viral RNA in the feces.â
âFecal-oral transmission is still a strong possibility for SARS-COV-2, and proper hand hygiene must be emphasized,â he said. âWe should not let down our guard in patients who are discharged after treatment for COVID-19 and declared virus free, as they may still be shedding the virus in the feces.â
When itâs 5AM and the radio starts playing âIâve Got You Babeâ
Interesting review of biologicals
https://onlinelibrary.wiley.com/doi/full/10.1111/all.14221?af=R
Good discussion and differentiation.
Liu, J., Cao, R., Xu, M. et al.
Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro.
Cell Discov 6, 16 (2020). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting SARS-CoV-2 infection in vitro | Cell Discovery
"Clinical investigation found that high concentration of cytokines were detected in the plasma of critically ill patients infected with SARS-CoV-2, suggesting that cytokine storm was associated with disease severity.
Other than its direct antiviral activity, HCQ is a safe and successful anti-inflammatory agent that has been used extensively in autoimmune diseases and can significantly decrease the production of cytokines and, in particular, pro-inflammatory factors.
Therefore, in COVID-19 patients, HCQ may also contribute to attenuating the inflammatory response.
In conclusion, our results show that HCQ can efficiently inhibit SARS-CoV-2 infection in vitro. In combination with its anti-inflammatory function, we predict that the drug has a good potential to combat the disease. This possibility awaits confirmation by clinical trials.
We need to point out, although HCQ is less toxic than CQ, prolonged and overdose usage can still cause poisoning."
Follow up on Cardiovascular info
SPECIAL REPORT
ReninâAngiotensinâAldosterone System Inhibitors in Patients with Covid-19
Muthiah Vaduganathan, M.D., M.P.H., Orly Vardeny, Pharm.D., Thomas Michel, M.D., Ph.D., John J.V. McMurray, M.D., et al.
March 30, 2020
DOI: 10.1056/NEJMsr2005760