A little over a month ago, I remember people sharing whatsapp videos about weird bat soups and some strange virus called coronavirus. Most of us scoffed at it, given that we knew very little about the proportions of the problem as reported by China. It was mid February where there was widespread knowledge about a lockdown in Hubei province and the rest as they say is history.
As of now, my brother, is on the front-lines in Barcelona. He works in the “Ultimo Paso” department since they were short of staff and few people were willing to work there. They’re dealing with a high mortality census, staff suicides and shortages of every kind. Their PPE equipment is handed down each shift to the next. It’s not a very good situation. Thankfully the military is helping in Spain. We’re down on our knees praying Spain (and everywhere else) can see the other side soon. So here’s what we now know about the Coronavirus.
He’s told me of how various doctors from Germany, Italy and France have shared information so that they prevent any mistakes they made. I’m not sure how the clinical decisions are made elsewhere in the world but I’m sure most doctors read individually and then form their own guidelines through trial and error.
To help my brother, I do a lot of reading and then we discuss treatment plans, variations in treatment strategy and clinical papers. I’m sharing some of what I’ve read with you.
Discovery of the Virus
The Chinese government’s military published its paper recently. According to the paper, the the 2019 novel coronavirus (2019-nCoV) was discovered in December 2019. Several pneumonia cases in quick succession caused concern and testing in Wuhan. They spoke of an epidemic. The World Health Organization (WHO) named it officially on 12 January 2020.
Not all the cases had a connection with the seafood testing where the first pneumonia cases came from but by mid January Wuhan had about 437 cases with ARDS and 80 deaths. That was enough to raise an alarm.
Host
It was suggested that bats might be the probable host. This was entirely due to the fact that it is similar to bat derived coronavirus or pangolin derived viruses. It has more than 85% homology with SARSr-CoV (bat-SL-CoVZC45). However, these are just probable sources. Researchers from the NIH have explained that the development of the virus has been similar to SARS and MERS. In that, it used an intermediate host like civets and camels to make the transition to humans. Now, it has mutated to attack a molecular feature outside the cell, namely the ACE 2 receptors. The ACE 2 receptors are abundant in the lungs and testes, which is probably why men seem to be having higher mortality rates.
Nextstrain, an independent, scientific open source group that shares pathogen genome data, suggests that there are 8 possible strains. The virus has mutated up an down, with cases showing three mutations away from the original Wuhan cases. You can see the phylogenetic trees and situation reports here. This would also partly explain why the virus has been more virulen in certain parts of the world and not others.
Transmission
Respiratory droplet transmission is the main route of transmission. Contact and human to human transmission. There have been so many cliams about sneezing and the distance of spread. 6 feet apart, 27 feet apart, but really I’m not sure if the distance apart really makes a difference. The CDC has changed its mind along with the WHO, but in its latest directive has asked people to wear masks to contain droplet spread.
Screening for Coronavirus
So suspected cases are screened by looking for any 2 of the following clinical features and any epidemiological risk:
(1) clinical features: fever, features of pneumonia on imaging, normal or decreased white blood cell count, or reduced lymphocyte count in the early stages of the disease onset.
(2) epidemiologic risk: This risk includes travel to a hotspot. I know in India and Kuwait, since they closed flights to all countries by mid February, epidemiological risk is very high on the screening checklist.
Cornfirmed cases are those with with one of the following:
(1) positive for the 2019-nCoV by the real-time PCR test for nucleic acid in respiratory or blood samples
(2) viral gene sequencing shows highly homogeneity to the known 2019-nCoV in respiratory or blood samples.
Whether you’re using the oral swab or the NP swab, the research is very thin on which is more sensitive. German scientists have tried to compare them but it’s unclear if the primer is the same or not. Either way, real-time RT-PCR (RdRp gene) assay is the preferred screening. With constant mutations, it’s not definite if the testing in different countries is accurate or sensitive enough.
Prevention
So close contacts of all the confirmed cases have to be careful.Once fever, respiratory symptoms such as coughing, shortness of breath, or diarrhea, develop they should speak to their doctors immediately. Contact surveillance is being advocated and has been successful in many countries including Taiwan and South Korea. Of course, these were countries had reported many deaths with SARS in 2003 and MERS and had effective plans long put in place to deal with a future flu like situation.
Diagnosis of Coronavirus
Most cases have symptoms like fever, fatigue, dry cough, dyspnea with or without nasal congestion. They are upper respiratory symptoms. Atypical symptoms have been reported in various case series including conjunctivitis and diarrhea.
On physical exam, mild cases may not have any signs. Severe cases may have dyspnea, soft rales in lungs, weakened breath sounds, dullness to percussion, and increased or decreased speech tremor.
Imaging varies according to age, immunity status, disease stage, underlying diseases, and drug interventions.
However, typical imaging features include:
(1) general distribution often subpleural, especially along the bronchial vascular bundles;
(2) more than three or more lesions;
(3) patchy, large block, nodular, lumpy, honeycomb-like or grid-like, depending on the stage;
(4) uneven density and interlobular septal thickening, consolidation and thickened bronchial wall; and
(5) concomitant signs vary could be rare pleural effusion and mediastinal lymph nodes enlargement.
CT Staging
CT demonstrates five stages of the virus. And right now this seems to be best instrument to diagnose where on the curve your patient lies.
1. Ultra-early stage: Patients without clinical manifestation, negative laboratory test but positive throat swab for 2019-nCoV within 1–2 weeks after being exposure. Imaging shows single, double or scattered focal ground-glass opacity, nodules located in central lobule surrounded by patchy ground-glass opacities, patchy consolidation and intra-bronchial air-bronchogram, in the middle and lower pleura.
2. Early stage: This stage lasts 1–3 days after fever, cough, dry cough. On imaging you see, dilatation and congestion of alveolar septal capillary, fluid exudates in alveoli and interlobular interstitial edema. There are single or multiple scattered patchy or agglomerated ground-glass opacities, separated by honeycomb-like interlobular septa.
3. Rapid progression stage: About 3–7 days after clinical manifestations start. There’s accumulation of cell-rich exudates in the alveolar cavity, vascular expansion and exudation in the interstitium. The fibrous exudate connects each alveolus through the inter-alveolar space causing them to fuse.
4. Consolidation stage: Around 7–14 days after clinical manifestations. On imaging, there are fibrous exudates of the alveoli and the disappearance of capillary congestion in the alveolar wall. CT imaging shows lesser multiple patchy consolidations.
Dissipation stage: Between 2 and 3 weeks after the onset of clinical manifestations. Lesions were further reduced. CT imaging shows patchy consolidation or strip-like opacity.
At George Washington University Hospital, they’ve used 3D reconstruction to demonstrate lung damage.
Since I like AI based tools, I had to look up if there was something for coronavirus. NYU Langone has used AI algorithms with some success. Although, it’s early days. The AI tool found three important feature changes: levels of the liver enzyme alanine aminotransferase (ALT), reported myalgia, and increased hemoglobin levels. Age and gender didn’t help.
Testing Coronavirus
In addition to antigens and hematology, other diagnostic tests include blood gas analysis, liver and kidney function, myocardial enzyme, myoglobin, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Procalcitonin (PCT), lactate, D-dimer, coagulation image, urine routine test, inflammatory factors (interleukin(IL)-6, IL-10, TNF – α), items of tuberculosis (TB) subgroup, complement, anti-acid staining.
Treatment
1.Bed rest, monitor vital signs (heart rate, pulse oxygen saturation, respiratory rate, blood pressure). Supportive treatment to ensure sufficient energy intake and balance for water, electrolytes, acid-base levels.
2. Monitor routine blood, CRP, PCT, organ function (liver enzyme, bilirubin, myocardial enzyme, creatinine, urea nitrogen, urine volume, coagulation function, arterial blood gas analysis and chest imaging
3. Oxygen therapy, including nasal catheter, mask oxygen, high flow nasal oxygen therapy (HFNO), non-invasive ventilation (NIV) or invasive mechanical ventilation.
4. Extracorporeal Membrane Oxygenation (ECMO) should be considered for the patients with refractory hypoxemia.
At present, there are no RCT’s to support specific drug treatment against the new coronavirus in suspected.
What’s been tried:
1.The α-interferon atomization inhalation can be considered (5 million U per time for adults in sterile injection water, twice a day);
2. Lopinavir/ritonavir orally, 2 capsules each time, twice a day, can be also considered.
3. An RCT is underway with Vitamin C. 12g Vitamin C will be infused in the experimental group twice a day for 7 days by the infusion pump with a speed of 12ml/h
4. Certain molecule compounds like Ribavirin and Chloroquine have a 60% structural match to antivirals that can have potential use against Coronavirus.
5. Camostat, a serine protease inhibitor has been shown by German scientists to block the entry of the coronavirus through the ACE2 receptor.
6. Avoid blind use of antibacterial drugs. Give appropriate antibacterial drugs when there’s secondary bacterial infection. This is so important because as my own brother reported, most of the patients die from secondary infections. Some of the autopsy reports come back with bowel infections or urine infections as cause of death. And that’s the problem, the body is too weak to fight off an infection, sometimes failing to defend itself from it’s own flora.
7. The use of corticosteroids for severe ARDS is controversial. Methylprednisolone can be used for patients with rapid disease progression or severe illness at 40 to 80 mg of methylprednisolone per day. Total daily dose should not exceed 2 mg/kg.
8. SARS management showed that use of non-invasive continuous positive airway pressure and corticosteroids is an effective strategy for increased lung shadows and increased dyspnea. There’s a lot of debate here. Some suggest it’s pointless since it increases oxygenation and work of breathing but does not help with viral clearance. Others suggest it helps. In Italy, they seemed to be claiming better results.
9. Symptomatic treatment of fever if higher than 38.5 ℃, ibuprofen can be used for antipyretic (oral, 0.2 g per time, it can be used every 4–6 h) till temperature below 38 ℃.
10. Nutrition support treatment. Inpatients are screened for nutrition risk based on the NRS2002 score when they are admitted to the hospital. It is recommended to increase protein intake by oral nutrition supplement, 2–3 times/day (≥ 18 g protein/time).
11. Reduce the incidence of stress ulcers and gastrointestinal bleeding. Use receptor antagonists or proton pump inhibitors in patients with GI bleed bleeding risk factors. The risk factors include mechanical ventilation ≥48 h, coagulation dysfunction, renal replacement therapy, liver disease and other organ failure
12. Reduce respiratory secretions and improve the respiratory function. It is recommended to use selective (M1, M3) receptor anticholinergic drugs to reduce the secretion, relax the smooth muscle in airway, relieve airway spasm and improve the pulmonary ventilation. Postural positioning also helps to improve drainage of secretions.
13. Reduce the incidence of venous embolism and use low-molecular-weight heparin or heparin in high-risk patients without contraindications.
Criteria to withdraw ECLS
Researchers advise withdrawing ECLS when:
- Remove VV-ECMO when the oxygen concentration of the ECMO air-oxygen mixer has dropped to 21%, the air flow rate has dropped to 0, and the ventilator is not strong enough. If for 2–3 h, the respiratory rate is within 25 breaths/min, SpO2 > 92%, PaCO2.
- Remove VA-ECMO when he blood flow rate is reduced to 0.2 to 0.5 L / min every 5 to 6 h from 3 L/min. Additionally, the hemodynamic condition is stable. If hemodynamics are stable for at least 6 h, consider removing the machine.
Challenges with Coronavirus
1.Preventing nosocomial infections: We all know that ventilators are notorious when it comes to secondary infections. One of my mentors in medicine used to say, the goal for every patient is to get out of the hospital and get out fast.
2. The Lack of symptoms: People are contagious long before they have signs and symptoms. So we’re going to end up having to test everyone.
3. Reinfection rates: There have been articles of those who survived the first brush with Coronavirus getting reinfected.
4. Building Herd Immunity: I grew up with the strong surveillance of polio and its concepts. Occasionally, I’m critical too. So I’m a big supporter of building herd immunity which is why I think the response of South Korea, Taiwan, Sweden have appealed to me. Eventually, we’re going to have to come down to this. It’s not a matter of if, but a matter of when.
5. Healthcare burden: Its certainly a strain on the medical community and a big ask as a lot of them will be carriers to their own families. Hospitals are petri dishes where a shared air-conditioning and highly concentrated areas of the virus lurk. What’s the plan for them?
Final Thoughts
This is definitely history as it unfolds. It’s quite evident that we’re going to be facing challenging times ahead. What we do and how we do will depend on making long term plans while reviewing short term goals. Select governments have managed to learn from the past and prepare for the future.
Select governments have also measured their responses instead of having a daily goal. We need to be making long term plans. Alternatively, we should stop looking at projections and algorithms and focus on facts. We treat patients not numbers. The media needs to educate rather than create fear and panic. Viruses are ubiquitous. We have to survive and survive with a plan.
I’m sure I’ve left out many details even though I tried to be as comprehensive as possible. If you have a paper coming out or findings that you’d like to share, send it to me and I’ll update the article accordingly.
Stay Safe!