WHO recommends against the use of remdesivir in COVID-19 patients

By Dr Deepu Changappa Cheriamane

WHO has issued a conditional recommendation against the use of remdesivir in hospitalized patients, regardless of disease severity, as there is currently no evidence that remdesivir improves survival and other outcomes in these patients.

This recommendation, released on 20 November, is part of a living guideline on clinical care for COVID-19. It was developed by an international guideline development group, which includes 28 clinical care experts, 4 patient-partners and one ethicist.

The guidelines were developed in collaboration with the non-profit Magic Evidence Ecosystem Foundation (MAGIC), which provided methodologic support. The guidelines are an innovation, matching scientific standards with the speed required to respond to an ongoing pandemic.

Work on this began on 15 October when the WHO Solidarity Trial published its interim results. Data reviewed by the panel included results from this trial, as well as 3 other randomized controlled trials. In all, data from over 7000 patients across the 4 trials were considered.

The evidence suggested no important effect on mortality, need for mechanical ventilation, time to clinical improvement, and other patient-important outcomes.

The guideline development group recognized that more research is needed, especially to provide higher certainty of evidence for specific groups of patients. They supported continued enrollment in trials evaluating remdesivir.

Chest X Ray pattern in COVID 19

By Dr Deepu Changappa Cheriamane

Today in AIIMS grand rounds they have discussed  6 patterns of COVID on chest xray

Pattern 1 - Reverse Batwing 

Pattern 2 - Multifocal lower lobe predominant consolidation

Pattern 3 - Peribronchial rounded consolidations

Pattern 4 - Multifocal bilateral consolidations

Pattern 5 - Ball pattern or round pneumonia

Pattern 6 - Bilateral symmetrical diffuse lung involvement

Here is YouTube video on COVID grand rounds 

 

CDC releases new guidelines on Isolation and ending isolation in COVID 19

By Dr Deepu Changappa Cheriamane

People who have been confirmed with mild to moderate COVID-19 can leave their isolation without receiving a negative test, according to recently revised guidance from the Centers for Disease Control and Prevention.

Increasing evidence shows that most people are no longer infectious 10 days after they begin having symptoms of COVID-19. As a result, the CDC is discouraging people from getting tested a second time after they recover.

The CDC has said

“For most persons with COVID-19 illness, isolation and precautions can generally be discontinued 10 days after symptom onset and resolution of fever for at least 24 hours, without the use of fever-reducing medications, and with improvement of other symptoms,” 

For people who have tested positive but don't have symptoms, "isolation and other precautions can be discontinued 10 days after the date of their first positive RT-PCR test for SARS-CoV-2 RNA.

There are exceptions for the 10-day guidance, including people with compromised immune systems who may be infectious for a longer period of time.

The CDC also notes that virus fragments have been found in patients up to three months after the onset of the illness, although those pieces of virus have not been shown to be capable of transmitting the disease.

“You could be positive by PCR test long after no longer being infectious,”

A PCR or polymerase chain reaction test detects coronavirus genetic material that’s present when the virus is active. Clinicians typically collect a nasal or throat sample from someone with a long nasopharyngeal swab.

Joseph Petrosino, the chair of virology and microbiology at the Baylor College of Medicine, said: “ I think one of the nice things about the CDC recommendation was that they pulled together a lot of data from a lot of different places from around the world that show that a lot of these long-term shedders are not associated with new infections or virus transmission.”

The recommendation of 10 days is specifically for those who test positive for the coronavirus and have been asked to self-isolate. It doesn’t apply to people who need to quarantine to keep from possibly spreading the virus. The incubation period for the virus is 14 days, health experts say, so anyone who has been exposed to the virus would need to quarantine to see if they become sick.

Most people who are infected develop symptoms after about five days, although approximately 20 to 40 percent who are infected don’t develop any symptoms.

COVID19 Treatment

By Dr Deepu Changappa Cheriamane

Treatment

No specific treatment or vaccine exists for COVID-19 (July 2020). Therefore resources have been concentrated on public health measures to prevent further interhuman transmission of the virus. This has required a multipronged approach and for individuals includes meticulous personal hygiene, social distancing, the avoidance of large crowds/crowded environments and where necessary, self-isolation.

In healthcare facilities, concerted efforts are required to effect rapid diagnosis, quarantine infected cases and provide effective supportive therapies. This will encompass empirical treatments with antibiotics, antivirals, and supportive measures.

Mechanical ventilation, both invasive and non-invasive, and extracorporeal membrane oxygenation (ECMO) have also been used where clinically necessary.

Proning

Historical studies have demonstrated a net benefit for patients with moderate to severe ARDS being turned prone. Many health care facilities have adopted the practice of turning the sicker COVID-19 patients into a prone position, so-called "proning" to improve their lung oxygenation.

Antiviral therapy

Whilst specific antiviral therapies for SARS-2-CoV do not currently exist, the combination of the protease inhibitors, ritonavir, and lopinavir, or a triple combination of these antiviral agents with the addition of ribavirin, showed some success in the treatment of SARS, and early reports suggested similar efficacy in the treatment of COVID-19. However, a more recent randomized, controlled open-label trial failed to demonstrate any added benefit of lopinavir-ritonavir combination therapy.

Remdesivir, a drug originally developed to treat Ebola virus and shown to be effective against MERS-CoV and SARS-CoV, showed promising in vitro results against SARS-CoV-2. A preliminary trial in May 2020 showed a significant decrease in time to recovery, from 15 to 11 days, in those treated with remdesivir. Other antivirals in phase III trials include oseltamivir, ASC09F (HIV protease inhibitor), lopinavir, ritonavir, darunavir, and cobicistat.

Dexamethasone, was demonstrated in the large RECOVERY (Randomized Evaluation of COVid-19 thERapY) randomized controlled trial, in June 2020 to decrease deaths by a third in those on mechanical ventilation (p=0.0003), and by a fifth those non-ventilated patients requiring oxygen (p=0.0021). No benefit was seen in those not needing respiratory support.

In early 2020, published reports showed that two antimalarial drugs, chloroquine, and its close chemical derivative, hydroxychloroquine, had strong anti-SARS-2-CoV activity in vitro. An initial open-label, randomized clinical trial, demonstrated a significant reduction of viral carriage, and a lower average carrying duration in patients treated with hydroxychloroquine. Furthermore, a combination with the antibiotic azithromycin resulted in a synergistic effect. However this trial was later strongly criticized for methodological flaws and questionable conclusions. Later studies have failed to replicate beneficial effects of these agents and also highlight potential side-effects.

Passive immunity

Treatment with convalescent plasma (plasma from patients who have recovered from COVID-19 which therefore contains anti-SARS-CoV-2 antibodies) or hyperimmune immunoglobulin (purified antibodies prepared from convalescent plasma) has shown some success in some critically ill patients. Reports are still preliminary and about a small number of patients. A Cochrane review in May 2020 failed to find convincing evidence that convalescent plasma was an effective treatment, but this will be kept under active review.

Vaccines

The primary target in developing coronavirus vaccines has been the spike protein (S protein) which is on the surface of the virion particle, and in vivo is the most important antigen for triggering an immune response. Human vaccines for coronaviruses have been under development since the SARS outbreak, but none are yet available. Over 125 vaccine candidates are now in preclinical trials.

NSAIDs

Emerging expert opinion is that non-steroidal anti-inflammatory drugs (NSAIDs) are relatively contraindicated in those with COVID-19. This is based upon several strands of "evidence":

since 2019 the French government National Agency for the Safety of Medicines and Health Products has advised against the routine use of NSAIDs as antipyretic

previous research has shown that NSAIDs may suppress the immune system 

anecdotal reports from France suggest that young patients on NSAIDs, otherwise previously fit and well, developed more severe COVID-19 symptoms

However, it is important to note that there is currently (March 2020) no published scientific evidence showing that NSAIDs increase the risk of developing COVID-19 or worsen established disease. Also, at least one report shows antiviral activity by indomethacin (an NSAID) against SARS-CoV (cause of SARS).

Prognosis

Progressive deterioration of imaging changes despite medical treatment is thought to be associated with poor prognosis. There is an increased risk of death in men over the age of 60 years old. The mortality rate is estimated to be 3.6%.

Early reports show that in some well patients, the RT-PCR test remains falsely positive despite an apparent clinical recovery. This raises the concern that asymptomatic carriage may occur.

Risk factors for severe illness or poor outcome

general

1. old age

2. people in a long-term care facility or nursing home

3. male gender

comorbidities

4. cardiovascular disease

5. diabetes mellitus

6. hypertension

7. chronic respiratory disease, e.g. COPD

8. cancer

9. chronic liver disease

10. chronic renal disease

11. immunosuppression

patient condition and laboratory values at hospital admission 

12. high sequential organ failure assessment (SOFA) score on admission

13. D-dimer levels greater than 1µg/mL on hospital admission

14. elevated levels of IL-6, troponin I, lactate dehydrogenase

15. lymphopenia

Pregnancy

In general, pregnant women do not have worse outcomes than non-pregnant women with COVID-19.. In a cohort of 427 women in the UK, 10% required a admission to critical care for respiratory support and 1% succumbed to the disease .

How to protect from Corona Virus.

By Dr Deepu Changappa Cheriamane.

Hi friends this was sent by my friend. As I found it interesting, I thought of sharing it here. Please read this and follow the rules. 

If any of you want credit for the same please let me know.

How to protect yourself from Coronavirus ? Tips for health care workers as an Infectious Diseases physician.

"The most important defense that is going to protect you from the Coronavirus is still common sense with some soap, and not the N95 mask !"

       

       If you have a habit of touching the face with your unsanitized hand, eating snacks with a lowered mask, repositioning the mask with pinching on the front side, then probably you are already infected. You are done!

    1. First, know your enemy-simple two rules-the virus spreads through air at a very close distance or through contact. All your moves will be based on this information with eternal vigilance with improvement in each moment. 

    2. First you need to relax; understand the mortality figures you see in the newspapers.

       The virus runs an asymptomatic course probably in the majority.(1)⁠ Imagine the virus is sprayed on 100 peoples’ nose. 60 of them will never develop any symptoms and out of the rest 40, 20 may develop severe symptoms requiring hospital admission and out of these last 20, one person dies. The hospital will report the ‘case fatality rate’ as 1/20= 5%. Note that only 20 reached the hospital to get the testing done. The actual risk of death is 1/100 which is called the ‘infection fatality rate’. Its very difficult to find the figure, as no body knows the asymptomatic infection rates. For the current Corona epidemic it is estimated(2)⁠ by mathematicians to be around 0.5%. So don’t worry, 99.5% of the time, odds are in favor. 

    3. Being a health care worker (HCW), are you at higher risk of complications compared to public ? Probably no. All the complications depends on your age, and not the number of the viruses that goes inside. No significantly different viral loads in nasal swabs were observed between symptomatic and asymptomatic patients with SARS Cov-2 infection.(3)

    4. During a cough or sneeze, salivary spray contain different types of particles. The larger respiratory ‘droplets’, are >5-10 μm, and travel only 3-6 feet due to their weight. The transmission through this is called ‘droplet transmission’. Very small ‘droplet nuclei’, <5μm in diameter, can remain suspended in the air for long periods of time and travel greater than 1 m- Airborne transmission.

       

       In an analysis by WHO and China of 75,465 COVID-19 cases in China, airborne transmission was not reported.(4)

       ⁠

       Now let the fear factor disappear, and you can think clearly and calmly about the defense.

       

    5. N95 vs Surgical mask vs cloth masks- choose the right shield at right time.

       Hence use a surgical mask when you are sitting in OPD or taking rounds, and N95 (to filter small droplet nuclei) only when you are doing or near to an aerosol generating procedure. Wear a cloth mask when you are in community, as the purpose is to prevent transmission from you. Use resources intelligently and effectively. You may require it for the big and long battle, just in case.

    6. Don’t underestimate the surgical mask. It was found good even when intubating.(5)⁠⁠

    7. Refrain yourself from lowering mask for making phone calls, while talking to your colleague, or inside your OPD. Refrain yourself from touching the front side. Refrain yourself from saying that the mask is suffocating (it is and will be; you need to compromise).

    8. When you remove the mask for taking a tea, remove the lower tie first. Don't touch the front side. Keep the mask inside your table drawer on a tissue paper, frontside down carefully. Practice hand hygiene after handling it- after removing or putting it back.

    9. Make sure that, all around you are using the mask properly. If a friend lowers his mask for chatting with you (with a sigh of relief on his face)  he is ready to shoot 3000 droplets in 5 minutes into air. Shoot him before that.

    10. Don’t go near your colleagues wearing mask with nose exposed, over the head, under the chin. Preach to them from a distance.

    11. Don’t go to canteen or mess room; bring food and eat inside your room or order food. Ask your nurse or assistant to eat inside your room too. Don’t talk during chewing.

    12. Practice hand hygiene after each patient. Ask your colleague to monitor you. Watch your colleagues and give feedback; they shouldn't get infected so that you also won’t.

    13. Inside the OPD, install a good exhaust fan. Maintain good air circulation inside the room. Keep the temperature of AC to the highest tolerable; droplet wont travel towards sky. They will settle on floor soon. Install an exhaust inside the toilet also.

    14. Corona can enter through eyes. Always wear a mask and an eye visor/ face shield right from the parking lot of hospital (personal recommendation).If you practice strict hand hygiene along with mask and visor for each and every patient, you will be in lowest risk, in case tomorrow if he turns positive (personal recommendation). Do not remove it even while talking to your friend or nurse.

    15. Avoid lift and take the stairs. If you are using lift, stay facing the walls keeping social distancing.

    16. Always insist all the patients to wear a mask.

    17. Tell the front desk to advise to wear mask to who ever calls for an appointment.

    18. Start a separate fever clinic at some corner of your hospital. A doctor with full PPE can see patients here. Arrange a separate pharmacy for them.

    19. Don't go near the patients every time, unless absolutely needed. Turn their head to opposite side while auscultating, taking blood pressure, giving injections or drawing blood.

    20. Limit the number of nurse visit to patients room by clubbing all the activities together- like checking vitals and delivering food and medicine.

    21. Minimize transport of the patient inside the hospital, check the PPE of the accompanied persons. 

    22. All other staff stay outside the operation room, while the patient is being intubated and extubated during anesthesia.

    23. Try to settle thing over phone as far as possible. Use Telemedicine. Don’t offer excuse; learn it.

    24. Maintain social distancing inside the hospital like the same poles of a magnet. The droplets travel at very close distance only.

    25. At home, don't go near your parents. Ask them to wear mask. If you happen to cross their path, keep your breath in slow inspiration.

Dr. Rakesh T Parakadavathu

Infectious Diseases consultant

Gimcare hospital, Kannur, Kerala, India

(As the information is evolving, please update it in comments, I can corrrect)

References

1. Day M. Covid-19: identifying and isolating asymptomatic people helped eliminate virus in Italian village. BMJ. 2020 Mar 23;368:m1165. 

2. Russell TW, Hellewell J, Jarvis CI, van-Zandvoort K, Abbott S, Ratnayake R, et al. Estimating the infection and case fatality ratio for COVID-19 using age-adjusted data from the outbreak on the Diamond Princess cruise ship. medRxiv. 2020 Mar 9;2020.03.05.20031773. 

3. D C, M T, F R, V D, M A, P P, et al. The early phase of the COVID-19 outbreak in Lombardy, Italy. 2020 Mar 20; 

4. Aylward, Bruce (WHO); Liang W (PRC). Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19). WHO-China Jt Mission Coronavirus Dis 2019. 2020;2019(February):16–24.

5. Ng K, Poon BH, Kiat Puar TH, Shan Quah JL, Loh WJ, Wong YJ, et al. COVID-19 and the Risk to Health Care Workers: A Case Report. Ann Intern Med. 2020 Mar 16;