118 CMAAO CORONA FACTS and MYTH BUSTER: Home Management Guidelines

118 CMAAO CORONA FACTS and MYTH BUSTER: Home Management Guidelines

Dr K K Aggarwal

President CMAAO

942: Minutes of Virtual Meeting of CMAAO NMAs on “Home Management Guidelines”

6^th June, 2020, Saturday, 9.30am-10.30am

Participants Member NMAs

Dr KK Aggarwal, President CMAAO

Dr Yeh Woei Chong, Singapore Chair CMAAO

Dr Ravi Naidu, Past President CMAAO, Malaysia

Dr N Gnanabaskaran, President Malaysian Medical Association

Dr Thirunavukarasu Rajoo, Hon. General Secretary, Malaysian Medical Association

Dr Alvin Yee-Shing Chan, Hong Kong

Dr Marie Uzawa Urabe, Japan

Dr Sajjad Qaisar, Pakistan

Dr Deborah Cavalcanti, Brazil

Dr Marthanda Pillai, Member World Medical Council

Dr Md Jamaluddin Chowdhary, Bangladesh

Dr Prakash Budhathoky, Nepal

Dr Subramaniam Muniandy, Malaysia

Invitees

Dr Russell D’Souza, UNESCO Chair in Bioethics, Australia

Dr KK Kalra, Former CEO NABH

Dr Sanchita Sharma, Editor IJCP Group

KEY DISCUSSION POINTS

1. Should doctors have the right to know their Covid status? When should they get themselves tested? Is there a policy in CMAAO countries in this regard?

·        India: There are four epicenters including Mumbai, Delhi. Doctors are not allowed to be tested, even if exposed to Covid positive patients, unless they are symptomatic. In Kerala, work for one week and then one week quarantine.

·        Bangladesh: Earlier, 14 days quarantine (with 6 days at home) after 10 days of duty. Now, 7 days of duty followed by 7 days quarantine (in hotel); during this time, if they test negative or Covid, then they are allowed to go home and can resume work after 7 days.

·        Malaysia: In the public sector, those who are directly involved in testing are tested; the occupational health dept. stringently monitors all those who do not have PPE and are directly involved in sampling and also treating patients. As a result, Covid hospitals have no cases o infection among healthcare workers (HCW). Clinics have to adhere to all SOPs issued by the govt. to prevent spread of infection.

25000 tests per day are being done; focused group testing. New cases are coming down; more cases in detention centers (illegal immigrants). Social distancing is being observed even by Malaysians. More than one million people use the App launched by the Govt. last month. Disease Prevention Act 1998 is being used to enforce screening. More businesses have opened up; companies have been strictly ordered to shut down for 2 weeks if they find a cluster of cases; if no RT PCR screening, then construction industry cannot open

·        Pakistan: 7 days of duty followed by 14 days quarantine; if they develop symptoms, then they are tested. If no symptoms, then they come back to work. After quarantine, if somebody wants to go home, they are allowed to do so for 5-7 days, with duty covered by another doctor for this duration.

·        Australia: Everyone who comes in contact with a positive patient even if asymptomatic or those working in hospitals are tested

·        Singapore: Criteria driven policy in this regard; doctors can get tested if they have been exposed to a patient and feel the need to be tested. If they have symptoms like fever, they will be tested. All doctors should be tested as healthcare resources should be protected.

·        Hong Kong: A new cluster of 4 confirmed cases in one day has been found in a resurgence of infection as there had been no cases for almost a month. There is apprehension of a second wave. Utensils for eating may be carriers. Exhaust fans may be the portal of infection. More testing is needed; currently it is 2000/day, which is far from adequate. Doctors are urged to get tested if they think they have symptoms. But, the fear of stigmatization is why many are reluctant to get tested. But, they use level 3 face masks and PPE even in cases of flu, allergies. Doctors in ICU or infectious diseases use N95 masks. So far, no infection among medical personnel in hospital or clinic setting has been reported.

2. What is that parameter or trigger, which is indicative of “point of no return” in Covid-19 patients? What has been the experience of CMAAO countries?

Hypothesis: The triggering factor in Covid-19 patients is silent hypoxia. So, do not neglect patients after fever resolves. Monitor SpO2 levels regularly.

If oxygen saturation falls, when walking/talking, this is the earliest sign of oxygen fall.

If level falls to ≤90, oxygen therapy will prevent or reduce mortality. Till a hospital bed is available, use an oxygen concentrator and monitor oxygen. Give one shot of LMWH.

·        Bangladesh: High flow nasal cannula is used to avoid ventilator, which are a scarce resource in the country

·        Singapore: Portable pulse oximeters have been issued to migrant workers in dormitories with directive to monitor oxygen twice daily; if oxygen falls below 93%, then shift to hospital

·        Hong Kong: No cases of deaths due to hypoxia; people in quarantine have been given pulse oximeters to monitor oxygen.

·        Pakistan: There are cases of hypoxia, which need oxygen therapy. There are isolation centers, where cases are managed only symptomatically and oxygen therapy, if needed. No ICU/ high-dependency unit (HDU) at these centers.

·        Nepal: 98% positive cases are asymptomatic and have been discharged without any intervention; few have symptoms like malaise, fever, dry cough; only symptomatic treatment. No experience with hypoxia, but will now impose in govt. guidelines

·        Japan: Very few reported cases of hypoxia. Asymptomatic and mildly ill patients are monitoring oxygen with oximeter thrice or four times daily. If oxygen is low, then ICU care.

3. Hydroxychloroquine+Azithromycin

·        Lancet has withdrawn its article on hydroxychloroquine, which said that HCQ had no benefit and was associated with increased risk of death.

·        Japan has treated 30 patients with hydroxychloroquine + azithromycin and the results have been very good.

·        This combination is used routinely in India. Some may use doxycycline instead of azithromycin. Doctors are taking HCQ as prophylaxis against coronavirus. The govt. has recommended the prophylactic use of HCQ.

4. Vaccines

mRNA and Adenovirus (Oxford) vaccines are doing well in phase I human trials.

5. Proposed strike in Hong Kong

Young doctors in Hong Kong are planning a strike against the new law. But this is a difficult time for all; hence, a strike at this time is the not the best thing to do.

117 CMAAO CORONA FACTS and MYTH BUSTER: With covid or from covid

117 CMAAO CORONA FACTS and MYTH BUSTER: With covid or from covid

Dr K K Aggarwal

President CMAAO

941: Are Patients Dying 'From' COVID or 'With' COVID?

Death certificates are supposed to be completed by the attending physician, who is expected to know the most about the patient's medical conditions but in a hospital setting, often the physician who pronounces death may never have seen the patient before.

The death certificate form requires that an immediate cause of death be listed first. This is followed by a list of underlying (also referred to as predisposing) conditions that were contributory.

In influenza for example a range of predisposing factors that could increase the risk for a serious complication from influenza, including death include an age of 65 years or older, pregnancy, chronic lung disease, heart disease, diabetes, and cancer.

In COVID-19 similar factors seem to predispose to a more serious outcome: older age, chronic lung disease, serious heart conditions, being immunocompromised, and living in a long-term care facility.

The US CDC website reports a provisional COVID-19 death count. This tally includes thousands of deaths attributed solely to COVID-19. A second category of deaths from both pneumonia and COVID-19 includes thousands more persons. A third category of deaths lists three causes: pneumonia, influenza, and COVID-19. There are separate categories for deaths due to pneumonia or influenza alone.

Most patients are not dying from influenza but rather with influenza that is comorbid with something else lethal.

In India the covid deaths are counted if the primary cause of death is written as COVID 19 and not as the underlying cause

Imagine the attending physician may write the same situation

Immediate cause of death: Uncontrolled diabetes with ketoacidosis

Underlying cause: Covid 19

Or  

Immediate cause of death:  Covid 19

Underlying cause: Uncontrolled diabetes with ketoacidosis

Both means the same but the statistics changes

114 CMAAO CORONA FACTS and MYTH BUSTER: VERTICAL Transmission

114 CMAAO CORONA FACTS and MYTH BUSTER: VERTICAL Transmission

Dr K K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

938:  Vertical Transmission of Novel Coronavirus

Clinicians in Italy report two cases of possible vertical transmission of SARS-CoV-2, the virus responsible for COVID-19, from the mother to the baby in utero.

This is the first report of cases of positive polymerase chain reaction (PCR) for SARS-CoV-2 in mother, neonate and placental tissues," Dr. Luisa Patane and colleagues of ASST Papa Giovanni XXIII in Bergamo write in the American Journal of Obstetrics and Gynecology - Maternal Fetal Medicine.

Between March 5 and April 21, two of 22 babies born to women with COVID-19 were PCR positive for SARS-CoV-2 in nasopharyngeal (NP) swab samples.

The first baby, a boy, was born vaginally after spontaneous labor at around 37 weeks' gestation to a mother who was experiencing fever and cough and had a positive SARS-CoV-2 NP swab. The mother wore a surgical mask during labor and delivery, skin to skin contact was not allowed, but rooming-in and breastfeeding with mask were allowed.

The baby had positive NP swabs immediately at birth, after 24 hours, and after seven days. He remained asymptomatic, except for mild initial feeding difficulties, and was discharged from the hospital at 10 days of life.

The second baby, a girl, was delivered by cesarean section at 35 weeks' gestation to a mother who had also had fever and cough and positive COVID-19 NP swab. The baby was immediately separated from the mother at birth and admitted to the neonatal intensive-care unit.

The baby had a negative NP swab at birth and a positive NP swab at day seven, with no contact between mother and neonate during that period. No neonatal complications were observed, only some feeding difficulties were reported in the first days of life; she was discharged at 20 days life 20.

In both cases, SARS-CoV-2 RNA was found in placental tissue.

The presence of SARS-CoV-2 RNA in the syncytiothrophoblast - the epithelial covering of the embryonic placental villi, which invades the wall of the uterus to establish nutrient circulation between the embryo and the mother - signifies presence of the virus on the fetal side, the clinicians point out.

Risk for congenital infection

Possible vertical transmission has been reported in several cases of peripartum maternal infection in the third trimester, suggesting congenital infection is possible but uncommon [1].

There are no accepted criteria for definitive evidence of congenital infection. Most take criteria proposed by Shah et al 2]. This system takes into account maternal symptoms and epidemiologic exposure, results of maternal testing, clinical status of the neonate at birth, and results of neonatal testing:

Symptomatic mothers are classified as confirmed SARS-CoV-2 infection (positive test), possible infection (no test), unlikely to be infected (negative test but no other cause for symptoms identified), or not infected (negative test and another cause for symptoms identified). Asymptomatic mothers with a positive contact history are classified as confirmed infection (positive test), unlikely to be infected (a single negative test), or not infected (two negative tests at different time points).

Congenital infection with intrauterine fetal death/stillbirth is confirmed if virus is detected by polymerase chain reaction (PCR) from fetal or placental tissue or electron microscopic detection of viral particles in tissue or viral growth in culture of fetal or placental tissue. Detection of virus by PCR from a fetal surface or fetal side of the placenta would be classified as possible infection. Infection would be unlikely if virus is only detected by PCR in surface swab from maternal side of placenta only and no testing done or no detection of the virus by PCR from fetal or placental tissue. Absence of infection would be based on no detection of the virus by PCR or by electron microscopy in fetal tissue(s) on autopsy.

Congenital infection in a live born infant depends on presence or absence of clinical features of infection in a newborn and mother with SARS-CoV-2 infection. In symptomatic cases, congenital infection is confirmed if virus is detected by PCR in umbilical cord blood or neonatal blood collected within first 12 hours of birth or amniotic fluid collected prior to rupture of membranes. In asymptomatic cases, neonatal infection is confirmed if virus is detected by PCR in cord blood or neonatal blood collected within 12 hours of birth. Criteria for probable, possible, unlikely, or noninfected also exist.

Neonatal infection may be acquired intrapartum. For symptomatic newborns of infected mothers, intrapartum infection is confirmed if SARS-CoV-2 PCR of a nasopharyngeal swab at birth (after cleaning the infant) and at 24 to 48 hours of age are both positive and an alternative explanation for symptoms is excluded. Criteria for probable, possible, unlikely, or noninfected also exist.

For asymptomatic newborns of infected mothers, intrapartum infection is confirmed if SARS-CoV-2 PCR of a nasopharyngeal swab at birth (after cleaning the infant) and at 24 to 48 hours of age are both positive. Criteria for possible or noninfected also exist

Neonatal infection may be acquired postpartum. This is defined by clinical features of COVID-19 at ≥48 hours of age (regardless of parent/caregiver SARS-CoV-2) and confirmed if SARS-CoV-2 PCR of a respiratory sample at birth is negative but SARS-CoV-2 PCR of a nasopharyngeal/rectal swab is positive at 24 to 48 hours of age. Criteria for probable or noninfected also exist.

In most women who test positive for SARS-CoV-2 in the nasopharynx, vaginal and amniotic fluid specimens have been negative to date [3,4], but one patient with a positive vaginal swab has been reported [5].

Viremia rates in patients with COVID-19 appear to be low (1 percent in one study [6]) and transient, suggesting placental seeding and vertical transmission would be not common.

Most placentas studied so far had no evidence of infection, but the virus has been identified in a few cases [7-9].

In a patient with confirmed COVID-19 who had second-trimester miscarriage, samples taken from a placental cotyledon and submembrane were positive for SARS-CoV-2; all fetal, amniotic fluid, cord blood, and maternal blood and vaginal samples were negative [7].

Another report described one positive placental swab from the amniotic surface and two positive membrane swabs from between the amnion and chorion after manual separation of the membranes in women with severe or critical COVID-19 illness delivered by cesarean; none of the infants were positive for SARS-CoV-2 [8].

A third report described two SARS-CoV-2-positive mothers in whom the fetal side (syncytiotrophoblast) of their placentas and their neonates were also positive [9].

The extent and clinical significance of vertical transmission remain unclear.

The following findings support a diagnosis of congenital: the neonate was not in contact with vaginal secretions (documented as positive for SARS-CoV-2); membranes were intact before birth; there was no skin-to-skin contact with the mother before collection of the first neonatal nasopharyngeal swab.

1.          Egloff C, Vauloup-Fellous C, Picone O, et al. Evidence and possible mechanisms of rare maternal-fetal transmission of SARS-CoV-2. J Clin Virol 2020; 128:104447.

2.          Shah PS, Diambomba Y, Acharya G, et al. Classification system and case definition for SARS-CoV-2 infection in pregnant women, fetuses, and neonates. Acta Obstet Gynecol Scand 2020; 99:565.

3.          Qiu L, Liu X, Xiao M, et al. SARS-CoV-2 is not detectable in the vaginal fluid of women with severe COVID-19 infection. Clin Infect Dis 2020.

4.          Chen H, Guo J, Wang C, et al. Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet 2020; 395:809.

5.          Kirtsman M, Diambomba Y, Poutanen SM, et al. Probable congenital SARS-CoV-2 infection in a neonate born to a woman with active SARS-CoV-2 infection. CMAJ 2020.

6.          Wang W, Xu Y, Gao R, et al. Detection of SARS-CoV-2 in Different Types of Clinical Specimens. JAMA 2020.

7.          Baud D, Greub G, Favre G, et al. Second-Trimester Miscarriage in a Pregnant Woman With SARS-CoV-2 Infection. JAMA 2020.

8.          Penfield CA, Brubaker SG, Limaye MA, et al. Detection of SARS-COV-2 in Placental and Fetal Membrane Samples. Am J Obstet Gynecol MFM 2020; :100133.

9.          Patanè L, Morotti D, Giunta MR, et al. Vertical transmission of COVID-19: SARS-CoV-2 RNA on the fetal side of the placenta in pregnancies with COVID-19 positive mothers and neonates at birth. Am J Obstet Gynecol MFM 2020; :100145.

10.        Dong L, Tian J, He S, et al. Possible Vertical Transmission of SARS-CoV-2 From an Infected Mother to Her Newborn. JAMA 2020.

11.        Zeng L, Xia S, Yuan W, et al. Neonatal Early-Onset Infection With SARS-CoV-2 in 33 Neonates Born to Mothers With COVID-19 in Wuhan, China. JAMA Pediatr 2020.

12.        Zeng H, Xu C, Fan J, et al. Antibodies in Infants Born to Mothers With COVID-19 Pneumonia. JAMA 2020.

13.        Alzamora MC, Paredes T, Caceres D, et al. Severe COVID-19 during Pregnancy and Possible Vertical Transmission. Am J Perinatol 2020.

113 CMAAO CORONA FACTS and MYTH BUSTER: Thrombo Inflammation

113 CMAAO CORONA FACTS and MYTH BUSTER: Thrombo Inflammation

Dr K K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

937: IMA-CMAAO Webinar on Thromboinflammation

30th May, 2020, 4-5pm

Participants

Dr KK Aggarwal, President CMAAO; Dr Ramesh K Dutta; Dr K Kalra; Dr Sanchita Sharma

Faculty” Dr VP Choudhary Consultant Hematologist Fortis Escorts Hospital

• The virus has different presentations in different patients.

o   It is a viral disorder and is self-limiting in 90% patients. Antivirals should be given within 48 hours.

o   The virus behaves like HIV in some patients; if lymphopenia or reduced CD4 cell count, give anti-HIV drugs

o   It produces hyperimmune inflammation, so if there are signs of hyperinflammation such as high ESR, CRP and ferritin, anti-inflammatory drugs such as HCQ, indomethacin become important.

o   It behaves like bacteria, so azithromycin can be given; azithromycin may cause cardiotoxicity, so doxycycline may be given.

o   It produces thrombo-inflammation; fibrinogen and d-dimer levels are raised. Give anticoagulant – heparin, nafamostat

o   It produces silent hypoxia; oxygen level is very low, but CO2 level is normal; the person is conscious. Lung is compliant. In such patients, oxygen supplementation with high flow nasal cannula, BiPAP (if required) and ventilator (only 1%).

o   Cytokine storm and ARDS: this is terminal illness and managed as per protocol for ARDS. Non-compliant lung.

Coronavirus has a very wide spectrum of illness ranging from asymptomatic to cytokine storm. It has wide presentations, though the target organ is lung.

The immunoinflammation primarily occurs in the lungs, but the manifestations of thromboembolic phenomenon have a very wide presentation.

In the initial stages, the patients have marked leukopenia; lymphopenia in particular is a predominant feature. The platelet count may be normal or slightly low, d-dimer and ferritin (acute phase reactants) levels are very high, parallel to high CRP and procalcitonin levels. The smear shows no evidence of DIC, the fibrinogen level is normal, PT and aPTT are either normal or slightly prolonged, but d-dimer is very high, LDH is very high.

Lung pathology and pathology in other organs shows a hypercoagulable state with thromboembolic phenomenon taking place. Microthrombi are being formed, like Thrombotic thrombocytopenic purpura (TTP) but it is not TTP as there is no evidence of purpura or thrombocytopenia.

As the disease advances, d-dimer and ferritin levels keep on increasing → multiorgan failure, then the platelet count falls very rapidly → PT and aPTT are prolonged. In the later stage, it is somewhat similar to DIC.

In the initial stage of the illness, patient has predominantly thromboembolic phenomenon, a hypercoagulable state due to immunoinflammation. It mainly affects lungs, but can affect other organs also. Most patients do not have DIC like picture in the initial stage of the illness (In DIC, fibrinogen levels should be low, PT and aPTT should be prolonged, peripheral smear should show microangiopathy). But when patient develops multiorgan failure, a DIC-like picture is seen.

Monitoring: oxygen saturation, CO2; repeat CBC, platelets, d-dimer, ferritin, IL-6 every day or alternate days. Rapidly increasing levels are indicative of worsening of patient condition.  Act fast. A 3- to 4-fold rise in d-dimer means a critically ill patient, who may not survive.

Patients aged 60 years or above, or those who have comorbidities, are already decompensated to some extent. Survival is better in patients with no comorbidities.

Severe and persistent lymphopenia means that the virus is acting on the bone marrow and hematopoietic system. If neutropenia also occurs, this results in secondary infections. The virus has a more fulminant course in immunocompromised patients compared to those in whom the immune system is normal.

Cytokine levels are increased in these patients (TNF or IL-1, IL-6), the cytokines act on monocyte tissue factor expression, if there acted upon by IL-1 and IL-6, they stimulate the coagulation pathway → prothrombin generation → thromboembolic phenomenon.

Multiple mechanisms are in play in the pathgenesis of thromboembolic phenomenon.

Hypoxia is one of the factors stimulating hypercoagulation.

Nafamostat is an oral anticoagulant with antiviral activity. Maximum data available is on heparin and LMWH rather than nafamostat.

Kawasaki-like syndrome in children in UK; similar data in India not available or published.

Covid toes and fingers are not an acute manifestation, they occur after patient has recovered. Probably it is due to vasculitis persisting for some time after the disease has been taken care of.

Do tests: baseline, next day and then alternate days. If d-dimer is not increasing, then once every 3 days.

112 CMAAO CORONA FACTS and MYTH BUSTER: Prediction Formulas

112 CMAAO CORONA FACTS and MYTH BUSTER: Prediction Formulas

Dr K K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

936: Round Table Expert Zoom Meeting on “Formulas in relation to COVID-19 pandemic for better understanding of data”

30^th May, 2020; 11am-12pm

Participants: Dr KK Aggarwal; Dr Alex Thomas; Dr AK Agarwal; Dr DR Rai; Dr Suneela Garg; Dr Girdhar Gyani; Dr Ashok Gupta; Dr Jayakrishnan Alapet; Mr Bejon Misra; Dr K Kalra; Mrs Upasana Arora; Dr Major Prachi Garg; Ms Ira Gupta; Dr Sanchita Sharma

• It has been seen that 1% of symptomatic cases die.
• Expected number of symptomatic cases: Number of deaths x 100 will give the expected number of symptomatic cases in society on that day. For instance, if the number of deaths is 400. So, by this definition, the app. number of cases should be 40,000.

• Corrected death rate: Currently, the death rate is calculated as number of cases today vis a vis number of deaths today. Instead, it should be number of cases today vs number of cases 14 days back. The corrected death rate is 5.76%.

• Doubling time: The doubling time in India is 14 days, Russia 20 days, Brazil 13 days, whereas the doubling time is longer in other countries (USA 36 days, UK 37 days, Spain 40 days, Italy 57 days, France 52, Germany 55 days). If social distancing is not maintained, numbers in India are going to be very high. India will be in top 6 in one week.

• China conducted 6.5 million tests for coronavirus, where 6 new cases were detected two weeks ago; 200 cases were found, mostly people who showed no symptoms. The ratio of undocumented cases for each documented case in Wuhan is 1:33 i.e. there were 33 asymptomatic cases for every one new infection. This is a reliable study as the total population was tested and not a sample population.

• In a study from New York City, this ratio is 1:10 i.e., there were 10 asymptomatic patients, for every positive patient. New York conducted an antibody testing study, while Wuhan did antigen test. The reliability of antibody test is unknown. There are smaller studies from Iceland (1:2), Germany (1:5), California (1:5).

• According to CDC, the mortality is less than 0.3% as we are missing asymptomatic cases.

• As RTPCR is 67% specific add 30% in government figures of number of cases; more the number, less will be the mortality.

• People who are brought in dead are declared as COVID negative; COVID is not reported as the primary cause of death; therefore, these cases may not be counted.

• To get the actual number of deaths, multiply the government figures by 2.

• Deaths per million population: US 316, Spain 580, World 47.1, India 4. While this number for India may seem very good, we must not compare country to country. We must compare epicenter to epicenter. Mortality in China is very high, if only Wuhan is taken, but if you add rest of China, the mortality becomes very low.

• Herd immunity threshold (HIT): It is calculated as R0-1 divided by R0 (R0 or R naught is reproduction number).

o   If R0 is 3, then 66% of population would need to get infected to develop herd immunity

o   If R0 is 2, then 50% of population would need to get infected to develop herd immunity.

o   If R0 is 1.5, then 33% of population would need to get infected to develop herd immunity.

o   If R0 is 1.4, then 28.5% of population would need to get infected to develop herd immunity.

o   If R0 is 3.5, then 71.5% of population would need to get infected to develop herd immunity.

In New York, infection stopped when 23% of the population had the infection. Their R value was 1.3. The HIT was 23%.

So, the day we cross 20% of cases, we will see regression of infection with no new cases in the community. First to do this will be Delhi or Maharashtra, next will be Tamil Nadu and West Bengal.

Scenarios

• If no measures are taken (such as lockdown, social distancing, or any other), the disease continues to spread; R0 is 2.66.
• In moderate lockdown, transmission is reduced (R0) to 2 during the lockdown, transmission resumes at R0 of 2.4 after the lockdown; a surge in post-lockdown period is expected.
• Hard lockdown: R0 is reduced o 1.5 during lockdown, then transmission resumes at R0 of 2.4.
• Hard lockdown + continue social distancing/isolating symptomatic cases: R0 is reduced o 1.5 during lockdown, then we can continue at R0 of 2 through social distancing and isolation.

• Families rather than individuals are now being affected. During lockdown, the message that went out was to stay at home and wear a mask when going out. This message needs to be changed. People who go out and come back to their house should continue to wear a mask; else one person will infect the entire family. Social distancing at home is as important as social distancing in office or outside at other places.

• Every death should be audited to find out if these deaths could have been prevented.

• The virus has different presentations in different patients.

o   It is a viral disorder and is self-limiting in 90% patients. Antivirals should be given within 48 hours.

o   The virus behaves like HIV in some patients; if lymphopenia or reduced CD4 cell count, give anti-HIV drugs

o   It produces hyperimmune inflammation, so if there are signs of hyperinflammation such as high ESR, CRP and ferritin, anti-inflammatory drugs such as HCQ, indomethacin become important.

o   It behaves like bacteria, so azithromycin can be given; azithromycin may cause cardiotoxicity, so doxycycline may be given, which also covers atypical bacteria.

o   It produces thrombo-inflammation; fibrinogen and d-dimer levels are raised; such patients have moderate/ severe illness. Give anticoagulant – heparin, nafamostat

o   It produces silent hypoxia; oxygen supplementation with high flow nasal cannula, BiPAP (if required) and ventilator (only 1%).

o   Cytokine storm and ARDS: this is terminal illness and managed as per protocol for ARDS.

• The fear and stigma around a dead body (Covid) needs to be removed. Once a body is cleaned as per protocol and wrapped, it is not infected. There is no risk of spread of infection and so no need for PPE for cremations.

• The minimum space requirement for working in office, according to WHO, is 100 sq ft per person. In India, the standard is 75 sq ft per person for living.

• A patient who came to the clinic in the morning and tests positive in the evening, answer the following question:

o   Was the patient wearing a mask? If yes, then ask,

o   Was the doctor wearing a mask? If yes, then ask,

o   Was the surface decontaminated in the morning? If yes, then ask,

o   What was the contact time? If less than 30 min: Monitor; If more than 30min: Quarantine

• Best protection guidelines for doctors as well as patients should be displayed in each clinic.

111 CMAAO CORONA FACTS and MYTH BUSTER: Treatment Protocols

111 CMAAO CORONA FACTS and MYTH BUSTER: Treatment Protocols

Dr K K Aggarwal

President CMAAO

935: Minutes of Virtual Meeting of CMAAO NMAs

Treatment protocols in different countries and their experience with remdesivir

30^th May, 2020, Saturday

9.30am-10.30am

Participants

Member NMAs

Dr KK Aggarwal, President CMAAO

Dr Yeh Woei Chong, Singapore Chair CMAAO

Dr Ravi Naidu, Past President CMAAO, Malaysia

Dr N Gnanabaskaran, President Malaysian Medical Association

Dr Thirunavukarasu Rajoo, Hon. General Secretary, Malaysian Medical Association

Dr Ashok Philip, Malaysia

Dr Alvin Yee-Shing Chan, Hong Kong

Dr Marie Uzawa Urabe, Japan

Dr Md Jamaluddin Chowdhary, Bangladesh

Invitees

Dr Russell D’Souza, UNESCO Chair in Bioethics, Australia

Dr Sanchita Sharma, Editor IJCP Group

• There is a discrepancy in the number of deaths. To get the actual number of deaths, multiply the number of deaths with 2. This will cover the false negatives, sudden deaths etc.
• China conducted 6.5 million tests for coronavirus, where 6 new cases were detected two weeks ago; 200 cases were found, mostly people who showed no symptoms. The ratio of undocumented cases for each documented case in Wuhan is 1:33 i.e. there were 33 asymptomatic cases for every one new infection. This is a reliable study as the total population was studied and not a sample population.
• This ratio in New York City is 1:10 i.e., there were 10 asymptomatic patients, for every positive patient. New York conducted an antibody testing study, while Wuhan did antigen test. The reliability of antibody test is unknown.
• Treatment for mild/pre-symptomatic/pauci-symptomatic /asymptomatic cases (Pauci-symptomatic patients have transient symptoms e.g. mild fever or sore throat for 1-2 days): Paracetamol (for fever and myalgia), hydroxychloroquine (HCQ), azithromycin (this may have cardiac toxicity, so alternative is doxycycline), famotidine, ivermectin, ritonavir+lopinavir, nafamostat (anticoagulant), remdesivir
• India is trying to make a biosimilar of remdesivir to reduce the cost; it should be recommended to the respective governments that Asian countries should be allowed to make biosmilars in this time of a pandemic.

Malaysia protocol

• Management of Covid-19 is entirely in government hospitals by order of the government; no private hospital treats Covid patients.
• Treatment: Symptomatic treatment, combination of doxycycline and azithromycin, anti-HIV drug combination.
• The govt. had earlier stated that they would be participating in remdesivir trial, but there are no results of the trial
• The cost of remdesivir is likely to be high in Malaysia.

Singapore protocol

• Remdesivir has been used by NCID only in clinical trial with NIH, not otherwise.
• Kaletra (lopinavir+ritonavir) and beta-interferon have been used. Following a feedback from NICD about their relative lack of usefulness, Kaletra and beta-interferon are not used now for treatment of patients.
• Basic supportive care is still paramount.
• HCQ has not been used at all, not even in clinical trials.
• A study has found that on Day 11, there is minimal viral load, it is non infectious. Singapore has moved to time-based discharge i.e., after Day 14, patient is deemed to be free of Covid and can go to work after Day 21.

Hong Kong protocol

• Combination of ritonavir+lopinavir has been mainly used.
• Supportive is still the mainstay of treatment, for mild cases. All new cases are in people who have returned from overseas, they are mild or asymptomatic. No local cases for few weeks.
• Management of comorbid conditions such as diabetes is very important.
• Not tried remdesivir or HCQ

Bangladesh protocol

• Bangladesh has been using HCQ and azithromycin; but has recently temporarily stopped use of HCQ after a directive from technical committee in line with the WHO guidelines on this and an analysis published in The Lancet.
• Plasma therapy is being used.
• Production of remdesivir has started but not come to the market yet.

Patient-specific treatment

Covid-19 has the following presentations. We should be able to differentiate patients according to their manifestations. All patients do not show all manifestations.

Hypothesis: If we choose the right patient for the drug, the results would be very different.

• It is a viral disorder and is self-limiting in 90% patients. Earlier you give antivirals (within 48 hours), better it is. In India, Tamiflu (oseltamivir) is given on Day 1 before test results are available.
• The virus behaves like HIV in some patients; if lymphopenia or reduced CD4 cell count, give anti-HIV drugs
• It produces hyperimmune inflammation, so if there are signs of hyperinflammation such as high ESR, CRP and ferritin, anti-inflammatory drugs such as HCQ, indomethacin become important.
• It behaves like bacteria, so azithromycin can be given; azithromycin may cause cardiotoxicity, so doxycycline may be given, which also covers atypical bacteria.
• It produces thrombo-inflammation; fibrinogen and d-dimer levels are raised; such patients have moderate/ severe illness. Give anticoagulant – heparin, nafamostat
• It produces silent hypoxia; oxygen supplementation with high flow nasal cannula, BiPAP (if required) and ventilator (last resort).
• Cytokine storm and ARDS: this is terminal illness and managed as per protocol for ARDS.

Hyperimmune inflammation is mainly seen in Europe and the US and not much seen in Asian countries including India. Most CMAAO countries have not reported Kawasaki-like cases. There may be few scattered cases.

Use Remdesivir early as studies with Tamiflu have shown that if used very early, the difference in morbidity is significant. Start antivirals when symptoms are primarily due to the viral infection. Don’t wait for symptoms due to body’s immune response.

The minimum space requirement for working in office, according to WHO, is 100 sq ft per person. In India, the standard is 75 sq ft per person for living. In countries with high population density, social distancing may not be possible. So masks should be compulsorily used at all places, at least for the next 3 months.

Take same precautions at home as followed outside the home.

Recommendations for re-opening of schools

• Individual countries can form their rules about use of masks by children as they do not sit facing each other.
• No cafeteria/canteens in schools
• No mixing of classes
• Not more than 20-25 students in one class
• Break between classes will be divided
• India recommends starting from 9^th class onwards, while Europe recommends starting primary school first
• E-classes in high risk areas and for disabled
• Only soap and water to wash hands; use of sanitizer must be done only under supervision
• Teachers and staff to wear masks
• Every school should have a written policy on how to handle the first positive case in their school to avoid any kneejerk reaction and/or media circus

CMAAO CORONA FACTS and MYTH BUSTER 110: Wear face mask at home, patients with diarrhea ? super spreader

CMAAO CORONA FACTS and MYTH BUSTER 110: Wear face mask at home, patients with diarrhea ? super spreader

Dr K K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

934: Wear Face Masks at Home if you deal with public AND are people with diarrhea super spreaders

I have been saying about this and now a study has proven the same. During lock down wear mask when you go to buy essentials but after lockdown wear mask when you go for work involving meeting with [public or colleagues.

Now a new study conducted in China says wearing face masks at home greatly reduces a person’s risk of catching the coronavirus -- a major escalation from the most common advice on the cloth coverings, which is that they should be worn in public when social distancing can’t be practiced.

Researchers interviewed 335 people from 124 families in Beijing between late February and late March about their households during the pandemic. Each family had one confirmed case of coronavirus. The average family had four people, and most families had three generations.

Most person-to-person transmission occurred within households. Wearing face masks in the same house was 79% effective at curbing transmission, but only before symptoms emerge. Wearing masks really wasn’t protective after the symptoms started.

The daily use of chlorine or ethanol-based disinfectant was 77% effective at curbing transmission in the household.

This study confirms the highest risk of household transmission being prior to symptom onset, but that precautionary [non-pharmaceutical interventions], such as mask use, disinfection and social distancing in households can prevent COVID-19 transmission during the pandemic

BMJ Global health, the medical journal published the study. If the first person to become infected had diarrhea, the risk of passing the virus quadrupled.

Having close daily contact with the first person infected, such as eating meals or watching television together, had an 18-fold increased risk.

Overall, the study supports “universal face mask use, not just in public spaces, but also at home.