166 CMAAO CORONA FACTS and MYTH COVID Illness in Bangladesh

166 CMAAO CORONA FACTS and MYTH  COVID Illness in Bangladesh

Dr K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

1018: Minutes of Virtual Meeting of CMAAO NMAs on “CMAAO view on COVID-19 in Bangladesh”

25^th July, 2020, Saturday

9.30am-10.30am

Participants

Member NMAs

Dr KK Aggarwal, President CMAAO

Dr Yeh Woei Chong, Singapore Chair CMAAO

Dr Marie Uzawa Urabe, Japan

Dr Ashraf Nizami, Pakistan

Dr Sajjad Qaisar, Pakistan

Dr Md Jamaluddin Chowdhury, Bangladesh

Invitees

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

Dr S Sharma, Editor IJCP Group

Dr Md Jamaluddin Chowdhury from the Bangladesh Medical Association presented data on the situation of COVID-19 in Bangladesh. This was followed by a discussion among the participating NMAs on COVID-19 status in Bangladesh.

COVID-19 Situation in Bangladesh- Health Perspective

Dr Md Jamaluddin Chowdhury

Bangladesh Medical Association

• Bangladesh is the most densely populated country of the world with a population density of 1116/sq km.
• The first case of Covid in the country was detected on 8^th March.
• So far, Bangladesh has done more than one million tests; the number of tests conducted per million is 6629.
• Bangladesh allows private facilities to conduct Corona test by their own RT PCR machine.
• However, the number of tests has reduced; the reason for this decline is not known, the cost of the test may have been a factor.
• Bangladesh has not started antigen test yet. Also, antibody testing has not been started for surveillance.
• No. of confirmed cases is 218658; no. of deaths confirmed due to Covid-19 is 2836.
• No of total deaths (documented or undocumented) indicate the total number of infected cases.
• Analysis of one month data from 25^th June to 24^th July shows that the number of deaths (confirmed) is not so high and ranges between 35 and 50. But there may be some undocumented cases.
• The number of critical cases is reducing; the number of ICU beds dedicated for Covid-19 cases is 201; of these 133 are occupied.
• Initially there was a shortage of high flow nasal cannula; also initially private hospitals and clinics were not providing any service. Now they are given service, both diagnostic and curative.
• Hydroxychloroquine is not being used for patients; ivermectin is also not advised in the national guideline, but the patients are taking the drug randomly.
• An ongoing trial is investigating the efficacy of combination of ivermectin and doxycycline for treatment of Covid-19 patients with the approval of Bangladesh Medical Research Council.
• Health care workers who have treated patients infected with Covid-19 have faced social stigma from local people.
• The number of doctors infected is 2229; the number of doctors deceased is 68.
• Supply of PPE is now satisfactory. Initially there was question about its quality.
• Contact tracing is going on but it is insufficient due to shortage of employees or volunteers.
• Wearing mask has recently been made compulsory by law.
• A 45-day lockdown was ordered in the country, but was not observed strictly. At present, no significant lockdown program is on implementation.
• Most of the confirmed cases are in the age group 21-40 years.
• The number of cases in females is 29% vs 71% in males.
• The number of deaths in females is 23% vs 77% in males.

Other key points from the discussion

• Countries in South Asia (India, Bangladesh, Pakistan, Sri Lanka, Nepal) should have similar data.
• Mortality in Bangladesh is 1.2-1.3%; mortality in Delhi is now 0.3%; a sero-surveillance study in Delhi has shown that 22.8% have developed antibodies. Because the mortality is low, people are not accepting the lockdown guidelines.
• Mortality in our countries should be 0.1-0.3%; the virus is not so deadly here.
• Less than 1% needs ventilators; rest can be managed at home, nursing homes and smaller hospitals as long as there is facility for HFNC.
• Start early anticoagulant (LMWH); treat with tenecteplase if no improvement despite LMWH.
• All patients should identify Day zero. Measure SpO2 on Day 3-6. If there is exertional dyspnea, this means there is pneumonia + clot; give antiviral + LMWH + steroids, all should recover.
• We need to build up AII rooms similar to countries like China, Hong Kong, Singapore, South Korea.
• Hydroxychloroquine has no role if steroids are given; role of antibiotics is to prevent secondary infection.
• Start pool test; if positive then presume that all in family are infected. Singapore allows pooled test with 64 samples at a time; Kerala allows 20 samples and ICMR allows 5 samples.
• A lockdown now is not the answer.
• In India, doctors are on duty for 7 days; they are not allowed to go home; they stay in a hotel for 5 days and are allowed to go home only if they test negative.
• Asymptomatic people are not actually asymptomatic. They may be missing atypical symptoms such as headache, single diarrhea, sore throat, nasal obstruction etc. Even a single symptom can be Covid positive.
• Public should strictly follow the SOPs in their workplace.
• Undue interference by law has created confusion. The Supreme Court of India has given a decision that petitions against policy decisions regarding Covid-19 will not be entertained.
• Pakistan Medical Association has demanded home isolation with proper monitoring of the patients (by GPs/Family Practitioners), if the person has the capacity or resources to be isolated.
• In Singapore, enforcing of stay at home orders is done by security people, while medically, if people have illness, they are shifted out to a facility.
• Issues about stigmatization, ethics and interference in professional autonomy are very real. We have to be on alert about these.

165 CMAAO CORONA FACTS and MYTH COVID Post COVID Illness

165 CMAAO CORONA FACTS and MYTH COVID Post COVID Illness

Dr K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

1009: Can the Virus Disrupt the Endocrine System?

Through its effects on angiotensin-converting enzyme 2 (ACE2), researchers from Louisiana State University say that SARS-CoV-2 may disrupt various endocrine functions throughout the body.

1010: Potential Treatments, but Hard to Test

Dipyridamole a cheap, FDA-approved drug typically prescribed with blood thinners to prevent strokes, could help patients with COVID-19.

1011: Researchers at Johns Hopkins wanted to test another cheap generic drug — alpha-blocker prazosin, which prevents inflammatory surges.

1012: Oral petechial lesions observed in a small number of COVID-19 patients in addition to skin rash exanthem, is a new symptom of the virus. Madrid researchers examined the oral cavity of 21 patients with the virus who also had a skin rash, and published their findings in a research letter in JAMA Dermatology.  The presence of enanthem in a patient with a skin rash is a useful finding that suggests a viral aetiology rather than a drug reaction.

1012: Test to Guide Steroid Treatment: Hospitalized COVID-19 patients with high levels of inflammation may benefit significantly from dexamethasone and other steroids. Researchers at Albert Einstein College of Medicine and Montefiore Health System in the Bronx, New York, concluded that patients with low levels of inflammation may experience a significantly higher risk for severe outcomes with steroid use. They also found that a C-reactive protein test can help physicians decide which patients are likely to benefit.

1013: Combination Therapy Quells Cytokine Storm: In a new study, the combination of high-dose methylprednisolone and tocilizumab was associated with faster respiratory recovery, lower likelihood of mechanical ventilation, and fewer in-hospital deaths among COVID-19 patients experiencing a hyperinflammatory state known as a cytokine storm compared with those who received supportive care alone. Researchers compared patients who received the treatments with historic controls and found that participants in the treatment group were 79% more likely to achieve at least a two-stage improvement in respiratory status.

1014: Bleeding complications linked to antithrombotic strategy used in non‐critically ill COVID-19 patients: Findings from a study in the Journal of Thrombosis and Haemostasis dispute the currently adopted strategy of giving weight-adjusted doses of anticoagulants to non-critically ill patients with COVID-19 in the absence of thromboembolic complications. Researchers led by Raffaele Pesavento, MD, Department of Medicine, University of Padua, Padua, Italy, noted that "the increasing awareness that low-dose anticoagulants may be ineffective for prevention of thrombotic complications in the course of COVID-19, including the development of micro-thrombosis in the lung vessels, has induced several clinicians to consider the use of sub-therapeutic or even therapeutic doses of antithrombotic agents in all admitted patients, challenging their hemorrhagic potential. The results of our retrospective cohort study do not support this strategy."

"As (sub)-therapeutic doses of antithrombotic drugs failed to reduce the risk of fatal or non-fatal thrombotic complications while simultaneously increasing the haemorrhagic risk, their use in patients with non-critically ill COVID-19 should be discouraged," the authors said.

SOURCE: Journal of Thrombosis and Haemostasis

1015: Clinical improvement of severe COVID-19 pneumonia in a pregnant patient after caesarean delivery:  A case of COVID-19 in a pregnant patient with severe respiratory compromise, whose clinical status significantly improved after caesarean delivery was described in BMJ Case Reports.

 

A 35-year-old gravida 10 para 7 at 29 3/7 weeks gestation presented to the labour and delivery unit with a 2-week history of cough and fever. The patient also reported dyspnoea that worsened with ambulation, myalgias and dysuria. On the day of presentation, she became increasingly hypoxic, requiring 8 L/min of oxygen via nasal cannula. A COVID-19 nasopharyngeal PCR test on admission was positive and her laboratory results were significant for lymphopenia and elevated LDH, D-dimer and C reactive protein (CRP). Additionally, her chest X-ray findings were consistent with COVID-19, with extensive patchy airspace opacities in the middle and lower lung fields. 

In the SICU, the patient’s condition worsened on hospital day 2 with increasingly elevated oxygen requirements. On hospital day 3, she received tocilizumab 400 mg intravenously. Nonetheless, her respiratory status continued to worsen, and by hospital day 5, she required 15 L/min of oxygen through a Venturi mask with desaturation of her SpO₂ to the low 80th percentile on ambulation.

Despite worsening respiratory status, the patient’s acute phase reactants “remarkably” improved, where her CRP down-trended from 179 mg/L at admission to 7.4 mg/L by day 5. Throughout her hospitalisation in the SICU from hospital days 2 to 9, the patient remained afebrile but was visibly tachypneic with increased work of breathing. Meanwhile, her D-dimer level continued to rise, peaking at 3037 ng/mL. 

Because the patient remained dependent on 15 L/min of oxygen and showed signs of clinical worsening with potential imminent need for intubation, an interdisciplinary team agreed on proceeding with caesarean delivery with neuraxial anaesthesia for expedited delivery, and possible intraoperative intubation if the patient was unable to tolerate prolonged supine position. 

The patient eventually underwent an uncomplicated primary caesarean delivery at 30 5/7 weeks gestation with spinal anaesthesia on hospital day 10, while being maintained on 15 L/min of oxygen during the procedure and she did not require intubation. A male neonate was delivered and his chest X-ray on day of life 3 showed no evidence of pulmonary disease, and COVID-19 nasopharyngeal PCR testing collected 2 hours after delivery and on day of life 3 were negative.

The patient’s clinical status rapidly improved postoperatively, where she had a SpO2 to the low 90th percentile on room air at 2 hours post-caesarean, which improved to 100% on 15 L/min of oxygen in the recovery room, and her cough and work of breathing significantly improved. Her oxygen requirements gradually decreased, and by postoperative day 2, she was weaned to 4 L/min of oxygen via nasal cannula. 

The patient remained on therapeutic enoxaparin postpartum until she was stable enough to obtain a CT angiogram, given the continued concern for a concomitant pulmonary embolism. Her CT angiogram was negative for pulmonary embolism, but consistent with COVID-19 infection, showing extensive bilateral patchy ground glass infiltrates and small consolidations. Meanwhile, COVID-19 nasopharyngeal PCR tests continued to be positive on postoperative days 7, 8 and 9. Nonetheless, the patient was discharged on postoperative day 9 as she was symptomatically improved, saturating well on room air and meeting all postoperative milestones. Eventually, her COVID-19 test was negative on postoperative day 14.

In cases of severe respiratory distress from COVID-19 pneumonia, patients may experience a reversal in poor respiratory status after the physiological changes of pregnancy are removed.

This is the first case to describe the use of tocilizumab for COVID-19 infection in a pregnant patient.

Tocilizumab exposure during pregnancy has mostly been studied in patients with severe rheumatologic diseases.

SOURCE: BMJ Case Reports

1016: Antibody levels in patients with mild COVID-19, appear to drop by half within 36 days. The research was conducted by F. Javier Ibarrondo, PhD, and colleagues and was published online on July 21 in a letter to the editor of The New England Journal of Medicine. Ibarrondo is associate researcher at the David Geffen School of Medicine at University of California, Los Angeles (UCLA). (The original letter incorrectly calculated the half-life at 73 days.)

1017: Although acute kidney injury is seen in a substantial minority of patients with severe COVID-19, no evidence of the presence of SARS-CoV-2 was found in kidney biopsies from a small series of such patients, according to researchers.

Kidney biopsy research shows that the kidney injury from COVID-19 virus happens due to complications of the disease and is not because of direct viral infection of the kidney. [Journal of the American Society of Nephrology]

164 CMAAO CORONA FACTS and MYTH COVID Post COVID Illness

164 CMAAO CORONA FACTS and MYTH COVID Post COVID Illness

Dr K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

1008:

Chronic COVID or POST COVID illness

COVID-19 can mean weeks' long illness, even in young adults and those without chronic conditions who have mild disease and are treated in outpatient settings, according to survey results in today's Morbidity and Mortality Weekly Report from the Centres for Disease Control and Prevention (CDC).

In a multistate telephone survey of symptomatic adults who tested positive for SARS-CoV-2, 35% had not returned to their usual state of wellness when they were interviewed 2 to 3 weeks after testing.

Delayed recovery (symptoms of fatigue, cough, and shortness of breath) was evident in nearly a quarter of 18- to 34-year-olds and a third of 35- to 49-year-olds who were not sick enough to require hospitalization.

This is post Covid state

1.    On 9^th day virus is non infectious

2.    Is post Covid persistent inflammation or immunologic reactions

3.    Like arthritis in chikungunya

4.    Like post herpetic neuralgia

5.    Like post viral syndrome, CFS etc

6.    Is quite common and presents in India more with low grade fever and obstruction in throat. It can also present with SOB, exertional tachycardia and below knee pains.

163 CMAAO CORONA FACTS and MYTH COVID Cardiac Markers

163 CMAAO CORONA FACTS and MYTH  COVID Cardiac Markers

Dr K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

1007:  Redefine cardiac injury marker cut-offs to predict 28 days mortality in COVID-19 inpatients

The abnormal cardiac biomarker pattern seen in patients with COVID-19 is significantly associated with a higher risk of death, and the cut-offs of those markers for effective prognosis of 28-day mortality of COVID-19 appear to be much lower than for regular heart disease, at 49% of currently recommended thresholds, according to a study in Hypertension.

The biomarkers are high-sensitivity cardiac troponin I (hs-cTnI), creatine kinase-MB (CK-MB), NT-proB-type natriuretic peptide (NT-proBNP), creatine phosphokinase (CK) and myoglobin (MYO).

Their retrospective cohort study enrolled patients diagnosed as COVID-19 and admitted to 9 hospitals in Hubei Province, China, from December 31, 2019, to March 4, 2020. The study included 3219 patients with myocardial biomarker measurement, and 2814 without. The primary endpoint was 28-day all-cause mortality.

Compared to patients without cardiac injury biomarker measurement, patients with biomarker values were older (median age at 57) and had higher percentages of pre-existing comorbidities and more severe symptoms.

All five myocardial biomarkers were significantly associated with 28-day all-cause death of COVID-19. 

After adjusting for age, gender and comorbidities such as hypertension, diabetes, coronary heart disease and cerebrovascular disease, the 28-day mortality hazard ratio for hs-cTnI was 7.12, NT-proBNP was 5.11, CK-MB was 4.86, MYO was 4.50, and CK, a much less specific cardiac biomarker, was 3.56.

In patients showing heart injury during the entire hospitalization, neutrophil percentage and CRP were rapidly and simultaneously increased after disease onset, immediately followed by the increases of CK-MB, MYO, and hs-cTnI.

The significant elevation of IL-6 occurred only after the increases of these myocardial markers and was highly elevated mainly in patients with evidence of cardiac injury.

162 CMAAO CORONA FACTS and MYTH COVID Drugs Update

162 CMAAO CORONA FACTS and MYTH  COVID Drugs Update

Dr K Aggarwal

President CMAAO

With inputs from Dr Monica Vasudev

1003:  Pfizer will get $1.95 billion from the U.S. government to produce 100 million doses of their COVID-19 vaccine candidate. (Reuters)

1004: More data suggested humoral immunity faded quickly in people with mild COVID-19 illness. (New England Journal of Medicine)

1005: Small study suggests rapid decay of anti–SARS-CoV-2 antibodies in persons with mild COVID-19
DG Alert: Findings from a study published in The New England Journal of Medicine “raise concern” that humoral immunity against SARS-CoV-2 may not be long lasting in persons with mild illness. Javier Ibarrondo, David Geffen School of Medicine at University of California, Los Angeles, California, and colleagues evaluated 34 persons (20 females and 14 males; mean age: 43 years, [range, 21 to 68]). Of these, 30 participants had their infection confirmed by PCR, while the other 4 participants had CLI.  Most of the participants had mild illness.
A total of 31 of the 34 participants had two serial measurements of IgG levels, while the remaining 3 participants had three serial measurements. The first measurement was obtained at a mean of 37 days after the onset of symptoms (range, 18 to 65), and the last measurement was obtained at a mean of 86 days after the onset of symptoms (range, 44 to 119).
The initial mean IgG level was 3.48 log10 ng per milliliter (range, 2.52 to 4.41). On the basis of a linear regression model that included the participants’ age and sex, the days from symptom onset to the first measurement, and the first log10 antibody level, the estimated mean change (slope) was reported to be −0.0083 log10 ng per milliliter per day (range, −0.0352 to 0.0062). The authors noted that this corresponds to a half-life of approximately 73 days over the observation period. Further, they reported that the 95% confidence interval for the slope was −0.0115 to −0.0050 log10 ng per milliliter per day (half-life, 52 to 120 days).
The protective role of antibodies against SARS-CoV-2 is unknown, but these antibodies are usually a reasonable correlate of antiviral immunity, and anti–receptor-binding domain antibody levels correspond to plasma viral neutralizing activity. Given that early antibody decay after acute viral antigenic exposure is approximately exponential, we found antibody loss that was quicker than that reported for SARS-CoV-1.
Reference: https://www.nejm.org/doi/10.1056/NEJMc2025179

1006: Treatment of AMI and acute stroke will be  Tenecteplase

The COVID-19 pandemic could hasten the switch to tenecteplase for stroke and AMI treatment because it is given as a single, 5-second IV bolus that takes about 2 minutes to mix, prepare, and administer rather than the more than 1 hour for weight-based bolus and subsequent infusion of alteplase.

122 CMAAO CORONA FACTS and MYTH BUSTER: Myocardial injury

122 CMAAO CORONA FACTS and MYTH BUSTER:  Myocardial injury

Dr K K Aggarwal

President CMAAO

946: Myocardial Injury Among Hospitalised Patients With COVID-19 Associated With Higher Risk of Death

DG News Myocardial injury is prevalent among patients hospitalised with coronavirus disease 2019 (COVID-19) and is associated with higher risk of mortality, according to a study published in the Journal of the American College of Cardiology.

Anu Lala, MD, Icahn School of Medicine at Mount Sinai, New York, New York: “We found that 36% of patients who were hospitalised with COVID-19 had elevated troponin levels and were at higher risk of death. These findings, which are consistent with reports from China and Europe, are important for clinicians. If COVID-19-positive patients arrive in the emergency room and their initial test results show troponin levels are elevated, doctors may be able to better triage these patients and watch over them more closely, but this remains a testable hypothesis.”

Researchers analysed electronic health records of nearly 3,000 adult patients with confirmed positive COVID-19 admitted to 5 New York City hospitals within the Mount Sinai Health System between February 27, 2020, and April 12, 2020. The median age for patients analysed was 66 years and about 60% were male. One-quarter of all patients self-identified as African American and 27% self-identified as Latino. Roughly 25% of the patients had a history of heart disease and 25% had cardiovascular disease risk factors.

All patients had a blood test for troponin levels within 24 hours of admission, of which 64% had normal levels (0.00-0.03 ng/mL), 17% had mild elevation (>0.03-0.09 ng/mL), and 19% had higher elevation (>0.09 ng/mL). Higher troponin levels were more prevalent in patients who were aged older than 70 years old and had previously known conditions including diabetes, hypertension, atrial fibrillation, coronary artery disease, and heart failure.

Patients with milder forms of myocardial injury were associated with lower likelihood of hospital discharge and a 75% higher risk of death compared with patients with normal levels.

Patients with higher troponin concentrations were associated with a 3 times higher risk of death compared with those with normal levels. When adjusting for relevant factors such as heart disease, diabetes, and hypertension, troponin was independently associated with risk of death. More specifically, heart injury seems to be a more important indicator in predicting risk of death than a history of heart disease.

Reference: https://www.sciencedirect.com/science/article/abs/pii/S0735109720355522

121 CMAAO CORONA FACTS and MYTH BUSTER: Italy like situation

121 CMAAO CORONA FACTS and MYTH BUSTER:  Italy like situation

Dr K K Aggarwal

President CMAAO

945: Over Half of People Tested in Italian City of Bergamo Have COVID-19 Antibodies

A sample survey has shown that more than half the residents of the northern Italian city of Bergamo have COVID-19 antibodies. Of 9,965 residents who had blood tests between April 23 and June 3, 57% had antibodies indicating they had come into contact with the coronavirus. The city health authorities said the sample was "sufficiently broad" to be a reliable indicator of how many people had been infected in Bergamo, which became the epicentre of Italy's outbreak.

Antibodies were found in just over 30% of the 10,404 health operators tested although they are generally considered more at risk than other people.

In a report released in early May, national statistics institute ISTAT said the number of deaths in Bergamo was up 568% in March compared with the 2015-2019 average, making it Italy's worst-hit city in terms of deaths. Its hospitals were soon overwhelmed by infected people and, with morgues unable to keep up, convoys of army trucks carrying away the dead became a chilling symbol of the global pandemic.

Bergamo province has reported 13,609 coronavirus cases. Italy has reported almost 34,000 coronavirus deaths, with some 235,000 confirmed cases. The Lombardy region, which includes Bergamo, has registered over 16,000 deaths. Reuters

Lesson: In an Italy like situation 50% of the population is expected to get infected.

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.

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.