Pregnant people infected with Delta variant more likely to have severe COVID-19, new study
By Dr Deepu Changappa Cheriamane
The Delta variant that caused a surge in COVID-19 cases in the United States this summer is particularly dangerous for pregnant people, new research shows.The research paper says, pregnant people infected with the Delta variant are more likely to have severe COVID-19 cases, and the variant leads to even worse outcomes for unvaccinated pregnant people.
The findings were published in the American Journal of Obstetrics and Gynecology.
The researchers, prospectively studied pregnant patients diagnosed with SARS-CoV-2 by nasal or nasopharyngeal swab polymerase chain reaction, and Externally tested patients who received care at Parkland were also included in their study.
Positive tests were grouped into weekly epochs by the date of diagnosis and the maximum severity of symptoms.
Severe or critical illness was defined as that requiring supplemental oxygen, a high-flow nasal cannula, intensive care unit admission, or mechanical ventilation. The management of asymptomatic or mild-to-moderate illness in pregnancy included symptom treatment with isolation precautions and virtual or in-person follow-up. The routine management of severe or critical illness included the administration of dexamethasone or other therapies according to the National Institutes of Health guidance.The association between severe or critical illness and the week was evaluated for the trend using the Mantel-Haenszel chi-squared test for trend. Local SARS-CoV-2 Delta variant (B.1.617.2) sequencing was performed and the variant predominance was tracked weekly.
The COVID-19 vaccination rates in pregnancy or immediately after childbith were described.
The authors got the following results
1515 pregnant patients were diagnosed with COVID-19, and 7 (0.5%) had reinfection >90 days after the initial infection during pregnancy.
The infections included 690 (45%) patients from labor and delivery or inpatient units, 383 (25%) outpatient, 167 (11%) emergency department, and 282 (19%) external tests. Furthermore, 82 (5.4%) cases with severe or critical illness during pregnancy, were included.
The authors noted that as the Delta (B.1.617.2) variant predominated locally, both the case volume and the proportion of severe or critical illnesses increased significantly , with over a quarter of pregnant patients requiring admission for severe or critical illness.
The authors Concluded their study with the following remarks.
Increased morbidity was observed in pregnancy with COVID-19 during the recent surge with the Delta variant, in population where vaccine acceptance is low.
Here is the concluding remarks of the study "Our results highlight the urgency of the requirement of prevention measures including COVID-19 vaccination during pregnancy"
Studies suggest COVID-19 is evolving to spread more efficiently through air
By Dr Deepu Changappa Cheriamane
The newer variants of the coronavirus like Alpha and Delta are highly contagious, infecting far more people than the original virus. The virus is evolving to spread more efficiently through air. The studies have signalled the need for better masks in some situations, and indicate that the virus is changing in ways that make it more formidable. We still have best tools at our disposal, which still work well to halt the spread.
Even a loosefitting cloth and surgical masks block about half of the fine aerosols containing virus, according to the study of people infected with variants, published this month in the journal Clinical Infectious Diseases.
Here is a brief summary of the study.
The authors recruited COVID-19 cases to give blood, saliva, mid-turbinate and fomite (phone) swabs, and 30-minute breath samples while vocalizing into a Gesundheit-II, with and without masks at up to two visits two days apart. Later the researchers quantified and sequenced viral RNA, cultured virus, and assayed sera for anti-spike and anti-receptor binding domain antibodies.
The researchers enrolled 49 seronegative cases (mean days post onset 3.8 ±2.1), May 2020 through April 2021. They could detect SARS-CoV-2 RNA in 45% of fine (≤5 µm), 31% of coarse (>5 µm) aerosols, and 65% of fomite samples overall and in all samples from four alpha-variant cases. Masks reduced viral RNA by 48% (95% confidence interval [CI], 3 to 72%) in fine and by 77% (95% CI, 51 to 89%) in coarse aerosols; cloth and surgical masks were not significantly different.
They also found that the alpha variant was associated with a 43-fold (95% CI, 6.6 to 280-fold) increase in fine aerosol viral RNA, compared with earlier viruses, that remained a significant 18-fold (95% CI, 3.4 to 92-fold) increase adjusting for viral RNA in saliva, swabs, and other potential confounders.
Two fine aerosol samples, collected while participants wore masks, were culture-positive.
The authors concluded that the SARS-CoV-2 is evolving toward more efficient aerosol generation and loose-fitting masks provide significant but only modest source control. They ended quoting that "until 
vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.
vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary.
At least one long-term symptom found in 37% of patients with COVID-19, study shows
By Dr Deepu Changappa Cheriamane
Long-COVID refers to a variety of symptoms affecting different organs reported by people following Coronavirus Disease 2019 (COVID-19) infection. To date, there have been no robust estimates of the incidence and co-occurrence of long-COVID features, their relationship to age, sex, or severity of infection, and the extent to which they are specific to COVID-19. The aim was to address these issues.
Methods and findings
The authors did a retrospective cohort study based on linked electronic health records (EHRs) data from 81 million patients including 273,618 COVID-19 survivors. The incidence and co-occurrence within 6 months and in the 3 to 6 months after COVID-19 diagnosis were calculated for 9 core features of long-COVID (breathing difficulties/ breathlessness ,
fatigue/malaise, chest/throat pain, headache, abdominal symptoms, myalgia, other pain, cognitive symptoms, and anxiety/depression).
Among COVID-19 survivors 57.00% had one or more long-COVID feature recorded during the whole 6-month period (i.e., including the acute phase), and 36.55% between 3 and 6 months. The incidence of each feature was: abnormal breathing (18.71% in the 1- to 180-day period; 7.94% in the 90- to180-day period), fatigue/malaise (12.82%; 5.87%), chest/throat pain (12.60%; 5.71%), headache (8.67%; 4.63%), other pain (11.60%; 7.19%), abdominal symptoms (15.58%; 8.29%), myalgia (3.24%; 1.54%), cognitive symptoms (7.88%; 3.95%), and anxiety/depression (22.82%; 15.49%). All 9 features were more frequently reported after COVID-19 than after influenza , co-occurred more commonly, and formed a more interconnected network.
Significant differences in incidence and co-occurrence were associated with sex, age, and illness severity.
The authors Concluded that
Long-COVID clinical features occurred and co-occurred frequently and showed some specificity to COVID-19, though they were also observed after influenza. Different long-COVID clinical profiles were observed based on demographics and illness severity.
Author summary
Why was this study done?
Long-COVID has been described in recent studies. But we do not know the risk of developing features of this condition and how it is affected by factors such as age, sex, or severity of infection.
We do not know if the risk of having features of long-COVID is more likely after Coronavirus Disease 2019 (COVID-19) than after influenza.
We do not know about the extent to which different features of long-COVID co-occur.
What did the researchers do and find?
This research used data from electronic health records of 273,618 patients diagnosed with COVID-19 and estimated the risk of having long-COVID features in the 6 months after a diagnosis of COVID-19. It compared the risk of long-COVID features in different groups within the population and also compared the risk to that after influenza.
The research found that over 1 in 3 patients had one or more features of long-COVID recorded between 3 and 6 months after a diagnosis of COVID-19. This was significantly higher than after influenza.
For 2 in 5 of the patients who had long-COVID features in the 3- to 6-month period, they had no record of any such feature in the previous 3 months.
The risk of long-COVID features was higher in patients who had more severe COVID-19 illness, and slightly higher among females and young adults. White and non-white patients were equally affected.
What do these findings mean?
Knowing the risk of long-COVID features helps in planning the relevant healthcare service provision.
The fact that the risk is higher after COVID-19 than after influenza suggests that their origin might, in part, directly involve infection with SARS-CoV-2 and is not just a general consequence of viral infection. This might help in developing effective treatments against long-COVID.
The findings in the subgroups, and the fact that the majority of patients who have features of long-COVID in the 3- to 6-month period already had symptoms in the first 3 months, may help in identifying those at greatest risk.
Read more
Prime Minister of India Shri Narendra Modi Launches Massive COViD Vaccination Campaign
By Dr Deepu Changappa Cheriamane
Prime Minister Narendra Modi launched India's massive COVID-19 vaccination exercise via a video conference on January 16.
As of January 16, India had reported more than 1.05 crore confirmed COVID-19 cases. The death toll from the outbreak in the country stood at over 1.52 lakh. While more than 1.01 crore patients had recovered, 2.11 lakh cases remained ‘active'. Globally, more than 9.32 crore individuals have been infected by the virus and over 20 lakh people have died so far.
A speedy rollout of vaccines is being seen as the best way to curb the spread of COVID-19 and restore normalcy in the pandemic-battered global economy. More than 50 countries, including the United States and the United Kingdom, have already vaccinated a large number of people from high-risk groups.
“Everyone was asking as to when the vaccine will be available. It is available now. I congratulate all the countrymen on this occasion,” PM Modi said in his address.
The prime minister reiterated that those facing the highest risk will be vaccinated on priority. “Our doctors, nurses, medical staff and frontline workers, among others, have a right to be vaccinated first,” PM Modi said.
PM Modi also said that those getting vaccinated should make sure that they get the second dose – that is to be taken after a gap of around one month.
A total of 3,006 session sites across all states and Union Territories were virtually connected during the event. Authorities had planned vaccinating around 100 beneficiaries at each session site on the inaugural day.
Priority is being given to healthcare and frontline workers, who had already been registered on the purpose-built CoWIN application. This would be sequentially followed by people with comorbidities, senior citizens and finally, the general public. The Centre is hoping to vaccinate 30 crore people by July, in a bid to stop the novel coronavirus pandemic.
The Drugs Controller General of India (DCGI) has approved two vaccines – Covishield and Covaxin – for restricted emergency use. Beneficiaries will not be able to choose among the two jabs.
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 xrayPattern 1 - Reverse BatwingPattern 2 - Multifocal lower lobe predominant consolidationPattern 3 - Peribronchial rounded consolidationsPattern 4 - Multifocal bilateral consolidationsPattern 5 - Ball pattern or round pneumoniaPattern 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;
COVID-19 Radiology findings
By Dr Deepu Changappa Cheriamane
Radiographic features
The primary findings of COVID-19 on chest radiograph and CT are thos
e of atypical pneumonia or organizing pneumonia.
However imaging has limited sensitivity for COVID-19, as up to 18% demonstrate normal chest radiographs or CT when mild or early in the disease course, but this decreases to 3% in severe disease. Bilateral and/or multilobar involvement is common.
The current recommendation of the vast majority of learned societies and professional radiological associations is that imaging should not be employed as a screening/diagnostic tool for COVID-19, but reserved for the evaluation of complications.
Plain radiograph
Although less sensitive than chest CT, chest radiography is typically the first-line imaging modality used for patients with suspected COVID-19. For ease of decontamination, use of portable radiography units is preferred.
Chest radiographs may be normal in early/mild disease.
In those COVID-19 cases requiring hospitalization, 69% had an abnormal chest radiograph at the initial time of admission, and 80% had radiographic abnormalities sometime during hospitalization. Findings are most extensive about 10-12 days after symptom onset.
The most frequent findings are airspace opacities, whether described as consolidation or, less commonly, GGO. The distribution is most often bilateral, peripheral, and lower zone predominant 89.97. In contrast to parenchymal abnormalities, pleural effusion is rare (3%).
CT
The primary findings on CT in adults have been reported as
• ground-glass opacities (GGO): bilateral, subpleural, peripheral
• crazy paving appearance (GGOs and inter-/intra-lobular septal thickening)
• air space consolidation
• bronchovascular thickening in the lesion
• traction bronchiectasis
The ground-glass and/or consolidative opacities are usually bilateral, peripheral, and basal in distribution.
A retrospective study of 112 patients found 54% of asymptomatic patients had pneumonic changes on CT.
The following chest CT findings have been reported to have the highest discriminatory value (p<0.001).
peripheral distribution
ground-glass opacity
bronchovascular thickening (in lesions)
Atypical CT findings
These findings only seen in a small minority of patients should raise concern for superadded bacterial pneumonia or other diagnoses.
Temporal CT changes
Four stages on CT have been described
- early/initial stage (0-4 days): normal CT or GGO only
- halo half of patients have normal CT scans within two days of symptom onset
- progressive stage (5-8 days): increased GGO and crazy paving appearance
- peak stage (9-13 days): consolidation
- absorption stage (>14 days): with an improvement in the disease course, "fibrous stripes" appear and the abnormalities resolve at one month and beyond
Pediatric CT
In a small study of five children that had been admitted to hospital with positive COVID-19 RT-PCR tests and who had CT chest performed, only three children had abnormalities. The main abnormality was bilateral patchy ground-glass opacities, similar to the appearances in adults, but less florid, and in all three cases the opacities resolved as they clinically recovered.
On 18 March 2020, the details of a much larger cohort of 171 children with confirmed COVID-19, and evaluated in a hospital setting was published as a letter in the New England Journal of Medicine. Ground-glass opacities were seen in one-third of the total, whereas almost 16% of children had no imaging features of pneumonia.
Ultrasound
Initial work on patients in China suggests that lung ultrasound may be useful in the evaluation of critically ill COVID-19 patients. The following patterns have been observed, tending to have a bilateral and posterobasal predominance:
- multiple B-lines
- ranging from focal to diffuse with spared areas
- representing thickened subpleural interlobular septa
- may also manifest as a light beam sign, an evanescent, broad-based vertical reverberation artifact arising from a regular pleural line
- irregular, thickened pleural line with scattered discontinuities
- subpleural consolidations
- can be associated with a discrete, localized pleural effusion
- relatively avascular with color flow Doppler interrogation
- pneumonic consolidation typically associated with preservation of flow or hyperemia 65
- alveolar consolidation
- tissue-like appearance with dynamic and static air bronchograms
- associated with severe, progressive disease
- restitution of aeration during recovery
- reappearance of bilateral A-lines
Radiology report
The Radiological Society of North America (RSNA) has released a consensus statement endorsed by the Society of Thoracic Radiology and the American College of Radiology (ACR) that classifies the CT appearance of COVID-19 into four categories for standardized reporting language:
typical appearance
peripheral, bilateral, GGO +/- consolidation or visible intralobular lines (“crazy paving” pattern)
multifocal GGO of rounded morphology +/- consolidation or visible intralobular lines (“crazy paving” pattern)
reverse halo sign or other findings of organizing pneumonia
indeterminate appearance
absence of typical CT findings and the presence of
multifocal, diffuse, perihilar, or unilateral GGO +/- consolidation lacking a specific distribution and are non-rounded or non-peripheral
few very small GGO with a non-rounded and non-peripheral distribution
atypical appearance
absence of typical or indeterminate features and the presence of
isolated lobar or segmental consolidation without GGO
discrete small nodules (e.g. centrilobular, tree-in-bud)
lung cavitation
smoother interlobular septal thickening with pleural effusion
negative for pneumonia:
no CT features to suggest pneumonia, in particular, absent GGO and consolidation.
CO-RADS
In March 2020, the "COVID-19 standardized reporting working group" of the Dutch Association for Radiology (NVvR) proposed a CT scoring system for COVID-19. They called it CO-RADS (COVID-19 Reporting and Data System) to ensure CT reporting is uniform and replicable. This assigns a score of CO-RADS 1 to 5, dependent on the CT findings. In some cases a score of 0 or 6 may need to be assigned as an alternative. If the CT is uninterpretable then it is CO-RADS 0, and if there is a confirmed positive RT-PCR test then it is CO-RADS 6.
The first study investigating the use of CO-RADS found a reasonable level of interobserver variation, with a Fleiss' kappa score of 0.47 (cf. 0.24 for PI-RADS and 0.67 for Lung-RADS).
COVID-RADS
In April 2020, American radiologists based at the University of Southern California proposed the COVID-19 imaging reporting and data system (COVID-RADS), which has a confusingly similar name to CO-RADS (see above)
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COVID-19 Transmission
By Dr Deepu Changappa Cheriamane
Although originating from animals, COVID-19 is now considered to be an indirect zoonosis, as its transmission is now primarily human-to-human.
It is predominantly transmitted in a similar way to the common cold, via contact with droplets of infected individuals' upper respiratory tract secretions, e.g. from sneezing or coughing.
A recent Bayesian regression model has found that aerosol and fomite transmission are plausible.
Orofecal spread was seen with the SARS epidemic, and although it remains unclear if SARS-CoV-2 can be transmitted in this way, there is some evidence for it.
Sexual transmission has not been seen in the field but remains possible, not least because the SARS-CoV-2 virus has been found in all bodily secretions including seminal and vaginal fluids.
It remains unclear if COVID-19 could be transmitted through a blood transfusion although no cases have yet be seen. Nevertheless, many national bodies have instituted controls to reduce the chance of this happening including advising that potential donors do not give blood until 28 days after recovering from COVID-19.
Cohort studies have been unable to rule out the possibility of vertical transmission, but it seems to be a rare event if it does occur. A large prospective cohort study of 427 pregnant women from all 194 birth units across the UK found that 5% of 265 live births were confirmed as COVID-19 on RT-PCR.
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COVID 19 Pathophysiology
By Dr Deepu Changappa Cheriamane
The SARS-CoV-2 virus, like the closely-related MERS and SARS coronaviruses, effects its cellular entry via attachment of its virion spike protein (a.k.a. S protein) to the angiotensin-converting enzyme 2 (ACE2) receptor. This receptor is commonly found on alveolar cells of the lung epithelium, underlying the development of respiratory symptoms as the commonest presentation of COVID-19 50. It is thought that the mediation of the less common cardiovascular effects is also via the same ACE2 receptor, which is also commonly expressed on the cells of the cardiovascular system.
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COVID 19 Pathology
By Dr Deepu Changappa Cheriamane
Etiology
On 9 January 2020, the World Health Organization (WHO) confirmed that SARS-CoV-2 was the cause of COVID-19 (2019-nCoV was the name of the virus at that time). It is one of the two strains of the SARS-CoV species known to cause human disease, the other being the original severe acute respiratory syndrome coronavirus (SARS-CoV), the cause of SARS. It is a member of the Betacoronavirus genus, one of the genera of the Coronaviridae family of viruses. Coronaviruses are enveloped single-stranded RNA viruses that are found in humans, mammals and birds. These viruses are responsible for pulmonary, hepatic, CNS, and intestinal disease.
As with many human infections, SARS-CoV-2 is zoonotic. The closest animal coronavirus by genetic sequence is a bat coronavirus, and this is the likely ultimate origin of the virus. The disease can also be transmitted by snakes.
Six coronaviruses are known to cause human disease. Two are zoonoses: the severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), both of which may sometimes be fatal. The remaining four viruses all cause the common cold.
COVID19 Complications
Complications of COVID 19
In one of the largest studies of hospitalized patients, reviewing 1,099 individuals across China, the admission rate to the intensive care unit (ICU) was 5%.
In this same study, 6% of all patients required ventilation, whether invasive or non-invasive.
ICU patients tend to be older with more comorbidities.
Commonly reported sequelae are:
acute respiratory distress syndrome (ARDS): ~22.5% (range 17-29%)
acute thromboembolic disease
pulmonary embolism
deep vein thrombosis (DVT)
acute cardiac injury:
elevated troponin levels
myocardial ischemia
cardiac arrest
myocarditis
CNS
delirium
viral encephalitis
diffuse leukoencephalopathy
microhemorrhage (seen in juxtacortical white matter and corpus callosum particularly of the splenium)
stroke: cryptogenic/ischemic
higher mortality and greater severity of stroke in context of COVID-19
secondary infections, e.g. bacterial pneumonia
sepsis
acute kidney injury (AKI)
coagulopathy
disseminated intravascular coagulation (DIC)
multiorgan failure
In a small subgroup of severe ICU cases:
secondary hemophagocytic lymphohistiocytosis (a cytokine storm syndrome)
Risk factors for pulmonary embolism
In a multivariate analysis, an elevated risk of developing PE was associated with:
obesity
elevated D-dimer
elevated CRP
rising D-dimer over time
Pediatric complications
In April 2020, reports started to appear of critically-ill children presenting with a multisystem inflammatory state which bore some resemblance to Kawasaki disease and toxic shock syndrome. Typically abdominal pain and other GI symptoms were present and often evidence of a myocarditis. The presentations necessitated ICU admission and fatalities have been reported.
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COVID 19 Other investigations
By Dr Deepu Changappa Cheriamane
Laboratory tests
The most common ancillary laboratory findings in a study of 138 hospitalized patients were the following.
lymphopenia
increased prothrombin time (PT)
increased lactate dehydrogenase
Other commonly identified abnormalities include:
mild elevated inflammatory markers (CRP 89 and ESR)
elevated D-dimer
mildly elevated serum amylase: 17% patients (study of 52 cases)
frank acute pancreatitis has not been reported
mildly deranged liver function tests are common, primarily elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
bilirubin rise is generally mild
alkaline phosphatase (AKP) and gamma‐glutamyl transferase (GGT) levels remain normal
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COVID Radiology investigation
Chest X ray
It doesn't have any sensitivity or specificity in diagnosing COVID, but can lead to diagnosis with strong suspicion and further referral for PCR.
HRCT Thorax
Multiple radiological organizations and learned societies have stated that CT should not be relied upon as a diagnostic/screening tool for COVID-19. On 16 March 2020, an American-Singaporean panel published that CT findings were not part of the diagnostic criteria for COVID-19. However, CT findings have been used controversially as a surrogate diagnostic test by some.
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COVID19 Diagnostic tests
By Dr Deepu Changappa Cheriamane
RT-PCR
The definitive test for SARS-CoV-2 is the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) test. It is believed to be highly specific, but with sensitivity reported as low as 60-70% and as high as 95-97%. Meta-analysis has reported the pooled sensitivity of RT-PCR to be 89%. Thus, false negatives are a real clinical problem, and several negative tests might be required in a single case to be confident about excluding the disease.
Its sensitivity is predicated on time since exposure to SARS-CoV-2, with a false negative rate of 100% on the first day after exposure, dropping to 67% on the fourth day. On the day of symptom onset (~4 days after exposure) the false negative rate remains at 38%, and it reaches its nadir of 20% three days after symptoms begin (8 days post exposure). From this point on, the false negative rate starts to climb again reaching 66% on day 21 after exposure.
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COVID clinical presentation
By Dr Deepu Changappa Cheriamane
Clinical presentation
COVID-19 typically presents with systemic and/or respiratory manifestations. Some individuals infected with SARS-CoV-2 are asymptomatic and can act as carriers. Some also experience mild gastrointestinal or cardiovascular symptoms, although these are much less common.
The full spectrum of clinical manifestation of COVID-19 remains to be determined. Symptoms and signs are non-specific:
Common
fever (85-90%)
cough (65-70%)
disturbed taste and smell (40-50%)
fatigue (35-40%)
sputum production (30-35%)
shortness of breath (15-20%)
Less common
myalgia/arthralgia (10-15%)
headaches (10-36%)
sore throat (10-15%)
chills (10-12%)
pleuritic pain
Rare
nausea, vomiting, nasal congestion (<10%), diarrhea (<5%)
palpitations, chest tightness
hemoptysis (<5%)
confusion, seizures, paraesthesia, altered consciousness
stroke(most commonly cryptogenic)
COVID-19 sufferers have reported high rates of disturbances of smell and taste, including anosmia, hyposmia, ageusia, and dysgeusia. The numbers of patients affected vary and current evidence points more towards a neurological than a conductive cause of the olfactory dysfunction.
Various reports suggest patients with the disease may have symptoms of conjunctivitis, and those affected, may have positive viral PCR in their conjunctival fluid. However a meta-analysis of over 1,100 patients found that conjunctivitis was only present in 1.1% cases. A small case series found conjunctivitis to be the only clinical manifestation in some patients with COVID-19.
Cutaneous lesions may also be seen, similar to many other viral infections. In a cohort of 88 patients, 20% developed skin disease, most commonly an erythematous rash. Most of the skin abnormalities were self-limited, resolving in a few days.
Pediatric
In the main, the clinical presentation in children with COVID-19 is milder than in adults. Symptoms are similar to any acute chest infection, encompassing most commonly pyrexia, dry cough, sore throat, sneezing, myalgia and lethargy. Wheezing has also been noted. Other less common (<10%) symptoms in children included diarrhea, lethargy, rhinorrhea and vomiting.
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COVID - Epidemiology
By Dr Deepu Changappa Cheriamane
Epidemiology
As of July 2020, the number of cases of confirmed COVID-19 globally is over 11 million affecting virtually every territory, other than isolated South Pacific island states and Antarctica, according to an online virus tracker created by the medical journal, The Lancet, and hosted by Johns Hopkins University. As of June 2020, the United States had more than two million cases, Brazil more than one million, with Russia and India with >500,000 cases.
The R0 (basic reproduction number) of SARS-CoV-2 has been estimated between 2.2 and 3.28 in a non-lockdown population, that is each infected individual, on average, causes between 2-3 new infections.
The incubation period for COVID-19 was initially calculated to be about five days, which was based on 10 patients only. An American group performed an epidemiological analysis of 181 cases, for which days of exposure and symptom onset could be estimated accurately. They calculated a median incubation period of 5.1 days, that 97.5% became symptomatic within 11.5 days (CI 8.2 to 15.6 days) of being infected, and that extending the cohort to the 99th percentile results in almost all cases developing symptoms in 14 days after exposure to SARS-CoV-2.
As of June 2020 the number of deaths from COVID-19 passed half a million globally. The case fatality rate is ~2-3%. It is speculated that the true case fatality rate is lower than this because many mild/asymptomatic cases are not being tested, which thus skews the apparent death rate upwards.
A paper published by the Chinese Center for Disease Control and Prevention (CCDC) analyzed all 44,672 cases diagnosed up to 11 February 2020. Of these, ~1% were asymptomatic, and ~80% were classed as "mild".
Another study looked at clinical characteristics in COVID-19 positively tested close contacts of COVID-19 patients. Approximately 30% of those COVID-19 positive close contacts never developed any symptoms or changes on chest CT scans. The remainder showed changes in CT, but ~20% reportedly developed symptoms during their hospital course, none of them developed severe disease. This suggests that a high percentage of COVID-19 carriers are asymptomatic.
In the Chinese population, 55-60%% of COVID-19 patients were male; the median age has been reported between 47 and 59 years.
Pediatric
Children seem to be relatively unaffected by this virus, or indeed other closely-related coronaviruses.with large cohort studies reporting that 1-2% of COVID-19 patients are children. However, there have been cases of critically-ill children with infants under 12 months likely to be more seriously affected. A very low number of pediatric deaths has been reported . In children, male gender does not seem to be a risk factor. The incubation period has been reported to be shorter than in adults, at about two days.
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