COVID 19

Updates in COVID 19 31-3-2020

1. بسم الله الرحمن الرحيم

2. COVID-19 Gamal Agmy , MD, FCCP Professor and Head of Chest Department , Assiut University, Egypt

3. COVID-19  ( coronavirus disease 2019 ) is an infectious disease caused by  severe acute respiratory syndrome coronavirus 2  ( SARS-CoV-2) , previously known as  2019 novel coronavirus   ( 2019-nCoV ), a strain of  Corona Virus

4. The first cases were seen in Wuhan, China in December 2019 before spreading globally. The current outbreak   was recognized as a Pandemic   on 11 March 2020.

5. Most people infected with the COVID-19 virus will experience mild to moderate respiratory illness and recover without requiring special treatment .  Older people, and those with underlying medical problems like cardiovascular disease, diabetes, chronic respiratory disease, and cancer are more likely to develop serious illness .

6. The best way to prevent and slow down transmission is be well informed about the COVID-19 virus, the disease it causes and how it spreads. Protect yourself and others from infection by washing your hands or using an alcohol based rub frequently and not touching your face . 

7. The COVID-19 virus spreads primarily through droplets of saliva or discharge from the nose when an infected person coughs or sneezes , so it’s important that you also practice respiratory etiquette (for example, by coughing into a flexed elbow ).

8. Terminology The WHO originally called this illness "novel coronavirus-infected pneumonia (NCIP)" and the virus itself had been named "2019 novel coronavirus (2019-nCoV) On 11 February 2020, the WHO officially renamed the clinical condition COVID-19 (a shortening of COronaVIrus Disease-19)  .

9. Terminology Coincidentally, on the same day, the Coronavirus Study Group (CSG) of the International Committee on Taxonomy of Viruses renamed the virus "severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2)  .   

10. Terminology The official virus name is similar to SARS- CoV , the virus strain that caused epidemic  Severe Acute Respiratory Syndrome(SARS)  in 2002-2004, potentially causing confusion . The WHO has stated it will use "COVID-19 virus" or the "virus that causes COVID-19" instead of its official name, SARS-CoV-2, in dealings with the public.

11. Epidemiology As of 31 March 2020, 754.948 cases of COVID-19 have been confirmed worldwide, having been diagnosed in 203 countries , with 36.571 confirmed deaths . There are nine countries with >10,000 confirmed cases and 27 countries with between 1000 and 10,000 confirmed cases. On 27 March 2020, the USA surpassed China as the country with the most confirmed cases

12. Epidemiology The R0(basic reproduction number)  of SARS-CoV-2 has been estimated between 2.2 and 3.28 , that is each infected individual , on average, causes between 2-3 new infections .  

13. Epidemiology The Incubation period for COVID-19 was initially calculated to be ~5 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 ( 8.2 to 15.6 days) of being infected, and that extending the cohort to the 99 th  percentile results in almost all cases developing symptoms in 14 days after exposure to SARS-CoV-2

14. Epidemiology The number of deaths from COVID-19 is 36.571 (31 March), with a case fatality rate  of 2-3% . It is speculated that the true case fatality rate is lower than this, because many mild 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, 1.2% were asymptomatic and 80.9% were classed as "mild"

15. Epidemiology Another study looked at clinical characteristics in COVID-19 positively tested closed 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 on 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 .

16. Epidemiology In the Chinese population, 55-60% of COVID-19 patients were males and the median age has been reported between 47 and 59 years 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 .  

17. Epidemiology   However, there have been cases of critically-il l children with infants under 12 months likely to be more seriously affected . A very low number of pediatric deaths have been reported  . In children, male gender does not seem to be a risk factor . The incubation period has been reported to shorter than adults , at about two days   .

18. 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   1

19. Clinical presentation Common: Fever (85-90%) Cough (65-70%) fatigue (35-40%) sputum production (30-35%) shortness of breath (15-20%) Less common : Mylagia /arthralgia (10-15%) headaches (10-15%) sore throat (10-15%) chills (10-12%) pleuritic pain

20. Clinical presentation Rare: nausea, vomiting, nasal congestion (<10%), diarrhoea (<5%)  Palpitation and chest tightness

21. Clinical presentation 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 

22. Diagnosis

23. Diagnosis The definitive test for SARS-CoV-2 is the  real-time reverse transcriptase-polymerase chain reaction  ( RT-PCR )  test  and is believed to be highly specific but with  sensitivity  reported as low as 60-70%   and as high as 95-97%  . 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.

24. 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 Mild elevations of inflammatory markers ( CRP and ESR) and D-dimer  are also seen

25. Radiographic features The primary findings of COVID-19 on chest radiograph and CT are those of  atypical pneumonia or organizing pneumonia . Imaging has limited sensitivity for COVID-19, up to 18% demonstrate normal chest x-rays 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

26. Radiographic features Plain radiograph may be normal in initial stages asymmetric patchy or diffuse airspace opacities have been descibed  

27. Halo Sign CT shows nodular consolidation associated with a halo of ground-glass opacity (GGO) in both apices resulting from invasive pulmonary aspergillosis . This halo represents hemorrhage. When seen in leukemic patients, is highly suggestive of the diagnosis of invasive pulmonary aspergillosis .

28. CT Halo Sign

29. Reverse Halo Sign •Central ground-glass opacity surrounded by denser consolidation of crescentic or ring shape, at least 2 mm thick •First described by Voloudaki in 1996 •Kim in 2003 used the term reverse halo •Found to be relatively specific for crypto- genic organizing pneumonia (COP )

30. Reverse Halo Sign Seen in other conditions: •Wegener’s granulomatosis • lymphomatoid granulomatosis • paracoccidiodomycosis •neoplastic (metastasis) •invasive aspergillosis •lipoid pneumonia

31. Tree-in-Bud Sign •

32. Secondary lobule Basic anatomic unit of pulmonary structure and function. 1-2 cm and is made up of 5-15 pulmonary acini Supplied by a small bronchiole (terminal bronchiole) in the center, that is parallelled by the centrilobular artery. Pulmonary veins and lymphatics run in the periphery Two lymphatic systems: central network peripheral network

33. Perilymphatic distribution Centrilobular distribution Random distribution

34. Crazy Paving in a patient with Alveolar proteinosis.

35. Radiographic features

36. Radiographic features CT Typical findings ( Radiopaedia ) The primary findings on CT in adults have been reported : 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

37. Radiographic features Ultrasound

38. Interstitial syndrome

39. A lines = default normal Horizontal echo reflection at exact multiples of intervals from surface to bright reflector. Dry lung OR PNTX Decay with depth Obliterated by B pleura A A A A A A

40.   Tissue pattern   representative of Alveolar Consolidation Presence of hyperechoic punctiform images representative of air bronchograms Pleural effusion Lower lobe

41. Radiographic features ( Radiopaedia ) CT excluding findings mediastinal lymphadenopathy pleural effusions multiple tiny pulmonary nodules (unlike many other viral pneumonia ) tree-in-bud appearance pneumothorax cavitation

42. Radiographic features Temporal CT Four stages on CT have been described : early/initial stage (0-4 days): normal CT or GGO only up to half of patients have normal CT scans within 2 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 1 month and beyond

43. Radiographic features Paediatric 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   .

44. Radiographic features Pediatric CT 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  .

45. Radiographic features Ultrsound 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  representative of thickened subpleural interlobular septa irregular, thickened pleural line with scattered discontinuities  

46. Radiographic features Ultrasound subpleural consolidations pneumonic consolidation typically associated with preservation of flow or hyperemia   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

47. Egyptian Ministry of Health and Population The key + ve CT findings: 1-ground glass opacity 100% 2-Involvement of multiple lobes (100%) 3-Subpleural or peripheral distribution (100%) 4-Consolidations(87.8%) 5-Septal thickening(55.6%) 6-Bronchial dilatation and wall thickening (55.6 %)

48. Egyptian Ministry of Health and Population The key - ve CT findings: 1-Pleural effusion 0% 2-Mediastinal lymphadenopathy 0% 3-Lung nodules 0% 4-specific Zonal predominance (variable)

49. Pathology 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 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 . 

50. Pathology Etiology:   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 cause the common cold.

51. Transmission Although originating from animals, COVID-19 is not considered a direct zoonosis as its transmission is now primarily human-to-human . It is primarily 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 .

52. Transmission A recently published cohort study (26 March 2020)  could not rule out the possibility of vertical transmission with 9% of neonates (n=3/33) developing an early onset SARS-CoV-2 infection despite strict infection control measures during delivery . However, a retrospective study of nine pregnant patients infected by SARS-CoV-2 did not show any evidence of vertical/intrauterine infection . More recent published (20 March 2020) guidance from a joint American-Chinese consensus panel stated that it remains unclear if vertical transmission can occur.

53. Complications 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 . Common reported sequelae include the following: acute respiratory distress syndrome (ARDS): ~22.5% (range 17-29%) 

54. Complications acute cardiac injury: elevated troponin levels myocardial ischemia cardiac arrest secondary infections sepsis acute kidney injury (AKI) multiorgan failure In a small subgroup of severe ICU cases: secondary hemophagocytic lymphohistiocytosis  (a cytokine storm syndrome

55. Differential diagnoses viral pneumonia including : influenza pneumonia A and B distribution more along the bronchovascular bundles bronchial wall thickening paramyxovirus pneumonia cytomegalovirus (CMV) pneumonia adenovirus pneumonia SARS- CoV pneumonia MERS coronavirus HSV pneumonia in immunocompromised patients  

56. Differential diagnoses respiratory syncytial virus (RSV) pneumonia atypical bacterial pneumonia mycoplasma pneumonia mainly children and adolescents bronchial wall thickening centrilobular nodule chlamydia pneumonia ​pulmonary edema interstitial lung disease cryptogenic organizing pneumonia chronic eosinophilic pneumonia (CEP)  acute fibrinous organizing pneumonia rheumatoid arthritis-associated pneumonia

57. Blood from people who recover from coronavirus could provide a treatment Plasma is being studied as a way to fight off the virus

58. FDA Approves Plasma Treatment for Coronavirus on Conditional Basis Survivors Of COVID-19 May Hold The Key For Everyone Else — In Their Blood This week, researchers in New York City started collecting blood from COVID-19 survivors. The hope is that their immunity can be shared with others.

59. Treatment and prognosis NSAIDs Emerging expert opinion is that non-steroidal anti-inflammatory drugs (NSAIDs) are relatively contra-indicated in those with COVID-19. This is based upon several strands of "evidence“ : 1-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 2-previous research has shown that NSAIDs may suppress the immune system 

60. Treatment and prognosis NSAIDs 3-anecdotal reports from France suggest that young patients on NSAIDs, otherwise previously fit and well, developed more severe COVID-19 symptoms.

61. Treatment and prognosis NSAIDs 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

62. 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 asymptomati c carriage may occur

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