Updates on covid 19 by Dr monisha yadav - Comment
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Updated info from reliable source. It helps in understanding complications due to covid . It is handy for interns and postgraduates to act when cases come. Information covered in this presentation slides: 1. UPDATES ON COVID -19 MONISHA J YADAV GUIDANCE : TEAM B 2. CORONAVIRUS - FAMILY : Coronaviridae - It is spherical particle with crown like projection - Average diameter – 125nm - Viral envelope consists of lipid bilayer with anchored proteins - Nucleocapsid – N protein and positive sense single stranded RNA genome 3. REPLICATION CYCLE 1. ENTRY – S protein + ACE2 2. TRANSLATION : virus particle uncoated and attaches to ribosome Host ribosome translates open reading frames ORF1a and ORF1b into polyproteins pp1a and pp1b . Polyproteins are cleaved by PROTEASES into 16 nonstructural proteins 4. - Includes RNA dependent RNA polymerase , RNA helicase - Number of nsp’s coalesce to form replicase transcriptase complex (RTC) - RdRp mediates replication of viral genome 3. TRANSCRIPTION – genomic RNA to mRNAs . - In host endoplasmic reticulum RNA translation to structural proteins happen. - In Golgi apparatus assembly of virions happen and forms secretory vesicles - Progeny virus are released by exocytosis . 5. PATHOGENESIS - Viral antigens presented to APC - Stimulates cellular and humoral immunity - IgM and IgG antibodies are formed . They are S and N protein specific . - CD4 and CD8 T cells are activated . - Overproduction of proinflammatory cytokines - IL-6 , IL-1β, Tumour necrosis factor : CYTOKINE STORM 6. THREE PHASES - STAGE 1 : asymptomatic state - Nasal cavity epithelial cells are infected - Virus starts multiplying and propagating down - Innate immunity acts - Most infectious period - Nasal swabs detect virus - Mason rj et all , national jewishealth , USA 7. STAGE 2 - Upper airway and conducting airway response - Epithelial cells are infected - Beta and lamba interferons produced - CXCL 10 – interferon gamma induced protein 10 is a disease marker . - Disease will be mild . Symptomatic therapy is advised 8. STAGE 3 - 20% infected patients progress . - Viral particles infect type 2 cells of alveoli - Self replicating pulmonary toxin is released - Causes diffuse alveolar damage with fibrin rich hyaline membrane and multinucleated giant cells - Severe scarring and fibrosis - Wound healing is also impaired - Leads to severe ARDS . 9. CYTOKINE STORM - Leads to vascular hyperpermeability - Defective procoagulant – anticoagulant balance - Leads to formation of thrombin - Thrombin activates protease activated receptor 1 on platelets and leads to aggregation and microthrombosis 10. HYPERCOAGULABLE STATE - Endothelial injury : due to direct invasion by virus and cytokine storm . - Stasis : immobilization in critically ill patients . - Decrease in Antithrombin , Protein S and Protein C . - Elevated factor vш , Fibrinogen , VWF UPTODATE 11. INCUBATION PERIOD - 2-14 days - Mean is 5 days after exposure . - CDC 12. MODES OF TRANSMISSION - PERSON – PERSON : - DROPLET transmission - Infected person coughs , sneezes or talks - direct contact - Droplets donot travel more than 6 feet . - Indirect spread – touching an infected surface followed by eyes , nose or mouth International pulmonary consensus 13. - VIABILITY : - Aerosols – 3 hours - Plastic and stainless steel – 72 hours - Copper – 4 hours - Cardboard – 24 hours - Clothes – 8 hours CDC 14. RISK FACTORS - Asthma - Chronic lung diseases - Chronic kidney disease - Chronic liver disease - Diabetes mellitus - Hypertension - Cardiovascular disease - Obesity - People above 65 years old - People living in long term care facility - Thalasemmia - Sickle cell disease uptodate 15. CLINICAL PRESENTATION - Fever (83-99%) - Cough (59-82%) - Fatigue (44-77%) - Anorexia (4-84%) - Shortness of breath (31-40%) - Myalgias(11-35%) - Loss of smell ( anosmia ) - Loss of taste (ageusia ) - GI symptoms - Sore throat - nasal congestion WHO 16. COVID 19 DISEASE SEVERITY - MILD DISEASE : symptomatic patients without evidence of pneumonia or hypoxia. - MODERATE DISEASE : clinical signs of pneumonia but no signs of severe pneumonia . - SEVERE DISEASE : Severe pneumonia : clinical signs of pneumonia plus one of the following RR- > 30 breaths/min Severe respiratory distress Saturation < 90 % on room air WHO 17. CRITICAL DISEASE - 1. ARDS - ONEST : within 1 week of known pneumonia or worsening respiratory symptoms . - CHEST IMAGING : bilateral opacities , not fully explained by volume overload , nodules - MILD ARDS – PaO2 / FiO2 200-300 mmHg - MODERATE – PaO2 /FiO2 100-200 mmHg - SEVERE – PaO2/FiO2 < 100 mmHg 18. 2. SEPSIS - Acute life threatening organ dysfunction - Weak pulse , tachycardia , hypotension - Low oxygen saturation , difficulty in breathing - Altered mental status - Reduced urine output - Lab evidence of coagulopathy , thrombocytopenia , acidosis , high lactate , hyperbilirubinemia . 19. 3. SEPTIC SHOCK - Persistent hypotension despite volume resuscitation - Requiring vasopressors to maintain MAP > 65mmHG - Serum lactate level > 2 mmol/L. 20. CUTANEOUS MANIFESTATIONS 1. COVID toes : erythematous or purpuric macules on toes , lateral aspect of feet , fingers , elbows Pernio like lesions of acral surfaces Pathogenesis : ? Inflammatory cause New onset , pernio like lesions with no clear cause should be tested for covid 19 TREATMENT : topical corticosteroids to reduce discomfort . UPTODATE 21. - Livedo reticularis - Necrotic vascular lesions - Histopathology shows : thrombotic vasculopathy with laboratory coagulation alterations 22. - MORBILIFORM RASH : this rash involves trunk - Most common manifestation - Noted after recovery 23. - Urtiaria : acute urticaria with fever is presenting sign of covid infection - VARICELLA – like eruptions: small papules , vesicles , pustules appears 4-30 days after symptoms of covid - Resolves in about 10 days - Fluid from vesicle tested negative by RTPCR 24. COMPLICATIONS British cardiovascular society 25. NEUROLOGICAL MANIFESTATIONS Acute cerebrovascular disease : cerebrovascular hemorrhage. And ischemic stroke ( most common ) 1. Hypercoagulable state 2. Low platelet count 3. Elderly patients . Liu k et al , BMJ 26. INTRACRANIAL INFECTION WITH SARS-COV 2 - Headache - Disturbance in consciousness - Convulsions - First reported case in Beijing with covid encephalitis . - CSF postive for RTPCR . 27. - Peripheral nervous system : hypogeusia , hyposmia . - Deficit in visual function - Neuralgia . - MUSCLE DAMAGE RELATED : fatigue , muscle soreness . - Elevated muscle enzyme - Due to inflammation of muscles , 28. ICMR STRATEGY FOR TESTING COVID 19 - 1. symptomatic ILI individuals with history of international travel in last 14 days . 2. Symptomatic contacts of laboratory confirmed case . 3. Symptomatic health care workers 4. All patients of severe acute respiratory infections . 5 . Asymptomatic direct and high risk contacts of a confirmed case on day 5 and day 10 of exposure . 29. 6 .All symptomatic ILI within containment zones 7 . All hospitalised patients who develop ILI symptoms 8. All symptomatic ILI among returnees and migrants within 7 days of illness CLOSE CONTACT : Cohabiting family members of covid 19 patient . Atleast 15 minutes within 6 feet of a patient with confirmed covid . 30. RT-PCR - Diagnosis of covid 19 is made by direct detection of SARS-CoV2 RNA by reverse transcription polymerase chain reaction - TARGET GENES : 1. nucleocapsid (N) 2. spike (S) 3. envelope (E) 4. RNA dependent RNA polymerase 31. COVID TESTING POSITIVITY RATES Sl no . TYPE OF SPECIMEN POSITIVE 1. Bronchoalveolar lavage fluid 93% 2. Sputum 72% 3. Nasopharyngeal swab 63% 4. Oropharyngeal swab 32% 5. Feces 29% 6. Blood 1% 7. Urine 0% International pulmonary consensus 2nd edition 32. FALSE NEGATIVE RATES - 100% on day of exposure - 38% on day 5 - 20 % at day 8 - 66% at day 21 CDC 33. SEROLOGIC ASSAY - It has Emergency Use Authorization(EUA) by U.S. FDA . - Detects past infection and measures host humoral immune response . - Plays important role in virus epidemiology - IgM and IgG antibodies arise within 2-3 weeks simultaneously . - Helps to establish diagnosis when patient presents with late complications - People presenting 9-14 days after illness onset this test supports clinical diagnosis . - Positive test qualifies a person to donate blood to manufacture covalescent plasma . CDC 34. BINDING ANTIBODY DETECTION - These tests use purified proteins of SARS-CoV-2 - Duration : < 30 minutes . - 1. point of care (POC) tests : detects antibodies using whole blood obtained by fingerstick . - 2. lab tests using ELISA . Requires trained laboratrians , specialized instruments and reagents . CDC 35. ANTIGEN BASED - On MAY 9 2020 U.S. FDA issued emergency use authorization for antigen test . - Highly specific - Not sensitive as RTPCR. - It can detect active infection . - Helps prevent spread by identifying patients early . - Detects fragments of protein found on or within virus . - Samples : nasal cavity swab - Lower cost and test results within minutes - False negative rate is high , suspected cases must undergo RTPCR CDC 36. OTHER INVESTIGATIONS ABNORMALITY POSSIBLE THRESHOLD D-dimer > 1000 ng/ml ( normal < 500 ng/ml ) CRP > 100 mg /L ( normal < 8 mg/L ) LDH > 245 units /L ( 110-210 units /L) Troponin > 2 times upper limit Ferritin > 500 mcg/L ( 10-300 mcg/L) CPK > 2 times upper limit Neutrophil/lymphocyte ratio > 3.5 uptodate 37. RADIOLOGICAL - CHEST XRAY : includes bilateral lobar/multilobar consolidation . - CT CHEST : - EARLY STAGE (0-4 days ) ground glass opacities , subpleural distribution predominantly in lower lobes . - . PROGRESSIVE STAGE ( 5-8 days ) : rapidly involves both lungs , multi lobar distribution . Crazy paving pattern International pulmonary consensus 2nd edition 38. - . - PEAK STAGE ( 9-13 days ) : consolidation becomes denser - ABSORPTION STAGE ( > 14 days ) : no crazy paving pattern , GGO remains - LUNG ULTRASOUND : preferred as it is done bedside . - Subpleural areas of consolidation - Areas of white lung 39. MANAGEMENT - Isolation protocol - General measures - Specific therapy - Managing chronic conditions - Management guidelines approved by RGUHS 40. TYPES OF COVID DEDICATED FACILITIES - 1. COVID care center – hostel, hotels for mild suspected cases . - 2. Dedicated COVID health center – full hospital or a block for moderate suspect cases . - 3. Dedicated COVID hospital – for severe suspected cases till results are obtained admitted in ICU 41. GENERAL MEASURES - Empiric antibiotics if secondary bacterial pneumonia is suspected . - Avoid nebulized medications . - Glucocorticoids - according to WHO and CDC is not indicated . - Prevention of venous thromboembolism ; Prophylactic dose : inj Enoxaparin 40 mg once a day . Full dose : Enoxaparin 1 mg / kg every 12 hours . uptodate 42. EMERGENCY USE AUTHORIZATION MANAGEMENT FOR COVID 19 - 1. Chloroquine and Hydroxychloroquine . - 2. Remdesivir - 3 . Convalescent plasma - 4. Hyperimmune globulin . 43. REMDESIVIR - It is an adenosine nucleotide prodrug - Competes for incorporation into RNA chains - Delayed chain termination during viral RNA replication . - DOSING : I.V. 200 mg on day 1 - Followed by 100 mg OD for 5 or 10 days based on severity . 44. HYDROXYCHLOROQUINE / CHLOROQUINE - Changes pH at cell membrane surface - Inhibits viral fusion - Inhibits nucleic acid replication , viral assembly and release . - DOSE: as per FDA 1. 800 mg PO on day 1 2. 400 mg PO OD for 4-7 days . Baseline : ECG , RFT , electrolytes , LFT to be done . Repeat ECG 2-4 hours , 48 hours and 96 hours after 1st dose . 45. PLASMA THERAPY - It is a strategy of passive immunization . - Apheresis is the recommended procedure to obtain plasma - 1. neutralising antibodies – ANTIVIRAL EFFECTS . - 2. contains : antithrombotic factors , immunoglobulins , antibodies that block complement , inflammatory cytokines TNα and IL-1β – IMMUNOMODULATORY EFFECTS . Manuel Rojas et al , Elsevier on April 11 2020 46. - PATIENT ELIGIBILITY : 1. Laboratory confirmed covid 19 2.Informed consent by patient or attenders 3.Severe and critical disease – as per WHO . DONOR ELIGIBILITY : 1. Evidence of covid – 19 documented by RTPCR or serology . 2. Complete resolution of symptoms atleast 14 days before donation . 3. Female donors who have not been pregnant or negative for HLA antibodies .. FDA 47. - Dose : 3 ml/kg body weight in divided doses. - Covid 19 – convalescent plasma should be frozen within 8 hours of collection - Stored at – 18 C . - Expiration date – 1 year from date of collection . FDA 48. CLINICAL MANAGEMENT AS PER RGUHS GROUP A : TREATMENT : 1 . Cap oseltamivir 75mg bd for 5 days 2. Tab azithromycin 500 mg od for 5 days 3. Tab hydroxychloroquinine 400mg OD for 1 day followed by 200 mg BD for 4 days 49. 4. Inj ENOXIPARIN 40 mg , s/c , OD for 7 days ( if D-dimer > 1000 ng/ml or CT thorax showing ground glass opacities ) SUPPORTIVE : Tab zinc 50 mg od for 7days Tab vitamin C 500 mg TID for 7 days 50. GROUP B ( MODERATELY SICK PATIENTS) - Same as GROUP A - IV antibiotics according local antibiogram - Tab N-acetyl cysteine TID in patients with cough - Continous monitorong of oxygen saturation is advised - If saturation < 94 % to start on oxygen – 5L/ min via face mask or nasal prongs . 51. GROUP C ( CRITICALLY SICK PATIENT ) - Oral medications same as GROUP A - IV antiobiotics can be escalated - Inj Enoxaparin 1 mg/kg body weight s/c BD for 7 days - NOVEL THERAPY : - 1. TOCILIZUMAB - 2. REMDESIVIR - 3. CONVALESCENT PLASMA Lopinavir / Ritonavir to be used when there is no response for primary treatment . 52. - High flow nasal oxygen to be given - If patient deteriorates early intubation to be considered ABG to be done regularly for monitoring of acidosis and hypoxemia . Ionotrophic support to maintain MAP > 65 mmHg Correction of electrolyte abnormalities and acidosis Maintain HB > 8 gm % Group C patient progresses to ARDS , SHOCK novel therapy can be started 53. AIRWAY MANAGEMENT - COVID 19 is a hypoxemic respiratory failure . - High flow oxygen through nasal cannula upto 60 L/min should be started - If low flow oxygen therapy fails - Since NIV works well with hypercapnic failure it is not beneficial compared to high flow oxygen therapy - In later stages intubation to be done following AHA protocol creating a closed set up with HEPA filters at expiratory end and in line suction catheter - Minium oxygen fraction should be given to maintain spo2 0f 90-96% - Fio2 – 0.6 ideal . 54. DISCHARGE POLICY FOR COVID 19 - Mild : after 10 days of symptom onset , afebrile - 3 days - Moderate : after 10 days of symptom onset , afebrile and off oxygen for 3 days . - Severe : clinical recovery . - Only severe patients need RTPCR negative test before discharge - Mild and moderate – 7 days of home isolation following discharge , RTPCR not required MOHFW on 8/5/2020 55. PROPHYLAXIS – HYDROXYCHLOROQUINE Sl no. Category of personnel DOSAGE 1. Asymptomatic household contacts of lab confirmed patient 400 mg BD on day 1 400 mg weekly * 3 weeks 2. a. All asymptomatic HCW b. asymptomatic frontliners , surveillance team , paramilitary / police personnel in containment zone 400 mg bd on day 1 400 mg weekly once * 7 weeks As per Icmr on 22/5/2020 56. VACCINE TRIALS - Beijing Institute of Biotechnology , China conducted first human trial with adenovirus type 5 vectored COVID 19 vaccine . - It is a single centre , open label, non randomised dose escalation phase 1 trial . 108 covid negative participants were recruited - Confirmed by negative results of serum specific IgM and IgG with rapid test . - Negative RTPCR for covid in pharyngeal swabs , anal swabs . - Clear CT image with no evidence of lesions in lungs at the time of screening Feng-CaiZhu et al , Beijing institute of biotech , lancet article , may 22 2020 57. divided into 3 groups with 36 participants in each group. 1st group received mild dose 5 *10 10 . 2nd group received moderate dose 1*10 11. 3rd group received high dose 1.5 * 10 11 . received intramuscularly . 58. primary outcome after 7 days was adverse events , common injection site reaction was pain. systemic adverse reactions were fever , fatigue , headache and muscular pain . these reactions occurred within 24 hours post vaccination and persisted not more than 48 hours . 59. - Rapid binding antibody responses to RBD were observed in all 3 groups from day 14 . - Four- fold increase of anti – RBD antibodies was noted . - Neutralising antibodies against live SARS-CoV-2 were all negative at day 0 , increased at day 14 , peaking at 28 days post – vaccination . 60. - The Ad5 vectored COVID 19 vaccine is immunogenic , inducing humoral and T- cell responses peaking at day 14 and antibodies peaking at day 28 . - In conclusion , Ad5 vectored COVID 19 vaccine is tolerable and immunogenic in healthy adults 61. 1253 STUDIES ARE ONGOING FOR MANAGEMENT OF COVID 19 . - Includes hydroxychloroquine . - Plasma based therapy - Lopinavir/ Ritonavir - Azithromycin - Remdesivir - Vaccine - Tocilizumab - Favipiravir - Sarilumab - Anakinra - Interferon therapy - Umifenovir - Corticosteroids - Steam cell therapy 62. INDIAN TRIALS LISTED IN NATIONAL INSTITUTES OF HEALTH - 1. efficacy of HCQ as post exposure prophylaxis for prevention of COVID – 19 . By post graduate institute of medical education , Chandigarh with 200 participants started on march 1 2020 . - 2. Ivermectin versus standard treament by Max super speciality hospital, new Delhi with 50 participants start date on april 5 2020 , primary outcome being eradication of virus . 63. - 3. Efficacy of convalescent plasma therapy in severely sick covid 19 patients . Conducted by Maulana Azad Medical college . New Delhi and Institute of Liver and Biliary sciences with 40 participants started on April 21 2020 , primary outcome being patients remaining free of mechanical ventlation . 64. - 4. Low dose radiation therapy with a dose of 70 cGy in one fraction radiation for COVID 19 pneumonia by AIIMS , New Delhi with 10 participants estimated to start in june 2020 , primary outcome being symptomatic improvement and to reduce length of hospital stay , and ICUadmissions . 65. - 5 . A clinical trial of Mycobacterium w in critically ill COVID 19 patients conducted by AIIMS , Bhopal , MP and PG medical college , Chandigarh . With 40 participants started on April 30 , 2020 . - Suspension of heat killed Mycobacterium w , 0.3 ml of intradermal injection for 3 consecutive days were given along with standard therapy . - Primary outcome : to study effect of Mw on recovery of organ failure . 66. RAAS INHIBITORS AND RISK OF COVID - Harmonay et al from New York University conducted this study , published on May 1 2020 at NEJM. Total of 12,594 patients were tested for covid out of which 5894 were tested positive . 2573 patients had hypertension and were on - ACE inhibitors - ARB’s - Beta – blockers - Calcium channel blockers - Thiazide diuretic 67. - Previous treatment with medications acting on RAAS was not associated with higher risk of testing positive for covid 19 . - No high risk of severe Covid -19 associated with any of the medications studied.. - Medications can be continued unless contraindicated - Like: hypotension , hyperkalaemia , acute kidney injury . 68. COVID WITH DIABETES - Diabetes is a risk factor for development of severe pneumonia and sepsis , occurs in 20 % of patients . - ACUTE HYPERGLYCEMIA : upregulates ACE2 expression on cells facilitating virus cell entry . - ACE2 on pancreatic β cell leads to damage causing insulin deficiency. - Hence monitoring for new onset diabetes is important . Stefan et al , King’s college , London UK , LANCET diabetology on april 23 69. THERAPEUTIC AIMS - Plasma glucose concentration : 72-180 mg/dl - HBA1C : < 7 % INSULIN THERAPY : - Subcutaneous insulin therapy with basal or intermediate acting insulin along with meal time bolus of short acting insulin is preffered . - DPP4 inhibitors may be continued due to low risk of hypoglycemia , 70. THERAPY WHEN USED IN COVID 19 SUGGESTIONS FOR PRACTICE METFORMIN Risk of lactic acidosis in hypoxia and acute illness Stop if severley ill with hypoxia and hemodynamic instability SGLT2 inhibitors Risk of dehyration and euglycaemic ketoacidosis Stop in severely ill patients GLP-1 RAs Gastrointestinal side effects and risk of aspiration Not advised in severe disease SULFONYLURE AS Risk of hypoglycaemia due to poor oral intake and with use of HCQ’s Stop if poor oral intake or at risk of hypoglycaemia 71. THERAPEUTIC AGENT Adverse events Choloroquine/ HCQ 1.Hypoglycaemia . Caution with Insulin and Insulin secretagogues. 2. QT interval prolongation . Lopinavir / Ritonavir 1.Hyperglycaemia , Poor glycaemic control . 2. Interaction with statins , Increases risk of hepatotoxicity and muscle toxicity Glucocorticoids 1. Hyperglycaemia 2. susceptibility to secondary bacterial infection Remdesivir Caution with statins. Hepatotxicity 72. COVID AND PREGNANCY - Clinical characteristics of pregnant covid 19 positive patients are similar to non pregnant patients . - Risk of transmission to infant is very low . - There is no confirmed mother - to- child transmission , - no positive cord blood or vaginal samples 73. WHO GUIDELINES FOR PREGNANT WOMEN WITH COVID - Covid 19 positive status alone is not an indication for caesarean section . - Mode of birth should be individualized based on obstetric indications . - Mothers should not be separated from their infant unless mother is too sick to care for her baby - Breastfeeding to be initiated within 1 hour of birth . - Advised to follow strict hygienic measures while handling the baby . 74. GUIDANCE FOR STARTING AND CONTINUING RESUSCITATION . - Health care system should institute policies for front liners in determining the appropriateness of starting and terminating CPR . - Mortality of critically ill covid 19 patient is high - It is reasonable to consider age , co morbidities , severity of illness to start CPR - To balance the success against the risk of rescuers . - American Heart Association 75. GUIDELINES ON RATIONAL USE OF PPE - Out patient department – Triage area , temperature recording area , waiting area , Doctor’s chamber with moderate risk No aerosol generating procedure shall be allowed . N95 mask and Gloves are the recommended PPE as per Ministry of Health and Family Welfare . Icmr 76. IN- PATIENT SERVICES - Isolation rooms with moderate risk – N95 mask and gloves . - ICU with high risk aerosol generating activities performed – full component of PPE . - ICU – dead body packing full component PPE . 77. - Other services : - LABORATORY : sample collection and transportation – full component of PPE . - Sanitation , CSSD, Supportive staff only N95 mask and Gloves . - Other non – COVID treatment areas PPE as per hospital protocol . 78. REUSE OF N95 MASKS - Mask rotation : 5 masks as per CDC should be numbered , rotated every day - Allow them to dry > 72 hours - Store in clean paper bag . - Dispose the mask if exposed to aerosol producing procedures . - DECONTAMINATION : - Hydrogen peroxide vaporization . - UV treatment - Moist and Dry heat . - Baking , boiling , using bleach , alcohol , soapy water not approved . 79. INDIAN STATISTICS Confimed 2,17,187 Recovered 1,04,107 Deaths 6,088 Confimed Recovered Deaths 80. STATISTICS OF WORLD Confirmed 65,75,177 Recovered 31,71,783 Deaths 3,88,060 Confirmed Recovered Deaths 81. PROGNOSIS - INDIA : - Incidence per million : 132 - Recovery rate : 48.31 % - Case fatality rate : 2.82 % - 50 % death – senior citizens - 75% death – with co morbidities . 82. REFERANCES - UPTODATE - WHO guidelines on clinical management of covid 19 - International pulmonologist’s consensus on covid 19 - COVID 19 clinical management approved by RGUHS - Centers for disease control and prevention . - WORLD HEALTH ORGANIZATION - U.S Food and Drug Administration - ClinicalTrials.gov - Harmony et al RAAS inhibitors and risk of covid 19 from Grossman school of medicine , new york - Practical recommendations for management of diabetes in patients with Covid 19 by Stefan et al published in Lancet journal 83. THANK YOU |
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| Posted by : peter88 | Post date : 2020-06-12 23:24 | ||
| Category : Health & Medicine | Views : 304 | ||
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