2019 Novel Coronavirus Where are we at And

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2019 Novel Coronavirus Where are we at? And where are we going? Raquel Nahra

2019 Novel Coronavirus Where are we at? And where are we going? Raquel Nahra MD Henry Fraimow MD

2019 n. Co. V: A series of 11 Questions, only some with Answers (yet)

2019 n. Co. V: A series of 11 Questions, only some with Answers (yet) • • • Data: How do we know what we know (and what sources should we trust? ) What do we know about the novel Coronavirus? How does it compare to other respiratory Coronaviruses? Where did it come from? How sick can it make you? How transmissible is it? Can we test for it? What are our infection prevention strategies? Can we treat it? What is Cooper doing about it?

Where do we get up-to-date Information? • https: //gisanddata. maps. arcgis. com/apps/opsdashboard/index. html#/bda 75

Where do we get up-to-date Information? • https: //gisanddata. maps. arcgis. com/apps/opsdashboard/index. html#/bda 75 94740 fd 40299423467 b 48 e 9 ecf 6 • https: //www. ecdc. europa. eu/en/geographical-distribution-2019 -ncov-cases • https: //www. who. int/emergencies/diseases/novel-coronavirus-2019 • https: //www. who. int/emergencies/diseases/novel-coronavirus-2019/situation-reports/ • • • https: //www. cdc. gov/coronavirus/2019 -ncov/index. html https: //www. nj. gov/health/cd/topics/ncov. shtml https: //www. thelancet. com/coronavirus https: //www. idsociety. org/public-health/novel-Coronavirus/ https: //www. nejm. org/coronavirus The news media- but be careful!

SARS-Co. V-2 • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co. V-2) by the Coronavirus

SARS-Co. V-2 • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co. V-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses COVID-19 • Coronavir-disease 19

A brief Timeline: An epidemic in Real Time 1 st patient presents: December 8,

A brief Timeline: An epidemic in Real Time 1 st patient presents: December 8, 2019; probable earlier case December 1, 2019 Lancet, January 24, 2020

https: //gisanddata. maps. arcgis. com/apps/opsdashboard/index. html#/bda 7594740 fd 40299423467 b 48 e 9 ecf

https: //gisanddata. maps. arcgis. com/apps/opsdashboard/index. html#/bda 7594740 fd 40299423467 b 48 e 9 ecf 6 https: //www. ecdc. europa. eu/en/geographical-distribution-2019 -ncov-cases

What do we know about the virus? And how does it compare to other

What do we know about the virus? And how does it compare to other Coronaviruses? • • • Coronaviruses Enveloped, SS RNA virus Named for their “spiked” appearance Mammals and Humans, Zoonotic Ubiquitous respiratory viruses But virulent clades, genetically distinct from common respiratory strains: • SARS • MERS • 2019 n. Co. V Centers for Disease Control and Prevention's Public Health Image Library (PHIL)

Pathogen Detection among U. S. Adults with Community-Acquired Pneumonia Requiring Hospitalization, 2010– 2012. Jain

Pathogen Detection among U. S. Adults with Community-Acquired Pneumonia Requiring Hospitalization, 2010– 2012. Jain S et al. N Engl J Med 2015; 373: 415 -427

Prior Severe Coronavirus Pneumonias: SARS (2002 -3) and MERS-Co. V (2012 -20) • SARS:

Prior Severe Coronavirus Pneumonias: SARS (2002 -3) and MERS-Co. V (2012 -20) • SARS: Bat virus but ? Via civets or other • Binds to ACE-2 • >8000 ill/≈ 800 deaths • Biphasic illness viremic/systemic then recurrent fever, hypoxia, pneumonia, 20% ARDS • Household and HCWs • MERS -Co. V similar to bat viruses. Link to camels • Approx 2500 ill, 850 deaths (July 2019), > 80 % in Saudi Arabia • Spread to Korea (186) from 1 case, 2 US cases • Sx: severe acute resp illness, fever, cough, SOB • Household and HCW cases

Characteristics of Patients infected with 2019 n. Co. V vs MERS-Co. V vs SARS-Co.

Characteristics of Patients infected with 2019 n. Co. V vs MERS-Co. V vs SARS-Co. V www. thelancet. com Published online January 24, 2020 https: //doi. org/10. 1016/S 0140 -6736(20)30185 -9

SARS vs. n. Co. V 2019 n. Co. V outbreak Dec 8 2019 -

SARS vs. n. Co. V 2019 n. Co. V outbreak Dec 8 2019 - Feb 3, 2020 SARS 2002 -2003 outbreak

Coronavirus vs. Influenza: Is it worse? • CDC uses the cumulative rates of influenza-associated

Coronavirus vs. Influenza: Is it worse? • CDC uses the cumulative rates of influenza-associated hospitalizations reported through Flu. Surv-NET and a mathematical model**** to estimate the number of persons who have been symptomatically ill with influenza who had a medical visit, were hospitalized, or died related to influenza. Using data available from October 1, 2018, to May 4, 2019, CDC estimates that influenza virus infection has caused 37. 4 million– 42. 9 million symptomatic illnesses; 17. 3 million– 20. 1 million medical visits; 531, 000– 647, 000 hospitalizations; and 36, 400 – 61, 200 deaths in the United States. https: //www. cdc. gov/mmwr/volumes/68/wr/mm 6824 a 3. htm? s_cid= mm 6824 a 3_w#F 1_down Mortality rate from Influenza 2018 -9: ~0. 1% Est. Mortality from Spanish Flu 1918 -9: 10%

What do we know about Transmissibility? Early on: Point Source Outbreak Later pattern of

What do we know about Transmissibility? Early on: Point Source Outbreak Later pattern of ongoing person to person transmission to sustain the outbreak and increasing the R 0

 • At this point in time the mode of transmission is presumed Droplet

• At this point in time the mode of transmission is presumed Droplet • ? Fecal oral transmissibility ( like instances observed with SARS) • 1 st US 2019 n. Co. V case had virus transiently detected in stool https: //www. nejm. org/doi/full/10. 1056/NEJMoa 2001191? query=feat ured_coronavirus Infect Dis Clin North Am. 2019 Dec; 33(4): 869 -889. doi: 10. 1016/j. idc. 2019. 07. 001. Severe Acute Respiratory Syndrome: Historical, Epidemiologic, and Clinical Features. Hui DSC, Zumla A

Transmissibility • It is notable that few of the early cases occurred in children

Transmissibility • It is notable that few of the early cases occurred in children • Bias of case definition (initial focus of case detection was on patients with pneumonia, some patients can present with gastrointestinal symptoms) • Children might be less likely to become infected vs an asymptomatic infection in a children) • if infected, may show milder symptoms, and either of these situations would account for underrepresentation in the confirmed case count. • Serosurveys after the first wave of the epidemic would clarify this question

How does 2019 n. Co. V cause the infection? Pathogenesis SARS-Co. V 2019 Co.

How does 2019 n. Co. V cause the infection? Pathogenesis SARS-Co. V 2019 Co. V • Infect several organs and cell types during the course of the disease, Respiratory, intestinal mucosal cells, renal tubular epithelial cells, neurons, and cells of the lymphoid and reticuloendothelial system. • Entry of SARS-Co. V is mediated by angiotensin -converting enzyme 2 (ACE 2), a metallopeptidase that is expressed on many human organ tissues, as the host functional receptor. • ACE 2 is present abundantly in the epithelia of human lungs and small intestine. • Pathogenesis more complex than this • Preliminary analyses indicate that 2019 -n. Co. V has some amino acid homology to SARS-Co. V and may be able to use ACE 2 as a receptor. This has important implications for predicting pandemic potential moving forward. Infect Dis Clin North Am. 2019 Dec; 33(4): 869 -889. doi: 10. 1016/j. idc. 2019. 07. 001. Severe Acute Respiratory Syndrome: Historical, Epidemiologic, and Clinical Features. Hui DSC, Zumla A

 • ACE-2 has a key protective role in acute lung injury by reducing

• ACE-2 has a key protective role in acute lung injury by reducing alveolar fluid, and thus the binding of SARS-Co. V to ACE-2 may contribute to the dysregulation of fluid balance in the alveolar space

NEJM Januarny 24, 2020

NEJM Januarny 24, 2020

How sick can n. Co. V make you? And how often? • We have

How sick can n. Co. V make you? And how often? • We have a lot of data on the earliest, sicker cases but less data on the minimally sick • How many infections are mildly symptomatic or asymptomatic?

Key Time-to-Event Distributions. Q Li et al. N Engl J Med 2020. DOI: 10.

Key Time-to-Event Distributions. Q Li et al. N Engl J Med 2020. DOI: 10. 1056/NEJMoa 2001316

Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization,

Symptoms and Maximum Body Temperatures According to Day of Illness and Day of Hospitalization, January 16 to January 30, 2020. ML Holshue et al. N Engl J Med 2020. DOI: 10. 1056/NEJMoa 2001191

Clinical Characteristics of Coronavirus Disease 2019 in China • Fever was defined as an

Clinical Characteristics of Coronavirus Disease 2019 in China • Fever was defined as an axillary temperature of 37. 5°C or higher • Lymphocytopenia was defined as a lymphocyte count of less than 1500 cells per cubic millimeter. • Thrombocytopenia was defined as a platelet count of less than 150, 000 per cubic millimeter

PUI criteria as of 3/8/20

PUI criteria as of 3/8/20

Testing • State • Commercial lab

Testing • State • Commercial lab

Preventive and mitigation measures • The most effective preventive measures in the community include:

Preventive and mitigation measures • The most effective preventive measures in the community include: – performing hand hygiene frequently with an alcohol-based hand rub if your hands are not visibly dirty or with soap and water if hands are dirty; – avoiding touching your eyes, nose and mouth; – practicing respiratory hygiene by coughing or sneezing into a bent elbow or tissue and then immediately disposing of the tissue; – wearing a medical mask if you have respiratory symptoms and performing hand hygiene after disposing of the mask; – maintaining social distance (a minimum of 1 m) from individuals with respiratory symptoms.

PPE • ILI – Wear a Facemask /shield and gloves – Probable PUI High

PPE • ILI – Wear a Facemask /shield and gloves – Probable PUI High Risk will go on Air borne IF available • PUI who rules in for other viruses will be placed in precautions consistent with their diagnosis • PUI that the state is not testing and /or deemed low risk or moderate risk the patient will be removed from isolation • If a case is not deemed PUI isolation will be removed

What about HCWs? • HCW have been infected, though the proportion has not been

What about HCWs? • HCW have been infected, though the proportion has not been as high as during the SARS and MERS outbreaks • One of the features of SARS and MERS outbreaks is heterogeneity in transmissibility, and in particular the occurrence of super-spreading events, mostly in hospitals • No super-spreaders effect noted yet with 2019 n Co. V

What have we learned from SARS Co. V outbreak 2002 -2003 as far as

What have we learned from SARS Co. V outbreak 2002 -2003 as far as infection prevention ? Independent risk factors of superspreading nosocomial outbreaks of SARS • Performance of resuscitation (OR = 3. 81; 95% CI, 1. 04– 13. 87; P =. 04). • Staff working while experiencing symptoms (OR = 10. 55; 95% CI, 2. 28– 48. 87; P =. 003) • Patients with SARS requiring oxygen therapy at least 6 L/min (OR = 4. 30; 95% CI, 1. 00– 18. 43; P =. 05) • Patients with SARS requiring noninvasive positive pressure ventilation (OR = 11. 82; 95% CI, 1. 97– 70. 80; P =. 007) Respiratory procedures associated with increased risk of transmission to health care workers • Tracheal intubation (n = 4 cohorts; 6. 6 [2. 3, 18. 9], and n = 4 case-controls; 6. 6 [4. 1, 10. 6]); • Noninvasive ventilation (n = 2 cohorts; OR = 3. 1 [1. 4, 6. 8]); • Tracheotomy (n = 1 case-control; 4. 2 [1. 5, 11. 5]); • Manual ventilation before intubation (n = 1 cohort; OR = 2. 8 [1. 3, 6. 4]). • Minimum distance between beds <1 m (OR = 6. 98; 95% CI, 1. 68– 28. 75; P =. 008) • Washing or changing facilities for staff (OR = 0. 12; 95% CI, 0. 02– 0. 97; P =. 05) I. T. Yu, Z. H. Xie, K. K. Tsoi, et al. Why did outbreaks of severe acute respiratory syndrome occur in some hospital wards but not in others? Clin Infect Dis, 44 (2007), pp. 1017 -1025 K. Tran, K. Cimon, M. Severn, et al. Aerosol generating procedures and risk of transmission of acute respiratory infections to healthcare workers: a systematic review PLo. S One, 7 (2012), p. e 35797

Can we treat it? At this point in time Treatment is supportive Antibiotics were

Can we treat it? At this point in time Treatment is supportive Antibiotics were used to treat secondary infection Antiviral Oseltamivir (75 mg every 12 h, orally) Ganciclovir (0· 25 g every 12 h, intra venously) Lopinavir and ritonavir tablets (500 mg twice daily, orally). The duration of antiviral treatment was 3– 14 days www. thelancet. com Published online January 29, 2020 https: //doi. org/10. 1016/S 01406736(20)30211 -7

 • The treatment for SARS is largely supportive with low tidal volume mechanical

• The treatment for SARS is largely supportive with low tidal volume mechanical ventilation • ECMO Crit Care. 2008; 12(4): 219. doi: 10. 1186/cc 6917. Epub 2008 Jul 17. Bench-to-bedside review: rare and common viral infections in the intensive care unit--linking pathophysiology to clinical presentation. Stollenwerk N 1, Harper RW, Sandrock CE.

Treatment extrapolated from SARS /MERS • No antiviral agents have been found to provide

Treatment extrapolated from SARS /MERS • No antiviral agents have been found to provide benefit for treating SARS. • No approved antivirals to treat Coronaviruses (Co. Vs) infections. • Development of nucleoside-based therapeutics for Co. V infections has been hampered by the presence of a proofreading exoribonuclease SARS: systematic review of treatment effects. Stockman LJ 1, Bellamy R, Garner P. a virus, has activity against the SARS and MERS coronaviruses

Clinical outcome Dose/route Number of papers Take Ribavirin Variables/IV or PO 24 ( most

Clinical outcome Dose/route Number of papers Take Ribavirin Variables/IV or PO 24 ( most had no control group) 3 papers concluded harmful 21 Inconclusive Ribavirin given at 1. 2 g three times a day orally for 2 wk resulted in a drop in hemoglobin of >2 g/d. L from baseline in 59% of patients, with evidence of hemolysis documented in 36%. Based on a higher dosage of ribavirin for treating hemorrhagic fever virus, patients with SARS-Co. V infection in Toronto developed more toxicity, including elevated transaminases and bradycardia Corticosteroids MP/Hydrocostisone IV or pulse 15 papers 2 harmful 13 inconclusive Clinical improvement in some patients with resolution of fever and lung consolidation following treatment with intravenously pulsed MP Retrospective cohort analysis in Hong Kong showed that the use of pulsed MP was actually associated with an increased risk of 30 -day mortality (adjusted odds ratio

Clinical outcome Dose/route Number of papers Take Protease inhibitors Lopinavir/ritonavir Lopinavir 400 mg/ritonavir 100

Clinical outcome Dose/route Number of papers Take Protease inhibitors Lopinavir/ritonavir Lopinavir 400 mg/ritonavir 100 mg orally every 12 hours 2 studies Inconclusive Too many interventions at the Same time Interferon-alpha sc or IM 2 studies inconclusive In an uncontrolled study in Toronto, interferon-alfacon-1 given within 5 d of illness resulted in improved oxygen saturation, more rapid resolution of radiographic lung opacities, and lower rates of intubation (11. 1% vs 23. 1%) and death (0. 0% vs 7. 7%); however, the sample size was small (n = 9 vs 13) and confounded by the concomitant use of systemic corticosteroid IVIG or convalescent plasma IV 5 ( too many intervention at same time or used as rescues ) Inconclusive n a study comparing patients with SARSCo. V infection who did and did not receive convalescent plasma, 19 patients who received such therapy had higher survival rate (100% vs 66. 2%) and higher discharge rate (77. 8% vs 23. 0%) compared with 21 controls Early administration seems to be recommended More studies needed

Lopinavir /Ritonavir data Lopinavir and Ritonavir Lopinavir 400 mg/ritonavir 100 mg orally every 12

Lopinavir /Ritonavir data Lopinavir and Ritonavir Lopinavir 400 mg/ritonavir 100 mg orally every 12 hours Death rate in LPV/r initial treatment group: 2. 3% Death rate control: 15. 6%. Death rate in LPV/r rescue group: 12. 9% Death rate control: 14%. The addition of LPV/r to a standard treatment protocol as an initial treatment appears to be associated with reduction mortality rate, reduction in intubation and reduction of rescue steroids. Large study of 1052 patients who were not randomly assigned to treatment and control groups, however patients were matched on prognostic factors. Physicians assigned treatment regimen and may have treated more severe patients with the LPV/r rescue protocol. Chan et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J 2003; 9(6): 399 -406. Lopinavir 400 mg/ritonavir 100 mg orally every 12 hours Composite outcome up to 21 days of severe hypoxaemia or death: 1/41 for LPV/r v 32/111 for control. LPV/r was associated with better outcome in a multivariate analysis. 29/41 LPV/r treated had a >2 g/dl fall in haemoglobin. Patients with LPV/r as an initial treatment seemed to run a milder disease and had a reduction in viral load A historical control group was used. There were differences in treatment and control group in terms of sex, platelet counts, LDH level. Positive effect of L/R could have been exaggerated by worse than expected outcome in controls. Chu et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004; 59(3): 252 -6.

Remdesivir (GS-5734)- Used on the Washington case as compassionate use on day 7 of

Remdesivir (GS-5734)- Used on the Washington case as compassionate use on day 7 of illness • an experimental agent whose development was accelerated because of its activity against Ebola and Marburg virus • GS-5734 potently inhibits Co. Vs with intact proofreading and the virus mutated and became low level resistant it also only partially impaired fitness and virulence of SARS-Co. V 1 -Agostini ML, Andres EL, Sims AC, et al. Coronavirus Susceptibility to the Antiviral Remdesivir (GS-5734) Is Mediated by the Viral Polymerase and the Proofreading Exoribonuclease. m. Bio. 2018; 9(2): e 00221 -18. Published 2018 Mar 6. doi: 10. 1128/m. Bio. 00221 -18 2 -First Case of 2019 Novel Coronavirus in the United States. Michelle L. Holshue, M. P. H. , et al. NEJM, Jan 31 2020

Treatment references • Knowles et al. Common adverse events associated with the use of

Treatment references • Knowles et al. Common adverse events associated with the use of ribavirin for severe acute respiratory syndrome in Canada. Clin Infect Dis 2003; 37(8): 1139 -42. • Booth et al. Clinical features and short-term outcomes of 144 patients with SARS in the greater Toronto area. JAMA 2003; 289(21): 2801 -9. • Zhao et al. Description and clinical treatment of an early outbreak of severe acute respiratory syndrome (SARS) in Guangzhou, PR China. 2003; 52(8): 715 -20. • Cui et al. Serum hepatic enzyme manifestations in patients with severe acute respiratory syndrome: Retrospective analysis. World Journal of Gastroenterology 2004; 10(11): 1652 -5. • Chen et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol 2004; 31(1): 69 -75. • • Chu et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004; 59(3): 252 -6. Han et al. Noninvasive positive pressure ventilation treatment for acute respiratory failure in SARS. Sleep and Breathing 2004; 8(2): 97 -106. • • Cinatl et al. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003; 361(9374): 2045 -6. Sung et al. Severe acute respiratory syndrome: report of treatment and outcome after a major outbreak. Thorax 2004; 59(5): 414 -20. • • Morgenstern et al. Ribavirin and interferon-beta synergistically inhibit SARS-associated coronavirus replication in animal and human cell lines. Biochem Biophys Res Commun 2005; 326(4): 905 -8. Hon et al. Clinical presentations and outcome of severe acute respiratory syndrome in children. Lancet 2003; 361(9370): 1701 -3. • • Stroher et al. Severe acute respiratory syndrome-related coronavirus is inhibited by interferon- alpha. J Infect Dis 2004; 189(7): 1164 -7. Peiris et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. Lancet 2003; 361(9371): 1767 -72. • • Tan et al. Inhibition of SARS coronavirus infection in vitro with clinically approved antiviral drugs. Emerg Infect Dis 2004; 10(4): 581 -6. Ooi et al. Severe Acute Respiratory Syndrome: Radiographic Evaluation and Clinical Outcome Measures. Radiology 2003; 229(2): 500 -6. • Tsui et al. Severe acute respiratory syndrome: Clinical outcome and prognostic correlates. 2003; 9(9): 1064 -9. • Yamamoto et al. HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus. Biochem Biophys Res Commun 2004; 318(3): 719 -25. • Tsang et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med 2003; 348(20): 1977 -85. • Cinatl et al. Treatment of SARS with human interferons. Lancet 2003; 362(9380): 293 -4. • • Haagmans et al. Pegylated interferon-alpha protects type 1 pneumocytes against SARS coronavirus infection in macaques. Nat Med 2004; 10(3): 290 -3. Lee et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. New England Journal of Medicine 2003; 348(20): 1986 -94. • • He et al. Potent and selective inhibition of SARS coronavirus replication by aurintricarboxylic acid. Biochem Biophys Res Commun 2004; 320(4): 1199 -203. Gomersall et al. Short-term outcome of critically ill patients with severe acute respiratory syndrome. Intensive Care Med 2004; 30(3): 381 -7. • • Scagnolari C et al. Increased sensitivity of SARS-coronavirus to a combination of human type I and type II interferons. Antivir Ther 2004; 9(6): 1003 -11. Lee et al. Effects of early corticosteroid treatment on plasma SARS-associated Coronavirus RNA concentrations in adult patients. J Clin Virol 2004; 31(4): 304 -9. • • Spiegel et al. The antiviral effect of interferon-beta against SARS-coronavirus is not mediated by Mx. A protein. J Clin Virol 2004; 30(3): 211 -3. Ho et al. High-dose pulse versus nonpulse corticosteroid regimens in severe acute respiratory syndrome. Am J Respir Crit Care Med 2003; 168(12): 1449 -56. • • Zheng et al. Potent inhibition of SARS-associated coronavirus (SCOV) infection and replication by type I interferons (IFN-alpha/beta) but not by type II interferon (IFN-gamma). J Interferon Cytokine Res 2004; 24(7): 388 -90. Chan et al. Treatment of severe acute respiratory syndrome with lopinavir/ritonavir: a multicentre retrospective matched cohort study. Hong Kong Med J 2003; 9(6): 399 -406. • Chu et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004; 59(3): 252 -6. • Hensley et al. Interferon-beta 1 a and SARS coronavirus replication. Emerg Infect Dis 2004; 10(2): 317 -9. • • Sainz et al. Interferon-beta and interferon-gamma synergistically inhibit the replication of severe acute respiratory syndrome-associated coronavirus (SARS-Co. V). Virology 2004; 329(1): 11 -7. Loutfy et al. Interferon alfacon-1 plus corticosteroids in severe acute respiratory syndrome: a preliminary study. JAMA 2003; 290(24): 3222 -8. • Ho et al. Pentaglobin in steroid-resistant severe acute respiratory syndrome. Int J Tuberc Lung Dis 2004; 8(10): 1173 -9. • O. T. Tsang, T. N. Chau, K. W. Choi, et al. Coronavirus-positive nasopharyngeal aspirate as predictor for severe acute respiratory syndrome mortality Emerg Infect Dis, 9 (2003), pp. 1381 -1387

Where do we get up-to-date Information • https: //gisanddata. maps. arcgis. com/apps/opsdashboard/index. html# /bda

Where do we get up-to-date Information • https: //gisanddata. maps. arcgis. com/apps/opsdashboard/index. html# /bda 7594740 fd 40299423467 b 48 e 9 ecf 6 • https: //www. ecdc. europa. eu/en/geographical-distribution-2019 -ncov -cases • https: //www. who. int/emergencies/diseases/novel-coronavirus-2019 • https: //www. cdc. gov/coronavirus/2019 -ncov/index. html • https: //www. nj. gov/health/cd/topics/ncov. shtml • https: //www. thelancet. com/coronavirus • https: //www. idsociety. org/public-health/novel-Coronavirus/