DR. DANILYCHEV, MD
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​PLEASE NOTE, DUE TO MANY INCONSISTENCIES IN THE INFORMATION AVAILABLE ABOUT THE VIRUS (INCLUDING INFORMATION FROM THE OFFICIAL SOURCES AND FROM THE SCIENTIFIC STUDIES), I HAVE DECIDED NOT TO SHARE ANY ADDITIONAL DETAILS ABOUT THE VIRUS FOR THE TIME BEING.

THANK YOU FOR YOUR UNDERSTANDING!


​CORONAVIRUS INFORMATION FOR HEALTHCARE PROFESSIONALS

LAST UPDATE ON 03/25/2020.
COVID-19 "HACKS"
DATA FROM CHINA
DATA FROM ITALY
DIAGNOSIS
EPIDEMIOLOGY
MORTALITY
PREGNANCY
PROGNOSTICATION
REFERENCES
RISK FACTORS
SYMPTOMS
TRANSMISSION
TREATMENT

THANK YOU FOR YOUR HARD WORK AND SACRIFICE!

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BACKGROUND

Coronaviruses (CoVs) cause a variety of diseases in mammals (including humans) and birds, including a wide range of enteric, hepatic, neurological diseases and respiratory tract infections. [1]

  • Enveloped, positive-sense single-stranded RNA virus
  • ~125 nm sphere with club-shape spike projections on the surface making them look similar to a solar corona (hence the name)
  • Realm: Riboviria, phylum Incertae sedis, order Nidoviales, family Coronviridae
  • Coronaviruses are divided into 4 groups: alpha, beta, gamma and delta 

Although most Coronaviruses tend to only cause mild respiratory tract infections in Humans, a couple of them have gotten our attention over the past two decades. Both of these Coronaviruses were group 2b β-coronaviruses: Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) which caused SARS outbreak in 2002-2003 and Middle Eastern Respiratory Syndrome Coronavirus (MERS-CoV) which emerged in 2012 in the Middle East.  Both SARS and MERS had a high mortality rate especially in the elderly, but a relatively low transmission rate. 

Current Coronavirus pandemic started in December 2019, with the first outbreak of a respiratory infection in Wuhan, China. It is due to Severe Acute Respiratory Syndrome Coronavirus 2” (SARS-CoV-2) which causes Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 was not known until then.


TRANSMISSION

Typical route of transmission of SARS-CoV-2 is respiratory droplets, but the virus may also be present in stool, saliva and urine, so fomite and fecal/oral transmission may take place. Median incubation period is 3 days (range 0-24).  [2]

It appears that fecal SARS-CoV-2 positivity may persist for days after negative oropharyngeal or nasopharyngeal swab [reference to follow]
SARS-CoV-2 may remain on surfaces for hours and days. Here is an image from the NEJM Correspondence section form 03/17/2020. [6] 
Picture
SARS-CoV-2 is in red.

My interpretation of the results:

Minimum time to "safe" contact with exposed surfaces:
- ? for air (still present after 3 hours)
- 8 hours for copper
- 24 hours for cardboard (think packages)
- 48 hours for stainless steel
- 96 hours for plastic (possibly slightly less)
SARS-CoV-2 presence on surfaces also depends on the quantity of the inoculum.

Good news is that decrease in the quantity of viral particles on surfaces is exponential over time.

EXPERT VIEW ON TRANSMISSION

Check out this blog post with one doctor's view

RISK FACTORS

The main factors for developing COVID-19, mostly based on data mostly from hospitalized (so symptomatic) patients [specific references to follow]:
  • Hypertension
  • Obesity
  • Cardiovascular/Cerebrovascular diseases
  • Diabetes
  • Extensive smoking history
  • Lung disease
  • Renal disease
  • Other chronic diseases
  • Male gender (slightly higher risk, varies by location)

SYMPTOMS

The information about the virus is changing rapidly. I will summarize what I know here and will be adding reference later. Please forgive  me. I think it's more important that you have the information as soon as it becomes available and use your judgement on whether or not it is clinically useful to you, as opposed to me withholding what I know.

Between the data from Chinese and Italian hospitals, as well as the information I am getting first hand from my physician colleagues cross the USA, the following symptoms are common, so when thinking of COVID-19, please consider various combinations of symptoms below (with respiratory symptoms being the most common):
  • Cough 
  • Myalgias, arthralgias
  • Fever (often low grade, sometimes high fever, often delayed onset)
  • Dyspnea
  • Fatigue
  • Sore throat
  • Headaches
  • Sputum production
  • Nasal congesion
  • Anosmia
  • Nausea
  • Diarrhea (appears to be associated with higher morbidity)
  • Abdominal pain
  • Chest pain
  • Rash
  • Conjunctival erythema
  • Lymphadenopathy
  • Confusion (? if predominantly affects elderly and really sick patients)
  • Hemoptysis


DATA FROM CHINA

Summary of a study published on 02/06/2020 by Wei-jie Guan, et. al. which analyzed the data from patients in China with COVID-2 from the onset of the epidemic in 2019 through 01/29/2020. [2]

Median age is of COVID-19 patients is in the 40s. Hypertension is the most common comorbidity and is associated with worse outcomes. Typical route of transmission of SARS-CoV-2 is respiratory droplets, but the virus may also be present in stool, saliva and urine, so fomite and fecal/oral transmission may take place. Median incubation period is 3 days (range 0-24). The key symptoms of COVID-2 are cough, fatigue, fever (may be low grade to none on presentation), sputum production, and shortness of breath. Body aches, sore throat, and chills are also not uncommon. Nasal congestion and GI symptoms are relatively rare. Lymphopenia is very common. Ground glass opacities and bilateral patchy infiltrates on chest CT are commonly preset; however, admission chest X-rays may be negative in many cases. Median time from symptom onset to diagnosis of pneumonia is ~ 4 days. Mortality may range between 0.1 and 8%+


Patient characteristics:
  • 1,099 patients from 552 hospitals in 31 provinces.
  • Of them 82.3% were hospitalized.
  • ​Median incubation period was 3.0 days (range, 0 to 24.0 days). 
  • Age: median age 47
  • Gender:  58.2% male, 41.8% female
  • Smoking:  85.4% never smokers, 12.6 % current smokers
  • Comorbidities:
    • Hypertension 14.8%
    • Diabetes 7.4%
    • Coronary artery disease 2.5%
    • Hepatitis B 2.1%
    • Cerebrovascular disease 1.4%
    • COPD 1.1%
    • Cancer 0.9%
    • Chronic kidney disease 0.7%
    • Immunodeficiency 0.2%

Symptoms: 
  • Fever
    • 43.1% of patients had a fever on admission (About 56% had temperature < 37.5 on admission!)
    • 87.9% of patients had a fever during hospitalization (about 46% patients had a temperature between 38.1 and 39 while hospitalized)
  • Cough 67.7%
  • Fatigue 38.1%
  • Sputum production 33.0%
  • Shortness of breath 18.6%
  • Myalgia or arthralgia 14.8%
  • Sore throat 13.9%
  • Headache 13.6%
  • Chills 11.4%
  • Nausea or vomiting 5.0%
  • Nasal congestion 4.8% 
  • Diarrhea 3.7%
  • Tonsil enlargement 2.1%
  • Throat congestion 1.7%
  • Hemoptysis 0.9%
  • Conjunctival erythema 0.8%
  • Lymphadenopathy 0.2%
  • Rash 0.2%

Lymphopenia was observed in 82.1% of patients!

CXR abnormalities were only found in 14.7% of cases!
  • Bilateral patchy Infiltrates 9.1%
  • Local patchy infiltrates 7.0%  
  • Ground-glass opacity 5.0%
  • Interstitial abnormalities 1.1% 

Abnormalities on chest CT 76.4%
  • Ground-glass opacities 50.0% on admission
  • Bilateral patchy infiltrates  46.0%
  • Local patchy infiltrates 37.2% 
  •  Interstitial abnormalities 13.0%

Complications:
  • Pneumonia 79.1%
  • ARDS 3.37%
  • Shock 1.00%. 

Outcomes:
  • "Severe pneumonia, lymphopenia and interstitial abnormality on chest X-ray were associated with the poor outcomes."

Retrospective, single-centre study in Wuhan Jinyintan Hospital, published on 01/30/2020 in Lancet, COVID-10 cases from 01/01/2020 to 01/20/2020 were reviewed. [3]

​
SUMMARY

99 hospitalized COVID-10 patients (mean age 55.5), nearly half of whom were exposed to SARS-CoV-2 at the Huanan seafood market [believed to be the epicenter of the pandemic] in Wuhan, China. Majority of the patients were febrile on admission, cough, shortness of breath, muscle aches and confusion were the most common symptoms in this study. 15% had a combination of three : fever, cough and shortness of breath. 11% mortality rate not including the data of the patients who remained in the hospital whose outcomes was not counted. Lymphopenia, bilateral pneumonia, HTN, heavy smoking were risk factors for higher mortality.

Exposure:
49% of patients were a cluster with exposure at Huanan seafood market [believed to be the epicenter of the pandemic]. 47 (47%) of the patients had long-term exposure (worked at the market), 2 in this cluster had short-term exposure (shoppers).

Patient characteristics:
  • 99 patients from 1 hospitals in in Wuhan, China (all hospitalized)
  • Age: mean age 55.5 (age range 21-82)
  • Gender:  68% male, 32% female
  • Comorbidities:
    • Cardiovascular and cerebrovascular diseases 40% (does't specify if includes hypertension)
    • Digestive system diseases 11% (does not specify which kinds, ? if includes liver disease)
    • Diabetes 12%
    • Cancer 1%
    • Nervous system disease 1%
    • Respiratory system disease 1%
    • Immunodeficiency 0.2%

Symptoms:
  • Fever (83%) - (most patients had fever on admission, degree of fever unspecified)
  • Cough (82%)
  • Shortness of breath (31%)
  • Muscle ache (11%)
  • Confusion (9%)
  • Headache (8%)
  • Sore throat (5%)
  • Rhinorrhoea (4%)
  • Chest pain (2%)
  • Diarrhea (2%)
  • Nausea and vomiting (1%)
  • More than one sign or symptom (90%)
  • Fever, cough, and shortness of breath (15%)

Labs (based on results from 73 patients)
  • Elevated LDH 76%
  • 73 patients were tested for C-reactive protein, most of whom had levels above the normal range
  • Decreased Hb 50% 
  • Abnormal LFTs 43% 
  • Lymphopenia was observed in 35% of patients
  • Elevated WBCs in 24% of cases on admission
  • Elevated CPK 13% 
  • Platelets were below the normal range in 12%
  • Renal dysfunction 7%
  • Procalcitonin above the normal range 6%
  • Most patients had serum ferritin above the normal range

Radiological abnormalities (includes combined CXR and CT results)
  • Bilateral pneumonia 75%
  • Unilateral pneumonia 25%
  • Multiple mottling and ground-glass opacity 14%

Treatment:
  • Oxygen therapy 76%
  • Mechanical ventilation (Non-invasive 13%, Invasive 4%)
  • CRRT9 9%
  • ECMO3 3%

Medications:
  • Antivirals received by 76% of patients
    • oseltamivir 75 mg PO Q12H, ganciclovir 0·25 g Q12H IV, lopinavir and ritonavir tablets .500 mg PO BID.
    • The duration of antiviral treatment was 3–14 days (median 3 days )
  • Antibiotics received by 71% of patients
    • cephalosporins, quinolones, carbapenems, tigecycline, linezolid.
    • The duration of antibiotic treatment was 3–17 days (median 5 days)
    • 25% treated with a single antibiotic and 45% given combination therapy. 
  • Intravenous immunoglobulin therapy 27%
  • Glucocorticoids 19%
    • methylprednisolone, and dexamethasone for 3–15 days (median 5)
  • Antifungals 5%

Complications:
  • ARDS 17%
  • Acute respiratory injury 8%
  • Acute renal injury 4% acute renal injury
  • Septic shock 4%
  • Ventilator-associated pneumonia 1%
  • Pneumothorax 1%

Coinfections*:
  • Fungal (Aspergillus flavus, Candida glabrata, Candida albicans.)
  • Bacterial (Acinetobacter baumannii, Klebsiella pneumoniae)
  • Respiratory viruses 0%

*Acinetobacter baumannii, Klebsiella pneumoniae, and Aspergillus flavus were all cultured in one patient. A baumannii turned out to be highly resistant to antibiotics. 1 Candida glabrata, 3 Candida albicans.

Outcomes:
  • Discharged 50%
  • Remained hospitalized 31% (outcomes of hospitalization of these patients are not known)
  • Died 11%
  • Rapid deterioration from symptom onset to pneumonia, lymphopenia, bilateral pneumonia, age > 60, and HTN, and heavy smoking appear to be risk factors for higher mortality​

In this smaller study, the patients were slightly older on average, there were more males, more smokers. Patients with hypertension were not specifically identified from the group of cardiovascular and cerebrovascular disease which lumped into a single comorbidity. Based on a high rate of delirium on admission, high rate of patients with a fever on admission, and high mortality rate, one may speculate that at least some of the patient's in this study were hospitalized later in the course of their disease. 


DATA FROM ITALY

The Higher Institute of Health [Of Italy - L’Istituto Superiore di Sanità (ISS)]  has disseminated a report on the characteristics of the coronavirus positive patients in Italy, based on the data up to 17th of March, 2020. [7]
​
(Translated from the original text by Dr. Maria Danilychev, MD)

As far as the geographic location of the deceased, out of 2003 deaths the  vast majority 1,425 (71.1%) lived in Lom Lombardia , 346 (17.3%) in Emilia-Romagna , 79 (3.9%) in Veneto , 36 (1.8%)in Piemonte, and  23  (1.1%) in Liguria. The other regions registered less than 1% of the total.

Demographics

Average age of the COVID-19 patients who died was 79.5 years old. 602 (30.0%) women. Median age of the COVID-19 + patients who died [from the disease] is 15 years higher comparing to the patients who have contracted the infection (median age: patients who died 80.5 yo, patients who had the infection 63 yo). Women who died after contracting infection were older comparing to men (median age: of women 83.8, of men 79.5). ​
Picture
Fig.1. Median age of the deceased COVID-19 patients
Picture
Fig. 2. Numbers of the deceased stratified by age. (Blue - women, orange - men, gray - all).
Pre-existing conditions
​As far as the most common chronic pre-existing conditions (diagnosed before the contracting the infection), the data was obtained in 355 ot 2003 deceased (17.7% of the overall sample [size]). The average number of comorbidities in that population is 2.7 [for each person]. Overall, 3 patients (0.8% of sample) had 0 comorbidities, 89 (25.1%) had 1 comorbidity, 91 (25.6%)  had 2 comorbidities, and 172 (48.5%) had 3 or more comorbid conditions. The most common comorbidities can be found in the table below.
Picture
Table 1. (English translation) The most common comorbidities observed in patients who died as a result of COVID-2019 infection
Picture
Table 1. (Original)

​Symptoms
Most common symptoms observed before admission of the patients who died were dyspnea and fever. Less common were cough, diarrhea, and hemoptysis. 5.2% of people did not have any symptoms at the time of the admission. Respiratory failure was the most common complication observed in this sample (97.2% of cases), acute renal failure (27.8), followed by acute myocardial damage (10.8%), and secondary infection 10.2%.

Table 3. Legend: green - hemoptysis, aqua - diarrhea, purple - dyspnea, red - cough, blue - fever
Picture
Fig. 3. Most common symptoms of the COVID-19 patients who died
Treatment
[La terapia antibiotica è stata quella più utilizzata] Antibiotics has been the most commonly utilized treatment for COVID-19 positive patients who subsequently died (83% of cases), less frequently used was antiviral therapy (52%), and steroids were used the least (27%). The wide use of the antibiotics could be explained by the presence of secondary infections or it is [also] compatible with initial empiric treatment in patients with pneumonia pending the laboratory confirmation of COVID-19. In 25 cases (14.9%) all three [types of] treatment were used. ​

Fig. 4 Legend: purple - antibiotics, red - steroids, blue, antivirals
Picture
Fig. 4. Therapies administered to COVID-19 patients who died

In media 8 giorni tra SINTOMI e decesso per #coronavirus Terapia antibiotica la più utilizzata (83% dei casi) a causa di sovrainfezioni. Complessivamente, 3 pazienti presentavano 0 patologie. Leggi il comunicato https://t.co/mRoKvLXf7H

— ISS (@istsupsan) March 18, 2020
Translation of ISS @istsupsan March 18, 2020 tweet:
"On average 8 days between SYMPTOMS and death for #coronavirus Treatment with antibiotics most utilized (83% of cases) due to secondary infections. Overall, 3 patients presented with no past medical history. Read the press release: https://tinyurl.com/u9c2rzs"
Timeline
Figure 5 [shows] median time in day from the onset of symptoms till death (8 days), from onset of symptoms till hospitalization (4 days) and from admission to the hospital until death (4 days). The time from hospitalization till death was 1 day longer in those who were transferred to the ICU comparing to those who were not transferred (5 days vs. 4 days).

Fig. 5. Median hospitalization times (in days) for deceased COVID-19 positive patients. [X axis = median number of days]


Picture
Fig. 5. Legend translation:
  • top bar (blue): onset of symptoms --> death
  • second from the top bar (red): onset of symptoms --> hospitalization
  • middle bar (orange-red):  onset of symptoms --> death
  • forth from the top bar (red lines): hospital admission --> death (NO ICU)
  • bottom bar (red checkers): hospital admission --> death (YES ICU)
Deaths under 50
​
As of 17th of March, 17 COVID-19 positive patients under the age of 50 have died. In particular, 5 of those [patients] were under the age of 40, all were all of men of age range between 31 and 39 [and] with severe preexisting comorbidities (cardiovascular disease, renal [disease], psychiatric [disorders], diabetes, obesity).

Expert opinion:
  • Coronavirus, l’infettivologo Galli sui tanti casi in Italia: «Il contagio in ospedale, la situazione più sfortunata»
  • Coronavirus, parla il primario del Sacco. Galli: «Virus imprevedibile, una persona sola può infettarne molte»
  • Coronavirus, il primario del Sacco di Milano: «Così abbiamo dimostrato che non è nato in laboratorio»
  • «Tecnicamente il coronavirus è già una pandemia. Ma la sfida si gioca nei pronto soccorso, non ai confini» – L’intervista al virologo Lopalco
  • Coronavirus, l’errore dietro l’impennata di contagi in Italia. Ricciardi (Oms): «Grave non isolare gli arrivi dalla Cina»
  • Coronavirus, la nuova fase: da infezioni importate a circolazione locale del virus. Cosa dice la task force del ministero della Salute
  • Ricciardi (Oms): «Coronavirus più letale dell’influenza. Per il vaccino servono due anni»
  • Coronavirus, «È una follia questa emergenza». Il duro dissenso del capo del laboratorio del Sacco. E sforna i numeri
  • Burioni ribatte alla dottoressa del Sacco con le cifre dell’emergenza: «Coronavirus come l’influenza? Scemenza gigantesca»
  • Coronavirus, lo scontro tra virologi: perché Burioni ha ragione
  • Coronavirus, lo scontro tra virologi: perché Gismondo ha ragione
  • I numeri in chiaro. Il prof. Clementi: «Trend preoccupante a Brescia, Bergamo e Milano» – La videointervista

Also read:
  • Coronavirus, tutte le notizie della notte: New York e Los Angeles chiudono cinema, bar, ristoranti. Solo 16 nuovi casi in Cina (4 a Wuhan)
  • Israele punta su tecnologie antiterrorismo per sconfiggere il coronavirus. Ma c’è il problema privacy
  • Coronavirus, la mamma medico che non abbraccia suo figlio da settimane: «Stiamo crollando, ora ci serve uno psicologo»
  • Coronavirus, rinviato il Salone del Libro di Torino. Lagioia: «Non c’è ancora una data, prima torniamo alla vita normale»
  • Coronavirus, in Emilia Romagna 62 morti in un giorno. Salgono a 3522 i positivi, 197 in terapia intensiva
  • Coronavirus, le direttive per lo smartworking della Commissione Ue ai dipendenti: «Non mangiate un arrosto alle 4 del mattino»
  • Coronavirus, la storia di Carlo: «Io, in quarantena in Cina, internato in una camera d’albergo di 13 mq» – Il video
  • Coronavirus, il monito di Papa Francesco: «Riscoprite la bellezza dei piccoli gesti, non sprecate questi giorni»
  • Coronavirus, al via sperimentazione di un farmaco per l’artrite reumatoide
  • Coronavirus. Il gruppo sanguigno può determinare la probabilità di essere infettati? Improbabile!
  • Serie A, Gravina conferma: il taglio degli stipendi non è un tabù
  • Coronavirus, è giusto geolocalizzare i positivi?


DIAGNOSIS

As of 03/21/2020 a new rapid test for SARS-CoV-2 has been approved by the FDA. Developed by Cepheid this test should become available in many hospitals and labs as early as next week!
LEARN MORE
Updated on 03/23/2020.

This is a summary from what I've learned from extensive literature review and talking to colleagues who are dealing with COVID-19 every day. Again, my apologies for not adding direct references for each of my statements below, I just want to give you the info now to be efficient and will add references later.

LABS:
  • Lymphopenia - very common
  • Elevated CRP
  • Elevated LFTs
  • Elevated CPK
  • Leukocytosis
  • Mild thrombocytopenia - (? associated with higher morbidity)
  • Mild anemia
  • Elevated procalcitonin
  • Increased creatinine

IMAGING (CXR may be normal on presentation; CT findings may be incidental in cases of patients presenting with abdominal pain/GI symptoms):
  • Bilateral patchy infiltrates
  • Ground-glass opacity on CT (? apical involvement might be associated with higher morbidity)
  • Unilateral pneumonia


PROGNOSTICATION

"The disease severity (including oxygen saturation, respiratory rate, blood leukocyte/lymphocyte count and chest X-ray/CT manifestations) predict poor clinical outcomes." [2]

"Old age, obesity, and presence of comorbidity might be associated with increased mortality." [3] 

Rapid deterioration from symptom onset to pneumonia, lymphopenia, bilateral pneumonia, age >60, HTN and heavy smoking appear to be risk factors for higher mortality in COVID-19 patients. [3]

MuLBSTA score may help predict 90-day mortality in patients with viral pneumonia based on six readily available parameters in a hospital setting: Multilobar infiltrate, hypo-Lymphocytosis, Bacterial coinfection, Smoking history, hyperTension and Age. Although not yet validated for COVID-19, the MuLBSTA score may be a potential tool to assess mortality in COVID-19 patients. (MuLBSTA 0-11 (‘low-risk’, mortality = 5.07%); MuLBSTA 12–22 (‘high-risk’, mortality = 33.92%). A higher MuLBSTA score might be used as a good predictor of prognosis.) [4]  Online MuLBSTA Score Calculator [5] 

Additionally, from talking to my physician colleagues in the US, it appears, that patients who present with GI symptoms/diarrhea tend to do worse. Also patients with thrombocytopenia appear to have greater morbidity.[references to follow]


MORTALITY

Officially, as of 03/13/2020, World Health Organization is estimating the overall worldwide COVID-19 mortality rate at 3.4%. However, the mortality rates depend on a wide range of factors and will vary in each region, healthcare system, and in each specific patient population. 

​Time from first symptoms to death may be as short a few weeks.

Mortality tends to be higher in the older patients (age >70), with hypertension,  people with multiple underlying health problems such as heart disease, diabetes, chronic lung disease, cancer, obesity, and smokers among others. Mortality appears to be slightly higher in men comparing to women.


EPIDEMIOLOGY

Here are some of the best statistical and epidemiological resources and maps that I have found.
Picture

INTERNATIONAL SOCIETY FOR INFECTIOUS DISEASES

Fantastic underused resource on COVID-19! 
​Tons of updates!
Picture

WORLDOMETER

Current COVID-19 case and death data with references.
As of 03/17/2020 predominantly raw data resource (absolute numbers,  as opposed to per/population data
Picture

JOHNS HOPKINS UNIVERSITY INTERACTIVE MAP

Very helpful resource - interactive COVID-10 map

CORONAVIRUS 10-DAY PREDICTIVE MODEL

Check out this excellent predictive model! You can select individual countries and run live predictions. You can find more information on Coronavirus forecast here.
Picture
Click to set custom HTML

WWW.OURWORLDINDATA.ORG

Lots of really useful data in text and visual format. Below are some of the examples. CLICK HERE to go to Our World In Data website.


TREATMENT

The data is still very new; more RTC are needed. I will continue updating this section as more research becomes available.

Favipiravir and Nafamostat

Please forgive me for sharing anecdotal information (in gray below). Doing it out of desperation, since we have so little to work with. Hope it helps somehow. Maybe it can spark ideas in terms of doing new randomized controlled trials.
Favipiravir has a broad-spectrum anti-RNA virus activity, which was originally developed in Japan as an anti influenza treatment under a trade name Avigan [アビガン]. It appears that it is being being used in Japan since last month [in clinical trials] for SARS-CoV-2. but has not yet been officially approved for wide-use for COVID-19.  Apparently there have been some positive preliminary results from Chinese research on it's use in COVID-19 patients. [?] 

In Italy, according to the Italian Ministry of Health, Favipiravir data is still too preliminary They believe that the drug has potential, but that RCT are needed to assess its effectiveness.

In addition, it appears that in Japan, they are also beginning to use Nafamostat (an anticoagulant) for patients with Covid-19. (From conversations with some of my ICU colleagues who are actively treating COVID-19 patients, these patients may be prone to thrombotic events.)

I will keep you updated on this. This is really new information, and very little is available in English. Please stay tuned.

​PS: I am not ready to get my hopes up - most of this info is from the Japanese & Chinese news as opposed to scientific publications

CDC View on COVID-19 Treatment Options

As of 03/23/2020:

"Information for Clinicians on Therapeutic Options for COVID-19 Patients

There are no US Food and Drug Administration (FDA)-approved drugs specifically for the treatment of patients with COVID-19.  At present clinical management includes infection prevention and control measures and supportive care, including supplementary oxygen and mechanical ventilatory support when indicated.  An array of drugs approved for other indications as well as several investigational drugs are being studied in several hundred clinical trials that are underway across the globe. The purpose of this document is to provide information on two of the approved drugs (chloroquine and hydroxychloroquine) and one of the investigational agents (remdesivir) currently in use in the United States.

Remdesivir

Remdesivir is an investigational intravenous drug with broad antiviral activity that inhibits viral replication through premature termination of RNA transcription and has in-vitro activity against SARS-CoV-2 and in-vitro and in-vivo activity against related betacoronaviruses [1-3].
There are currently four options for obtaining remdesivir for treatment of hospitalized patients with COVID-19 and pneumonia in the United States:
  • A National Institutes of Health (NIH)-sponsored adaptive double-blinded, placebo-controlled trial of remdesivir versus placebo in COVID-19 patients with pneumonia and hypoxia is enrolling non-pregnant persons aged 18 years and older with oxygen saturation of ≤94% on room air or requiring supplemental oxygen or mechanical ventilation (https://clinicaltrials.gov/ct2/show/NCT04280705external icon). Exclusion criteria include alanine aminotransaminase or aspartate aminotransaminase levels >5 times the upper limit of normal, stage 4 severe chronic kidney disease or a requirement for dialysis (i.e., estimated glomerular filtration rate (eGFR) <30);
  • Two phase 3 randomized open-label trials of remdesivir (5-days versus 10-days versus standard of care) are open to enrollment in persons aged 18 years and older with COVID-19, radiographic evidence of pneumonia and oxygen saturation of ≤94% on room air (severe disease https://clinicaltrials.gov/ct2/show/NCT04292899external icon) or >94% on room air (moderate disease https://clinicaltrials.gov/ct2/show/NCT04292730external icon). Exclusion criteria include alanine aminotransaminase or aspartate aminotransaminase levels >5 times the upper limit of normal, participation in another clinical trial of an experimental treatment for COVID-19, requirement for mechanical ventilation, or creatinine clearance <50 mL/min; and
  • Finally, in areas without clinical trials, COVID-19 patients in the United States and other countries have been treated with remdesivir on an uncontrolled compassionate use basis. The manufacturer is currently transitioning the provision of emergency access to remdesivir from individual compassionate use requests to an expanded access program.  The expanded access program for the United States is under rapid development. Further information is available at: https://rdvcu.gilead.com/external icon

​Hydroxychloroquine and Chloroquine

Hydroxychloroquine and chloroquine are oral prescription drugs that have been used for treatment of malaria and certain inflammatory conditions. Chloroquine has been used for malaria treatment and chemoprophylaxis, and hydroxychloroquine is used for treatment of rheumatoid arthritis, systemic lupus erythematosus and porphyria cutanea tarda. Both drugs have in-vitro activity against SARS-CoV, SARS-CoV-2, and other coronaviruses, with hydroxychloroquine having relatively higher potency against SARS-CoV-2 [1,4,5]. A study in China reported that chloroquine treatment of COVID-19 patients had clinical and virologic benefit versus a comparison group, and chloroquine was added as a recommended antiviral for treatment of COVID-19 in China [6]. Based upon limited in-vitro and anecdotal data, chloroquine or hydroxychloroquine are currently recommended for treatment of hospitalized COVID-19 patients in several countries. Both chloroquine and hydroxychloroquine have known safety profiles with the main concerns being cardiotoxicity (prolonged QT syndrome) with prolonged use in patients with hepatic or renal dysfunction and immunosuppression but have been reportedly well-tolerated in COVID-19 patients.

Due to higher in-vitro activity against SARS-CoV-2 and its wider availability in the United States compared with chloroquine, hydroxychloroquine has been administered to hospitalized COVID-19 patients on an uncontrolled basis in multiple countries, including in the United States. One small study reported that hydroxychloroquine alone or in combination with azithromycin reduced detection of SARS-CoV-2 RNA in upper respiratory tract specimens compared with a non-randomized control group but did not assess clinical benefit [7]. Hydroxychloroquine and azithromycin are associated with QT prolongation and caution is advised when considering these drugs in patients with chronic medical conditions (e.g. renal failure, hepatic disease) or who are receiving medications that might interact to cause arrythmias.

Hydroxychloroquine is currently under investigation in clinical trials for pre-exposure or post-exposure prophylaxis of SARS-CoV-2 infection, and treatment of patients with mild, moderate, and severe COVID-19. In the United States, several clinical trials of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection are planned or will be enrolling soon.  More information on trials can be found at:  https://clinicaltrials.gov/external icon.

There are no currently available data from Randomized Clinical Trials (RCTs) to inform clinical guidance on the use, dosing, or duration of hydroxychloroquine for prophylaxis or treatment of SARS-CoV-2 infection.  Although optimal dosing and duration of hydroxychloroquine for treatment of COVID-19 are unknown, some U.S. clinicians have reported anecdotally different hydroxychloroquine dosing such as: 400mg BID on day one, then daily for 5 days; 400 mg BID on day one, then 200mg BID for 4 days; 600 mg BID on day one, then 400mg daily on days 2-5.

Other Drugs
​

Lopinavir-ritonavir did not show promise for treatment of hospitalized COVID-19 patients with pneumonia in a recent clinical trial in China [8].  This trial was underpowered, and lopinavir-ritonavir is under investigation in a World Health Organization study.
Several other drugs are under investigation in clinical trials or are being considered for clinical trials of prophylaxis or treatment of COVID-19 in the United States and worldwide. Information on registered clinical trials for COVID-19 in the United States is available at: https://clinicaltrials.gov/external icon.
References
  1. Wang M, Cao R, Zhang L, Yang X, Liu J, Xu M, Shi Z, Hu Z, Zhong W, Xiao G. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. 2020 Mar;30(3):269-271.
  2. Sheahan TP, Sims AC, Leist SR, Schäfer A, Won J, Brown AJ, Montgomery SA, Hogg A, Babusis D, Clarke MO, Spahn JE, Bauer L, Sellers S, Porter D, Feng JY, Cihlar T, Jordan R, Denison MR, Baric RS. Comparative therapeutic efficacy of remdesivir and combination lopinavir, ritonavir, and interferon beta against MERS-CoV. Nat Commun. 2020 Jan 10;11(1):222.
  3. Sheahan TP, Sims AC, Graham RL, Menachery VD, Gralinski LE, Case JB, Leist SR, Pyrc K, Feng JY, Trantcheva I, Bannister R, Park Y, Babusis D, Clarke MO, Mackman RL, Spahn JE, Palmiotti CA, Siegel D, Ray AS, Cihlar T, Jordan R, Denison MR, Baric RS. Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses. Sci Transl Med. 2017 Jun 28;9(396).
  4. Colson P, Rolain JM, Lagier JC, Brouqui P, Raoult D. Chloroquine and hydroxychloroquine as available weapons to fight COVID-19. Int J Antimicrob Agents. 2020 Mar 4:105932. doi: 10.1016/j.ijantimicag.2020.105932. [Epub ahead of print]
  5. Yao X, Ye F, Zhang M, Cui C, Huang B, Niu P, Liu X, Zhao L, Dong E, Song C, Zhan S, Lu R, Li H, Tan W, Liu D. In Vitro Antiviral Activity and Projection of Optimized Dosing Design of Hydroxychloroquine for the Treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Clin Infect Dis. 2020 Mar 9. pii: ciaa237. doi: 10.1093/cid/ciaa237. [Epub ahead of print]
  6. Gao J, Tian Z, Yang X. Breakthrough: Chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. Biosci Trends. 2020 Mar 16;14(1):72-73
  7. Gautret P, Lagier J, Parola P, Hoang V, Meddeb L, Mailhe M, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial. International Journal of Antimicrobial Agents. In Press.
  8. Cao B, Wang Y, Wen D, Liu W, Wang J, Fan G, Ruan L, Song B, Cai Y, Wei M, Li X, Xia J, Chen N, Xiang J, Yu T, Bai T, Xie X, Zhang L, Li C, Yuan Y, Chen H, Li H, Huang H, Tu S, Gong F, Liu Y, Wei Y, Dong C, Zhou F, Gu X, Xu J, Liu Z, Zhang Y, Li H, Shang L, Wang K, Li K, Zhou X, Dong X, Qu Z, Lu S, Hu X, Ruan S, Luo S, Wu J, Peng L, Cheng F, Pan L, Zou J, Jia C, Wang J, Liu X, Wang S, Wu X, Ge Q, He J, Zhan H, Qiu F, Guo L, Huang C, Jaki T, Hayden FG, Horby PW, Zhang D, Wang C. A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19. N Engl J Med. 2020 Mar 18. doi: 10.1056/NEJMoa2001282. [Epub ahead of print]


COVID-19 AND PREGNANCY

Expert summary slides from 03/19/2020 by UCLA docs - link to dropbox file below:
DOWNLOAD SLIDES


COVID-19 "HACKS"

Hospital Doesn't Give You PPE? Try CNN!

SHARE YOUR STORY!

N95 Alternatives

Picture

Reuse of N95

Quoting another physician (I do not personally have a confirmation of validity of the information below. Boldface my own):
"I contacted Dr. Peter Tsai, the INVENTOR of the filtration fabric in the N95 mask. N95 masks are made of polypropylene material, and are designed to tightly fit over your face with little leakage around the edge of the mask. I asked Dr. Tsai about reusing the N95 respirator, and what materials could be added in homemade masks to make them more effective. He responded with the following:

MASK REUSE METHOD #1
When reusing N95 masks, leave a used respirator in dry, atmosphere air for 3-4 days to dry it out. Polypropylene in N95 masks is hydrophobic, and contains zero moisture. COVID-19 needs a host to survive--it can survive on a metal surface for up to 48 hours, on plastic for 72 hours, and on cardboard for 24 hours. When the respirator is dry in 3-4 days, the virus will not have survived.
Take four N95 masks, and number them (#1-4).
On day 1, use mask #1, then let it dry it out for 3-4 days.
On day 2, use mask #2, then let it dry out for 3-4 days.
Same for day 3, and day 4…

MASK REUSE METHOD #2
You can also sterilize the N95 mask by hanging it in the oven (without contacting metal) at 70C (158F) for 30 minutes—it is reported that COVID-19 cannot survive at 65C (149F) for 30 minutes.
Use a wood clip to hang the respirator in the kitchen oven to do the sterilization.
When sterilizing N95 masks, be wary of using UV light--keep N95 masks away from UV light / sunlight. N95 masks are degraded by UV light because it damages the electrostatic charges in the polypropylene material. It is unclear how long the masks can be exposed to UV light before they are ineffective.

TIPS FOR REUSE METHOD #1 AND METHOD #2
DO NOT place the respirator on a metal surface, or too close to metal--the temperature on the metal surface is higher than the air temperature.
Keep N95 masks away from UV light / sunlight.
When removing the mask, hold the edge of the straps attached to take off the N95 mask. Your hands may be contaminated at this time--don’t touch the inside part of the respirator. Wash your hands with soap for 20 seconds afterward.

HOMEMADE MASKS
It is not a good idea to use cotton masks when taking care of infected patients. The effectiveness of a material made of cotton is not high—it’s fiber is not fine enough, and it cannot be charged. An N95 mask is so thin because it uses Polypropylene which is made of millions of microfibers layered on top of each other that have been permanently electrostatically charged. An electrical field ionizes the air, and forces the ions deep into the microfibers which allows the polypropylene to act as a filter.
However, using a HEPA filter with a face mask might increase its effectiveness, but it may make it harder to breathe. If you place another media over a face mask, the resistance to breathing increases—it is the sum of the two together. When adding an extra layer, make sure it perfectly covers the whole mask. Keep in mind it may make it more difficult to breathe."

How to Use One Ventilator To Save Multiple Lives

Yes, this is for the worst case scenario. Use your judgement.

Helmet-Style Non-Invesive Ventilation in ARDS

A consideration. May prevent intubation in ARDS and may decrease 90-day mortality. [8], [9]


REFERENCES

MAP - Coronavirus interactive map
WHO - online training
CDC - for healthcare professionals
Stanford coronavirus study - please share
  1. Anthony R. Fehr and Stanley Perlman Coronaviruses: An Overview of Their Replication and Pathogenesis. Methods Mol Biol. 2015; 1282: 1–23.
  2. Dawei Wang, MD1; Bo Hu, MD1; Chang Hu, MD1; et al. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-1069. ​
  3. Nanshan Chen*, Min Zhou*, Xuan Dong*, Jieming Qu*, Fengyun Gong, Yang Han, Yang Qiu, Jingli Wang, Ying Liu, Yuan Wei, Jia’an Xia, Ting Yu, Xinxin Zhang, Li Zhang. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-513.
  4. Lingxi Guo, Dong Wei, Xinxin Zhang, Yurong Wu, Qingyun Li, Min Zhou, and Jieming Qu. Clinical Features Predicting Mortality Risk in Patients With Viral Pneumonia: The MulBSTA Score. Front Microbiol. 2019;102752
  5. MuLBSTA Score Calculator by Medcal.com
  6. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. March 17, 2020. DOI: 10.1056/NEJMc2004973
  7. Coronavirus, Higher Institute of Health [Instituto Superiore di Sanita]: average age of the diseased is almost 80. One of four did not have a fever. 03/18/2020.
  8. Bhakti K. Patel, MD1; Krysta S. Wolfe, MD1; Anne S. Pohlman, MSN1; et alJesse B. Hall, MD1; John P. Kress, MD1. Preliminary Communication. Caring for the Critically Ill Patient. Effect of Noninvasive Ventilation Delivered by Helmet vs. Face Mask of Rate of Endotracheal Intubation in Patients With Acute Respiratory Distress Syndrome. A Randomized Clinical Trial. JAMA. 2016;315(22):2435-2441. 
  9. John Easton. Helmet-based ventilation is superior to face masks for patients with respiratory distress. 05/16/2016



  10. Symptoms of Novel Coronavirus (2019-nCoV) - United States Centers for Disease Control and Prevention (CDC)
  11. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China - JAMA, Wang et al., February 7, 2020
  12. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China - Huang et al., The Lancet. January 24, 2020
  13. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study - Chen et al, The Lancet, January 30, 2020
  14. Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19) [Pdf] - World Health Organization, Feb. 28, 2020
  15. The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19) - China CCDC, February 17 2020
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  17. Novel Coronavirus (2019-nCoV) Situation Report-7 - World Health Organization (WHO), January 27, 2020
  18. China's National Health Commission news conference on coronavirus - Al Jazeera. January 26, 2020
  19. Symptoms of Novel Coronavirus (2019-nCoV) - CDC
  20. Novel coronavirus (2019-nCoV) - Australian Government Department of Health
  21. Transmission of 2019-nCoV Infection from an Asymptomatic Contact in Germany - The New England Journal of Medicine, Jan. 30, 2020
  22. 'There's no doubt': Top US infectious disease doctor says Wuhan coronavirus can spread even when people have no symptoms - CNN, Jan. 31, 2020
  23. Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus–Infected Pneumonia - Qun Li et al., New England Journal of Medicine, Jan. 29, 2020
  24. Asymptomatic #2019nCoV infection - WHO Tweet, Feb. 1, 2020
  25. Philippines reports coronavirus death, as China toll reaches 304 - Al Jazeera, Feb. 2, 2020
  26. Backer Jantien A, Klinkenberg Don, Wallinga Jacco. Incubation period of 2019 novel coronavirus (2019-nCoV) infections among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill. 2020;25(5):pii=2000062. https://doi.org/10.2807/1560-7917.ES.2020.25.5.2000062
  27. Clinical characteristics of 2019 novel coronavirus infection in China, Guan WJ, Ni ZY, Hu Y, et al., February 9, 2020.
  28. Coronavirus incubation could be as long as 27 days, Chinese provincial government says - Reuters, Feb. 22, 2020
  29. Presumed Asymptomatic Carrier Transmission of COVID-19. JAMA. Bai Y, Yao L, Wei T, et al., February 21, 2020.
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  33. Novel coronavirus (2019-nCoV) - Australian Government Department of Health
  34. Novel coronavirus 2019-nCoV: early estimation of epidemiological parameters and epidemic prediction - Jonathan M. Read et al, Jan. 23,2020.
  35. Early Transmissibility Assessment of a Novel Coronavirus in Wuhan, China - Maimuna Majumder and Kenneth D. Mandl, Harvard University - Computational Health Informatics Program - Posted: 24 Jan 2020 Last revised: 27 Jan 2020
  36. Report 3: Transmissibility of 2019-nCoV - 25 January 2020 - Imperial College London‌
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  41. Wuhan lockdown 'unprecedented', shows commitment to contain virus: WHO representative in China - Reuters. January 23, 2020
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  46. CDC Confirms Person-to-Person Spread of New Coronavirus in the United States - CDC Press Release, Jan. 30, 2020
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  58. Case fatality risk of influenza A(H1N1pdm09): a systematic review - Epidemiology. Nov. 24, 2013
  59. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China - Huang et al., The Lancet. January 24, 2020
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  62. Methods for Estimating the Case Fatality Ratio for a Novel, Emerging Infectious Disease - Ghani et al, American Journal of Epidemiology
  63. Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China - Wang et. al, JAMA, Feb. 7, 2020
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  65. Coronavirus: 100,000 may already be infected, experts warn - The Guardian, Jan. 26, 2020
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