The bat 5.0.36.2 keygen

The bat 5.0.36.2 keygen

The bat 5.0.36.2 keygen

The bat 5.0.36.2 keygen

The Bat! (64bit) 7.4.12

The Bat!is a secure email client software, built to protect your correspondence against third-parties.

The Bat!protects your information through multiple encryption streams with the options to encrypt your emails on disk and during communication through an SSL/TLS connection. Free of global email providers that keep your messages in the cloud, and free of Web clients, The Bat!ensures your data stays private.

The Bat!Windows mail client is able to process and store an unlimited number of messages and has no restriction on the number of email accounts you can use.

More key features include:

  • PGP, GnuPG and S/MIME support
  • Internal HTML Viewer
  • Safe handling of attached files
  • Selective download
  • Powerful filtering system
  • The Bat!’s own Address Book
  • Handy templates
  • RSS Feed subscriptions
Version 7.4.12

Improvements

  • Increased speed of entering a folder or sorting messages in the list by "From/To/Subject" columns if there are only Latin characters. The speed increase is mostly noticeable in folders with more than 100 thousand messages
  • If you have Account|Properties|Verbose log turned on, then The Bat!, on the "Send queued mail" command will write addition information to the log: on total number of messages in the outbox, and on the number that has not been selected for sending because of "parked" or "sending" status
  • The Bat! can log Simple MAPI calls. To enable logging, do the following. Uder "HKEY_CURRENT_USER\SOFTWARE\RIT\The Bat!" add DWORD value named "LogMapiCalls", value "1". Then, restart The Bat!. After that, The Bat! will create mapi_log.txt file in the %EMAIL% directory and will append lines to it every time an application like MS Word or MSIE wants to send a message or do any other MAPI function
  • Welcome message (in "Inbox") is no longer used for IMAP accounts
  • MD5 hash has been removed from the S/MIME preferences
  • When non-OpenPGP mode is selected, the PGP menu items in the message editor are hidden
  • (#0000062) The Bat! didn't highlight addresses with equal sign ("=") in the local-part. If such addresses were displayed in the headers, there were no menus to carry out operations over them such as adding to the address book
  • Import S/MIME certificates(s) from a signed message didn't always work

Fixes

  • Malformed account transport settings on high resolution monitors
  • (#0001066) Untranslatable tooltips in the print preview
  • Fixed several memory leaks: when deleting messages, when working with the text editor and the spell checker
  • (#0000933) Unable to start The Bat! if on-the-fly encryption (OTFE) setup had been cancelled
  • Better error handling of The Bat! version checking via DNS, sometimes invalid responses could cause an Access Violation error
  • (#0000880) Opening mail shows error popup "TMailMessage.FindIdx --- ALREADY DESTROYED!" (Fixed "ALREADY DESTROYED!" or "METHOD CALLED ON FREED OBJECT!" errors when selecting different folders on IMAP while The Bat! filters messages on IMAP)
  • Fixed an Access Violation error at start related to Quick Reply, also fixed the "ClassName: EComponentError / Message: A component named __ already exists" error related to quick reply
  • (#0001146) Messages arrived to an IMAP folder aren't filtered if they arrive while other messages are filtered
  • (#0000193) If an IMAP filter has multiple actions, sometimes only some of them are executed
  • Minor speed increase when working with internal hash structures
  • (#0000841) The Bat! didn't properly support character encodings when working with HunSpell dictionaries, e.g. the Latvian special symbols are replaced with Cyrillic symbols in the Spell Checker
  • (#0001147) Filtering on IMAP stops with an Access Violation error while setting color groups
  • (#0001142) Drop-downs on the main toolbar have areas with no reaction to mouse clicks
  • Editor text color and search highlight text colors were hardcoded as "black" and "white", while they had to take colors from Windows system colors (Themes)
  • There was an error when trying to run The Bat! while another The Bat! process didn't exit for some reason
  • (#0000152) Automatic filters stop working altogether for certain IMAP folders, restarting didn't help, newly arrived messages were not filtered too
  • (#0001144) Wrong size of fonts in print preview and the printed message (in tags like "small")
  • (#0001012) Print preview looks OK but the final print is not formatted properly
  • (#0001140) The HTML is viewed OK but in print or print preview, margins are incorrectly calculated and the text is trimmed at the right
  • There were redundant right and bottom margins on printed pages
  • (#0001143) Searching for messages using the mid: links in other folders didn't work since 5.0.36.2 released on 02-Mar-2012
  • [#0001139] If there were national characters in mailto: url and The Bat! was set as a default mailto: handler, these national characters were replaced to question marks. As a result, description of web-pages with national characters sent from browsers appears as question marks in Subject.
  • (#0001134) Filling the background color of table cells fails
  • (#0001131) "Minus" closing buttons in the message finder didn't scale on high-definition monitors; besides that, these buttons were two pixels higher than needed
  • (#0000462) OpenPGP Error Window does not show national characters
  • (#0001141) Truncated text field in QR-Code Generator (German GUI)
  • (#0000539) Decryption of an email with large attachment takes much time if internal OpenPGP implementation is used
  • If you collapse an account in the folder tree and restart The Bat!, this account again becomes expanded, if you had clicked the folder tabs before
  • The Bat! didn't start on single-processor single-core computers, it gave an Access Violation error
  • Fixed an access violation error on exit that could prevent from saving toolbar configuration data
  • There were an error after closing a separate window that shows an HTML message and opening it again and clicking to load external images while using The Bat! HTML viewer
  • (#0001166) The printed text is tiny, although the print preview is ok
  • (#0001153) IMG ALT was printed with tiny font
  • (#0000718) Support for modern GnuPG 2.1
  • PGP 10.4 was not supported
Источник: [https://torrent-igruha.org/3551-portal.html]
, The bat 5.0.36.2 keygen

Key Trade and Risk June 21 2010

Equity Research
21 June 2010

Key Trades and Risks


Emerging Markets Equity Strategy

• Equities are fundamentally attractive. Global growth in our view is Emerging Markets Equity Strategy
sustainable. This growth is combined with low inflation and interest Adrian Mowat
AC

rates. (852) 2800-8599


adrian.mowat@jpmorgan.com
• This is likely to be a volatile summer. Markets will focus on PMI data J.P. Morgan Securities (Asia Pacific) Limited
for evidence of financial market weakness feeding through to the real
Ben Laidler
economy. We believe investors are over estimating their influence on the (1-212) 622-5252
real economy. Regulatory reform and fiscal policy are additional sources ben.m.laidler@jpmchase.com
of volatility. J.P. Morgan Securities Inc.

• The rebalancing of the Chinese economy from investment to Deanne Gordon


(27-21) 712-0875
consumption is healthy. But mind the gap, the near term impact would deanne.gordon@jpmorgan.com
be lower commodity prices and potentially lower profit margins. We
J.P. Morgan Equities Ltd.
expect that commodity prices will correct this summer which could
potentially lead to weaker EM equities. Rajiv Batra
(91-22) 6157-3568

• Our key trades ranked by conviction are: rajiv.j.batra@jpmorgan.com

J.P. Morgan India Private Limited


• CEMBI Surfers; Overweight India and Turkey Sanaya Tavaria
(91-22) 6157-3312
• Growth surprise from developed, not emerging, sanaya.x.tavaria@jpmorgan.com
economies. Overweight Mexico, Taiwan and Turkey J.P. Morgan India Private Limited
plus technology and transportation.
Ankita Kochar
• Macro policy and rising inflation - QR not QE in EM: (91-22) 6157-3263
ankita.x.kochar@jpmorgan.com
Underweight Brazil, China, energy and commodities
J.P. Morgan India Private Limited

• The main risk to our view is that financial market stress results in
Figure 1: MSCI EM relative performance
weaker European growth than a bearish consensus. For more on risks
see page 8. 140
120
• Key asset allocation calls:
OW: Taiwan, Korea, India, Mexico, South Africa, Turkey and the 100 v s World
Philippines
80
OW: Technology and industrial cyclicals (i.e. transportation)
60
UW: China and Brazil
UW: Commodities, energy, telecoms and Utilities 40 v s USA
20
• For our ‘Key Trade’ stock ideas, click here to download the Bloomberg
96 98 00 02 04 06 08 10
sheet.
Source: Bloomberg, 14 June 2010.

See page 90 for analyst certification and important disclosures, including non-US analyst disclosures.
J.P. Morgan does and seeks to do business with companies covered in its research reports. As a result, investors should be aware that the firm may
have a conflict of interest that could affect the objectivity of this report. Investors should consider this report as only a single factor in making their
investment decision.
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

In this report, we highlight: Table of Contents


Our top trade ideas
Summer Swings........................................................................3
Risks
Risks to our strategy................................................................8
Our model portfolio
Global emerging markets model portfolio by country ........14
Valuation stress test

Key ratios for EMBIG 100


Global emerging markets model portfolio by sector...........15
Consensus country weights Key Trades ..............................................................................16
China: Mind the gap ...............................................................26
We have two pages on each Brazil: Better Outlook for Domestics....................................28
significant emerging market. The
first page has a qualitative South Korea: Buying opportunity .........................................30
review of events driving the past
12 months, the outlook and a Taiwan: Potentially Oversold ................................................32
comment on valuations; the
second page displays the Russia: Strong balance sheet and earnings ........................34
scorecard, which presents key
economic and equity market
India: Global concerns drag Indian equities ........................36
data South Africa: A low beta equity market................................38
Mexico: Cyclical Macro Momentum ......................................40
The extended markers: This
report contains 36 pages of data Malaysia: Reform agenda keeping the buzz ........................42
designed to help track emerging
economies and markets Thailand: Resilient despite turmoil .......................................44
Indonesia: An eye on politics ................................................46
The emerging market Turkey: Cyclical view… secular trend ..................................48
dashboards efficiently display
key economic, equity and debt Philippines: Market re-rating likely .......................................50
data, demonstrating change and
perspective. Extended markers ..................................................................53
Consensus Asset Allocation .................................................55
Hindsight trades: What has worked......................................56
Composite valuation indicators ............................................58
EMBIG100................................................................................62
Emerging Markets Strategy Dashboards .............................70

2
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

Summer Swings
There is a conflict in our strategy. This is a serious economic advantages. It helps address China’s strained
conflict that could damage performance. Investors in our social contract by increasing household income as a share
view are too, and increasingly pessimistic, on the of GDP at the expense of corporate profits (see risk
sustainability of the recovery. Our base case remains that section on page 8). There is a leveraged impact on
the global recovery is led by the private sector and is discretionary income. Economists may argue that a
sustainable. Economic growth combined with falling stronger currency would indirectly boost real income due
core inflation is a strong fundamental backdrop for to lower inflation but there are higher tangible benefits to
equities. Note that J.P. Morgan's economists just pushed workers of higher wages rather than a lower cost of
out the first increase in Fed Funds rate to 4Q11 (See A imported goods.
change to our Fed call, Michael Feroli et al, 17 June
2010). But EM investors need to consider the risk of the Figure 2: Monitor European PMIs
correlation between EM equities and commodities. In our 65 Germany
view commodity investors are not pricing in China's 60
changing growth model. Euro area
55
50
Recognizing the conflict and risk, we are setting an
45
artificial time limit on the fear of a correction in
40 Spain
commodities. The time limit is September 2010. By then Greece
we believe that the decline in bulk commodity prices will 35
"scare" the new investors in commodities to redeem, 30
generating a broader correction. 25
Jun-07 May -08 Apr-09 Mar-10
Market confidence in a sustainable economic recovery is
Source: J.P. Morgan Economics, May 2010
waning. It is the risk of too rapid a fiscal consolidation
that is hitting confidence. We agree this risk has Figure 3: Domestic Savings as a percent of GDP in China
increased but we also believe that financial investors are
25 1997-99 2005-07 21 22
over estimating their influence on the real economy. Post
18
the sub-prime crisis, business and consumer respect for 20
financial institutions and markets has declined. In 13
15
responding to the conflicting signals of weaker capital 9
10
markets and stronger than expected demand (see Figure 3
2) manufacturers should be more influenced by their 5 1 1
customer orders than stock market levels. This is 0
Institutions
Enterprises

Households
Government
Financial

particularly true when investors appear shell-shocked in


their over-reaction to poor fundamental data.

Our expectation is that manufacturing PMIs will decline


Source: IMF
from their post recovery highs but remain in an
expansionary range. Growth should hopefully broaden to Figure 4: China consumption as a % of GDP
the service sectors. If this occurs then investor
55
confidence in a sustainable recovery would increase.

China's economic and policy dynamics are changing. 50


Consumption as a percentage of GDP declined in the last
decade. This is partly a function of the decline in the 45
share of household income as a percentage of GDP. The
tacit support for recent wage disputes may indicate a 40
more proactive policy to boost household income and
thus consumption (see Figure 4). Reducing China's 35
export competitiveness through higher wages, rather than 78 80 82 84 86 88 90 92 94 96 98 00 02 04 06 08
a stronger Renminbi, has a number of political and
Source: J.P. Morgan economics, 2008.

3
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

With such a clear policy to boost consumption investors Commodity markets are technically weak. Investor
will desire exposure. But only 11% of MSCI China is confidence in the asset class is falling due to poor returns
consumer companies. High growth and low free floats and a diminished diversification benefit. A broad
result in high relative valuations. There is a similar trend correction in commodity prices would require these
in US where the EPS CAGR, since 1973, for consumer investors to reverse a long standing trend to increase
discretionary at 10.5% is a premium to the market's asset allocation to commodities (See Figure 15 and
7.5%. Its long term average PE at 20 is also a premium to Figure 16).
the market average of 15.
Figure 5: China iron ore spot and contract prices
A recent Xinhau news article was critical of state owned 200
enterprises. It noted that SoEs’ scale and influence on the China iron ore spot price
Chinese economy may hinder economic growth. The 150
government controls these companies and can accelerate
the shift of GDP from corporate to household. Note that 100
80% of MSCI China is SoEs.
50
There is a Mexican stand-off in the property market.
Landed cost of contract iron ore in China
Successive anti-asset-price-inflation measures have 0
discouraged buyers who now expect prices to fall. But Apr 02 Apr 04 Apr 06 Apr 08 Apr 10
cash rich property companies and home owners mean a
lack of forced sellers. The result is a sharp decline in Source: Bloomberg. Note: The landed cost of contract iron ore are Vale's SSF cost +
freight costs from Brazil to China. For 3Q10 forecasts, Vale's SSF costs are calculated as
property transactions. This in turn would lead to a fall in the average of the spot prices from Mar 10 to May 10. The freight costs in 3Q10 are
construction activity. Infrastructure spending is assumed to remain unchanged at today's levels.
decelerating. Bank loans funded the bulk of last year’s
stimulus program. Greater regulatory scrutiny of lending Figure 6: MSCI EM Energy relative to MSCI EM
to local government funding vehicles is likely to lead to 130
less capital for infrastructure. These measures are
consistent with a policy to rebalance growth from 120
investment to consumption.
110

The demand for bulk commodities and energy is 100


declining as the growth driver shifts from fixed asset
90
investment to consumption in China. There is renewed
focus on energy efficiency. The five year plan target to 80
reduce energy use per unit of GDP by 20% has not been Jan 07 Jul 07 Jan 08 Jul 08 Jan 09 Jul 09 Jan 10
met. Beijing is putting pressure on energy intensive and
polluting industries to close capacity. The market is also Source: Bloomberg. Note: Index rebased to 100 from January 2007.
applying pressure with steel prices declining while
contract iron ore and coking coal prices increase. Chinese Figure 7: MSCI EM Materials relative to MSCI EM
steel mills could make a loss in 3Q10. 140

130
Weak steel and aluminum prices may already be
indicating a slowdown in FAI. If our rebalancing thesis is 120
correct then steel prices should continue to fall. It is this 110
signal that we believe could lead to a broader correction 100
in commodity markets. The numerous presentations on
90
China’s significant demand for commodities at our China
conference this month reflects China’s key role in the 80
commodity super-cycle debate. Evidence of slowing Jan 07 Jul 07 Jan 08 Jul 08 Jan 09 Jul 09 Jan 10
Chinese demand when combined with increased supply
could lead to disproportionate corrections in commodity Source: Bloomberg. Note: Index rebased to 100 from January 2007.

prices.

4
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

If the commodity market corrects then EM equities are Figure 8: MSCI Korea Forward PE relative to MSCI EM
likely to decline led by Brazil and Russia. This 1.3
potentially would lead to redemptions in EM funds
1.2
leading to a broader correction (See Figure 11and Figure
12). We would view this event as an exceptional buying 1.1 +1SD
opportunity.
1.0
Av g
Upgrading Korea to overweight 0.9

We upgraded Korea to overweight from neutral on 2 0.8


-1SD
June in both Asian and Emerging Market portfolios. The 0.7
market has underperformed EM by 3% since 3 May -05 Jan-06 Sep-06 May -07 Jan-08 Sep-08 May -09 Jan-10
September 2009. Prior to that, from 26 February 2008 to
9 March 2009, MSCI Korea outperformed MSCI EM by Source: IBES, MSCI, Datastream, 31 May 2010.
26%.
Figure 9: REER deviation from long term mean since 1975 -An
Our upgrade was opportunistic. On 20 May, the South undervalued Won
Korean government released a multinational combined 100
intelligence report that concluded that the South Korean 80
navy ship Cheonan was torpedoed by a DPRK 60
submarine. The report accelerated the correction in the 40
market and currency. 20
0
The Won declined by 9% in May. The result is that -20
MSCI Korea is the cheapest market in APxJ (PE 9.3) and -40
one of the most undervalued currencies in EM (REER). -60

IDR

TWD
PHP

THB
CHF

HUF
AUD

USD

KRW
BRL
RUB
CLP
CZK

CNY

TRY
ZAR

PLN

MXN

EUR
We are more positive on global growth than the
pessimistic consensus. This, plus a competitive currency Source: J.P. Morgan.

is positive for exporters (note Yen and NT dollar cross


Figure 10: Performance of KRW/USD
rates). Banks are inexpensive, in our view. The end of
price controls should boost domestic margins. 1600

Our preferred sectors are exporters, banks and domestics. 1400


Our top picks include Hyundai Mobis, HMC, Kia
05-07 Av erage FX rate: 969
Motors, Hyundai Department Store, Shinsegae, Lotte 1200
Shopping, KB Financial, Hynix and SEC.
1000
The risks to our view are: (1) a further deterioration in
the North Korean situation, (2) weaker global demand, 800
(3) price controls remaining, and (4) excessive tech Jan-05 Jan-06 Jan-07 Jan-08 Jan-09 Jan-10
capex.
Source: Bloomberg, 21 June 2010.

5
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

Conclusion 4. EM inflation and speed of policy normalization


Equities are fundamentally attractive with a backdrop of 5. Lack of G3 policy flexibility
sustainable growth and low core inflation. We wish to
6. Central banks target asset prices
add EM equity risk but fear a correction in commodity
prices. A change in China’s perceived demand for 7. Commodity EM equities feedback loop
commodities as its economy rebalances is the catalyst for
8. Trade friction
the correction in commodity prices. We hope this will
provide an outstanding buying opportunity. Evidence of 9. Tension between the two Koreas
China's slowing commodity demand should appear over
10. Thai political unrest
the next few months. If no correction occurs before
September we will review our thesis and are likely to add 11. Bond market volatility
risk then.
12. Election-induced volatility
Few investors share J.P. Morgan's optimism on For more details on these risks, please see page 8.
sustainable growth. European PMIs are forecast to
decline from recovery highs but remain above 50. Please see pages 26 to 50 for our detailed country views.

Key asset allocation calls Figure 11: S&P GSCI Industrial Metals Index
• OW: Taiwan, Korea, India, Mexico, South Africa, 2500
Turkey and the Philippines
2000
• OW: Technology and industrial cyclicals (i.e.
transportation)
1500
• UW: China and Brazil
1000
• UW: Commodities, energy, telecoms and Utilities
Our key trades ranked by conviction are: 500
1. CEMBI Surfers; OW India and Turkey Jan 07 Jul 07 Jan 08 Jul 08 Jan 09 Jul 09 Jan 10

2. Growth surprise from developed, not emerging, Source: Bloomberg


economies. OW Mexico, Taiwan and Turkey plus
technology and transportation Figure 12: Cumulative inflows into commodity fund by year (US
4billion)
3. Macro policy and rising inflation – QR not QE in
60 2004 2005 2006
EM: UW Brazil, China, energy and commodities 2007 2008 2009
50 2010 50.4
For more details on these key trades, please see page 16
40

Please see pages 13, 14, 15 for our Global Emerging 30


18.4
Markets model portfolio and descriptions of changes 20 16.3
10 16.0
made this month. 11.8
8.9
0
5.7
Risks – are many: -10
1. Strained social contract
Dec
Oct
Mar
Apr
Jan
Feb

Jun

Aug
Sep
Jul
May

Nov

2. Underestimating euro sovereign stress contagion risk


Source: J.P. Morgan, May 2010
3. Rising economic risks

6
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

Focus on sectors within countries rather than country recommendations


The table below provides a level summary of our views on sectors within countries. Financials is 25%, Materials is 15% and
Energy is 14% of EM. All recommendations are relative to EM. The Industrials sector consists of an eclectic group of
stocks. We are overweight technology and transportation.
Table 1: Key country and sector recommendations
Country/Sector Weight Reco US$ Return (%) PE 09 PE PE EPS EPS EPS DY ROE ROE
10E 11E Growth Growth Growth 10E 10E
09 10E (%)
1 yr 3 yr 5 yr X X X (%) (%) CAGR % % 03-08
05-10E Avg
EM 100 -- 18 (3) 86 14.3 11.2 9.6 2 28 8.8 2.9 15.3 16.2
China 18.7 UW 5 10 157 15.8 12.6 10.7 17 25 13.3 2.9 16.2 16.1
China Financials 7.1 N 7 23 265 14.5 11.5 9.4 25 25 28.5 3.2 17.8 13.3
China Energy 3.2 UW 10 14 161 13.4 10.6 9.6 (5) 26 8.3 3.8 17.8 21.4
China Telecom 2.5 UW (6) 11 174 12.3 12.1 11.5 (4) 1 14.8 3.6 15.0 18.2
China Industrials 1.4 n/a (10) (25) 55 20.3 13.3 11.8 58 53 5.4 2.1 11.0 12.8
Brazil 16.1 UW 20 28 243 13.5 11.2 9.0 7 20 6.1 3.4 16.1 18.8
Brazil Materials 4.3 UW 31 29 308 19.2 9.3 6.6 (40) 106 10.1 3.2 19.2 27.9
Brazil Energy 3.7 N (0) 62 310 10.3 10.8 9.5 (5) (5) 2.8 2.5 15.5 25.3
Brazil Financials 3.8 OW 27 21 243 11.9 11.5 9.5 45 4 5.9 3.6 16.1 22.4
Korea 13.1 OW 23 (22) 47 13.8 9.5 9.1 56 45 8.4 1.2 15.4 14.3
Korea IT 4.0 OW 40 3 38 18.1 10.0 11.1 (2,217) 81 13.7 0.2 18.1 17.0
Korea Financials 2.2 OW 16 (43) 32 15.6 8.8 7.6 (31) 77 3.0 2.2 11.7 13.3
Korea Industrials 1.8 n/a (3) (49) 71 14.9 11.4 10.4 26 30 10.6 1.3 11.4 12.0
Korea Materials 1.7 N 27 0 173 10.7 8.9 8.2 (2) 20 7.7 1.2 32.1 17.6
Korea CD 1.8 OW 50 23 72 9.3 8.1 7.8 125 15 16.9 0.8 20.2 13.4
Korea CS 0.6 N 12 (25) 46 15.0 13.7 11.8 7 9 11.3 1.7 14.4 14.9
Taiwan 10.7 OW 12 (12) 15 24.6 12.8 11.3 36 92 5.1 3.8 13.5 13.3
Taiwan IT 6.5 OW 16 (17) 12 29.1 12.0 10.9 9 143 11.5 3.6 16.9 14.3
Taiwan Financials 1.5 N (4) (21) (19) 19.6 13.2 10.6 859 48 9.3 3.3 8.7 6.6
Taiwan Materials 1.3 UW 16 7 78 17.1 14.5 12.0 NM 18 (7.8) 4.8 10.5 20.7
India 8.0 OW 15 9 143 21.4 17.2 13.6 3 25 13.4 1.3 16.3 21.0
India Financials 2.0 OW 14 3 148 23.5 19.3 15.3 0 22 13.7 1.2 12.3 14.9
India Energy 1.2 N (7) 12 285 20.5 14.4 12.0 (0) 42 14.7 1.2 16.3 21.1
India IT 1.3 OW 54 3 104 24.2 21.1 17.4 5 15 16.1 1.2 24.4 31.3
South Africa 7.4 OW 21 4 93 16.6 12.3 9.8 (18) 35 10.7 3.2 16.3 19.1
SA Materials 2.1 OW 15 (13) 97 47.0 16.8 11.9 (54) 179 22.2 2.1 13.5 9.9
SA Financials 1.9 OW 36 8 82 13.1 10.7 8.8 (15) 23 5.9 4.5 15.0 19.6
SA Telecom 0.9 UW (2) (1) 95 12.3 10.2 8.7 (10) 20 10.2 3.0 20.0 28.9
SA Cons Discr 0.9 N 50 25 119 16.2 13.2 10.5 10 23 10.9 2.4 17.0 23.1
SA Energy 0.7 UW (5) 18 59 11.9 9.9 7.7 (22) 20 6.3 3.6 17.2 23.8
Russia 6.5 N 11 (31) 56 8.2 6.4 5.1 (21) 29 9.1 2.2 13.8 16.6
Russia Energy 3.8 N (2) (33) 34 5.7 5.0 4.6 (12) 14 6.0 2.3 13.7 16.6
Mexico 4.8 OW 38 (14) 102 18.0 14.4 12.1 2 25 7.7 2.7 16.7 19.1
Mexico Telecom 1.9 UW 33 (13) 154 14.3 12.4 10.9 (2) 15 16.4 4.1 36.5 31.2
Mexico CS 1.1 N 52 21 133 18.9 19.0 15.8 54 (0) 14.1 1.7 15.1 16.0
Mexico Materials 0.8 OW 45 (41) 32 30.8 14.6 10.9 (16) 111 (8.8) 1.6 8.0 15.8
Malaysia 2.9 N 28 7 96 18.2 14.8 12.7 (1) 23 7.5 3.5 12.5 13.2
Indonesia 2.3 N 44 53 206 16.3 13.8 11.9 21 18 16.4 3.0 23.8 25.4
Turkey 1.6 OW 56 7 88 11.0 9.5 8.3 3 16 12.8 3.1 17.4 17.2
Turkey Financials 1.0 OW 74 29 129 9.7 8.8 7.8 30 11 18.4 2.4 18.1 16.6
Chile 1.5 n/a 26 25 127 18.7 16.2 13.5 NM 15 19.1 2.3 11.2 10.1
Thailand 1.5 N 25 23 79 12.8 11.2 9.6 33 14 (0.9) 4.0 15.1 19.4
Poland 1.4 N 22 (39) 28 15.2 13.2 11.0 (26) 15 (1.4) 3.7 11.7 17.0
Hungary 0.4 N 11 (40) (8) 12.1 10.9 8.5 (37) 11 (2.7) 3.6 11.9 23.8
Philippines 0.5 OW 25 (6) 114 17.3 15.4 13.4 25 13 5.5 3.9 15.6 14.4
Source: J.P. Morgan Asian strategy team, MSCI, Datastream. Table sorted by descending weight in index, countries first followed by country-sectors, 10 June 2010.

7
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

Risks to our strategy


Strained social contract banks continue to face a difficult funding environment.
Political and regulatory risk is high. The corporate sector The primary market for unsecured bank debt remains in
has emerged from the global recession and credit crunch hibernation. The contraction in the CP/CD issued by
stronger than the households. Note the profits as a share European banks in the US is accelerating. Note that
of GDP are near cycle highs but unemployment is 10%. European banks need to refinance nearly $130bn per
Policy makers constrained by high fiscal deficits are month for the remainder of the year.
likely to redress this imbalance through higher taxes and
increased regulation. Rising economic risks
Private payrolls at 41K for the month of May were
As is the case in the US, Chinese corporates share of disappointing. Note that firms are using their existing
GDP increased while the household share decreased. workers more intensively as they lengthen the work
Labour disputes and subsequent large pay increases may week, and companies cannot increase work hours
start to reverse this trend. This rebalancing is healthy and indefinitely. Private sector job creation should improve
should move China to a more sustainable growth model. over the rest of the year. However, if the job data
But near term the result is lower profit margins. continues to be below expectations, it could adversely
impact consumer spending and a sustained economic
Underestimating Euro sovereign stress contagion risk recovery.
After Greece, there is speculation that Spain might reach
out to the EU or IMF for financial support. The Spanish Figure 13: Strained social contract: US profit share and
banking system is under significant pressure to address unemployment
its solvency issues, especially among its saving banks. % sa
22 Profit share 0
These concerns have impaired the ability of Spanish
20
banks to raise market funding, and increased the 3
18
possibility of seeking external liquidity support. If this
16
were to be true, Spanish bond yields which have already 6
increased by 50 bps in the last one week would likely rise 14

further and issuance become more difficult. 12 9


Unemploy ment rate (inv erted)
10
Euro sovereign stress generates both economic and 8 12
market risk. The economic risk is that business in core 70 75 80 85 90 95 00 05 10
Europe slows investment decisions. As we witnessed in
2008, rational individual risk reduction results in a Source: J.P. Morgan. Note: Chart shows % share of gross value added, JPMorgan
forecast for 2010.
destructive downward spiral in risk assets.
Figure 14: Spread between Spanish and German 10 year bond
In Emerging Markets Outlook and Strategy, June 8, yield
2010, Joyce Chang, our Global head of Emerging
250
Markets and Credit Research, notes two scenarios.
Scenario 1: Deeper economic and financial crisis, but 200
contained to peripheral Europe. Scenario2: Crisis spreads
to core Europe due to contagion from the periphery, 150
pushing the Euro area into a double dip recession. If the
crisis were to spread to core Europe, it could have a 100
significant impact on emerging markets. In such a
50
scenario, emerging markets would reverse incipient
tightening. Emerging markets may also have to resort to 0
greater fiscal stimulus to offset the weakness in the Jan 08 Jul 08 Jan 09 Jul 09 Jan 10
private sector. (Please see Page 23 for more details)
Source: Bloomberg
The feedback loop between banks struggling to fund and
a subsequent reduction in the availability of credit is
another key risk. Nikolaos Panigirtzoglou in his weekly,
Flows and Liquidity, 4 June 2010 notes that: European

8
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

EM inflation and speed of policy normalization Tension between the two Koreas
Our base case is that inflation plateaus mid-year as the On 20 May, the South Korean government released a
base effect becomes more favorable. If we are wrong and multinational combined intelligence task force report that
inflation continues to rise then this is bearish for equities. concluded that the South Korean navy warship was
The EM dashboard has a sheet designed to help monitor torpedoed by a DPRK submarine on 26 March. The
inflation across EM countries. Remember modeling Korean Won has weakened by 5% in the last one month
inflation in emerging economies is difficult due to the to KRW/USD1213.
short history of floating exchange rates and large
weighting of food and other primary products. Thai political unrest
The Thai market and baht are remarkably resilient
Lack of G3 policy flexibility considering the violence in Bangkok.
High fiscal deficits and record-low interest rates limit
policymakers’ ability to respond to a relapse in growth. A Figure 15: Oil forward curve ($/bbl)
growth relapse is not our base case. If it occurred, it 95 Crude Oil, WTI : 6/9/2010
would be a serious blow to risk assets. Credit spreads
could widen and equities would fall. 90

85
Central banks target asset prices
Central banks are targeting asset prices in EM, notably in 80
China. These policies introduce economic and sector
specific risk. Note how poorly real estate stocks have 75
performed in EM despite low interest rates.
70

Commodity EM equities feedback loop Jul-10 Jul-12 Jul-14 Jul-16 Jul-18


Commodity markets are in our view vulnerable. Investors
are frustrated by low to negative returns due to the high Source: Bloomberg. 9 June 2010.

roll cost in forward markets in contango. In 2009, net


Figure 16: Underperformance of TR Crude Oil Index and Energy
retail inflows into commodity funds were $50billion; this vs WTI
year, subscriptions have slowed sharply. A combination
of negative momentum and Chinese economic 220 WTI JPM Crude Oil TR JPM Energy TR
rebalancing could be a catalyst for significant
190
redemptions. The liquidation of contango arbitrage
inventory (i.e. leasing supertankers to buy spot and sell 160
forward) adds to the downside risk for commodities.
Weak commodity prices will drive Brazilian, Russian 130
and Indonesian markets lower, in our view. It is
100
reasonable to expect redemptions in BRIC funds.
70
Trade friction Jan-09 Apr-09 Jul-09 Oct-09 Jan-10 Apr-10
It is no fun being a politician today. High fiscal deficits
in the developed economies and rising inflation in Source: Bloomberg.
emerging economies will mean uncomfortable policy
choices. In this environment it is appealing to look for
others to blame. A building risk is trade sanctions against
China. The rhetoric on the Renminbi is heating up.
China's priority is to manage a rebalancing economy. We
doubt Beijing wishes to add currency volatility to the
mix. Hopefully this war will be fought in the media
rather than with sanctions. Our overweight exporters is
very exposed to a trade war.

9
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

Bond market volatility Figure 17: Global bond supply ($tr)


The end of QE plus banks’ unwillingness to add to $7 Gov ernment Agencies, Supra, Muni, etc
duration risk is a dangerous technical situation for Corporates incl Gov t Guranteed Securitized
government bonds. Risk assets typically struggle as bond
$6
yields rapidly increase to “normal” levels. EM equities
typically correct when bond market volatility rises. Our
work on quantifying the relationship between the $5
direction of US Treasury yields and EM equity returns
suggests that the probability of such a correction in 2010 $4
is high if UST yields rise rapidly and increases the risk of
a rapid adjustment. We advise investors to monitor the
$3
pace of change in 10-year UST yields in 2010.

Election-induced volatility $2
Brazilian elections in October 2010 are likely to be a
source of volatility rather than a change in macro- $1
economic policy.
$0
2009 2010

Source: J.P. Morgan. Global bond supply and demand 2009 and 2010 in $tr, demand and
supply figures are annualized, supply is calculated by the change in bond out standings at
face value, demand is calculated by the change in bond out standings at market value.

Figure 18: Global bond demand ($tr)


QE Banks
FX Reserv es Retail Bond Funds
$7 Insurance + Pension Other

$6

$5

$4

$3

$2

$1

$0
2009 2010

Source: J.P. Morgan. Global bond supply and demand 2009 and 2010 in $tr, demand and
supply figures are annualized, supply is calculated by the change in bond out standings at
face value, demand is calculated by the change in bond out standings at market value.

10
Adrian Mowat Emerging Markets Equity Research
(852) 2800-8599 21 June 2010
adrian.mowat@jpmorgan.com

Figure 19: Public Debt and Fiscal Balance as a % of GDP for EM and DM in 2010
0
Korea

Peru
-2 ChinaIndonesia
Thai
Mex ico Brazil
EM
Australia Turkey
Russia
-4
Phil Hungary
Chile Czech
Malay sia Italy
India Germany
Poland
-6 S Africa
Fiscal Balance

Portugal
Euro area

Japan

Источник: [https://torrent-igruha.org/3551-portal.html]
The bat 5.0.36.2 keygen

PMC

Huipeng Ge

Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road No 87, Changsha, 41008 Hunan China

Xiufen Wang

Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road No 87, Changsha, 41008 Hunan China

Xiangning Yuan

Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road No 87, Changsha, 41008 Hunan China

Gong Xiao

Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road No 87, Changsha, 41008 Hunan China

Chengzhi Wang

Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road No 87, Changsha, 41008 Hunan China

Tianci Deng

Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road No 87, Changsha, 41008 Hunan China

Qiongjing Yuan

Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road No 87, Changsha, 41008 Hunan China

Xiangcheng Xiao

Department of Nephrology, Xiangya Hospital, Central South University, Xiangya Road No 87, Changsha, 41008 Hunan China

Received 2020 Mar 6; Accepted 2020 Mar 20.
Copyright © Springer-Verlag GmbH Germany, part of Springer Nature 2020
This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
This article has been cited by other articles in PMC.

Abstract

In December 2019, pneumonia of unknown cause occurred in Wuhan, Hubei Province, China. On 7 January 2020, a novel coronavirus, named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was identified in the throat swab sample of one patient. The World Health Organization (WHO) announced the epidemic disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). Currently, COVID-19 has spread widely around the world, affecting more than seventy countries. China, with a huge burden of this disease, has taken strong measures to control the spread and improve the curative rate of COVID-19. In this review, we summarized the epidemiological characteristics, clinical features, diagnosis, treatment, and prognosis of COVID-19. A comprehensive understanding will help to control the disease.

Keywords: Severe acute respiratory syndrome coronavirus-2, Coronavirus disease 2019, Epidemiology, Clinical, Pathology, Treatment

Introductions

At the end of 2019, several cases of pneumonia with unknown etiology emerged in Wuhan, Hubei Province, China [1–3]. The pneumonia spread quickly to other provinces of China and overseas. At early stage, it was reported that most patients had the contact history with Huanan seafood market [1–3]. After that, more and more patients had fever and cough symptoms. On 7 January 2020, a novel coronavirus was identified in the throat swab sample of one patient by the Chinese Center for Disease Control and Prevention (CDC), and was subsequently named as 2019­nCoV by World Health Organization (WHO) [1, 2]. As the situation got worse, the WHO declared the outbreak as the public health emergency of international concern (PHEIC) [4]. On 11 February 2020, the International Committee on Taxonomy of Viruses renamed the virus as severe acute respiratory syndrome coronaviruse-2(SARS-CoV-2) [5]. And WHO announced the epidemic disease caused by SARS-CoV-2 as coronavirus disease 2019 (COVID-19) [6].

This is the third coronavirus pneumonia in the past 20 years around the world. In November 2002, a novel betacoronavirus called severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in Guangdong, China, and resulted in more than 8000 infections and 774 deaths in 37 countries. In 2012, Middle East respiratory syndrome coronavirus (MERS-CoV), which was first detected in Saudi Arabia, affected 2494 individuals and caused 858 fatalities [7, 8]. After the outbreak of COVID-19, the Chinese government has initiated a level-1 public health response to prevent the spread of the disease on 26 January 2020 [9]. As of 24:00 on 3 March 2020 (Beijing time), the SARS-CoV-2 has resulted in 80,270 laboratory and clinical confirmed cases in the mainland of China, and 2981 patient deaths [10].

Currently, there are many studies of SARS-CoV-2 and COVID-19. This review makes a comprehensive introduction about this disease, including the genome structure and receptor of SARS-CoV-2, epidemiology, clinical features, diagnosis, treatment, and prognosis of COVID-19. We hope our work can provide more information in understanding this disease, and more research findings are needed to help to limit spread of the disease and to invent vaccine and specific drugs.

The genome structure and receptor of human cells of SARS-CoV-2

Coronaviruses are the largest, enveloped, single-stranded positive-sense RNA viruses, including 4 genera: Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. Alpha- and Betacoronaviruses mainly infect mammals; the rest of two primarily infect birds [11, 12]. Seven coronaviruses that related to human disease had been identified [12]. Four human coronaviruses (HCoV 229E, NL63, OC43, and HKU1) had been endemic globally and just resulted in upper respiratory tract infections in adults. The SARS-CoV, MERS-CoV, and SARS-CoV-2 are the most severe type that can lead to lower respiratory tract infections [11, 13] and acute respiratory distress syndrome (ARDS), which can cause patient deaths. At first, Wei et al. [14] found that the virus appeared to be recombinant by a codon usage analyses. However, this opinion was rejected by Paraskevis’s full-genome evolutionary analysis and Chen’s simplot analysis [14, 15]. Currently, the SARS-CoV-2 was found to be a novel positive-sense RNA virus, which belonged to the Betacoronavirus genus in the Coronaviridae family [7, 15, 16]. Similar to the SARS-CoV and MERS-CoV, the SARS-CoV-2 genome contains two untranslated regions (UTRs): 5′-cap structure and 3′-poly-A tail, and a single open reading frame (ORF) encoding a polyprotein [16, 17]. The SARS-CoV-2 genome is ordered by 5′- the viral replicase (ORF 1a and ORF1b)-structural proteins [Spike(S)-Envelope(E)-Membrane (M)-Nucleocapsid(N)]-3′; some genes of accessory proteins, such as ORF 3a, 7, and 8, are inserted in genes of structural proteins [7, 15–19]. Figure ​Figure11 shows the genome structure of SARS-CoV-2 in different studies. In the genome of coronaviruses, the gene of ORF1a and ORF1b occupies about two thirds of the overall genome, encoding 16 non-structural proteins (nsps), while the remaining one-third encodes accessory proteins and structural proteins [12, 16]. As shown in Fig. 1, there are some slight differences in the reported genome structure, mainly in accessory proteins [7, 12, 15, 17–19]. For example, the significant difference of two accessory proteins (ORF3b and ORF8) on the gene sequence between SARS-CoV-2 and SARS-CoV was reported by several studies [12, 16]. Using the different genome sequences as comparison can partly account for the results. As for the novel proteins of SARS-CoV-2, whether involving in pathogenesis of the virus or not is unclear.

Genome organization of SARS-CoV-2 in different studies [7, 12, 15, 17–19]. ORF = open reading frame (orange). Structural proteins including S, E, M, N (blue) (S = spike, E = envelope, M = membrane, N = nucleocapsid). Accessory proteins including 3, 3a, 3b, 6, 7, 8, 9a, 9b, 10b, 13, 14 (purple). SP = signal peptide. S1 = subunit 1. S2 = subunit 2. NTD = N-terminal domain. RBD = receptor binding domain. ESD = external subdomain. FP = fusion peptide. HR1 = heptad repeat 1. HR2 = heptad repeat 2. TM = transmembrane domain. CP = cytoplasmic domain. The length of genes is not drawn in scale

Inspired by the pathogenesis of SARS-CoV, the SARS-CoV-2 was presumed to infect the human cells by spike glycoprotein binding to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). In fact, current evidence supports this idea. As for the spike protein of SARS-CoV-2, it contains two regions, S1 subunit and S2 subunit, which consists of 1253 amino acids [20]. The amino acid identity of spike protein between SARS-CoV-2 and SARS-CoV was about 75% [21, 22]. Generally, S1 domain is linked to receptor binding; S2 domain is linked to cell membrane fusion. Similar to SARS-CoV, S1 contains the N-terminal domain (NTD) and a receptor-binding domain (RBD) which contains core domain and external subdomain (ESD). S2 contains three functional domains, fusion peptide (FP), and heptad repeat (HR) 1 and 2 (Fig. ​(Fig.1).1). Whether SARS-CoV-2 can combine with host cells or not is determined by the affinity between the viral RBD and ACE2 of human cells [22]. Once RBD binds to the receptor, the S2 changes conformation to facilitate the membrane fusion by three functional domains. Although SARS-CoV is not the closest to SARS-CoV-2 at the whole-genome level, the RBD of SARS-CoV-2 is closer to that of SARS-CoV, and 72–74.9% amino acid sequences of RBD in both are identical [7, 19, 23]. Several critical residues in SARS-CoV-2 RBD have good interactions with human ACE2. Most residues of RBD interacting with ACE2 are fully conserved [22, 24]. As for function domains of S2, there is no difference between SARS-CoV-2 and SARS-CoV except some non-critical amino acids in HR1 region [22]. Another strong piece of evidence supporting ACE2 as a receptor of cells is that HR1 and HR2 domain of SARS-CoV-2 can fuse with each other to form 6-HB following SARS-CoV’s fusion mechanism [25]. Despite this, several studies speculated SARS-CoV-2 has less affinity with ACE2 than SARS-CoV [20, 21, 26]. On the contrary, Chen et al. [23] reported SARS-CoV-2 provided a stronger interaction with ACE2 than SARS-CoV by structure analysis of the receptor binding of SARS-CoV-2. By elucidating cryo-EM structure of SARS-CoV-2 spike protein, Wrapp et al. [27] also found that compared with SARS-CoV, SARS-CoV-2 bound to ACE2 with 10- to 20-fold higher affinity. In order to identify the suppose of entering cellular by ACE2, Peng et al. [28] found that SARS-CoV-2 was able to use ACE2 protein of many kinds of cells, including human cells, as an entry receptor in the ACE2-expressing cells, but not cells without ACE2. It also could not use aminopeptidase N and dipeptidyl peptidase which are other coronaviruses’ receptors. In most recent studies, the results provided direct evidence to support ACE2 as the receptor. Yan et al. [29] reported the ACE2-B0AT1 (a neutral amino acid transporter) complex can combine with two spike proteins by structural modeling in a structure analysis of full-length human ACE2, and the extracellular peptidase domain (PD) of ACE2 has the direct interaction with polar residues of RBD [29, 30].

Overall, there is sufficient evidence to support that SARS-CoV-2 infects cells by using the human ACE2. As the cryo-EM structure of spike protein and human ACE2 were revealed successfully, we have more opportunity to clarify the detailed process of entering cells [27, 29, 30].

Epidemiology of COVID-19

In early studies, 49–66% patients had the contact history of Huanan seafood market, where various kinds of living wild animals were on sale, including poultry, bats, and marmots [1, 2, 31]. It is currently speculated that the outbreak of COVID-19 in Wuhan is associated with wild animals. According to WHO, the environmental samples taken from Huanan seafood market were tested positive for SARS-CoV-2 [21], but the specific animals associated with the virus have not been identified. Based on previous evidence, the bats, the host of more than 30 coronaviruses [32], may be the origin of COVID-19. The bats are the natural reservoir of SARS-CoV and MERS-CoV, and spread to human through the palm civets and dromedary camels, respectively [8]. The RaTG13, which is a short RNA-dependent RNA polymerase (RdRp) region from a bat coronavirus, was closest to SARS-CoV-2 with 96.2–98.7% identity in whole-genome sequence [11, 15, 16, 28]. The other two bat-derived SARS-like coronaviruses, bat-SL-CoVZXC21 and bat-SL-CoVZC45, were closer to SARS-CoV-2 than SARS-CoV and MERS-CoV, which have approximately 88% nucleotide identity [7, 15–18]. As for the intermediate hosts of SARS-CoV-2, recent studies suggested pangolins were the most probable animal. Two sub-lineages of SARS-CoV-2 were found in organs of pangolins obtained from anti-smuggling activities in Guangdong and Guangxi Province of China by metagenomic sequence [33]. Xiao et al. [34] reported the SARS-CoV-2 was derived from the reorganization of pangolin-CoV-like virus and a Bat-CoV-RaTG13-like virus. However, the pangolin may not be the only intermediate reservoir, because SARS-CoV-2 was not originated from pangolin-CoV-like virus directly, which was demonstrated by the molecular and phylogenetic analyses in Liu’s study [35].

To sum up, the bats are the most probable original reservoir based on the current evidence. However, it is notable that Wuhan Huanan seafood market may not be the only source of SARS-CoV-2 spreading globally. Cohen pointed out Wuhan Huanan seafood market was not the only origin of SARS-CoV-2 by analyzing the epidemiology of 41 cases in the earliest study [36] . Pangolins may act as one of intermediate hosts. More work is needed to provide more precise information about original reservoir and intermediate hosts of SARS-CoV-2. Table ​Table11 lists some information of studies about the genome sequence identity with SARS-CoV-2.

Table 1

Genome identity between SARS-CoV-2 and other bat-like coronavirus

StudySample sizeSequence identity of sample (%)Source of sampleHuanan seafood marketLung lesionApproachGenome lengthType of coronavirusGene sequence identity (%)
RdRp gene*bat-SL-CoV ZC45bat-SL-CoV ZXC21SARS-CoVMERS-CoV
Lu [7]a9> 99.98BALF or throat swabs8/9YesNGS-β-Cov-87.9987.2379.050.0
Wu [12]3Almost identityObtain from ViPR and NCBI--In-depth genome annotation29.8 kbβ-Cov-CloserCloser-Distant
D. Paraskevis [15]1-Downloaded from NCBI--NGS-β-Cov96.3----
Chen [16]2-BALF2/2YesmNGS29,881ntβ-Cov98.787.987.979.7-
Chan [17]1-Obtain from GenBank--Phylogenetic analysis29,891ntβ-Cov-89.089.082.0-
Chan [18]699.99Respiratory samples0/5YesRT-PCR sequence29.8 kbβ-Cov-89.0---
Wu [19]1-BALF1/1YesmNGS29,903 ntβ-Cov-89.1---
Zhou [28]a799.9BALF6/7YesmNGS29.9Kbβ-Cov96.288.188.079.5-

Transmissibility is an important factor of an epidemic [37]. Data as reported by 10 AM CET on 3 March 2020, SARS-CoV-2 has been responsible for 90,870 confirmed cases with 3112 (3.4%) deaths around the world [38]. The reported median age of patients was ranged from 41 to 57 years [1, 2, 39]. Male made up the majority of patients with the proportion of 50–75% [1–3, 39]. Due to different data sources, the infection rate of medical staff has a huge difference, with 2.1–29% [3, 40]. Approximately 25.2–50.5% SARS-CoV-2infected patients had one or more underlying diseases (Table ​(Table2),2), including hypertension, diabetes, chronic obstructive pulmonary disease, cardiovascular disease, and malignancy [1–3, 39, 41]. The COVID-19’s median incubation period from exposure to illness onset was 3.0 days in a 1099-case cohort and 4.0 days in a 62-case cohort [39, 41]. It was also reported the longest incubation period was 24 days [41]. The percentage of patients exposed to Huanan seafood market varies between 8.7% and 66% [1–3, 42]. Patients with no contact history of Huanan seafood market and medical staff infection [18, 21, 43] indicated human-to-human transmission mainly via droplets from coughing or sneezing or direct contact [18, 44–47]. In addition, several studies reported fecal-mouth pathway may also be a potential way for the transmission of SARS-CoV-2 [23, 48], and the SARS-CoV-2 was also isolated from urine of a patient in a recent new [49]. But it is unclear whether human-to-human transmission can be implemented by the above routes.

Table 2

Clinical and laboratory findings of patients with SARS-CoV-2 infection [1–3, 39, 41]

Common symptomsLaboratory findings
  Fever77.4–98.6%Lymphopenia35.3–82.1%
  Cough59.4–81.8%Thrombocytopenia5.0–36.2%
  Fatigue38.1–69.6%Leukopenia9.1–33.7%
  Dyspnea3.2–55.0%Increased CRP60.7–86.3%
  Myalgia11.1–34.8%Increased d-dimer36.4–46.4%
  Sputum production28.2–56.5%Increased LDH27.4–75.8%
  Headache6.5–33.9%Increased CK8.0–32.5%
Underlying diseases25.2–50.5%Prolonged prothrombin time58.0%
ComplicationIncreased ALT16.1–28.3%
  ARDS3.4–29.3%Increased AST22.2–36.7%
  Shock1.0–8.7%Increased interleulin-651.5%
  Acute renal injury0.5–7.3%Increased serum fenitin62.6%
  Acute cardiac injury7.2–12.2%Increased ESR84.8%
  Secondary infections9.8%Increased procalcitonin5.5–11.3%
Increased troponin I12.2%
Increased creatinine1.9–9.8%

The basic reproduction number R0, the important property of transmission, is commonly used to estimate the average number of secondary cases generated by an infectious case in a fully susceptible population during the early phase of the outbreak [37, 50]. If the R0 is more than 1, human-to-human transmission may persist. A range from 1.4 to 6.49 of R0 was estimated by various methods [44, 51–53]. The different values of estimated R0 can attribute to different data and different modeling methods [53]. Liu et al. [53] came to conclusion that the average of estimate R0 was 3.28 with a median of 2.79 by an analysis of 12 studies. So, around 2–3 is indeed a reliable range, suggesting the potential of sustained human-to-human transmission [50, 53]. Additionally, so many factors can affect the value of R0, including estimation period, utilized models, and datasets [54]. As various aspects of measures have taken effect, the estimated R0 is mutable. As David said, it is impossible to know what will happen so early in this SARS-CoV-2 epidemic [37]. The initial R0 estimation for SARS-CoV was more than 2.0, but the predicted large outbreak did not occur [8, 37]. It is also notable that asymptomatic patients can also be a source of infection [43, 48]. The super communicator is worthy of notice, who can infect more than 100 individuals [52]. The immediate priority is to clarify all potential routes of transmission. After all, superspreading has a huge impact on the epidemic. Anyway, it is necessary for us to take effective measures and keep alert to control the epidemic. Fortunately, the number of confirmed cases maintains at a lower level in mainland of China with 119 confirmed cases on 3 March 2020 [10]. At this critical period, it is apparently wise to continue taking steps to control the outbreak.

Clinical features and diagnosis

Clinical manifestations

The clinical manifestations of SARS-CoV-2-infected patients ranged from mild non-specific symptoms to severe pneumonia with organ function damage. The common symptoms were fever (77.4–98.6%), cough (59.4–81.8%), fatigue (38.1–69.6%), dyspnea (3.2–55.0%), myalgia (11.1–34.8%), sputum production (28.2–56.5%), and headache (6.5–33.9%) [1–3, 39, 41] (Table ​(Table2).2). Sore throat, rhinorrhea, chest pain, hemoptysis, conjunctival congestion, diarrhea, nausea, and vomiting were less common [1–3, 39, 41]. But one study showed 39.6% of 140 confirmed COVID-19 patients had gastrointestinal symptoms [40], and 10.1% patients presented with gastrointestinal discomfort at onset in Wang’s study [3]. Patients did not necessarily have fever at onset, some patients developed after hospitalization [41], and some severe patients even did not have fever. SARS-CoV-2, SARS-CoV, and MERS-CoV infections share many similar clinical symptoms [8], including fever, cough, myalgia, and dyspnea. However, patients with SARS and MERS have more gastrointestinal involvement (about one-third) than COVID-19 patients [55]. And MERS has a high incidence of renal failure, which is a typical characteristic not often found in other human coronavirus infections [56, 57].

Laboratory and radiologic characteristics

Of confirmed patients, 35.3–82.1%, 5.0–36.2%, and 9.1–33.7% had lymphopenia, thrombocytopenia, and leukopenia, respectively [1–3, 39, 41] (Table ​(Table2).2). C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), serum ferritin, and interleukin-6 (IL6) elevated prominently in Chen’s research [2]. Many patients also had increased levels of d-dimer, lactate dehydrogenase (LDH), creatine kinase (CK), prolonged prothrombin time, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) [1–3, 39, 41, 58]. However, elevated levels of procalcitonin, troponin I, and creatinine were uncommon [1, 39, 41].

The typical imaging features of chest computed tomography (CT) for novel coronavirus pneumonia (NCP) included ground-glass opacity, bilateral patchy shadows, and subsegmental areas of consolidation, sometimes with a rounded morphology and a peripheral lung distribution [1–3, 40, 41, 59]. Changes in the disease were accompanied by changes in CT imaging, reflecting the severity of the disease [58]. Pan et al. [60] analyzed 21 NCP patients from initial diagnosis until recovery (without severe respiratory distress during a hospital stay), and they found chest CT scan showed that the lung abnormalities were the most severe about 10 days after the initial symptoms onset. Overall, the CT manifestations of NCP were diverse and fast-changing [61]. However, a normal chest CT image cannot exclude the diagnosis of SARS-CoV-2 infection [62].

Pathological finding

By obtaining biopsy samples at autopsy of one COVID-19 patient [63], the lung biopsy specimens showed bilateral diffuse alveolar damage with cellular fibromyxoid exudates. Bilateral lung tissue indicated pulmonary edema with hyaline membrane formation, reflecting ARDS. Meanwhile, flow cytometric analysis of peripheral blood suggested the reduced counts of peripheral CD4 and CD8 T cells but a hyperactivated status. A report on systemic anatomy at autopsy from the other patient [64] indicated gray white patchy lesions in lungs, gray white viscous fluid overflow in the lung section, and pulmonary fiber bands, reflecting that COVID-19 caused an inflammatory response characterized by deep airway and alveolar damage. The pathological results of the first one resembled those seen in SARS-CoV and MERS-CoV infection [63]. However, the latter found pulmonary fibrosis and consolidation were less severe than SARS, but exudation was more obvious [64]. These findings, with more pathological research, will make a great importance in understanding the pathogenesis and making therapeutic strategy for COVID-19.

Diagnosis

The COVID-19 patients around the world were diagnosed based on World Health Organization interim guidance [65], and China updated the novel coronavirus pneumonia diagnosis and treatment program (trial version) (in Chinese) according to epidemic situation and improved awareness of disease. A laboratory confirmed case with SARS-CoV-2 infection was defined as a positive result to high-throughput sequencing or real-time reverse-transcriptase polymerase-chain-reaction (RT-PCR) assay for SARS-CoV-2 [65, 66]. Chest CT, as a diagnostic method for COVID-19 with a high sensitivity, is being given more important value for diagnosis [67]. In the fifth trial version of novel coronavirus pneumonia diagnosis and treatment program (in Chinese) [68], clinical diagnosis was proposed for cases in Hubei Province, who had epidemiology history, the above clinical features along with typical chest CT imaging. And more than 10,000 patients for clinical diagnosis got early treatment [69]. The sixth trial version (in Chinese) removed the clinical diagnosis, for reduced suspected cases and improved nucleic acid detection capability [66].

Treatment

In several clinical studies of confirmed cases, strategies for COVID-19 patients included antiviral treatment, empirical antibiotic treatment, corticosteroid, intravenous immunoglobulin therapy, oxygen support (nasal cannula, mask oxygen inhalation, non-invasive ventilation, invasive mechanical ventilation), continuous renal replacement therapy (CRRT), and extracorporeal membrane oxygenation (ECMO) [1–3, 39, 41].

Due to the absence of clinical evidence, there were no approved drugs for antiviral therapy against SARS-CoV-2. Of three clinical cohort studies, oseltamivir was used for antiviral therapy in 35.8% (393/1099) patients, 89.9% (124/138) patients, and 92.7% (38/41) patients, respectively [1, 2, 41]. Another research [2] included 99 COVID-19 patients, in which 76.0% patients received antiviral treatment, including oseltamivir, ganciclovir, and lopinavir and ritonavir tablets, and the duration of antiviral treatment was 3–14 days. Though oseltamivir had high application rate in the early cohort studies, its drug efficacy on COVID-19 was not obvious, and the sixth trial version of novel coronavirus pneumonia diagnosis and treatment program (in Chinese) did not recommend it [66]. Case report implied that lopinavir and ritonavir therapy may be beneficial for COVID-19 cases [70, 71]. Remdesivir, a nucleotide analogue RNA polymerase inhibitor with broad-spectrum antiviral activity, was demonstrated that it could be against Ebola virus in rhesus monkeys [72]. Wang et al. [73] found that remdesivir and chloroquine were highly effective in the control of SARS-CoV-2 infection in vitro. What’s more, the first reported COVID-19 case of the USA was cured by intravenous remdesivir [58] and other supportive care. More researches from cells, animals, and clinical need to explore the effect of remdesivir on SARS-CoV-2. Other methods of antiviral drug administration may also have some certain function. It was reported that different combinations of interferon alpha inhalation, lopinavir/ritonavir, and arbidol may have some effects [39]. Furthermore, combined Chinese and Western medicine treatment, including lopinavir/ritonavir, arbidol, and Shufeng Jiedu Capsule (a traditional Chinese medicine) may also be beneficial to treatment which deserved further study [74].

As for the corticosteroid therapy for SARS-CoV-2, current interim guidance from WHO on clinical management of severe acute respiratory infection, when SARS-CoV-2 infection is suspected (released Jan 28, 2020), suggests not routinely using systemic corticosteroids unless indicated for another reason [65], and there were contradictory opinions from professors [75, 76]. Corticosteroid therapy was used in approximately 20–44.9% COVID-19 patients [1–3, 39, 41]. Compared with non-severe patients, severe patients got more corticosteroid therapy (44.5% vs. 13.7%) with the median of maximal daily dose up to 30.0 (1.0–40.0) (mg/kg) [41]. According to pathological findings of one COVID-19 patient, proper use of corticosteroid together with other support care should be considered for the severe patients to prevent ARDS development [63].

There are more than 80 running or pending clinical trials on potential treatments for COVID-19 in China [77]. Studies of recombinant human angiotensin-converting enzyme 2 (rhACE2), mesenchymal stem cell, PD-1 blocking antibody, bevacizumab injection, and immunoglobulin of cured patients are registered in the website of Clinical Trial [78], and some are recruiting patients. Safe and effective clinical trials will find more therapeutic possibilities for COVID-19 patients.

Prognosis

Many patients infected withSARS-CoV-2, especially for severe patients, had complications (Table ​(Table2),2), including ARDS, shock, acute renal injury, acute cardiac injury, and secondary infection [1–3, 41].

The mortality rate of COVID-19 ranged from 0 to 14.6% [1–3, 39, 41, 79]. However, Yang et al. [42] reported 32 of 52 (61.5%) critically ill adult ICU patients had died at 28 days. It is not hard to know the disease severity is an independent predictor of poor prognosis [41, 42]. Compared with non-ICU patients, the ICU patients were older with a greater number of comorbid conditions and had more common symptoms of dyspnea, abdominal pain, and anorexia [3]. Meanwhile, it was reported that ICU patients had higher plasma cytokine and chemokine levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα [1]. Non-survivors had more severe lymphopenia and higher blood cell counts, neutrophil counts, d-dimer and fibrin degradation product than survivors [3, 63]. Wang et al. [80] analyzed the first 17 deaths up to 22 January 2020, announced by The China National Health Commission found that the median days from first symptom to death were 14.0 (range 6–41) days, and seemed to be shorter among old people [80]. In Yang’s study [42], the survival time of the non-survivors is likely to be within 1–2 weeks after ICU admission.

In summary, severe patients or ICU patients have a relatively higher mortality [41, 42]. Age, comorbidity, some symptoms (dyspnea, abdominal pain, etc.), and more prominent laboratory abnormalities (lymphopenia, elevated d-dimer, etc.) may be risk factors for poor outcome [3, 40, 42, 80].

According to the latest data released at 24:00 on 3 March 2020 (Beijing time), the fatality is 3.7% and 4.6% for the mainland of China and Wuhan, Hubei Province, respectively [10]. Overall, SARS-CoV-2 has a relatively lower mortality rate than SARS-CoV and MERS-CoV (9.6% and 40.0%, respectively) [55].

Conclusion

COVID-19 has spread to 73 countries, territories, or areas around the world, and is responsible for 90,870 patients as of 10 AM CET on 3 March 2020. The virus may be related to bats, but Wuhan Huanan seafood market may not be its sole origin. Whatever the case, banning of wildlife sales and removing them from wet markets are beneficial to control the epidemic. Except several genes of accessory proteins, SARS-CoV-2 is almost identical to SARS-CoV in genome organization. Hence, we obtain the fact that ACE2 is the receptor of SARS-CoV-2 entering cells. Human to human transmission can be realized mainly by droplets from coughing or sneezing or direct contact. Fever and cough are the main symptoms. Chest CT examination is an important tool for diagnosis, and confirmed cases are diagnosed by detecting SARS-CoV-2 of specimens taken from the upper respiratory tract and lower respiratory tract. As for the treatment, there are no specific drugs for the infection, and many therapies, with preliminary good clinical response, are being tested in clinical trials. We hope that increased awareness of the virus and ongoing clinical trials can help to find effective treatment against SARS-CoV-2. Though the fatality of SARS-CoV-2 is lower than SARS-CoV and MERS-CoV, the overall mortality of SARS-CoV-2 remains to be established in the future, because a large number of confirmed and suspected cases are still in hospital; even worse, the confirmed cases are increasing in other countries, like Korea and Japan. Further study is necessary for us to control this epidemic disease.

Authors’ contribution

Huipeng Ge, Xiufen Wang: manuscript writing, bibliographic retrieval, making tables and figure.

Xiangning Yuan, Gong Xiao, Chengzhi Wang, Tianci Deng: manuscript writing.

Qiongjing Yuan, Xiangcheng Xiao: manuscript editing and critical review.

Funding information

This work was supported by the National Natural Science Foundation of China under Grant no. 81770743, and by the Natural Science Foundation of Hunan province China under Grant no. 2018JJ2654.

Compliance with ethical standards

Conflict of interest

All authors declared that they had no conflicts of interest.

Footnotes

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Huipeng Ge and Xiufen Wang contributed equally to this work.

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