For citation: Centre for Infectious Disease and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Aug 27

COVID-19 Situation Report 210

Centre for Infectious Disease Epidemiology and Research (CIDER) For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

i. Background

In December, China notified the World Health Organization (WHO) of several cases of human respiratory illness, which appeared to be linked to an open seafood and livestock market in the city of Wuhan. The infecting agent has since been identified as a novel , previously known as 2019-nCoV and now called SAR-CoV-2; The new name of the disease has also been termed COVID-19, as of 11th February 2020. Although the is presumed zoonotic in origin, person-to-person spread is evident. Screening of travellers, travel bans and quarantine measures are being implemented in many countries. Despite these precautions, it is anticipated that more cases will be seen both inside China and internationally. The WHO declared the outbreak of COVID-19 constitutes a Public Health Emergency of International Concern on 30 January. On 11 March, 2020, WHO declared the coronavirus outbreak a pandemic as the global death toll rose above 4,600 and the number of confirmed cases topped 125,000. This report aims to update Global Risk Assessment, Global Epidemiology, Quarantine Orders, Travel Ban/Advisory by countries, WHO’s and CDC’s Guidance and Protocols and Scientific publication on a daily basis. New updates in the tables are bolded.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

ii. Global Risk Assessment Table 1. Risk assessment of COVID-19 by WHO regions (Updated as of 27 August, 15:00 SGT) Over Severity Availability of Treatment/ Environmental Risk Transmissibility all of Disease # Risk Global (n=197 countries) High Moderate High Limited

Globally, 183 (92.9%) Based on recent Case As of early August, there’re currently 26 countries (excluding CDC data, fatality candidates that either have been territories*) have reported the rate is tested on humans or have received median R0 is outbreak. currently approval to do so. This includes Duke- estimated to be Parts of China including Hubei at 3.41% NUS & Arcturus Therapeutics’ vaccine have relaxed lock-down 5.8 (95% CI 4.4– globally. candidate, Lunar-Cov19. On 11 August, measures; As of 8 April, China 7.7), but the Most Russia claimed to have developed the lifted its 76-day lockdown in estimated mean cases first validated vaccine in the world, Wuhan. time-varying present as despite limited evidence.[1] effective R^ in flu-like The latest data from the 119 countries illness. Many countries, including South Korea, United Nations specialized US & UK are using Remdesivir even ranged from 0.7 agency for tourism shows that though the drugmaker has yet to gain $ 100% of destinations as of 20 to 1.9. regulatory approval in several markets April have restrictions in place. and is still ramping up production of the

This represents the most anti-viral drug. Remdesivir is the first severe restriction on drug to show benefit in a large placebo- international travel in history. controlled trial— a NIAID trial showed the drug cut hospital stays by 31per cent, At least 130 countries or about four days, compared with a High worldwide have imposed placebo. [2] lockdowns of varying scales; Singapore implemented Phase On 4th July, WHO accepted the 2 starting June 19th in which recommendation from the Solidarity most businesses and social Trial’s International Steering Committee activities will be allowed [16] to discontinue the trial’s hydroxychloroquine and China has raised its lopinavir/ritonavir arms. These interim emergency warning to its trial results show that second-highest level and hydroxychloroquine and cancelled more than 60 per lopinavir/ritonavir individually produce cent of flights to Beijing amid little or no reduction in the mortality of a new coronavirus outbreak in hospitalized COVID-19 patients when the capital. [18] compared to standard of care.

WHO has reported that the Anti-viral drug Favilavir was approved in th coronavirus has entered a China on 18 February 2020 The drug is “new and dangerous phase” also tested for treatment in Japan [4]. As th as daily cases hit high record of 25 May, Japan will delay approving on 18 June. [19] the drug by the end of May, as Kyodo reported no clear evidence of its efficacy [5];

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Actemra (Tocilizumab) was approved for use in treatment of serious COVID-19 patients with lung damage in China as of 4th March 2020 [6];

The U.S. Food and Drug Administration on Monday revoked the emergency use authorization for malaria drugs as a treatment for COVID-19 and announced that oral formulations of hydroxychloroquine and the related drug chloroquine may be ineffective in treating the respiratory illness caused by the novel coronavirus. [17]

Of 19 in human trials, only two are in the final Phase III - one by China's Sinopharm and another by AstraZeneca and the University of Oxford [27]. Western Pacific Region and South-East Asia Region (n=41 countries) High Moderate Moderate Limited

28 (68.3%) countries have As of July 11, Case Malaysia is using Tocilizumab while reported outbreaks; the estimated fatality concurrently evaluating them in clinical effective rate is trials for severe cases of Covid-19 [10]. At least 22 countries have 1.91%. reproduction imposed lockdowns Japan has approved the use of antiviral (nationwide or state-specific) no. of 16 drug remdesivir against severe COVID-19 since the pandemic escalated, countries cases [8]. On 21 July 2020, 11 of which have reportedly ranged from was approved as the extended their restriction 0.9-1.6.$ second drug for COVID-19 treatment measures. [28].

Singapore has approved remdesivir administration to patients with low High oxygen saturation levels less than or equal to 94 per cent, or who might require supplemental oxygen or more intensive breathing support such as extracorporeal membrane oxygenation or invasive [14].

Use investigational antiviral medication remdesivir in treating India’s Covid-19 patients has been approved on 13 June [15].

India has approved Glenmark Pharmaceuticals Ltd to make and sell oral

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antiviral drug favipiravir to treat mild-to- moderate COVID-19 patients for restricted emergency use where consent must be taken before treatment. [20]

India has appoved Hetero Labs and Cipla Ltd to make and sell their generic version of remdesivir- Covifor and Cipremi. [22]

The Ad5-nCoV developed by the military and CanSino Biologics has been approved for military use on June 25 for a period of a year. It cannot be expanded to a broader vaccination range with the approval of the military logistics support department. While phase 1 and 2 clinical tirals have shown its potential, its commercial success cannot be guaranteed. [24]

Australia approved the anti-viral drug remdesivir for treatment of Covid-19 on Friday, July 10 following a similar decision from the European Commission. It is the first drug approved by Australian authorities to treat the virus [26].

Taiwan has provincially approved dexamethasone to treat Covid-19. [30]

China has approved the emergency use of vaccine by Sinopharm on 22 July. High risk group such as medical workers, customs and border officials were eligible to receive the vaccine. [32] European Region (n=53 countries) High Moderate High Limited

52 (98.1%) countries have As of July 11, Case Britain will provide Remdesivir to COVID- reported with outbreaks; the estimated fatality 19 patients who are most likely to benefit effective rate is [12]. At least 41 countries have 5.33%. reproduction imposed lockdowns Russia secured regulatory approval for no. of 46 High (nationwide or state-specific) the use of its antiviral drug Coronavir, to since the pandemic escalated, countries treat mild and moderate patients of 14 of which have reportedly ranged from extended their restriction 0.9-1.9.$ Covid-19 [25]. measures.

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Eastern Mediterranean Region (n=22 countries) High Moderate Moderate Limited

22 (100%) countries have As of July 11, Case An Israeli firm is using placenta pluristem reported with outbreak; the estimated fatality cells to treat COVID-19 patients on a effective rate is compassionate use basis. [11] At least 19 countries have 2.67%. reproduction imposed lockdowns As of June 25, the Abu Dhabi Stem Cell High (nationwide or state-specific) no. of 20 Centre has treated more than 2,000 since the pandemic escalated, countries COVID-19 patients using UAECell19. 11 of which have reportedly ranged from 1,200 have fully recovered. [23] extended their restriction 0.9-1.4.$ measures. Region of the Americas (n=35 countries) High Moderate High Limited

35 (100%) countries have As of July 11, Case Anti-viral drug Remdesivir (by Gilead reported with outbreak; the estimated fatality Sciences Inc.) was approved by US FDA effective rate is for emergency use in COVID-19 patients At least 24 countries have 3.52%. with low blood-oxygen levels or who reproduction imposed lockdowns need breathing support [8]. (nationwide or state-specific) no. of 21 High since the pandemic escalated, countries RLF-100 (aviptadil) by NeuroRx and Relief 11 of which have reportedly ranged from Therapeutics was approved for extended their restriction 0.9-1.3.$ emergency use in COVID-19 patients who measures. are too ill to participate in the trial. [29]

FDA has issued emergency authorisation for convalescent plasma to treat COVID- 19. [31] African Region (n=46 countries) High Moderate Moderate Limited

46 (100%) countries have As of July 11, Case Ethiopia has approved the use of reported with outbreak; the estimated fatality Dexamethasone treatment for seriously effective rate is ill COVID-19 patients. [21] At least 26 countries have 2.06%. reproduction High imposed lockdowns (nationwide or state-specific) no. of 36 since the pandemic escalated, countries 10 of which have reportedly ranged from extended their restriction 0.7-1.8.$ measures. *Only WHO member states are included. 30 territories that have reported cases (with the exception of Palestine) are excluded from the tabulation of total countries affected/imported/local cases and case fatality rate. Refer to WHO situation reports or table 4 for information. **The travel ban consists of both certain areas of China, Japan, Korea, Italy and Iran or the whole country # Ongoing clinical trials of and treatment are summarised in section X, under table 7 and table 8. %This is by no means an exhaustive list of lockdowns imposed globally. Tally is subjected to publication bias whereby certain countries may receive less media attention and hence, coverage on their lockdowns. Lockdowns of varying scales are imposed across nations, for this compilation, all countries that have imposed some form of movement restriction, nationwide or state-specific are included. $ https://epiforecasts.io/covid/posts/global/ ^Differences between R0 and effective R can be found here https://www.coronavirustoday.com/r-number-refers-either-basic-or-effective- reproduction-number

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020 iii. Global Epidemiology Table 2. Summary of COVID-19 cases & fatalities globally (Updated as of 27 August, 15:00 SGT) Case- No. of Total Cases Case- Total Fatality Countries/ Outside Total Fatality Global Rate (%) R0 Territories Mainland Deaths Rate (%) Cases [outside with Cases China [overall] China] 213 24,344,815 24,259,811 829,778 3.41% 3.40% 5.8 (95% CI 4.4–7.7)^ ^Based on early release as of 10th April, 2020: https://wwwnc.cdc.gov/eid/article/26/7/20-0282_article

Table 3. Comparison with other Virus Incubation Period (Days) Case Fatality Rate (%) R0 Median = 5.1$ SARS-CoV-2 3.41 5.8 (95% CI 4.4–7.7) ^ (2-14) or up to 24* SARS-CoV 2-7 9.6 2.0 <1 (higher in health MERS-CoV 5 (2-14) 34 care setting) Swine Flu 1-4 0.02 1.2-1.6 *Data on 1099 patients from 552 hospitals in 31 provinces of China ^https://wwwnc.cdc.gov/eid/article/26/7/20-0282_article $Data on 181 cases outside china

Figure 1. Growth Factor of Daily New Cases (Mainland China+ Other countries)

Growth Factor = every day’s cases/cases on previous day. A growth factor above 1 indicates an increase, whereas one between 0 and 1 it is a sign of decline, with the quantity eventually becoming zero. A growth factor below 1 (or above 1 but trending downward) is a positive sign, whereas a growth factor constantly above 1 is the sign of exponential growth. *Huge jump in cases on Feb. 12 is attributed to the change in diagnostic criteria in China.

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Figure 2. Growth Factor excluding mainland China

Figure 3. Growth Factor of Novel Coronavirus Daily Deaths (Mainland China + Other Countries)

Growth Factor = every day’s cases/cases on previous day. A growth factor above 1 indicates an increase, whereas one between 0 and 1 it is a sign of decline, with the quantity eventually becoming zero. A growth factor below 1 (or above 1 but trending downward) is a positive sign, whereas a growth factor constantly above 1 is the sign of exponential growth. Source: https://www.worldometers.info/coronavirus/coronavirus-cases/

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Case Breakdown by Countries Live update of COVID-19 global cases can be found at https://storymaps.arcgis.com/stories/a1746ada9bff48c09ef76e5a788b5910

Table 4. Breakdown of COVID-19 confirmed cases and deaths (Updated as of 27 August, 15:00 SGT) Total Total Country Total Cases Change Change Region Deaths Recovered 1 USA 6,001,017 +44981 183663 +1251 3314305 Americas 2 Brazil 3,722,004 +47828 117756 +1090 2908848 Americas 3 India 3,314,953 +79228 60652 +1020 2524518 SEARO 4 Russia 970,865 +4676 16683 +115 786150 EURO 5 South Africa 615,701 +2684 13502 +194 525242 Africa 6 Peru 613,378 +5996 28124 +123 421877 Americas 7 Mexico 573,888 +5267 62076 +626 396758 Americas 8 Colombia 572,270 +10142 18184 +295 407121 Americas 9 Spain 426,818 +3594 28971 +47 N/A EURO 10 Chile 402,365 +1380 10990 +32 376268 Americas 11 Argentina 370,188 +10550 7839 +276 268801 Americas 12 Iran 365,606 +2243 21020 +119 314870 EMRO 13 UK 328,846 +1048 41465 +16 N/A EURO 14 Saudi Arabia 310,836 +1068 3755 +33 284945 EMRO 15 Bangladesh 302,147 +2519 4082 +54 190183 SEARO 16 Pakistan 294,638 +445 6274 +7 279561 EMRO 17 Italy 262,540 +1366 35458 +13 206329 EURO 18 Turkey 262,507 +1313 6183 +20 239797 EURO 19 France 253,587 +5429 30544 0 85524 EURO 20 Germany 239,000 +1428 9352 +7 214233 EURO 21 Iraq 215,784 +3837 6668 +72 157215 EMRO 22 Philippines 202,361 +5197 3137 +99 133460 WPRO 23 Indonesia 160,165 +2306 6944 +86 115409 SEARO 24 126,417 +448 9094 +4 112455 Americas 25 Qatar 117,742 +244 194 0 114558 EMRO 26 Bolivia 112,094 +1095 4726 +62 50397 Americas 27 Ukraine 112,059 +1974 2403 +85 54217 EURO 28 Ecuador 110,549 +1519 6410 +42 95097 Americas 29 Israel 108,964 +1886 875 +16 87011 EURO 30 Kazakhstan 105,243 +168 1523 0 94713 EURO 31 Egypt 97,825 +206 5317 +19 68713 EMRO 32 Dominican Republic 92,557 +340 1613 +28 63478 Americas 33 Panama 89,082 +701 1932 +13 63595 Americas 34 Sweden 87,072 +181 5817 +3 N/A EURO 35 China 85,004 +8 4634 0 80046 WPRO 36 Oman 84,818 +166 646 +4 79409 EMRO 37 Belgium 83,030 +583 9879 -117* 18331 EURO

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38 Kuwait 82,271 +698 521 +2 73906 EMRO 39 Romania 81,646 +1256 3421 +54 36286 EURO 40 Belarus 70,974 +247 657 +5 69378 EURO 41 Guatemala 70,714 +1063 2662 +32 58783 Americas 42 Netherlands 68,114 +571 6215 +8 N/A EURO 43 UAE 68,020 +399 378 +1 59070 EMRO 44 Japan 63,822 +701 1209 +13 51688 WPRO 45 Poland 63,802 +729 1994 +17 43399 EURO 46 Honduras 56,649 +772 1747 +44 9169 Americas 47 Singapore 56,495 0 27 0 54971 WPRO 48 Portugal 56,274 +362 1807 +2 41184 EURO 49 Morocco 55,864 +1336 984 +29 40586 EMRO 50 Nigeria 53,021 +221 1010 +3 40281 Africa 51 Bahrain 50,393 +317 186 0 47049 EMRO 52 Ethiopia 45,221 +1533 725 +16 16311 Africa 53 Ghana 43,769 +52 270 0 42048 Africa 54 Kyrgyzstan 43,459 +101 1057 0 37492 EURO 55 Armenia 43,270 +203 864 +3 36988 EURO 56 Algeria 42,619 +391 1465 +9 29886 Africa 57 Venezuela 41,965 +807 351 +8 32931 Americas 58 Switzerland 40,645 +383 2003 +1 34800 EURO 59 Uzbekistan 40,195 +405 295 +6 36562 EURO 60 Afghanistan 38,129 +59 1401 +4 29046 EMRO 61 Costa Rica 36,307 +1002 386 +10 13317 Americas 62 Azerbaijan 35,707 +148 522 +1 33281 EURO 63 Moldova 34,982 +624 967 +7 24156 EURO 64 Nepal 34,418 +885 175 +11 19504 SEARO 65 Kenya 33,016 +213 564 +5 19296 Africa 66 Serbia 30,974 +154 707 +2 29343 EURO 67 Ireland 28,363 +162 1777 0 23364 EURO 68 Austria 26,033 +327 733 0 22145 EURO 69 Australia 25,322 +118 572 +23 20100 WPRO 70 El Salvador 25,284 +298 694 +7 13291 Americas 71 Czechia 22,951 +403 418 +2 16954 EURO 72 Palestine 20,155 +477 137 +4 13929 EMRO 73 Cameroon 18,973 0 410 0 16540 Africa 74 S. Korea 18,706 +441 313 +1 14461 WPRO 75 Bosnia and Herzegovina 18,609 +283 571 +11 12336 EURO 76 Ivory Coast 17,603 +41 114 0 15941 Africa 77 Denmark 16,537 +57 623 0 14603 EURO 78 Bulgaria 15,751 +162 586 +14 10750 EURO 79 Paraguay 14,872 +644 247 +16 8134 Americas 80 Madagascar 14,554 +79 181 +3 13582 Africa 81 Lebanon 14,248 +561 139 +1 3955 EMRO

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82 North Macedonia 13,914 +115 578 +5 10507 EURO 83 Senegal 13,186 +130 275 +1 8852 Africa 84 Sudan 12,974 0 819 0 6557 EMRO 85 Libya 11,834 +553 210 +7 1152 EMRO 86 Zambia 11,376 +91 282 0 10693 Africa 87 Norway 10,504 +50 264 0 9150 EURO 88 DRC 9,912 +21 254 +3 8987 Africa 89 Malaysia 9,291 +6 125 0 8978 WPRO 90 Greece 9,280 +293 248 +5 3804 EURO 91 Guinea 9,167 +39 57 0 8150 Africa 92 French Guiana 8,936 +32 56 0 8461 Non 93 Albania 8,927 +168 263 +4 4633 EURO 94 Croatia 8,888 +358 175 0 6362 EURO 95 Gabon 8,468 +59 53 0 7066 Africa 96 Tajikistan 8,413 +34 67 0 7214 EURO 97 Haiti 8,122 +10 197 +1 5677 Americas 98 Finland 8,002 +21 335 0 7200 EURO 99 Luxembourg 7,928 +90 124 0 7140 EURO 100 Maldives 7,225 +178 28 0 4561 SEARO 101 Mauritania 6,977 +17 158 0 6356 Africa 102 Namibia 6,431 +271 59 +2 2734 Africa 103 Zimbabwe 6,251 +55 179 +13 5001 Africa 104 Malawi 5,474 +51 173 +3 3085 Africa 105 Djibouti 5,383 0 60 0 5297 EMRO 106 Hungary 5,379 +91 614 0 3757 EURO 107 Equatorial Guinea 4,928 +2 83 0 3798 Africa 108 Hong Kong 4,736 +25 79 +1 4161 WPRO 109 CAR 4,698 +7 61 0 1778 Africa 110 Montenegro 4,499 +55 88 +1 3558 EURO 111 Nicaragua 4,494 0 137 0 2913 Americas 112 Eswatini 4,387 +60 88 +2 3078 Non 113 Congo 3,979 0 78 0 1742 Africa 114 Cuba 3,759 +15 92 +1 3159 Americas 115 Suriname 3,724 +26 62 +1 2863 Americas 116 Cabo Verde 3,630 +62 38 +1 2713 Africa 117 Rwanda 3,625 +88 15 0 1810 Africa 118 Mozambique 3,590 +82 21 0 1927 Africa 119 Slovakia 3,536 +84 33 0 2192 EURO 120 Thailand 3,404 +1 58 0 3237 SEARO 121 Somalia 3,275 0 95 0 2443 EMRO 122 Mayotte 3,237 0 39 0 2964 Non 123 Tunisia 3,206 +137 71 0 1476 EMRO 124 Sri Lanka 2,984 +13 12 0 2819 SEARO 125 Lithuania 2,726 +32 85 0 1794 EURO

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126 Slovenia 2,722 +36 133 0 2170 EURO 127 Mali 2,717 +4 126 +1 2052 Africa 128 Gambia 2,708 +22 93 +3 611 Africa 129 Uganda 2,524 +98 26 +1 1268 Africa 130 South Sudan 2,510 +3 47 0 1290 Africa 131 Syria 2,440 +75 98 +3 550 EMRO 132 Angola 2,332 +49 103 +1 977 Africa 133 Estonia 2,311 +17 64 0 2054 EURO 134 Guinea-Bissau 2,205 +56 34 +1 1127 Africa 135 Benin 2,145 +30 40 +1 1738 Africa 136 Iceland 2,082 +5 10 0 1957 EURO 137 Sierra Leone 2,003 +2 69 0 1577 Africa 138 Yemen 1,930 +6 560 +3 1097 EMRO 139 Bahamas 1,813 +15 48 +2 634 Americas 140 Jamaica 1,804 +72 19 0 846 Americas 141 Aruba 1,760 +90 8 0 587 Non 142 Jordan 1,756 +40 15 +1 1355 EMRO 143 Malta 1,751 +46 10 0 1077 EURO 144 New Zealand 1,702 +7 22 0 1554 WPRO 145 Botswana 1,633 +71 6 +3 224 Africa 146 Uruguay 1,543 +7 43 0 1322 Americas 147 Cyprus 1,484 +10 20 0 935 EURO 148 Georgia 1,447 +11 19 0 1190 EURO 149 Trinidad and Tobago 1,411 +159 15 0 192 Americas 150 Réunion 1,372 +80 6 0 692 Non 151 Latvia 1,360 +18 33 0 1135 EURO 152 Burkina Faso 1,352 +14 55 0 1058 Africa 153 Togo 1,326 +17 27 0 946 Africa 154 Liberia 1,298 +3 82 0 832 Africa 155 Niger 1173 0 69 0 1084 Africa 156 Andorra 1098 +38 53 0 893 EURO 157 Guyana 1093 +33 31 0 534 Americas 158 Lesotho 1051 +2 31 +1 526 Africa 159 Vietnam 1034 +5 30 +2 632 WPRO 160 Chad 998 +3 77 0 873 Africa 161 Guadeloupe 935 0 15 0 289 Non 162 Sao Tome and Principe 892 0 15 0 842 Africa 163 Belize 760 +30 11 +1 54 Americas 164 712 0 13 0 651 NA 165 San Marino 710 0 42 0 658 EURO 166 Channel Islands 623 +3 48 0 545 Non 167 Martinique 596 +132 16 0 98 Non 168 Myanmar 586 +82 6 0 345 SEARO 169 Tanzania 509 0 21 0 183 Africa

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170 Taiwan 487 0 7 0 462 WPRO 171 Turks and Caicos 464 +33 3 +1 102 Non 172 Sint Maarten 442 +24 17 0 179 Non 173 Burundi 430 0 1 0 345 Africa 174 Papua New Guinea 419 0 4 0 232 WPRO 175 Comoros 417 0 7 0 399 Africa 176 French Polynesia 415 +43 0 0 202 Non 177 Faeroe Islands 411 0 0 0 357 Non 178 Mauritius 354 +6 10 0 335 Africa 179 Isle of Man 336 0 24 0 312 Non 180 Eritrea 315 0 0 0 276 Africa 181 Mongolia 301 +1 0 0 291 WPRO 182 Cambodia 273 0 0 0 264 WPRO 183 Gibraltar 270 +14 0 0 203 Non 184 Cayman Islands 205 0 1 0 202 Non 185 Saint Martin 198 0 5 0 52 Non 186 Bhutan 183 +10 0 0 118 SEARO 187 Bermuda 168 0 9 0 151 Non 188 Barbados 165 +1 7 0 139 Americas 189 Brunei 144 0 3 0 139 WPRO 190 Seychelles 136 0 0 0 127 Africa 191 Monaco 122 +1 1 0 85 EURO 192 Liechtenstein 102 0 1 0 94 Non 193 Antigua and Barbuda 94 0 3 0 89 Americas 194 St. Vincent Grenadines 58 0 0 0 57 Americas 195 Curaçao 53 +4 1 0 34 Non 196 Macao 46 0 0 0 46 WPRO 197 Fiji 28 0 2 +1 23 WPRO 198 British Virgin Islands 26 0 1 0 8 Non 199 Saint Lucia 26 0 0 0 25 Americas 200 Timor-Leste 26 0 0 0 25 SEARO 201 Grenada 24 0 0 0 24 Americas 202 New Caledonia 23 0 0 0 23 Non 203 Laos 22 0 0 0 21 WPRO 204 Dominica 20 0 0 0 18 Americas 205 St. Barth 17 0 0 0 9 Non 206 Saint Kitts and Nevis 17 0 0 0 17 Americas 207 Greenland 14 0 0 0 14 Non 208 Montserrat 13 0 1 0 12 Non 209 Caribbean Netherlands 13 0 0 0 7 Non 210 Falkland Islands 13 0 0 0 13 Non 211 Vatican City 12 0 0 0 12 Non 212 Western Sahara 10 0 1 0 8 Non 213 MS Zaandam 9 0 2 0 0 NA

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214 Saint Pierre Miquelon 5 0 0 0 1 Non 215 Anguilla 3 0 0 0 3 Non

Total 24,344,815 +278679 829,778 +6206 16,672,838 *Death cases have been revised due to counting error in Flemish nursing homes. Source: https://www.brusselstimes.com/belgium/128541/belgium-in-brief-further-from-10000-deaths-than-before/

Figure 4. Areas with reported confirmed cases of COVID-19 (17 August – 23 August 2020)

Source: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/situation-reports

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Table 5. COVID-19 cases and deaths reported by provinces in China (Updated as of 27 August, 15:00 SGT) Existing Change from Total Change from Area Active previous day Diagnosed Deaths previous day Recovered Cases (Active cases) Cases (Deaths) Xinjiang 107 -17 902 3 0 792 Shanghai 74 0 888 7 0 807 Shandong 23 0 831 7 0 801 Sichuan 22 +2 644 3 0 619 Guangdong 20 -2 1734 8 0 1706 Tianjin 14 0 220 3 0 203 Hebei 13 +2 362 6 0 343 Zhejiang 8 0 1277 1 0 1268 Jiangsu 8 -1 665 0 0 657 Fujian 8 -1 375 1 0 366 Shaanxi 8 -4 364 3 0 353 Yunnan 8 0 199 2 0 189 Liaoning 6 0 262 2 0 254 Jiangxi 2 -1 935 1 0 932 Inner Mongolia 2 0 260 1 0 257 Hubei 1 0 68139 4512 0 63626 Heilongjiang 1 0 948 13 0 934 Shanxi 1 0 202 0 0 201 Henan 0 0 1276 22 0 1254 Hunan 0 0 1019 4 0 1015 Anhui 0 0 991 6 0 985 Beijing 0 0 935 9 0 926 Chongqing 0 0 583 6 0 577 Guangxi 0 0 255 2 0 253 Hainan 0 0 171 6 0 165 Gansu 0 0 169 2 0 167 Jilin 0 0 157 2 0 155 Guizhou 0 0 147 2 0 145 Ningxia 0 0 75 0 0 75 Qinghai 0 0 18 0 0 18 Tibet 0 0 1 0 0 1 Source: https://ncov.dxy.cn/ncovh5/view/pneumonia

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Table 6. COVID-19 cases by states/provinces/cities/territories of each country Country Areas affected 1 Afghanistan Herat, Kabul, Samangan, Kandahar 2 Albania Durrës, Fier, Elbasan, Gjirokastër 3 Algeria Alger, Blida, Tizi Ouzou 4 Andorra Andorra la Vella 5 Argentina Buenos Aires, Cordoba, Capital Federal, Chaco, Santa Fe 6 Armenia Erevan, Ararat, Kotayk’ Queensland, Victoria, New South Wales, South Australia, Western Australia, 7 Australia Tasmania, Jarvis Bay Territory Wien, Niederosterreich, Steiermark, Salzburg, Tyrol, Vorarlberg, Burgenland, 8 Austria Karnten, Obersterreich 9 Bahrain Al Manamah 10 Bangladesh Dhaka Minsk, Horad Minsk, Vitsyebskaya, Mahilyowskaya, Homyel’ Voblasc’, 11 Belarus Brestskaya, Hrodzenskaya 12 Belgium Brussels, Vlaamse Gewest, Wallonne 13 Bhutan Thimphu 14 Bolivia Oruro, Santa Cruz Bosnia and 15 Republika Srpska, Federacija Bosna i Hercegovina Herzegovina São Paulo, Rio de Janeiro, Bahia, Espirito Santo, Paraná, Goiás, Rio Grande do Sul, Minas Gerais, Pernambuco, Santa Catarina, Ceará, Amazonas, Rio Grande 16 Brazil do Norte, Maranhão, Parã, Goiãs, Amapã, Paraíba, Alagoas, Roraima, Acre, Sergipe, Piauí, Rondônia, Tocantins, Mato Grosso 17 Brunei Tutong 18 Bulgaria Sofija, Gabrovo, Pleven, Shumen, Kyustendil 19 Burkina Faso Centre-Ouest 20 Cambodia Kampong Chaam, Krong Preah Sihanouk, Phnom Penh, Banteay Mean Chey 21 Cameroon Centre, Littoral Ontario, British Columbia, Quebec, Alberta, Manitoba, New Brunswick, 22 Canada Saskatchewan, Newfoundland and Labrador, Nova Scotia Valparaíso, Santiago Metropolitan Region, Biobío, Araucania, Los Lagos, 23 Chile Magallanes, Libertador General Bernardo O'Higgins, Maule, Antofagasta 24 China See Table 4 Bogotá (Distrito Capital), Antioquia, Bolivar, Cundinamarca, Valle del Cauca, 25 Colombia Meta, Atlántico 26 Congo DRC Kinshasa 27 Costa Rica Limon, San Jose, Heredia, Alajuela Grad Zagreb, Primorsko-goranska, Istarska, Varazdinska, Osjecko-baranjska, 28 Croatia Splitsko-dalmatinska 29 Cuba Sancti Spíritus, La Habana, Isla de la Juventud 30 Cyprus Lemesos, Larnaka Praha, Olomoucky, Ustecky, Jihočeský, Stredocesky, Plzensky, Kralovehradecky, Czech 31 Vysocina, Pardubicky, Moravskoslezský, Jihomoravský, Zlínský, Karlovarskym, Republic Liberecky 32 Denmark Sjaelland, Hovedstaden, Midtylland, Faroe Islands

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Dominican 33 Monte Plata, Distrito Nacional, Santiago, Santo Domingo, Duarte, La vega Republic 34 Ecuador Orellana, Guayas, Los Ríos, Pichincha, Azuay, Manabí, El Oro, Santa Elena 35 Egypt Al Uqsur, Al Qahirah 36 El Salvador San Salvador 37 Estonia Harjumaa, Saaremaa, Virumaa, Pärnumaa, Tartumaa, Ida-Virumaa Rovaniemi, Uusimaa, Lappi, Varsinais-Suomi, Pirkanmaa, Kanta-Hame, Pohjois- 38 Finland Karjala, Keski-Pohjanmaa, Pohjois-Savo, Pohjois-Pohjanmaa, Satakunta, Etelä- Pohjanmaa, Kainuu, Pirkanmaa Bordeaux, Ile-de-France, Rhone-Alpes, Aquitaine, Bourgogne, Bretagne, Cote d’Azur, Nord-Pas-de-Calais, Centre, Hauts-de-France, Grand Est, Occitanie, 39 France Normandie, Rhone-Alpes, Corse, Pays de la Loire, French Guiana, Martinique, Saint Martin, Réunion, French Polynesia, Guadeloupe, Mayotte 40 Gabon Estuaire 41 Georgia T’bilisi Bavaria, Munich, Hessen, Bayern, North Rhine-Westphalia, Baden- Wurttemberg, Rheinland-Pflaz, Hamburg, Schleswig-Holstein, Bremen, 42 Germany Niedersachsen, Thuringen, Berlin, Saxony, Brandenburg, Saarland, Sachsen- Anhalt, Mecklenburg-Vorpommern 43 Ghana Ashanti, Greater Accra 44 Greece Attiki, Kentriki Makedonia, Dytiki Ellada, Peloponnisos, Attiki 45 Guatemala Guatemala 46 Guinea Conakry 47 Guinea-Bissau Bissau 48 Guyana Cuyuni-Mazaruni 49 Honduras Cortés, Francisco Morazan, Colon, Atlantida 50 Hong Kong To Kwa Wan, Kowloon, Lam Tin, Tsuen Wan New Town, Tsing Yi, Aberdeen 51 Hungary Budapest, Pest 52 Iceland Reykjavik, Hofuoborgarsvaei utan Reykjavikur, Suðurland Kerala, Delhi, Punjab, Haryana, Bihar, Maharastra, Telangana, Karnataka, 53 India Rajasthan, Uttar Pradesh, Jammu and Kashmir, Lakshadweep, Gujarat, Tamil Nadu, Madhya Pradesh, Andhra Pradesh, West Bengal, Haryana Jakarta, Jawa Barat (west), Banten, Jawa Timur (east), Jawa Tengah, Jawa 54 Indonesia Tengah (central), Sulawesi Selatan (south) Qom, Arak, Tehran, Gilan, Markazi, Tonekabon, Lorestan, Kermanshah, Khuzestan, Mazandaran, Sistan va Baluchestan, Hormozgan, Kohkiluyeh and Buyer Ahmad, Semnan, Ardabil, Kordestan, Azarbayjan-e-sharqi, Hamadan, Qazvin, Alborz, Fars, Golestan, Khorasan-e Razavi, Khorasan-e Janubi, 55 Iran Azarbayjan-e-Gharbi, Esfahan, Markazi, Kerman, Zanjan, Yazd, Ilam, Kerman, Chahar Mahall va Bakhtiari, Khorasan-e Shemali, Bushehr, Azarbayjan-e-Sharqi (east), Azarbayjan-e-Gharbi (west), Khorasan-e Shemali (north), Hamadan, At Ta’mim, An Najaf, Baghdad, Babil, As Sulaymaniyah, Maysan, Wasit, Karbala, 56 Iraq Arbil, Al Anbar, Al Basrah 57 Ireland Leinster, Connaught, Munster, Ulster (north) 58 Israel Tel Aviv, HaMerkaz, HaZafon, HaDarom, Palestine, Yerushalayim, Hefa Rome, Padua, Lombardy, Veneto, Venice, Emilia-Romagna, Piedmont, Lazio, 59 Italy Tuscany, Sicily, Liguria, Autonomous Province of Balzano, Marche, Campania,

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Abruzzo, Alto Adige, Puglia, Umbria, Calabria, Friulia-Venzia Giulia, Basilicata, Sardegna, Trento & Bolzano, Valle d'Aosta, Molise 60 Jamaica Kingston Kanagawa, Chiba, Osaka, Nara, Mie, Kyoto, Yokohama, Tokyo, Aichi (Nagoya), Hokkaido, Okinawa, Saitama, Wakayama, Sapporo, Ishikawa, Hukuoka, 61 Japan Tokushima, Gifu, Fukuoka, Kumamoto, Nagano, Tochigi, Miyagi, Hyogo, Koti, Sizuoka, Ehime, Niigata, Gunma, Yamaguti, Akita, Yamanasi, Hukui, Kyoto 62 Jordan Ma’an 63 Kazakhstan Almaty, Astana 64 Kenya Nairobi City 65 Kuwait Al Ahmadi 66 Kyrgyzstan Bishkek 67 Latvia Riga 68 Lebanon Liban-Nord, Mont-Liban 69 Liechtenstein Triesenberg 70 Lithuania Siauliu, Vilniaus, Kauno, Klaipedos 71 Luxembourg Luxembourg 72 Macau Lotus Bridge, Barrier Gate checkpoint Johor, Kedah, Langkawi, Sarawak, Selangor, Negeri Sembilan, Kuala Lumpur, 73 Malaysia Kelantan, Sabah, Penang, Melaka, Pahang, Perak, Perlis, Terengganu 74 Malta Malta 75 Mauritius Mauritius 76 Maldives Uthuru 77 Mali Kayes Distrito Federal, Sinaloa, Chiapas, Coahuila, Jalisco, Nuevo León, Puebla, 78 Mexico Baja California, Sinaloa, Quintana Roo, Tabasco, Veracruz, Chihuahua, Morelos, Yucatán 79 Moldova Chisinau, Lapusna, Soroca, Cahul 80 Montenegro Montenegro 81 Monaco Monaco Grand Casablanca, Marrakech-Tensift-Al Haouz, Rabat-Salé-Zemmour-Zaer, 82 Morocco Laâyoune-Boujdour-Sakia El Hamra, Fès-Boulemane, Tangier-Tetouan 83 Nepal Bagmati Gelderland, Noord-Holland, Noord-Brabant, Zuid-Holland, Utrecht, South- 84 Netherlands Holland, Limburg, Drenthe, Overijssel, Overijssel, Friesland, Flevoland, Groningen, Zeeland 85 New Zealand Auckland, Wellington, Marlborough, Southland, Waikato, Cantebury North 86 Centar, Centar Zupa, Sopiste Macedonia 87 Niger Niamey, Tahoua, Tillabéri Lagos, Kano, FCT, Borno, Gombe, Katsine, Bauchi, Ogun, Kaduna, Sokoto, Jigawa, Edo, Zamfara, Oyo, Osun, Kwara, Kebbi, Akwa Ibom, Delta, Rivers, 88 Nigeria Adamawa, Taraba, Ondo, Yobe, Ekiti, Nasarawa, Enugu, Niger, Bayelsa, Ebonyi, Plateau, Abia, Benue, Imo, Anambra North 89 Centar, Sopiste, Debar, Kumanovo Macedonia

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Birgen, Trondelag, Troms, Oslo, Akershus, Hordaland, Aust, Agder, Rogaland, 90 Norway Finnmark, Vestfold og Telemark , Viken, Vestland, Innlandet, More og Romsdal, Nordland, Troms 91 Oman Masqat Karachi, Islamabad, Sind, Punjab, Federally Administered Tribal Areas, North- 92 Pakistan West Frontier, Northern Areas 93 Paraguay Asunción Lima, Huenuco, Loreto, El Callao, Lambayeque, Piura, Ancash, La Libertad, 94 Peru Ucayali, Arequipa, Ica, 95 Philippines Manila, Cavite, Bataan Lubuskie, Slaskie, Dolnoslaskie, Lubelskie, Mazowieckie, Wielkopolskie, 96 Poland Warminsko-mazurskie, Podkarpackie, Zachodniopomorskie, Lodz, Opolskie, Malopolskie, Kujawsko-pomorskie, Zachodniopomorskie, Podlaskie 97 Portugal Porto, Viseu, Lisboa, Coimbra, Faro, Castelo Branco, Beja 98 Qatar Ad Daw ah Gorj, Maramures, Timis, Bucuresti, Hunedoara, Iasi, Arad, Constanta, Covasna, 99 Romania Moskovskaya, Brasov, Ilfov, Arges, Suceava, Brasov, Constanta, Arad, Neamt, Cluj, Hunedoara, Timis, Mures, Galati, Botosani, Bihor Zabaikalsky, Tyumen (Tyumenskaya), Buryatiya, Moskva, Lipetskaya, Sankt- Peterburg, Komi, Nizhegorodskaya, Krasnodyarskiy, Leningradskaya, Murmanskaya, Dagestan, Bryanskaya, Bashkortostan, Tul'skaya, Rostovskaya, Ingushskaya, Ryazanskaya, Mordoviya, Tverskaya, Tatarstan, Mariy El, Kaluzhskaya, Chechenskaya, Vladimirskaya, Stavropol'skiy, Khabarovskiy, Chuvashskaya, Kurskaya, Sverdlovskaya, Severnaya Osetiya, Tambovskaya, 100 Russia Yaroslavskaya, Kabardino-Balkarskaya, Yamalo-Nenentskiy, Chelyabinskaya, Orlovskaya, Novosibirskaya, Saratovskaya, Orenburgskaya, Voronezhskaya, Permskiy, Kirovskaya, Primorskiy, Lipetskaya, Samarskaya, Volgogradskaya, Penzenskaya, Kaliningradskaya, Altay, Ul'yanovskaya, Astrakhanskaya, Smolenskaya, Belgorodskaya, Ivanovskaya, Khanty-Mansiyskiy, Karachayevo- Cherkesskaya, Sakha, Kalmykiya, Arkhangel'skaya 101 Rwanda Ville de Kigali 102 San Marino San Marino 103 Saudi Arabia Ar Riyad Vojvodina, Beograd, Raska, Toplica, Zajecar, Zlatibor, Kolubara, Nisava, 104 Serbia Pomoravlje, Jablanica 105 Senegal Dakar Bratislavsky kraj, Zilinsky kraj, Kosicky kraj, Trenciansky kraj, Nitriansky kraj, 106 Slovakia Presovsky kraj 107 Slovenia Ljubljana, Murska Sobota, Postojna, Metlika, Novo Mesto, Celje, Maribor, Koper 108 South Africa Gauteng, KwaZulu-Natal, Western Cape, Eastern Cape Cities: Incheon, Seoul, Gwangju, Daegu, Jeju, Cheongdo, Busan, Daejeon, Ulsan; Provinces: Hyeongbuk, Kyeongnam, Chungnam, Gyeonggu, Jeonbuk, 109 S. Korea Gyeongnam, Gyeonggido, Gyeongbuk, Gangwon, Jeolla-nam, Jeolla-buk, Sejoing, Chungbuk Yong Thai Hang medicinal shop, The Life Church and Missions Singapore, Grand 110 Singapore Hyatt Singapore, Seletar Aerospace Heights, Assembly of God church, Wizlearn Technologies, SAFRA Jurong La Gomera, Illes Balears, Tenerife, Barcelona, Valencia, Madrid, Catalunya, 111 Spain Catalonia, Canaries, Castilla y Leon, Andalucia, Aragon, Basnahira, Pais Vasco,

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Extremadura, Asturias, Navarra, La Rioja, Galicia, Basque Country, Castilla-La Mancha, Murcia, Cantabria, Melilla, Ceuta 112 Sri Lanka Colombo, Basnahira 113 Sudan Jonkopings, Vastra Gotalands, Stockholms, Uppsala, Skane, Varmlands, Östergötland, Södermanland, Kronobergs, Västernorrland, Jamtlands, Orebro, 114 Sweden Västerbotten, Blekinge, Norrbottens, Gavleborgs, Vastmanlands, Dalarnas, Dalarnas, Gotlands, Hallands, Gavleborgs Graubunden, Geneve, Ticino, Aargau, Basel-Stadt, Vaud, Zurich, Basel- Landschaft, Bern, Fribourg, Valais, Schwyz, Neuchatel, Sankt Gallen, Zug, 115 Switzerland Luzern, Jura, Solothurn, Nidwalden, Appenzell Ausserrhoden, Glarus, Obwalden, Thurgau, Uri Taipei, Changhua, Kaohsiung, Nantou, Taoyuan, Yilan, New Taipei, Tainan, 116 Taiwan Taichung 117 Tajikistan Region of Republican Subordination Bangkok, Rayong, Sattahip, Nakhon Pathom and Samitivej hospitals, Chiang 118 Thailand mai, Krung Thep Maha Nakhon, Nonthaburi, Chon Buri, Ratchaburi, Chai Nat, Phuket 119 Timor-Leste Timor-Leste Trinidad and 120 Trinidad Tobago 121 Tunisia Tunis, Bizerte, Siliana, La Manouba Ankara, Istanbul, Konya, Kocaeli, Isparta, Sakarya, Adana, Bursa, Samsun, 122 Turkey Zonguldak, Kayseri, Antalya, Izmir, Tekirda, Eskiehir, Yalova, Balikesir, Manisa 123 U.A.E. Dubai, Abu Dhabi 124 U.K. England, Gibraltar, Northern Ireland, Scotland and Wales, Jersey, Isle of Man Chernihivska, Kyivs'ka, Kyiv, Ternopil's'ka, Ivano-Frankivsk, Vinnyts’ka, 125 Ukraine Rivnens'ka, Dnipropetrovs'ka, L'vivs'ka, Odes'ka, Zakarpats'ka, Kharkivs'ka 126 Uruguay Montevideo, Canelones Alabama, Alaska, Arizona, Arkansas, California, Colorado, Connecticut, Delaware, Florida, Georgia, Guam, Idaho, Illinois, Indiana, Iowa , Kansas, Kentucky, Maryland, Maine, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nebraska, Nevada, New Hampshire, New Jersey, New 127 USA Mexico, New York, North Carolina, North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Rhode Island, South Carolina, South Dakota, Tennessee, Texas, Utah, Washington, West Virginia, Wisconsin, Wyoming, Vermont, Virginia, District of Columbia, Hawaii, Puerto Rico, US military, *Navajo Nation, Federal Prisions 128 Uruguay Maldonado 129 Uzbekistan Toshkent, Buxoro 130 Venezuela Miranda, Distrito Federal Ho Chi Minh City, Hanoi, Vinh Phuc, Thanh Hoa, Nha Trang, Khanh Hoa, Quang 131 Vietnam Nam, Quang Ninh, Da Nang, Lai Chau, Lao Cai, Binh Thuan 132 Zambia Lusaka Main source: https://early-alert.maps.arcgis.com/apps/opsdashboard/index.html#/20bfbf89c8e74c0494c90b1ae0fa7b78 *US territories

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020 iv. Travel Bans/Advisories & Quarantine Orders

 Fiji- Travelers from New Zealand and Australia will need to have a negative COVID-19 test and undergo 14-days quarantine in a Fijian government quarantine facility before proceeding to the designated resorts for their Bula Bubble vacation. [109]  Germany- Travel warning for countries outside of European Union has been extended to 14 Sept. [140]  Japan- Travel advisory for 13 countries mainly in Africa has been raised to warn against travel to these places. The 13 countries added are Bhutan, Trinidad and Tobago, Belize, Ethiopia, Gambia, Zambia, Zimbabwe, Tunisia, Nigeria, Malawi, South Sudan, Rwanda and Lesotho, bringing the total countries and region under Level 3 advisory to 159. [222]  Norway- Travelers from Germany and Liechtenstein will need to undergo a 10-days quarantine from 29 Aug. Two additional regions in Sweden have also been added to the list. Norwegians are also advised against travelling to these locations. [291]  Ukraine- Travelers will be temporarily banned from entering the country until 28 Sept with the exceptions of diplomats and transiting travelers. [387] v. Lockdowns

 Colombia- The national emergency has been extended but the lockdown measures in the capital Bogota and the city of Medellin will be lifted gradually from 1 Sept. The government will continue to implement specific restriction in places with outbreak. In Bogota, occupancy limit for public transport will be 35% by having differentiated work shift. In Antioquia, intermunicipal travel will remain closed except for the southwest area. Restaurants and gyms will reopen after 1 Sept. [151]  Kenya- National lockdown has been extended by another 30 days and bars and nightclubs will be closed. Sale of alcohol by licensed hotels with residence will resume and closing time for restaurants and eateries will be pushed back to 8pm. Gathering limit for wedding and funeral will be 100 with compliance to the protocol. [464]  Libya- A four days total lockdown in the capital Tripoli will be imposed. Curfew timing of 9pm- 6pm will be implemented after the lockdown for 10 days while full curfew will be implemented on Friday and Saturday. During the lockdown, mass gatherings and all religious and national festivals will be suspended while markets will be closed. [486]  Myanmar- Lockdown in Rakhine has been expanded to include four more townships, Kyaukphyu, An, Taungup and Thandwe. People will have to stay at home except for civil servants and factory workers while only one member of each household will be allowed to leave the house for essentials shopping. All schools have also been instructed to close. [522]  Nepal- Lockdown in Kathmandu Valley will be extended by another week with restriction in place until 2 Sept. [536]  Gaza- Lockdown has been extended at least until Sunday (30 Aug). Mosques, schools and most businesses have been instructed to close. Gazans have been asked to remain at home and wear masks when shopping for essentials. Israel and Egypt have also imposed tight movement restriction on the entry and exit of Gaza. [592]

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

 Qatar- All mosque will be reopened for daily and Friday prayers from 1 Sept as part of the fourth and final phase of the plan. [644]  Romania- Theatres and cinemas will reopen from 1 Sept with preventive measures in place. Resumption of indoor restaurants will be subjected to new cases in each region. Schools will reopen on 14 Sept on case-by-case basis, with online classes for the affected towns. [648]  South Korea- Businesses have been urged to allow employees to have flexible work hours, work from home and working staggered hours. [723]  Ukraine- Lockdown measures have been extended until end October and will re-impose some restriction such as limiting public transport. [818]  US- Chicago will remove Arizona and North Carolina from the quarantine order from Friday (28 Aug) but will add South Dakota to the list. [950]

vi. Military Surveillance

Update: 8 new COVID-19 cases in United States military in Japan [1]

On 26 August, the US military in Japan had reported 8 new cases. Six new cases were identified in Yokosuka Naval Base since last Friday. The other two cases were identified in Okinawa. In Yokosuka Naval Base, four of the new cases had close contact with the infected individuals and the other two were tested positive in quarantine after arriving in Japan. 11 people have recovered bringing the total active case in Yokosuka to 39. In Okinawa, one case was identified in Camp Kinser who was already in quarantine. The other case was from Kadena Air Base, where the individual has displayed coronavirus symptoms and was tested positive during quarantine. The individual had contact with a positive case off base and there was no contact with the on base community during initial contact tracing. The Marine Corps and Kadena have reported the recovery of 1 and 5 people, respectively.

Update: 1 new COVID-19 case in South Korea military [2]

An army reserve soldier who works at a community center in Seoul was found positive for coronavirus. This brings the total cases among the military members to 95. The private first class, who is a full-time reserve service member had violated the no-movement order and dined with an infected civilian last Friday. The soldier does not live in the military barrack and commutes to office from home. He was tested positive on 25 August and three of his colleagues who had contact with him are awaiting for results. Currently, 1055 service members are in isolation based on the health authorities guideline and additional 3,809 people were placed under quarantine by the military.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020 vii. WHO Guidance & Other Protocols

The following updates were published by the WHO on 25 and 26 August 2020:  Operational considerations for COVID-19 management in the accommodation sector: interim guidance Available at: https://www.who.int/publications/i/item/operational-considerations-for-covid- 19-management-in-the-accommodation-sector-interim-guidance  COVID-19 Essential Supplies Forecasting Tool Available at: https://www.who.int/publications/i/item/WHO-2019-nCoV-Tools- Essential_forecasting-Overview-2020.1  COVID-19 Essential Supplies Forecasting Tool Available at: https://www.who.int/publications/m/item/covid-19-essential-supplies- forecasting-tool

viii. CDC Guidance & Protocols

US CDC

The following updates were published by the US CDC on 26 August 2020:  Preparing K-12 School Administrators for a Safe Return to School in Fall 2020 Available at: https://www.cdc.gov/coronavirus/2019-ncov/community/schools- childcare/-safe-return.html  Operational Considerations for Adapting a Contact Tracing Program to Respond to the COVID-19 Pandemic Available at: https://www.cdc.gov/coronavirus/2019-ncov/global-covid-19/operational- considerations-contact-tracing.html  Investigating the Impact of COVID-19 during Pregnancy Available at: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/special- populations/pregnancy-data-on-covid-19/what-cdc-is-doing.html  What Utility Workers Need to Know about COVID-19 Available at: https://www.cdc.gov/coronavirus/2019-ncov/community/organizations/utility- employees.html  Contact Tracing: Frequently Asked Questions Available at: https://www.cdc.gov/coronavirus/2019-ncov/php/contact-tracing-faq.html  Frequently Asked Questions Available at: https://www.cdc.gov/coronavirus/2019-ncov/faq.html

EU CDC

No update was published by the EU CDC on 26 August 2020.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020 ix. Ongoing Clinical Trials for COVID-19

Noteworthy reports are included to inform main developments of COVID-19 pharmaceutics. This is by no means an exhaustive list of all ongoing trials of therapeutics and vaccines. A global map and registry of trials is also visualised & accessible at: https://www.covid-nma.com/dataviz/ and trial results are available at: https://covid-nma.com/living_data/index.php

Table 7: Clinical Trials for Vaccines Country Trial Reference WPRO China China has also approved the first for a vaccine (Ad5-nCoV, an [1] hybrid of “live virus” and “recombinant protein”) conducted by the [2] Academy of Military Medical Sciences. Recruitment commenced on 16th [3] March 2020. The Phase I trial was completed in April 2020 and Phase II [4] trials have commenced recruitment on 12 April 2020. [5] [6] The phase-II human clinical began in Wuhan with 500 volunteer [7] participants. [8] [9] China has approved 2 additional clinical trials for vaccines using [10] inactivated coronavirus pathogens. On 13th April, one vaccine developed [11] by a Beijing-based unit of Nasdaq-listed Sinovac Biotech was approved [12] and another vaccine, being developed by the Wuhan Institute of [13] Biological Products and the Wuhan Institute of Virology, was approved on [14] 12th April. China now has three different clinical trials for three possible [15] coronavirus vaccines in the works. [16] [17] China's inactivated COVID-19 vaccine entered 2nd-phase clinical trial on [18] 25th April. China has approved three COVID-19 vaccine candidates for [19] clinical trials. An adenovirus vector vaccine (Ad5 vectored vaccine by [20] CanSino) was the first COVID-19 vaccine in the world that has entered the [21] second phase of clinical trial. Registration records as indicate that Phase 3 [22] trials for the Ad5-nCoV vaccine has commenced on 14 August 2020 in [23] Russia. The trial aims to recruit 625 volunteers across 8 medical institutes to test the safety and effectiveness of the vaccine candidate.Phase III trials is planned to begin in Karachi, Pakistan in the week of 23 August 2020, and will involve up to 200 adult volunteers.

As of 15th May, China had 5 potential coronavirus vaccine in a human trial and more are on the way. So far there have been no "major adverse reactions" reported among the 2,575 volunteers participating in the five phase-two tests. If all goes well, these 5 trials would complete the second phase of clinical trials in July this year.

As of 17th May, it has been confirmed that 3 COVID-19 vaccines entered phase II clinical trials.

Sinovac Biotech has announced "positive preliminary" results of phase I and II clinical trials for its Covid-19 vaccine candidate, CoronaVac. It is now collaborating with Instituto Butantan in Brazil to prepare and

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

conduct a phase III clinical study. The phase III clinical study in Brazil will begin on 21 July 2020.

Clover Biopharmaceuticals in collaboration with GSK and Dynavax has entered its Phase 1 first-in-human study to evaluate the COVID-19 S- Trimer candidate (SCB-2019). Prelimary results are expected in August 2020. The study is conducted at Linear Clinical Research in Perth, Australia and is targeting 90 healthy adult participants and 60 healthy elderly participants.

As of 19 June, 3 of the 5 approved clinical trial for COVID-19 vaccine in China have completed phase 2.

The Institute of Medical Biology under the Chinese Academy of Medical Sciences has started its phase 2 clinical trial of an inactivated COVID-19 vaccine candidate in the southwestern province of Yunnan.

A coronavirus vaccine candidate developed by Chongqing Zhifei Biological Products unit, co-developed by Anhui Zhifei Longcom Biopharmaceutical and the Institute of Microbiology of the Chinese Academy of Sciences have been approved to conduct clinical trial.

Academy of Military Science (AMS) will begin phase 1 clinical trial on an mRNA vaccine, ARCoV from 25 June. People’s Liberation Army AMS, Suzhou Abogen Biosciences and Walvax Biotechnology jointly developed the vaccine.

The Ad5-nCoV developed by the military and CanSino Biologics has been approved for military use on June 25 for a period of a year. It cannot be expanded to a broader vaccination range with the approval of the military logistics support department. While phase 1 and 2 clinical tirals have shown its potential, its commercial success cannot be guaranteed.

The inactivated COVID-19 vaccine candidate developed by China National Pharmaceutical Group (Sinopharm), has entered Phase III trials on 17 July 2020 in partnership with G42 Healthcare in Abu Dhabi, UAE. A permit allowing up to 15,000 volunteers to be recruited have been issued by the UAE health authorities. Sinopharm claimed 180 volunteers amongst emplotees received inactivated COVID-19 at the end of May, and their antibodies have reached levels resistant to the coronavirus with a 100 percent protective rate.

Sinopharm has obtained the approval from Peru and Morocco to begin Phase 3. It has also obtained the approval from Bahrain which will recruit around 6000 participants.

Sinopharm has ontained the approval from Argentina and will partner with ELEA to conduct its phase 3 trial.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

China’s Shanghai Fosun Pharmaceutical and Germany’s BioNTech have begun their phase 1 clinical trial of BNT162b1 and will enrol up to 144 participants.

West China Hospital of Sichuan University in Chengdu has obtained the approval to conduct clinical trial for a vaccine cultivated within insect cells. Singapore The Agency for Science, Technology and Research has partnered with [24] Japanese pharmaceutical company Chugai Pharmabody Research to [25] develop an antibody that targets specific areas of the coronavirus, [26] preventing it from infecting cells.

Duke-NUS Medical School, together with United States medicine company Arcturus Therapeutics, is working on a vaccine that gets the human body to produce part of the virus in order to fight it. They plan to start human trials in August after promising initial responses in mice. The vaccine works on the relatively-untested Messenger RNA (mRNA) technology, which instructs human cells to make specific coronavirus proteins that produce an .

Home-grown contract development and manufacturing organisation Esco Aster is also collaborating with US biotech company Vivaldi Biosciences to develop a vaccine that protects against Covid-19 and the flu, and can be easily adapted if the coronavirus mutates.

Arcturus Therapeutics and Duke-NUS Medical School have received the approval to conduct Phase I/II clinical trial on LUNAR-COV19. The study will recruit up to 108 adults including older adults. Australia Phase I of NVX-CoV2373 by Novavax to commence in mid- [27] May 2020. [28] [29] Novavax has initiated Phase I/II clinical trial of its COVID-19 vaccine NVX- [30] CoV2373, enrolling approximately 130 healthy participants at 2 sites in [31] Australia. Preliminary results from Phase are expected in July 2002. Phase II is expected to be conducted in multiple countries including the United States.

Phase I trial for COVAX-19, a vaccine by Adelaide company Vaxine Pty Ltd began on July 2. 40 health individuals between 18 and 65 will receive 2 doses 3 weeks apart.

University of Queensland (UQ) scientists begin trialling its COVID-19 vaccine candidate in 120 people. Volunteers will receive the first vaccine dose on Monday, 13th July at UQ’s Medicine and Public Health in Herston, Brisbane. The human testing of the “molecular clamp” vaccine candidate follows encouraging results from animal testing trials conducted in the Netherlands. This is a first in-human, randomised, double-blind, placebo- controlled study, that will also have a dose escalation component to determine the optimal vaccine dose for future studies. All participants will be monitored for 12 months after the study.

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The vaccine, Covax-19, developed by Nikolai Petrovsky from Flinders University is the first Australian candidate to pass phase one. It will move to phase two in September and will recruit up to 500 volunteers. Thailand On 20th May, Thailand confirmed that the Thai mRNA (messenger RNA) [32] vaccine against the SARS-CoV-2 virus has been tested successfully on mice and it expects to have a COVID-19 vaccine next year. Bangladesh On 17 June started a randomised, double-blind, placebo-controlled [33] clinical trial to evaluate the safety and efficacy of anti-parasitic medicine Ivermectin in combination with antibiotic doxycycline or Ivermectin alone after getting positive results in patients administered with the mix of two drugs. The trial would be conducted on 72 infected patients in four hospitals treating COVID-19 in Dhaka. Japan A clinical test of a potential vaccine for the new coronavirus developed by [34] medical startup Anges Inc. will start June 30 in Japan. It will be the first clinical test (of a coronavirus vaccine) on humans in Japan, initially targeting 20 to 30 medical workers at Osaka City University Hospital and expand to hundreds by October. The envisioned vaccine will inject a genetically engineered circular DNA into the body, which is expected to stimulate the immune system and make antibodies against the coronavirus. South South Korea-based Genexine Inc. has begun phase I/II trial of a DNA [35] Korea vaccine, GX-19. The preliminary data from the initial trial will be expected in September and target to complete all stages by the end of 2021. Phase I trial will involve 40 healthy participants at Gangnam Severance Hospital while the phase IIa study will be conducted with participants from countries such as Indonesia and Thailand. India India’s first domestic vaccine candidate has been approved by the [36] government’s drug regulator for human trials. The vaccine by Bharat [37] Biotech, , will enter into Phase I and II clinical trials starting July. [38] [39] India approved the second Covid-19 vaccine, developed by Zydus Cadila [40] for clinical trials on July 3rd. The vaccine candidate, named ZyCoV-D, is a [41] DNA vaccine targeting the coronavirus membrane protein. [42]

Human clinical trials for two indigenously developed vaccine candidates has been initiated in the country with approximately 1,000 volunteers participating in the exercise. The two candidates, one developed by Bharat Biotech International Limited in collaboration with the Indian Council of Medical Research and another one by ZydasCadila Healthcare Ltd, will go in for the first and second phase of human clinical trials. Both have undergone successful toxicity studies in rats, mice and rabbits following which both got clearance to start an early phase human trials earlier this month.

The human trials for these 2 candidates commenced on 15 July 2020.

Bharat Biotech in collaboration with ICMR and Zydus Cadila Ltd have completed phase 1 of the trial and have moved to phase 2.

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Serum Institute of India has obtained the approval to conduct phase 2 and 3 human clinical trials of COVISHIELD (SII-ChAdOx1 nCoV-19) in healthy adult who are at risk.

Bharat Biotech International Limited has obtained the approval to conduct another clinical trial, Phase I/II of Covaxin administered through intradermal route. However, they will have to followed up with participants for six months for clinical and antibody tier assessment. The vaccine is currently tested through the intramuscular route.

Taiwan Human trials of Taiwan’s first COVID-19 vaccine candidate by Adimmune [43] Corporation is expected to launch in August. More than 1,000 healthy volunteers will be enrolled for the trial. Indonesia Sinovac Biotech in collaboration with PT Bio Farma and Padjadjaran [44] University Medical School has begun its phase 3 clinical trial for CoronaVac in Indonesia. The study will recruit about 1,620 people and is expected to last until December. EURO Germany CureVac (unlisted German company) aims to start testing an experimental [45] vaccine on humans by summer of 2020. [46] [47] CureVac has received the approval to begin its Phase I clinical trial of its Covid-19 vaccine candidate, CVnCoV in Germany and Belgium.

German vaccine regulators approved the clinical trial of BNT162 by BioNTech and Pfizer. 200 healthy people will be recruited for the trial. This marks the fourth COVID-19 vaccine trial worldwide.

United A million doses of a potential vaccine ChAdOx1-nCov-19 are currently [48] Kingdom being manufactured even before trials that prove its effectiveness. [49] Recruitment for phase 1 trials are ongoing. [50] [51] The trial for ChAdOx1-nCov-19, slated to begin on 23 April 2020, will be [52] tested in around 500 volunteers. The vaccine is a potentially ideal [53] candidate against the virus as it can generate a strong immune response [54] from one dose. [55] [56] The pre-print results showed that the "ChAdOx1 nCoV-19" vaccine has been effective in preventing damage to the lungs without any signs of immune-enhanced diseases. As on May 13, more than 1000 volunteers have already participated in human clinical trials of this vaccine.

Oxford University’s COVID-19 vaccine known as ChAdOx1 nCoV-19 failed to prevent the monkeys from being infected with the novel coronavirus in trials. The vaccine was among the top candidates that was currently being tested on humans.

An experimental Covid-19 vaccine developed by cigarette maker British American Tobacco Plc is slated to begin the first phase of human trials as soon as late June if authorized by drug regulators. Pre-clinical tests of the vaccine have shown positive immune response.

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AstraZeneca’s COVID-19 vaccine AZD1222 (previously ChAdOx1 nCov-19) has begun enrolling subjects in a phase 2/3 clinical trial.

The Imperial College of London is developing an RNA-based vaccine which carries the molecular instructions of making the vital of the novel coronavirus and instructs the human cells how to make it. As a result, the body’s immune response will get triggered and it will produce antibodies fight the coronavirus. The vaccine candidate is all set to enter phase 1 of human trials on June 15 with 300 people.

The COVID-19 trial run by Imperial College London will be expanded to additional sites across England from the last week of July. The vaccine will be trialled in more than 200 people across 6 new locations first - Chelsea and Westminster Hospital NHS Foundation Trust, Imperial College Healthcare NHS Trust, St George’s University Hospital NHS Foundation Trust and University College London NHS Foundation Trust. Kazakhstan The World Health Organization (WHO) registered the inert SARS-Cov2 [57] vaccine developed at the Kazakh Research Institute for Biological Safety Problems to the shortlist of COVID-19 candidate vaccines in preclinical evaluation on May 15 Russia [Reported on June 17] Vaccinations will commence in the coming days [58] with one group of participants initially receiving the vaccine at the end of [59] the two–week quarantine period. The aim is to assess the safety and [60] tolerability of the vaccine components. Both military and civilian [61] personnel will be enrolled for the trial. Based on the data from the first [62] group of volunteers, the remaining participants will be successively [63] vaccinated with the vaccine components. This part of the trial is intended [64] to evaluate the vaccine’s effectiveness and development of antibodies [65] against SARS-CoV-2. Prior to the human trials, the vaccine was tested for [66] its toxicity, safety, immunogenicity and effectiveness in large and small animals.

The clinical trials on volunteers at Sechenov First Moscow State Medical University which started on 18th June has been completed successfully, confirming the vaccine's safety for human health. This vaccine was in the form of a powder for the preparation of a solution for intramuscular administration. The first group of volunteers who participated in the study will be discharged on July 15th and the second on July 20th

Two groups of 18 volunteers were discharged from hospitals after separately taking part in 28-day clinical trials. The preliminary findings show the vaccines to be safe and well-tolerated with no serious complaints, complications or adverse reactions. On the 42nd day after the first vaccination, the volunteers will return to the hospital for a day to undergo a final medical examination and diagnosis. A larger-scale trial, intended to ascertain the strength of the immune response produced by the vaccine and how long protection will last, is expected to begin in Russia in mid-August.

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Russia’s second potential COVID-19 vaccine developed by the Siberian Vector institute will begin on July 27.

Russia is aiming to gain approval for a vaccine developed by the Moscow- based Gameleya Institute on August 10 or earlier. The vaccine would require patients to get a second booster shot. This comes despite the the absence of any results released on the vaccine tests yet.

On 11 August, Russian President Vladimir Putin announced the registration of what Russia claims to be the first vaccine for the coronavirus in the world and said one of his daughters had already taken it. Clinical trials of this Russian vaccine have been completed in less than two months and phase three trials are set to begin on 12 August, despite the vaccine having already been registered. Countries including the United Arab Emirates, the Philippines and Saudi Arabia are taking part in those trials.

[Reported on August 21] Russia will begin its phase 3 clinical trial for Sputnik-V from next week. It will enrol 40,000 people at more than 45 locations. The phase 3 trial will also begin in the Philippine in October.

AstraZeneca has obtained the approval to conduct part of a Phase III trial for AZD1222 vaccine on 150 participants. The trial will be handled by four medical facilities in St. Petersburg and Moscow. Italy Lazzaro Spallanzani National Institute for Infectious Diseases will begin its [67] phase 1 clinical trial of GRAd-COV2 vaccine under the sponsorship of Rome-based biopharmaceutical products developer and producer ReiThera. The study will recruit 90 healthy volunteers. The second phase of testing will be conducted in countries with higher rate such as Mexico and Brazil. EMRO UAE China National Pharmaceutical Group Sinopharm (Sinopharm) has [68] received the approval to begin the phase 3 clinical trial for its in UAE. Pakistan The University of Health Sciences (UHS) Punjab is collaborating with [69] Oxford University to test the vaccine, AZD1222 in Pakistan. Around 20,000 people will be recruited for the study.

AFRO South Africa University of the Witwatersrand, Johannesburg (Wits) is collaborating [70] with the University of Oxford and the Oxford Jenner Institute on the [71] South African trial on ChAdOx1 nCoV-19. The South African Ox1Cov-19 Vaccine VIDA-Trial will be conducted at multiple sites in South Africa, commencing on June 24. The study has begun screening participants and will vaccinate the first participant this week.

Phase 2b efficacy trial of NVX-CoV2373 by Novavax to commence in August in South Africa in approximately 2,665 healthy adults. A separate cohort will evaluate safety and immunogenicity in approximately 240

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medically stable, HIV-positive adults. The trial will be led by Wits University

Americas Brazil Oxford University will start its human clinical trials for ChAdOx1 vaccine [72] on 2,000 health workers volunteers in Sao Paulo and 1,000 people in Rio de Janeiro. Cuba Finlay Institute of Vaccines will begin its Phase I / II clinical trial of [73] Soberana 01 on 24 August 2020. It will recruit 676 people between 19 to 80 years old. The results of the trial will be available on 1 February. United The first clinical trial on a COVID-19 vaccine (mRNA-1273 by Moderna States Inc.) will begin in US the week of 23rd March 2020. [74] On 7 May, Moderna has been cleared by FDA to move into Phase II trial. [75] 600 participants will be enrolled in the coming weeks to begin assessing [76] whether the potential vaccine can induce antibodies production in the [77] human immune system that recognize SARS-CoV-2. Moderna reported [78] promising early results on Monday (May 18) from the first clinical tests [79] performed on a small number of volunteers. Interim Phase 1 data, while [80] early, demonstrate that vaccination with mRNA-1273 elicits an immune [81] response of the magnitude caused by natural infection. [82] [83] Moderna Inc on 11 June confirmed it plans to start a trial of 30,000 [84] volunteers of its much-anticipated coronavirus vaccine in July as the [85] company enters the final stage of testing. The primary goal of the study [86] would be to prevent symptomatic COVID-19, the key secondary goal [87] would be prevention of severe disease, as defined by keeping people out [88] of the hospital. It has selected the 100-microgram dose of the vaccine for [89] the late-stage study to maximize the immune response and minimize [90] adverse reactions.

Moderna has concluded participant enrolment for both cohorts in the Phase II clinical trial of its Covid-19 vaccine candidate, mRNA-1273. Moderna is conducting the placebo-controlled, dose-confirmation Phase II trial to assess the safety, reactogenicity and immunogenicity of two mRNA-1273 vaccinations administered 28 days apart.

The Moderna coronavirus 2019 (COVID-19) vaccine candidate mRNA- 1273 has induced immune responses in all 45 of its volunteer patients administered doses in the phase 1, dose-escalation, open-label trial. The findings, reported by the mRNA-1273 Study Group, supports the advancement of a 100-mcg dose vaccine to a phase 3 trial assessment in later summer 2020, while a phase 2 trial of a pair of different doses of the potential vaccine continue among 600 healthy adults.

Moderna Inc. said Tuesday it will start a final-stage clinical trial of a potential coronavirus vaccine involving 30,000 participants on July 27.

Another vaccine candidate (INO-4800) by Inovio Pharmaceuticals began Phase 1 trial on 6 April 2020.

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Cuba began recruitment for Phase I vaccine trial of their vaccine candidate (CIGB-2020) on 27 March 2020. A total of 37 subjects were enrolled for the study. Study will be completed in mid-July 2020

Pfizer and BioNTech have started dosing participants in the Phase I/II clinical trial assessing the BNT162 vaccine candidate in US. The study will look at the safety, immunogenicity and optimal dose level of four mRNA vaccine candidates in a single, continuous study and involves up to 360 healthy participants on the trial’s dose level escalation part.

Pfizer Inc and partner BioNTech SE on Monday, 13 July received 'fast track' designation from the US health agency, speeding up the regulatory review process for two of their experimental coronavirus vaccines; BNT162b1 and BNT162b2. The testing of two dosages of BNT162b1 on 24 healthy volunteers showed that after 28 days they had developed higher levels of COVID-19 antibodies than typically seen in infected people. The companies said they expect to start a large trial with up to 30,000 participants as soon as later this month, upon regulatory approval.

Novavax has seen promising results in the NVX-CoV2373 corona vaccine candidate. The company is now moving to the next stage -- testing on humans.

Johnson & Johnson’s vaccine candidate will enter clinical trials in the second half of July, 2 months earlier than previously planned. The trial will be conducted in both the US and Belgium on 1,045 healthy adults between 18-55 years old, and 65 years and above.

Johnson & Johnson has commenced its Phase 1/2a of Ad26.COV2.S and target to move to phase 3 in September.

Pfizer and BioNTech announced on July 27 that a phase 3 trial involving 30,000 patients has been started for its mRNA vaccine, BNT162b2. The vaccine will be given at a 2-dose regimen in participants aged 18-85 years. It has started in the US and is expected to include around 120 sites globally. The companies are hoping for a quick turnaround and to seek regulatory review as early as October 2020.

Cincinnati Children will move to phase III clinical trial of the vaccine, BNT162 and enrol up to 1,000 participants in the Tri-State.

Novavax has begun phase 2 of its clinical trial for NVX-CoV2373. It will enrol up to 1,500 healthy volunteers (aged 18 to 84 years) with 50% of participants ≥60 years old in about 40 sites in the U.S. and Australia.

Canada Medicago, a biopharmaceutical company headquartered in Quebec City, [91] began Phase I clinical trials for its plant-derived COVID-19 vaccine candidate yesterday, administering the first doses in healthy human volunteers. Medicago is also planning a Phase 2/3 trial to be initiated this October. The Phase I clinical trial is a randomized, partially blinded study of 180 normal healthy subjects, male and female aged 18-55, and will

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evaluate dosages of 3.75, 7.5 or 15 micrograms of the recombinant Coronavirus Virus-Like Particle (CoVLP) vaccine candidate alone or with an adjuvant in a prime-boost regimen.

Table 8: Clinical Trials for Therapeutics Country Trial Reference Global AstraZeneca on 14 April, mentioned it would start a new clinical trial of Calquence. [92] Early data suggests Calquence appears to reduce the severity of COVID-19-induced [93] respiratory distress. The goal of the new trial, called CALVARI, is to assess the [94] effectiveness and safety of the drug. [95] [96] The World Health Organisation launched an international clinical trial “Solidarity [97] Trial” to compare 4 treatment options against standard of care, and assess their [98] relative effectiveness. There are currently more than 100 participating countries. The treatments compared are Remdesivir; Lopinavir/Ritonavir; Lopinavir/Ritonavir with Interferon beta-1a; and Chloroquine/Hydroxychloroquine.

The first drug cleared for the treatment of COVID-19, Remdesivir by Gilead Sciences Inc, was found to be effective on patients who need extra oxygen but are not dependent on ventilators of heart-lung bypass machine. The high mortality rate despite use of the drug indicates that anti-viral drug as a standalone approach is insufficient.

The WHO has decided to temporarily suspend enrolment in hydroxychloroquine trials in its study of four treatment options in the . More data on the safety and efficacy of the drug will be gathered and discussed in 2 weeks. Randomised use of the drug may continue if no danger is found.

On 4th June, the WHO recommended the continuation of hydroxychloroquine following a review of safety data. Some observers welcomed the decision, citing hydroxychloroquine as a time tested drug in use for decades. Any positive outcome from the clinical exercise will be in the larger interest of the people globally.

On 4th July, WHO accepted the recommendation from the Solidarity Trial’s International Steering Committee to discontinue the trial’s hydroxychloroquine and lopinavir/ritonavir arms. These interim trial results show that hydroxychloroquine and lopinavir/ritonavir produce little or no reduction in the mortality of hospitalized COVID-19 patients when compared to standard of care.

Redhill Biopharma has initiated global phase 2/3 study involving up to 270 patients with severe COVID-19 across 40 clinical sites to evalulate its drug, Opaganib. It has obtained approval from UK and Russia and is under review in Italy, Brazil and Mexico. WPRO Tocilizumab is concurrently evaluated in clinical trials as it is used [99] Malaysia for severe cases of Covid-19.

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Singapore is looking at 11 recovered COVID-19 patients to donate [100] blood for plasma therapy treatment. [101] [102] About 90 severely ill Covid-19 patients who require oxygen [103] support, have been enrolled in three trials of remdesivir as of May 8th, two by drugmaker Gilead Sciences and one by the National Institute of Allergy and Infectious Diseases in the United States.

A Singaporean biotechnology firm, Tychan, will begin the first phase of its first human clinical trials next week (week of 15 June) Singapore on nearly two dozen healthy volunteers to determine the safety and tolerability of TY027, a , or immune system protein that specifically targets the virus that causes Covid- 19. The treatment is aimed at reducing the severity of the disease and speeding up recovery.

A team of Singapore scientists has discovered five antibodies that can block COVID-19 infection and protect against key mutations, as announced on Wednesday (Jun 17). Human trials for the lead antibody, AOD01, will commence in the coming months, pending approval. Takeda Pharmaceutical is aiming to roll out an antibody treatment [104] for COVID-19 as early as this year - a concentration of antibodies [105] taken from patients who have recovered from COVID-19. [106] [107] Japanese drugmaker Rohto Pharmaceutical Co. plans to launch a clinical trial using stem cells to develop a treatment for severe cases of COVID-19. The trial will use mesenchymal stem cells created from human adipose tissue to examine the efficacy and safety of the treatment after administering stem cells Japan intravenously.

Rohto Pharmaceutical Co. will begin their clinical trial in August using stem cells for severely ill patients with COVID-19. The trial is expected to run through December.

Clinical study of the antiviral drug Avigan, also known as favipiravir, has failed to demonstrate a clear efficacy in treating coronavirus patients at an early stage of the disease. However, the sample size was too small to yield a statistically meaningful difference Hong Kong is looking at the use of triple combination of interferon [108] Hong Kong beta-1b, lopinavir–ritonavir, and ribavirin and have found promising findings in its phase II trial. Glenmark Pharmaceuticals Limited is conducting Phase III clinical [109] trials of Favipiravir for COVID-19 patients. It is estimated to [110] complete by July/August 2020. [111] [112] India University of Hyderabad (UoH) and CSIR-Centre for Cellular and [113] Molecular Biology (CCMB) are collaborating with Vins Bioproducts [114] Ltd, to develop antibody fragment-based immunotherapy for [115] immediate treatment for COVID-19 pandemic. The antibodies, [116]

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raised in horses using inactivated coronavirus is fractionated and [117] purified to produce antibody fragments F(ab’)2 for neutralizing coronavirus in the patients for recovery.

Glenmark Pharmaceuticals will begin a clinical trial to test a combination of favipiravir and umifenovir. The trial aims to enrol 158 hospitalised patients with moderate COVID-19. The company has gained Indian regulatory approval but details on the commencement date have yet to be released.

The CSIR -- Central Drug Research Institute (CDRI) will be conducting Phase III clinical trials of antiviral drug Umifenovir at King George’s Medical University (KGMU).

Cipla on 8 July, launched its generic version of antiviral drug remdesivir at a subsidized price and has been approved by the Drug Controller General of India for restricted emergency use in the country as part of the accelerated approval process considering the urgent and unmet medical need.

India’s drug regulator has approved Itolizumab, a drug used to cure skin ailment psoriasis for “restricted emergency use” to treat moderate to severe Covid-19 patients.

Maharashstra will start clinical trials using convalescent plasma therapy for 472 patients acros 21 medical colleges next week. The “Platina trial” is the largest convalescent plasma therapy trial for treatment of severe COVID-19 patients.

Sun Pharma has obtained the approval to start clinical trial on Nafamostat Mesilate in COVID-19 patients.

Andra Medical College/King George Hospital has obtained the approval to conduct phase 2 clinical trial for CRO Navitas Life Sciences, 2-Deoxy- D-Glucose. It will be an adjunctive therapy to the standard of care of acute treatment for the moderate to severe COVID-19 patients. combination of antiprotozoal medicine called Ivermectin in a single [118] Bangladesh dose with Doxycycline, an antibiotic, has yielded astounding results with all of the 60 COVID-19 patients recovering Five innovative drugs have been approved for clinical trials, and all [119] of them have entered phase II clinical studies. [120] [121] The Institute of Microbiology of the Chinese Academy of Sciences (IMCAS) has been approved to conduct a phase 1 clinical trial of the China fully human monoclonal antibodiy (mAb) against COVID-19.

Innovent Biologics has strted its Phase Ia/Ib clinical trial of IBI322 in patients with advanced malignancies who did not have adequate reponse to the stardard therapy.

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On June 26, 15 candidates for COVID-19 treatment drugs and [122] vaccines have been approved by the Ministry of Food and Drug South Korea Safety in South Korea. Most are foreign candidates except 2 – Levovir (Hepatitis B) by Bukwang Pharmaceutical Co. and Nafabelltan (anticoagulant) by Chong Kun Dang Pharmaceutical Co. Australia approved the anti-viral drug remdesivir for treatment of [123] Covid-19 on Friday, July 10 following a similar decision from the Australia European Commission. It is the first drug approved by Australian authorities to treat the virus and promised to reduce hospitalisation time for coronavirus patients Philippine has begun clinical trials for Japanese anti-flu drug, [124] Philippine Avigan. Europe The UK Department of Health and Social Care and UK Research and [125] Innovation launched a national collaborative platform named [126] Accelerating, COVID-19 Research & Development (ACCORD). This is [127] a single, national multi-centre trial platform provided by the clinical [128] research company IQVIA, and the UK’s leading research expertise [129] through the National Institute for Health Research to rapidly test [130] potential drugs through early stage clinical trials and feed them [131] into the UK’s large-scale COVID-19 studies such as the RECOVERY [132] trial, currently the world’s largest randomised controlled clinical [133] trial for COVID-19 treatment. [134] [135] Bemcentinib developed by BerGenBio ADS is selected as the first [136] candidate to be tested under ACCORD study, will commence Phase [137] II clinical trial in 120 subjects across 6 UK NHS hospital trusts. [138] [139] two trials; TACTIC - to test whether re-purposing existing drugs, which target the body's own immune response, can prevent people suffering severe organ failure or death and – looking United at four approved drugs: Lopinavir (400 mg)-Ritonavir (100 mg), Kingdom dexamethasone, hydroxychloroquine and azithromycin (500 mg) amongst 12,000 patients who will receive one of the four drugs or the standard of care for 10 days or till the date of hospital discharge and a second randomization to receive tocilizumab or no treatment. This trial will be conducted across 170 hospitals in the U.K.

Researchers in the UK are set to conduct a clinical trial to assess TRV027, which is meant to prevent blood clots and lung damage, as a potential drug treatment for Covid-19 patients.

Steroidal drug, dexamethasone on Tuesday (Jun 16) showed to be the first drug to significantly reduce the risk of death among severe COVID-19 cases. Trial conducted by the RECOVERY research group from the University of Oxford administered the widely available drug to randomly assigned 2,104 patients and compared them with 4,321 patients getting only usual care. Among those who could only breathe with the help of a ventilator, dexamethasone reduced

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deaths by one third, and by one-fifth in other patients receiving oxygen only, according to preliminary results.

Evelo Biosciences Inc will be including the drug, EDP1815 as one of the two experimental therapies in their Phase 2/3 TACTIC-E COVID- 19 trial. The trial will enroll up to 469 COVID-19 patients per arm at Addenbrooke’s Hospital and other UK clinical centres. Interim result of the study will be expected in the fourth quarter of 2020.

The hydroxychloroquine arm of the RECOVERY trial will be stopped as no benefit in hospitalized patients was identified after reviewing.

Theravacne Biopharma has dosed the first participants in a Phase II clinical trial of TD-0903, a lung selective, nebulised Janus kinas inhibitor to address acute lung injury in hospitalised COVID-19 patients.

RevImmune has launched a phase II clinical trial of CYT107, an immune therapy for COVID-19. The therapy is a form of interleukin- 7 (IL-7), which is a master growth factor of T cells. The trial had opened in UK in mid-May, and is currently enrolling patients at 10 sites across UK. The trial had opened in France and Belgium in early June and preparations for US trials are underway.

A second phase of human trials for an experimental antiviral treatment called EIDD-2801, that could be given to COVID-19 patients in pill form has been initiated. The trial, which recently gained approval from the UK drug regulator, will be conducted at a clinical research unit at the Royal Liverpool University Hospital.

South Korea's Celltrion Inc has obtained the approval to begin phase I clinical trial of its COVID-19 antibody drug.

CytoDyn Inc. has received the approval to conduct phase 3 clinical trial of leronlimab (PRO 140) in severe-to-critical patients in the UK. It has completed phase 2 trial in US and is continuing with the enrolment for phase 3.

AstraZeneca has begun testing on its antibody-based cocktail, AZD7442 which is a combination of two monoclonal antibodies (mAbs). The study will recruit up to 48 healthy participants. If AZD7442 is found safe in the early stage trial, it will be tested as both a preventive treatment and medicine for COVID-19 in the larger mid-late stage of study. A candidate drug for treating the new coronavirus, favipiravir, has [140] produced promising results in early clinical trials in Russia, [141] Russia according to the Russian Direct Investment Fund (RDIF). 60% [142] percent of the 40 coronavirus patients taking tablets of favipiravir, which was first developed in Japan under the name Avigan, tested

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negative for the virus within five days and said the treatment could cut coronavirus recovery times in half.

Nearly two weeks since the antiviral drug, Avifavir received a temporary registration certificate from the Ministry of Health of the Russian Federation for the treatment of COVID-19. On Saturday, officials registered a second drug for treatment– Levilimab (trade name Ilsira).

Russian pharmaceutical company R-Pharm secured regulatory approval for the use of its antiviral drug Coronavir, to treat patients suffering from Covid-19. The approval came after a clinical trial in mild to moderate Covid-19 patients showed that the drug is highly effective in blocking replication of SARS-CoV-2. Germany's Max Planck Institute of Colloids and Interfaces in [143] Potsdam in collaboration with the US company ArtemiLife are [144] exploring a cell based study using test extracts from the Artemisia [145] annua plant, also known as sweet wormwood, as well as derivatives isolated from the plant such as artemisinin. The scientists expect results by the end of May and if found to be effective, clinical studies on humans, would be required.

Abivax has received regulatory approval from the German Germany authorities on its ABX464 CPVID-19 Phase 2b/3 trial. This is the second regulator to approve after France. The antiviral drug will be investigated for early treatment in 1,034 COVID-19 elderly or high- risk patients. Enrolment is expected to occur by end May and data from the trial is expected by the end of the year.

Philipps University of Marburg has obtained the approval from the German authorities to conduct a clinical trial of the cancer drug, Ruxolitinib in COVID-19 patients after successful treatment of a COVID-19 patient with ARDS. BerGenBio, based in Bergen, Norway, and Oxford, England, has [146] developed a drug called bemcentinib, initially developed to treat Norway cancer, is currently in phase two of clinical trials to benefit coronavirus patients. A group of Spanish scientists have identified a stem-cell treatment, [147] dubbed the BALMYS-19 project, which tests suggest can decrease [148] the mortality rate from 85 percent to 15 percent among critically ill Covid-19 patients.

Spain BioAegis Therapeutics Inc., received regulatory clearance for its Phase 2 Proof of Concept study of its lead product, recombinant human plasma gelsolin (rhu-pGSN) in hospitalized patients with severe COVID-19 pneumonia. BioAegis expects to recruit its first patient and begin the study shortly at Hospital Universitari Sant Joan de Reus in Tarragona, Spain In a new trial, Covidenza, Swedish researchers will investigate if the [149] Sweden drug Enzalutamide, normally used to treat prostate cancer can also be used to treat COVID-19 in patients. The desired effect is that the

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medicine will shorten the course of the disease and the need for intensive care. The trial will be conducted at voluntary basis on hospitalised patients treated for COVID-19, but who are not critically ill enough to require intensive care. The patients in this trial will be administered the drug in the form of pills over the course of five days during which they will be closely monitored. The result of this treatment will then be compared with a control group. The study has a capacity of recruiting up to 600 patients. Results from a retrospective study in 93 critically ill COVID-19 [150] patients show that IVIG treatment with octagam® 5% reduces Turkey inflammation, which is associated with poor clinical outcomes and death, and points to an increase in survival, in critically ill COVID-19 patients, when compared to a control group. EMRO The UAE is carrying out clinical trials of plasma therapy to treat [151] COVID-19 patients. [152]

As of June 25, Abu Dhabi Stem Cell Centre has treated more than United Arab 2,000 patients with UAECell19, an autologous stem cell based Emirates therapy. Patients treated were 3.1 times more likely to recover in less than 7 days than those treated with standard therapy. Phase 3 trials are in process to establish effectiveness, optimal efficacy of dosage, and efficacy in other respiratory diseases. A pluristem cell therapy (using placenta cells) by Israeli company [153] that is on compassionate use in US has successfully treated it first [154] American patient. The therapy had been utilised in the first six critically ill patients in Israel, all of whom survived a week later. As the treatment remains available to patients under compassionate Israel use through regulatory clearances in the US and Israel, the company is looking to initiate a multinational clinical study.

Itzchak Levy at the Sheba Medical Center in Israel launched a self- funded camostat trial in April which is a 35 year old pancreatitis drug made by Osaka-based Ono Pharmaceutical Co. AFRO Nigeria will begin a second trial launched in partnership with the [155] World Health Organisation to assess the efficacy of Nigeria hydroxychloroquine. Healthcare workers as well as close contacts of cases are recruited as participants for the study. Americas [156] Angion Biomedica Corp. has begun its phase 2 clinical trial of ANG- Brazil 3777 in patients with acute lung injury associated with COVID-19. Tetra Bio-Pharma has obtained the approval to begin phase 1 of [157] the synthetic cannabinoid drug, ARDS-003. It will begin enrollment Canada in December and plans to move to phase 2a studies in the second quarter of 2021 and final phase, Phase 2b/3 by the end of 2021. FDA has given a go-ahead for the human clinical testing of a new [158] drug named EIDD-2801, being developed at Emory University. It’s [159] United States been touted as a 'relief drug' for Covid-19 claiming to be effective [160] against the entire coronavirus family. [161]

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

[162] Ridgeback Biopharmaceuticals has begun two phase 2 clinical trial [163] of EIDD-2801. The first study will involve hospitalized COVID-19 [164] patients while the second involves symptomatic, newly diagnosed [165] COVID-19 patients who are at home or out of hospital setting. [166] [167] Fujifilm Corporation will begin its first US clinical trials of Avigan, a [168] Japanese anti-viral drug. The drug is currently tested for treatment [169] in China as well. [170] [171] FDA has approved a phase III trial by Novartis assessing [172] hydroxychloroquine in more than a dozen sites in the US. [173] Enrolment will begin in a few weeks from 20 April 2020. [174] [175] National Institutes of Health is conducting a clinical study to look at [176] the combination of antiviral drug remdesivir and anti-inflammatory [177] treatment baricitinib in COVID-19 patients. [178] [179] NIAID-funded AIDS Clinical Trials Group (ACTG) in collaboration [180] with Teva Pharmaceuticals has initiated a randomized matched pair [181] clinical trial to evaluate if a combination of hydroxychloroquine [182] together with the antibiotic azithromycin can prevent [183] hospitalization and death from COVID-19. The Phase 2b trial will [184] enroll approximaty 2,000 adults at participating ACTG sites across [185] the United States. The first participant was enrolled on 17th May in [186] San Diego, California. [187] [188] anti COVID-19 drug candidate, Brilacidin tested by Innovation [189] Pharmaceuticals, showed a reduction in the viral titer (load) of [190] SARS-CoV-2 by 75% after only 1 hour of pre-incubation prior to [191] infection at a concentration of 10μM as compared to vehicle [192] control in an in vitro experiment using VERO cells. [193] [194] John Hopkins Kimmel Cancer Center reported that prazosin, a [195] blood pressure drug, if given early enough, can potentially reduce [196] the risk of death due to complications caused by the novel [197] coronavirus infection. [198] [199] Atossa Therapeutics, Inc., announced the successful results from in [200] vitro testing of AT-H201, Atossa’s proprietary COVID-19 drug [201] candidate. The preliminary study results show that AT-H201 inhibits SARS-CoV-2 infectivity of VERO cells in a laboratory culture.

Dana-Farber Cancer Institute has launched prospective randomized trials of ibrutinib and a similar drug, zanubrutinib in COVID-19 patients in respiratory distress

Aldeyra Therapeutics (ALDX) - Aldeyra scientists pitted ADX-1612 against remdesivir as being as potent if not substantially more.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Regeneron Pharmaceuticals began human testing of its experimental antibody cocktail called REGN-COV2, which is being compared to a placebo treatment amongst four separate study populations, including hospitalized COVID-19 patients, non- hospitalized symptomatic COVID-19 patients, uninfected people that are high-risk, and uninfected people with close exposure to a COVID-19 patient.

U.S. FDA has given approval to conduct the phase 1 clinical trials of its HyLeukin-7 (GX-I7), a treatment for the Covid-19 patients. The study will be a multi-institutional, randomized, double-blind, placebo-controlled trial that will evaluate the tolerability, safety, and efficacy of GX-I7 in adult patients with mild Covid-19 .

Eli Lilly and Co on 15 June said it was launching a study of its rheumatoid arthritis drug baricitinib in patients hospitalized for COVID-19. The drug is being tested to see if it can reduce deaths from the COVID-19 illness and lessen its severity. The trial began dosing patients last week and plans to enroll around 400 patients globally.

Humanigen has launched a phase 3 trial of lenzilumab in COVID-19 after treatment with lenzilumab helped patients with severe and critical COVID-19 pneumonia recover after a median of five days in the 12-patient study, conducted by researchers at Mayo Clinic. The study aims to enroll 238 hospitalized patients who are not on invasive ventilation to see whether adding the drug to standard of care can reduce the need for such aggressive support or the incidence of death.

Mount Sinai Health System will be conducting Phase 2 randomized trial on peginterferon lambda with hospitalized patients receiving supplemental oxygen. Peginterferon lambda is expected help the immune system control the virus infection and decrease the duration and severity of COVID-19.

Gilead Sciences will be conducting a Phase II/III clinical trial of the antiviral drug remdesivir to treat paediatric patients hospitalised with Covid-19. They are targeting to recruit 50 moderate-to-severe Covid-19 paediatric patients, including newborns and adolescents, at more than 30 sites across the US and Europe.

Ampio Pharmaceuticals will begin its Phase 1 clinical trial to evaluate its intravenous ("IV") Ampion™ treatment for COVID-19 patients on supplemental oxygen.

Veru Inc. has started its Phase 2 clinical trial to evaluate the safety and efficacy of VERU-111 in treating COVID-19 patients.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Novartis has halt its hydroxychloroquine study due to enrolment challenges.

The U.S. National Institutes of Health has halted its clinical trial on hydroxychloroquine citing that despite no harm, it is unlikely to be beneficial to the hospitalized COVID-19 patient.

Gilead will begin its human trials for the inhaled version of its antiviral drug remdesivir in August. The drug will be administered through a nebulizer.

Clinical trial conducted by National Institute of Allergy and Infectious Diseases (NIAID) in exploring the short course of hydroxychloroquine and azithromycin will also stop due to recruitment challenge.

FibroGen, Inc has initiated Phase 2 clinical trial of pamrevlumab, a first-in-class antibody, in hospitalized patients with acute COVID-19 infection. The multicenter trial is conducted in the U.S. and target to recruit 130 patients with COVID-19.

The University of Texas Health Science Center at Houston (UTHealth) will be conducting phase 3 clinical trial of the drug canakinumab, an interleukin-1 (IL-1) blocker which has been approved for juvenile rheumatoid arthritis treatment, to treat Covid-19 patients with pneumonia.

As of June 26, Celltex has received approval from the US FDA to investigate the prophylactic efficacy of autologous adipose tissue- derived mesenchymal stem cells against COVID-19. The company will initiate a phase I multi-centre, randomised, double-blind, placebo-controlled study to evaluate ADMSCs.

As of 8th July, Corvus Pharmaceuticals has launched a Phase I clinical trial (30 patients to be enrolled across various US sites) of its new immunotherapy product, CPI-006, for the treatment of patients with Covid-19. CPI-006 is an agonistic humanised monoclonal antibody. The drug candidate was able to bind to different immune cells and trigger a humoral adaptive immune response in-vitro, as well as in-vivo studies in cancer patients.

The first patient has initiated treatment in the Phase 3 clinical study of INOpulse® inhaled nitric oxide (iNO) therapy for the treatment of COVID-19 (COViNOX) at Banner University Medical Center, Phoenix. The Phase 3 randomized, placebo-controlled COViNOX study, will evaluate the efficacy and safety of the investigational INOpulse therapy in patients diagnosed with COVID-19 who require supplemental oxygen

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

DURECT Corporation announced initiation of patient recruitment for a phase 2 safety and efficacy study of DUR-928 in COVID-19 patients with acute liver or kidney injury. The primary efficacy end point of the randomized, double-blind, placebo-controlled, multi- center study is a composite of survival and being free of organ failure at day 28

Researchers at the University of Cincinnati are testing a commonly used drug, called sirolimus, to determine its safety and efficacy in treating hospitalized patients with COVID-19 pneumonia in the placebo controlled, double-blind trial called Sirolimus Treatment in Hospitalized Patients with COVID-19 Pneumonia (SCOPE). The SCOPE trial began enrolling patients in May and hopes to reach a target total of 30 enrollees by fall. Adult participants are eligible to be included in the study if they have confirmed COVID-19 pneumonia and are sick enough to require hospitalization with the need for supplemental oxygen.

Octapharma has started a Phase 3, multicenter clinical trial on the efficacy and safety of octagam® 10% therapy in COVID-19 patients with severe disease progression. This study is currently being conducted in various centers in the United States and compares the efficacy and safety of IVIG plus standard of care (SOC) versus placebo in the treatment of COVID-19 patients at risk of requiring mechanical ventilation.

Regeneron has moved into the Phase 2/3 portion of two adaptive Phase 1/2/3 trials testing the cocktail's ability to treat hospitalized and non-hospitalized COVID-19 patients since early July. The two Phase 2/3 treatment trials in hospitalized (estimated enrollment =1,850) and non-hospitalized (estimated enrollment =1,050) patients are planned to be conducted at approximately 150 sites in the U.S., Brazil, Mexico and Chile A Phase 3 prevention trial is being conducted at approximately 100 sites and is expected to enroll 2,000 patients in the U.S.

The Yale School of Medicine and biopharmaceutical firm AI Therapeutics is enrolling 142 patients in a Phase II trial for LAM- 002A (apilimod). The drug has previously been proved to be effective for autoimmune disease and follicular lymphoma.

Direct Biologics will begin its phase II of ExoFlo therapy to evaluate its ability to improve moderate to severe acute respiratory distress syndrome in 60 COVID-19 patients.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Revive Therapeutics Ltd. has obtained the approval from U.S. FDA to conduct Phase 3 clinical trial on Bucillamine to evaluate its safety and efficacy in patients with mild-moderate COVID-19.

NeuroRx, Inc. and Relief Therapeutics Holdings AG are conducting a phase 2/3 clinical trial of RLF-100 with 70 Covid-19 patients.

The Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC—James) and The Ohio State University Wexner Medical Center will be conducted phase II clinical trial on ibrutinib in 78 immunocompromised patients with Covid-19.

Duke Human Vaccine Institute (DHVI) has obtained the approval to conduct phase 1 clinical trial of a antibody treatments for COVID- 19.

Eli Lilly and Co has started its phase III trial on LY-CoV555 in nursing home in Illinois. It will recruit up to 2,400 participants who live or work at the facilities with recent case of COVID-19.

AbbVie Inc, Amgen Inc and Takeda Pharmaceuticals Inc have begun a joint trial to treat Covid-19 patients. The first segment will involve Amgen's psoriasis drug Otezla, Takeda's anti-inflammatory Firazyr and AbbVie's cenicriviroc. The study will involve several treatment candidates to be tested at the same time where the most promising will continue and the least promising will drop out. These drugs will be dosed with the standard care, Gilead Sciences Inc's antiviral drug remdesivir and generic steroid dexamethasone. The comparison group will consists of only the standard care.

National Institutes of Health launches 2 clinical trials, ACTIV-2 and ACTIV-3 to test antibodies and other experimental therapeutics for mild and moderate COVID-19. The trial will begin to study on the monoclonal antibody LY-CoV555. The initial stage of ACTIV-2 will recruit approximately 200 volunteers presenting sysmptoms and were tested positive but not hospitalized. The initial stage of ACTIV-3 will recruit up to 1000 hospitalized patients with mild to moderate COVID-19 with fewer than 13 days of symptoms.

FOMAT Medical Research in Oxnard has begun 2 clinical trials for an antibody cocktail, REGN-COV2. One study will recruit Covid-19 participants while the other study will recruit participants who are tested negative but at higher risk of infection.

Algernon has begun its multinational phase 2b/3 clinical trial of NP-120 (Ifenprodil). Countries participating in the study include U.S., Australia, Romania and the Philippines. The trial will begin as phase 2b and recruit an aggregate of 150 patients.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020 x. Scientific Publications with Epidemiology and Clinical Focus

Only abstracts of new publications will be included in this section.

Immune Alterations in a Patient with SARS-CoV-2-Related Acute Respiratory Distress Syndrome [241]

We report a longitudinal analysis of the immune response associated with a fatal case of COVID-19 in Europe. This patient exhibited a rapid evolution towards multiorgan failure. SARS-CoV-2 was detected in multiple nasopharyngeal, blood, and pleural samples, despite antiviral and immunomodulator treatment. Clinical evolution in the blood was marked by an increase (2–3-fold) in differentiated effector T cells expressing exhaustion (PD-1) and senescence (CD57) markers, an expansion of antibody-secreting cells, a 15-fold increase in γδ T cell and proliferating NK-cell populations, and the total disappearance of monocytes, suggesting lung trafficking. In the serum, waves of a pro-inflammatory cytokine storm, Th1 and Th2 activation, and markers of T cell exhaustion, apoptosis, cell cytotoxicity, and endothelial activation were observed until the fatal outcome. This case underscores the need for well-designed studies to investigate complementary approaches to control viral replication, the source of the hyperinflammatory status, and immunomodulation to target the pathophysiological response. The investigation was conducted as part of an overall French clinical cohort assessing patients with COVID-19 and registered in clinicaltrials.gov under the following number: NCT04262921.

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020 xi. Sources

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24. https://www.scmp.com/news/hong-kong/health-environment/article/3048289/china-coronavirus- another-patient-tests-positive 25. https://www.channelnewsasia.com/news/singapore/wuhan-virus-singapore-new-confirmed-cases- 13-12369838 26. https://www.channelnewsasia.com/news/asia/wuhan-virus-thailand-first-human-coronavirus- transmission-12374356 27. https://www.straitstimes.com/asia/east-asia/wuhan-virus-japan-to-enforce-special-measures-for- coronavirus-from-saturday 28. https://edition.cnn.com/asia/live-news/coronavirus-outbreak-01-31-20-intl- hnk/h_d25fc709f2df82305c0ff3dc6f383449 29. https://www.dailymail.co.uk/health/article-7951403/Coronavirus-hits-UK.html 30. https://www.ecdc.europa.eu/sites/default/files/documents/novel-coronavirus-risk-assessment- china-second-update.pdf 31. https://gisanddata.maps.arcgis.com/apps/opsdashboard/index.html#/bda7594740fd40299423467b 48e9ecf6 32. http://3g.dxy.cn/newh5/view/pneumonia 33. http://outbreaknewstoday.com/japan-reports-3rd-locally-acquired-2019-ncov-case-this-case-from- chiba-65157/ 34. https://www.channelnewsasia.com/news/singapore/wuhan-virus-singapore-new-cases- coronavirus-china-12373156 35. https://www.chinadailyhk.com/article/119823 36. https://edition.cnn.com/asia/live-news/coronavirus-outbreak-02-01-20-intl-hnk/index.html 37. https://wsiltv.com/2020/01/31/the-latest-who-virus-could-overwhelm-africa-health-systems/ 38. https://www.cdc.gov/media/releases/2020/s0131-seventh-case-coronavirus.html 39. https://meduza.io/en/feature/2020/01/31/coronavirus-detected-in-russia-what-we-know-so-far 40. https://www.garda.com/crisis24/news-alerts/310456/sweden-health-officials-confirm-first-case-of- novel-coronavirus-january-31-update-1 41. https://www.garda.com/crisis24/news-alerts/310471/spain-health-officials-confirm-first-case-of- novel-coronavirus-january-31-update-1 42. https://vietnamnews.vn/society/591717/viet-nam-announces-sixth-coronavirus-case.html 43. https://www.hindustantimes.com/world-news/vietnam-suspends-mainland-china-flights-over-virus- fears/story-ECebpKNBKAekEG5uHXigjO.html 44. https://www.japantimes.co.jp/news/2020/02/01/national/shinzo-abe-combat-coronavirus- outbreak-japan/#.XjaZ4M4zZPY 45. https://newsinfo.inquirer.net/1222873/doh-confirms-second-case-of-ncov-in-ph 46. https://www.moh.gov.sg/news-highlights/details/two-more-confirmed-imported-cases-of-novel- coronavirus-infection-in-singapore 47. https://www.theweek.in/news/india/2020/02/02/second-case-of-novel-coronavirus-confirmed- kerala.html 48. https://www.health.gov.au/news/coronavirus-update-at-a-glance 49. https://www.nst.com.my/world/world/2020/02/561776/coronavirus-evacuees-arrive-germany-8th- infection-confirmed 50. https://www.zaobao.com.sg/realtime/china/story20200202-1025663 51. https://www.bostonherald.com/2020/02/01/first-case-of-coronavirus-confirmed-in-massachusetts- dph/ 52. https://www.wefornews.com/uae-confirms-5th-coronavirus-case/ 53. https://www.cdc.go.kr/board/board.es?mid=a30402000000&bid=0030

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

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53 | P a g e Centre for infectious di sease epidemiology and research

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Ongoing Clinical Trials

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For citation: Centre for Infectious Disease Epidemiology and Research-NUS. COVID-19 Situation Report 210. 27 August 2020

Acknowledgement:

Dr. Pang Junxiong, Vincent

Ms Chua Ee Yong Pearleen

Ms Chua Hui Lan

Ms Gwee Xiao Wei Sylvia

Ms Koh Jiayun

Ms Shah Shimoni Urvish

Ms Wang Min Xian

Any queries? Email Sylvia Gwee @ [email protected]

Centre for Infectious Disease Epidemiology and Research

Saw Swee Hock School of Public Health National University of Singapore Tahir Foundation Building 12 Science Drive 2 #10-01 Singapore 117549

For more information, please visit:

Our NUS website: https://sph.nus.edu.sg/partnerships/cider/ Our blog: https://blog.nus.edu.sg/nuscider/

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