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Supplementary Appendix

This appendix has been provided by the authors to give readers additional information about their work. Supplement to: José R R.Arribas, Sanjay Bhagani, Suzana M. Lobo, et al. Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19. NEJM Evidence, DOI: 10.1056/EVIDoa2100044

Molnupiravir in hospitalized patients - Supplementary appendix

Randomized Trial of Molnupiravir or Placebo in Patients Hospitalized with Covid-19

Table of Contents

Table S1: List of investigators who randomized at least one participant, by country ................... 2 Table S2: Number of participants randomized by country ............................................................ 9 Table S3. Additional participant baseline demographics and clinical characteristics ................. 10 Table S4. Clade distribution at baseline (from nasopharyngeal samples) .................................. 11 Table S5: Duration of time since onset of Covid-19 signs/symptoms prior to randomization (modified intent-to-treat population) ............................................................................................ 12 Table S6: Listing of specific treatment-emergent adverse events regardless of investigator-assessed causality to study intervention (safety population) ...................................................... 13 Table S7: Listing of specific adverse events assessed as drug-related by the investigator (safety population) .................................................................................................................................. 19 Table S8: Adverse event rates in (A) participants with prior/concomitant corticosteroids versus (B) participants without corticosteroids (safety population) ........................................................ 21 Table S9: Adverse events resulting in death (safety population) ................................................ 22 Table S10: Rates of sustained recovery through day 29 (A) overall and (B-F) by key participant subgroup (modified intent-to-treat population) ............................................................................ 24 Table S11: Changes in the WHO clinical progression scale over time (modified intent-to-treat population) .................................................................................................................................. 30 Table S12: Changes in the Pulmonary ordinal outcome over time (modified intent-to-treat population) .................................................................................................................................. 35 Table S13: Changes in the Pulmonary+ ordinal outcome over time (modified intent-to-treat population) .................................................................................................................................. 39 Table S14: National Early Warning Score at end-of-treatment (modified intent-to-treat population) .................................................................................................................................. 43 Table S15: SARS-CoV-2 viral RNA error rates (nasopharyngeal sample) as determined by next-generation sequencing (modified intent-to-treat population) ...................................................... 45 Table S16: Participants with undetectable SARS-CoV-2 RNA levels (nasopharyngeal sample) over time (modified intent-to-treat population) ............................................................................ 47 Table S17: Mean change in SARS-CoV-2 viral RNA from baseline (nasopharyngeal sample) over time (modified intent-to-treat population with baseline SARS-CoV-2 titer ≥500 copies/mL) .................................................................................................................................................... 49 Figure S1: Population pharmacokinetic model-estimated and observed plasma pharmacokinetics of NHC in patients hospitalized for Covid-19 (modified intent-to-treat population of MOVe-IN) compared with healthy volunteers ....................................................... 51 Figure S2: Disposition of deaths reported in the safety analysis and in the all-cause mortality analysis ....................................................................................................................................... 52 References ................................................................................................................................. 53

Molnupiravir in hospitalized patients - Supplementary appendix Table S1: List of investigators who randomized at least one participant, by country

Principal Investigator & Sub-Investigators

Institution, City

Brazil Antonio T. de Faria Freire Thayse F.C. Kayser Claudia M. Oliveira

Santa Casa de Misericordia de Belo Horizonte, Belo Horizonte

Nicole A. Golin Isabele Berti Franciele Debortoli Lucas O. Graciolli Júlia Villa

Hospital Tacchini, Bento Gonçalves

Suzana M. A. Lobo Mariana Buka Luana F. Machado Fernando H.S. Garcia Claudio H.D. Jorge Graziela D. Luckemeyer

FUNFARME Hospital de Base, São José do Rio Preto

Mônica M. Gomes da Silva Rafael Barbosa Luiza M. Almeida Lucas Moreira Juliana M.K. Murata Cristine S. Rosário Isadora L.A. Semione Rodolff N. da Silva

Hospital de Clínicas da Universidade Federal do Paraná, Curitiba

Chile Carlos Perez César Bustos Maria L. Endeiza Francisco Espinoza Maria S.O. Reyes Ronald Reid Javier Tinoco

Clínica Universidad de los Andes, Santiago

Martin F. L. Barret Paz Iturrieta Laura Martinez Carlos Morales

Hospital Sotero del Rio, Santiago

José G. Martinez Juan L. de Maturana Mauricio Madariaga Claudio Valdes

Servicio de Salud Sur Hospital Lucio Córdova, Santiago

Colombia Pablo A. Moncada Juan D. Vélez Julián Y. Munoz

Fundación Valle del Lili, Cali


Sandra L. Valderrama – Beltran Stela del Pilar Baracaldo Maria A.B. Diaz Silvia H. Galvis Maria J. Lopez Oscar M. Munoz

Hospital Universitario San Ignacio, Bogotá

Shirley P. Iglesias Elizabeth Borrero Leonardo Brochado Andres A. C. Bonfanti José Forero Kuang L. T. Kuang Favio F. V. Suarez

Clínica de la Costa Ltda., Barranquilla

Rubén D. Vargas Maria T. Avella Mario A. Chinchilla Mario G. Figueredo

Fundación Cardiovascular de Colombia, Bucaramanga

Angelica M. J. Bernal Sandra E.A. Vesga Heriberto J.C. Dajil Mara J.G. Posada Kelly J.V. Campo

IMAT Oncomedica S.A., Montería

France Pierre Delobel Fabienne Calvas Helene Catala Alexa Debard Monique Galitzky-Gerber Camile Garnier Geraldine Gaube Pauline Lansalot-Matras Lucie Lelievre Guillaume Martin-Blondel Marie Piffaut Lydie Porte Beatrice Riu Stella Rousset Claire Thalamas

Hôpital Purpan, Toulouse

Olivier Robineau Sabine Dambricourt François Demaeght Karim Gallouj Romana Ionita Barthelemy Lafon-Desmurs Andrea Lizio Agnes Meybeck Eric Senneville Pauline Thill

Centre Hospitalier de Tourcoing, Tourcoing


Jade Ghosn/Xavier Lescure Antoine Pierre Bachelard Laurene Deconinck Odile Fleurot Valentina Isernia Diane Le Pluart Christophe Rioux

Hôpital Bichat - Claude Bernard, Paris

Valérie Martinez Alexandre Bleibtreu Aziza Chermak Antoine Faycal Nagisa Godefroy Oula Itani Nadine Ktorza Gentiane Monsel Olivier Paccoud Luminita Schneider Marc-Antoine Valantin Armelle Wastiaux

Hôpital Universitaire la Pitié-Salpêtrière, Paris

Karine Lacombe Diane Bollens Thibault Chiarabini Patrick Ingiliz Jessica Krause Karine Lacombe Benedicte Lefebvre Zineb Ouazene Nadia Valin

CHU Hôpital Saint Antoine, Paris

Duc Nguyen Fabrice Bonnet Charles Cazanave Helene Chaussade Frederic Dauchy Arnaud Desclaux Mailys Ducours Alexandre Duvignaud Julie Leitao Denis Malvy Didier Neau Thierry Pistone Claire Rivoisy Anne-Sophie Wiet Gaetane Wirth

Groupe Hospitalier Pellegrin, Bordeaux

Israel Galia Rahav Ana Belkin Asaf Biber Marina Brod

Chaim Sheba Medical Center, Ramat Gan


Mayan Gilboa Tomer Hoffman Itzchak Levy Vladislav Litchevski Anat Wieder Tal Zilberman Daniels Khetam Husssein Eyal Fuchs Shadi Hamoud Tony Hayek Avivit Peer

Rambam Medical Center, Haifa

Yoseph Caraco Ibrahim Simon Awad Israa Aweidah Bilal Minzel Basel Maslamani

Hadassah Medical Center, Jerusalem

Mexico Roxana García Salcido Sara A.A Diaz Maria De la Luz Alcantar Vallin

Hospital Civil de Guadalajara Fray Antonio Alcalde, Guadalajara

Luis A. Ponce de León G. Maria F.G. Lara Luz Morales Genoveva I.O. Bedolla José S. Osornio

Instituto Nacional de Ciencias Medicas y Nutrición Salvador Zubiran, Cuidad de México

Adrián Camacho-Ortiz Susana D.C.C. Moreno Rómulo O.F. Perez Juan D.L. García Laura N. Shihadeh Eduardo P. Alba

Hospital Universitario Dr. José Eleuterio González, Monterrey

Juan L.M. Gómez Karen A.C. Meza Lourdes G. Munoz Jesús E. Salas Agustín R.U. Gonzalez

Hospital Regional de Alta Especialidad del Bajio, Leon

Philippines Virginia S.D. Reyes Krizelle L. Acibal Racquel C. Ibanez Gayle A. Ramos Kathy J.S. Tripole

Lung Center of the Philippines, Quezon

Poland Anna Piekarska Aleksandra Berkan Juliusz Kamerys Aleksandra Mamzer Kamila Wojcik-Cichy

Wojewodzki Szpital Specjalistyczny im. dr. Wladyslawa Bieganskiego, Lodz-Baluty


Krzysztof Tomasiewicz Agata H. Kozlowska Joanna Krzowska-Firych Anna Miklaszewska

Samodzielny Publiczny Szpital Kliniczny Nr 1 w Lublinie, Lublin

Russian Federation Ilsiyar Khaertynova Asiya Bulatova Elza Gaifullina Olga Lazarenko Venera Shakirova

Republican Clinical Infectious Hospital n.a. A.F. Agafonov, Kazan

Georgy Arbolishvili Andrey Andreev Nadegda Mazova Sergey V. Tsarenko

Moscow Clinical Hospital #52, Moscow

Nikita Lomakin Olga Kupriyanova Alexander Pavlov Anastasia Senichkina Ekaterina Trifonova Veronika Vasilyeva

FSBI Central Hospital with Policlinics, Moscow

Denis Protsenko Albina Bikmukhametova Svetlana Bobkova Tatiana Lisun Nikita Matushkov Valeriy Samoylenko Igor Tyurin

City Clinical Hospital #40, Moscow

Elena Simakina Yulia Gorodnaya Olga Rozinkova

City Clinical Hospital #1, Smolensk

Alina Agafina Anna Fedorova Anna Sarycheva Elena Shabalina Aleksandra S. Yashina

City Hospital #40, Saint Petersburg

Alexander Vishnevskiy Mariia V. Kiseleva Mikhail Kotov Evgeny A. Morozov Ilia Repnikov Mikhail Terskikh Vladislav Zykov

City Pokrovskaya Hospital, Saint Petersburg

South Africa Nyda Fourie Frederick C. Bester Fredericka J. Bosch Matthys G. Heyneke Phillip A. Hutton

IATROS International, Bloemfontein


Gysbert Top Republic of Korea Yeon-Sook Kim Shinhye Cheon

Chungnam National University Hospital, Daejeon

Sei Won Kim Jung W. Heo Heayon Lee Sang H. Lee Ji H. Lim Chang D. Yeo

The Catholic University of Korea Eunpyeong St Mary’s Hospital, Seoul

Spain José R. Arribas Francisco Arnalich Alberto M. Borobia Beatriz Díaz- Pollan Marta M. Diaz-Menéndez Jaime M. Villator Rocio Montejano. Marta Mora Maria C.Prados. Javier Queiruga Enrique Secor Mikel Urroz

Hospital Universitario La Paz, Madrid

Santiago M. Guillén Patricia A. García Yolanda A. García Francisco B. Sánchez Anaura C. Regalade Belen C. Fernández Maria D.C. Loarte Luis D. Vidal Francesca G. Gioia Raquel R. Gonzalez Marta R. Cancio Matilde S. Conde Pilar Vizcarra

Hospital Universitario Ramon y Cajal, Madrid

Maricela V. Minero Maria T. Aldamiz Cristina D. Romero Chiara Fanciulli Marina M. Vílchez Patricia M. García Maria O. Samperio Leyre P. Latorre Francisco T. Picado

Hospital Universitario Gregorio Maranon, Madrid

Lourdes Mateu Roger Paredes Cora Loste

Hospital Universitari Germans Trias i Pujol, Badalona


José R Santos Gemma Lladós Lucia Bailón Ivette Casafont Silvia Roure Laura Soldevila Anna Chamorro Anna Martinez Elena Abad Alex S. Viladomiu Celia C. Espinola Sabina H. Fernández Antonio Moreno Verónica R. Caballero

Hospital Clínic, Barcelona

Vicenç F. Ferrer Joaquín B. Cibrian Vicenç D. Jorro Ibai L.A. Bertiz Paula S. Diez

Hospital Universitari Vall d’Hebron, Barcelona

United Kingdom Sanjay Bhagani Simon Lee Rachel Moores Charlotte Patterson Alison Rodger Antonia Scobie Tara Sood

Royal Free London NHS Foundation Trust, London

Molnupiravir in hospitalized patients - Supplementary appendix Table S2: Number of participants randomized by country

Region & country Number of participants (% of total)

Total 304 (100.0) North America 46 (15.1) United States 46 (15.1) Latin America 86 (28.3) Mexico 23 (7.6) Brazil 32 (10.5) Chile 8 (2.6) Colombia 23 (7.6) Europe, the Middle East, and Africa 159 (52.3) Spain 34 (11.2) France 15 (4.9) Israel 15 (4.9) Poland 6 (2.0) Russian Federation 42 (13.8) South Africa 1 (0.3) Ukraine 25 (8.2) United Kingdom 21 (6.9) Asia-Pacific 13 (4.3) Philippines 1 (0.3) Republic of Korea 12 (3.9)


Table S3. Additional participant baseline demographics and clinical characteristics

Molnupiravir

200 mg N=75

Molnupiravir 400 mg

N=75

Molnupiravir 800 mg

N=76

Molnupiravir combined

N=226

Placebo

N=78 Ethnicity

Hispanic/Latino, No. (%) 27 (36.0) 32 (42.7) 28 (36.8) 87 (38.5) 27 (34.6)

Not Hispanic/Latino, No. (%) 47 (62.7) 42 (56.0) 46 (60.5) 135 (59.7) 49 (62.8)

Unknown/not reported, No. (%) 1 (1.3) 1 (1.3) 2 (2.6) 4 (1.8) 2 (2.6)

Region

North America, No. (%) 10 (13.3) 9 (12.0) 14 (18.4) 33 (14.6) 13 (16.7)

Latin America, No. (%) 19 (25.3) 25 (33.3) 21 (27.6) 65 (28.8) 21 (26.9)

Europe, Middle East, Africa, No. (%) 39 (52.0) 37 (49.3) 40 (52.6) 116 (51.3) 43 (55.1)

Asia Pacific, No. (%) 7 (9.3) 4 (5.3) 1 (1.3) 12 (5.3) 1 (1.3)

Most frequent risk factors for severe Covid-19b Age >60 years, No. (%) 31 (41.3) 30 (40.0) 32 (42.1) 93 (41.2) 33 (42.3)

Obesity,c No. (%) 29 (38.7) 29 (38.7) 34 (44.7) 92 (40.7) 30 (38.5)

Diabetes mellitus, No. (%) 18 (24.0) 21 (28.0) 17 (22.4) 56 (24.8) 14 (17.9)

Serious heart condition, No. (%) 13 (17.3) 10 (13.3) 7 (9.2) 30 (13.3) 7 (9.0)

Active cancer, No. (%) 0 0 2 (2.6) 2 (0.9) 4 (5.1)

Chronic kidney disease, No. (%) 4 (5.3) 6 (8.0) 3 (3.9) 13 (5.8) 4 (5.1)

Chronic pulmonary disease, No. (%) 3 (4.0) 5 (6.7) 5 (6.6) 13 (5.8) 6 (7.7)

Immunocompromised state, No. (%) 0 2 (2.7) 2 (2.6) 4 (1.8) 1 (1.3)

Data provided for all randomized participants. Ethnicity was self-reported by participants according to a set of available options.

N, number of participants randomized to the treatment group. No., number of participants in the treatment group with the respective baseline characteristic for that row.


Table S4. Clade (according to Nextstrain nomenclature) distribution at baseline (from nasopharyngeal samples)

Clade (variant)

Treatment assignment

Total (N=113)

No. (%)

Molnupiravir 200 mg

No.

Molnupiravir 400 mg

No.

Molnupiravir 800 mg

No.

Placebo

No. 20A 6 7 3 7 23 (20.4)

20B 11 15 17 15 58 (51.3)

20C 5 5 0 1 11 (9.7)

20D 1 0 0 0 1 (0.9)

20E (EU1) 2 1 1 3 7 (6.2)

20G 1 2 3 0 6 (5.3)

20H (Beta) 0 0 1 0 1 (0.9)

20I (Alpha) 1 1 1 1 4 (3.5)

Unknown 0 0 0 2 2 (1.8)

N, total number of participants with evaluable sequence data available. No., number of participants in the corresponding row and column.


Table S5: Duration of time since onset of Covid-19 signs/symptoms prior to randomization (modified intent-to-treat population)

Time since onset of Covid-19 signs/symptoms

Molnupiravir 200 mg

N=73

Molnupiravir 400 mg

N=73

Molnupiravir 800 mg

N=72


N=218

Placebo

N=75

≤3 days, No. (%) 5 (6.8) 4 (5.5) 9 (12.5) 18 (8.3) 6 (8.0)

≤24 hours, No. (%) 2 (2.7) 0 1 (1.4) 3 (1.4) 0

>24 to ≤48 hours, No. (%) 1 (1.4) 2 (2.7) 1 (1.4) 4 (1.8) 4 (5.3)

>48 to ≤72 hours, No. (%) 2 (2.7) 2 (2.7) 7 (9.7) 11 (5.0) 2 (2.7)

>3 to ≤5 days, No. (%) 12 (16.4) 10 (13.7) 7 (9.7) 29 (13.3) 13 (17.3)

>3 to ≤4 days, No. (%) 3 (4.1) 4 (5.5) 3 (4.2) 10 (4.6) 4 (5.3)

>4 to ≤5 days, No. (%) 9 (12.3) 6 (8.2) 4 (5.6) 19 (8.7) 9 (12.0)

>5 to ≤10 days, No. (%) 56 (76.7) 59 (80.8) 56 (77.8) 171 (78.4) 56 (74.7)

>5 to ≤6 days, No. (%) 10 (13.7) 10 (13.7) 8 (11.1) 28 (12.8) 10 (13.3)

>6 to ≤7 days, No. (%) 8 (11.0) 7 (9.6) 12 (16.7) 27 (12.4) 10 (13.3)

>7 to ≤8 days, No. (%) 16 (21.9) 18 (24.7) 14 (19.4) 48 (22.0) 14 (18.7)

>8 to ≤9 days, No. (%) 17 (23.3) 14 (19.2) 10 (13.9) 41 (18.8) 14 (18.7)

>9 to ≤10 days, No. (%) 5 (6.9) 10 (13.7) 12 (16.7) 27 (12.4) 8 (10.7)

N, number of participants randomized to the treatment group. No., number of participants in the corresponding row and column.


Table S6: Listing of specific treatment-emergent adverse events regardless of investigator-assessed causality to study intervention (safety population)

Molnupiravir 200 mg

Molnupiravir 400 mg

Molnupiravir 800 mg

Molnupiravir combined Placebo Total

No. (%) No. (%) No. (%) No. (%) No. (%) No. (%) Participants in population 73 73 72 218 75 293 with one or more adverse events 40 (54.8) 36 (49.3) 45 (62.5) 121 (55.5) 46 (61.3) 167 (57.0) with no adverse events 33 (45.2) 37 (50.7) 27 (37.5) 97 (44.5) 29 (38.7) 126 (43.0)

Blood and lymphatic system disorders 0 (0.0) 2 (2.7) 2 (2.8) 4 (1.8) 3 (4.0) 7 (2.4) Anemia 0 (0.0) 2 (2.7) 1 (1.4) 3 (1.4) 0 (0.0) 3 (1.0) Bicytopenia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Leukocytosis 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 1 (1.3) 2 (0.7) Neutrophilia 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Thrombocytopenia 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Thrombocytosis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Cardiac disorders 1 (1.4) 3 (4.1) 1 (1.4) 5 (2.3) 3 (4.0) 8 (2.7) Acute myocardial infarction 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Arrhythmia 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Atrial fibrillation 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Bradycardia 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Cardiac arrest 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Mitral valve incompetence 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Supraventricular tachycardia 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Tachycardia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Tricuspid valve incompetence 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Congenital, familial and genetic

disorders 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3)

Polycystic liver disease 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Eye disorders 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 0 (0.0) 2 (0.7) Vision blurred 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Visual impairment 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Gastrointestinal disorders 13 (17.8) 5 (6.8) 10 (13.9) 28 (12.8) 10 (13.3) 38 (13.0) Abdominal discomfort 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3)


Abdominal pain upper 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 1 (1.3) 3 (1.0) Anal incontinence 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Constipation 5 (6.8) 2 (2.7) 0 (0.0) 7 (3.2) 5 (6.7) 12 (4.1) Diarrhea 2 (2.7) 1 (1.4) 2 (2.8) 5 (2.3) 2 (2.7) 7 (2.4) Dyspepsia 0 (0.0) 1 (1.4) 1 (1.4) 2 (0.9) 2 (2.7) 4 (1.4) Gastroesophageal reflux disease 2 (2.7) 1 (1.4) 0 (0.0) 3 (1.4) 0 (0.0) 3 (1.0) Hemorrhoids 3 (4.1) 0 (0.0) 0 (0.0) 3 (1.4) 0 (0.0) 3 (1.0) Infrequent bowel movements 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Loose tooth 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Nausea 2 (2.7) 1 (1.4) 3 (4.2) 6 (2.8) 1 (1.3) 7 (2.4) Rectal hemorrhage 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Steatorrhea 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Stress ulcer 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Toothache 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Vomiting 1 (1.4) 0 (0.0) 2 (2.8) 3 (1.4) 0 (0.0) 3 (1.0) General disorders and administration

site conditions 2 (2.7) 3 (4.1) 2 (2.8) 7 (3.2) 1 (1.3) 8 (2.7)

Asthenia 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Chest pain 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Device intolerance 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Discomfort 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Feeling hot 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Injection site reaction 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Physical deconditioning 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Pyrexia 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Hepatobiliary disorders 2 (2.7) 2 (2.7) 2 (2.8) 6 (2.8) 2 (2.7) 8 (2.7) Cholestasis 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Gallbladder polyp 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Hepatic steatosis 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Hepatitis 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Hepatitis acute 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Hepatocellular injury 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Hepatorenal syndrome 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Immune system disorders 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Seasonal allergy 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3)

Infections and infestations 13 (17.8) 10 (13.7) 16 (22.2) 39 (17.9) 12 (16.0) 51 (17.4) Bacteremia 2 (2.7) 0 (0.0) 0 (0.0) 2 (0.9) 0 (0.0) 2 (0.7) Bacterial disease carrier 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Covid-19 7 (9.6) 6 (8.2) 5 (6.9) 18 (8.3) 7 (9.3) 25 (8.5)


Covid-19 pneumonia 0 (0.0) 1 (1.4) 3 (4.2) 4 (1.8) 5 (6.7) 9 (3.1) Campylobacter urinary tract infection 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3)

Candida infection 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Conjunctivitis 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Fungal infection 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Fungal skin infection 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Herpes simplex 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Lower respiratory tract infection 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Nasal herpes 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Oral herpes 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Peritonitis bacterial 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Pneumococcal infection 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Pneumonia 1 (1.4) 1 (1.4) 2 (2.8) 4 (1.8) 1 (1.3) 5 (1.7) Pneumonia bacterial 1 (1.4) 0 (0.0) 4 (5.6) 5 (2.3) 0 (0.0) 5 (1.7) Pneumonia pseudomonal 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Pulmonary sepsis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Septic shock 0 (0.0) 1 (1.4) 1 (1.4) 2 (0.9) 0 (0.0) 2 (0.7) Urinary tract infection enterococcal 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Vulvovaginal candidiasis 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Injury, poisoning and procedural

complications 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 1 (1.3) 2 (0.7)

Accidental overdose 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Pancreatic injury 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Investigations 9 (12.3) 11 (15.1) 15 (20.8) 35 (16.1) 19 (25.3) 54 (18.4) Alanine aminotransferase increased 4 (5.5) 5 (6.8) 7 (9.7) 16 (7.3) 8 (10.7) 24 (8.2) Amylase increased 0 (0.0) 1 (1.4) 1 (1.4) 2 (0.9) 3 (4.0) 5 (1.7) Aspartate aminotransferase increased 3 (4.1) 5 (6.8) 5 (6.9) 13 (6.0) 3 (4.0) 16 (5.5) Basophil count increased 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Blood albumin decreased 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Blood alkaline phosphatase decreased 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Blood alkaline phosphatase increased 0 (0.0) 2 (2.7) 1 (1.4) 3 (1.4) 2 (2.7) 5 (1.7) Blood calcium decreased 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Blood creatine phosphokinase increased 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 0 (0.0) 2 (0.7) Blood glucose increased 1 (1.4) 2 (2.7) 3 (4.2) 6 (2.8) 3 (4.0) 9 (3.1) Blood lactate dehydrogenase increased 2 (2.7) 3 (4.1) 2 (2.8) 7 (3.2) 1 (1.3) 8 (2.7) Blood potassium decreased 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Blood potassium increased 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Blood pressure increased 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3)


C-reactive protein increased 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 3 (4.0) 3 (1.0) Gamma-glutamyltransferase increased 0 (0.0) 2 (2.7) 0 (0.0) 2 (0.9) 3 (4.0) 5 (1.7) Glomerular filtration rate decreased 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 1 (1.3) 3 (1.0) Glomerular filtration rate increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Hemoglobin decreased 1 (1.4) 1 (1.4) 0 (0.0) 2 (0.9) 0 (0.0) 2 (0.7) Hepatic enzyme increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Lipase increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 2 (2.7) 3 (1.0) Liver function test increased 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Lymphocyte count decreased 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Monocyte count increased 0 (0.0) 1 (1.4) 1 (1.4) 2 (0.9) 0 (0.0) 2 (0.7) Myelocyte count increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Neutrophil count decreased 0 (0.0) 1 (1.4) 1 (1.4) 2 (0.9) 0 (0.0) 2 (0.7) Neutrophil count increased 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Oxygen saturation decreased 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Platelet count decreased 0 (0.0) 0 (0.0) 2 (2.8) 2 (0.9) 1 (1.3) 3 (1.0) Platelet count increased 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Protein total decreased 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Red blood cell count decreased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Serum ferritin increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Transaminases increased 1 (1.4) 3 (4.1) 2 (2.8) 6 (2.8) 1 (1.3) 7 (2.4) White blood cell count decreased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Metabolism and nutrition disorders 10 (13.7) 12 (16.4) 4 (5.6) 26 (11.9) 6 (8.0) 32 (10.9)

Decreased appetite 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Diabetes mellitus 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Electrolyte imbalance 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Gout 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Hyperchloremia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Hyperglycemia 4 (5.5) 5 (6.8) 0 (0.0) 9 (4.1) 1 (1.3) 10 (3.4) Hyperkalemia 2 (2.7) 1 (1.4) 0 (0.0) 3 (1.4) 2 (2.7) 5 (1.7) Hypernatremia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Hypokalemia 0 (0.0) 2 (2.7) 1 (1.4) 3 (1.4) 1 (1.3) 4 (1.4) Hypomagnesaemia 0 (0.0) 0 (0.0) 2 (2.8) 2 (0.9) 0 (0.0) 2 (0.7) Hyponatremia 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 0 (0.0) 2 (0.7) Hypoproteinemia 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Lactic acidosis 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Metabolic acidosis 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Metabolic alkalosis 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Obesity 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3)


Type 2 diabetes mellitus 1 (1.4) 1 (1.4) 0 (0.0) 2 (0.9) 1 (1.3) 3 (1.0) Musculoskeletal and connective tissue

disorders 3 (4.1) 0 (0.0) 0 (0.0) 3 (1.4) 1 (1.3) 4 (1.4)

Back pain 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Musculoskeletal chest pain 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Myalgia 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Myositis 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Pain in extremity 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Neoplasms benign, malignant and

unspecified (incl cysts and polyps) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3)

Clear cell renal cell carcinoma 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Nervous system disorders 3 (4.1) 2 (2.7) 1 (1.4) 6 (2.8) 3 (4.0) 9 (3.1) Dizziness 0 (0.0) 2 (2.7) 0 (0.0) 2 (0.9) 1 (1.3) 3 (1.0) Head discomfort 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Headache 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 1 (1.3) 3 (1.0) Multiple sclerosis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Seizure 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Psychiatric disorders 4 (5.5) 1 (1.4) 3 (4.2) 8 (3.7) 4 (5.3) 12 (4.1) Abnormal dreams 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 1 (1.3) 3 (1.0) Adjustment disorder 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Anxiety 1 (1.4) 1 (1.4) 1 (1.4) 3 (1.4) 2 (2.7) 5 (1.7) Anxiety disorder 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Confusional state 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Daydreaming 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Delirium 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Depression 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Insomnia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Mental status changes 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Renal and urinary disorders 2 (2.7) 0 (0.0) 6 (8.3) 8 (3.7) 2 (2.7) 10 (3.4) Acute kidney injury 1 (1.4) 0 (0.0) 2 (2.8) 3 (1.4) 0 (0.0) 3 (1.0) Chromaturia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Chronic kidney disease 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Dysuria 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 0 (0.0) 2 (0.7) Nocturia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Renal cyst 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Renal impairment 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Urinary retention 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Respiratory, thoracic, and mediastinal

disorders 8 (11.0) 7 (9.6) 9 (12.5) 24 (11.0) 11 (14.7) 35 (11.9)


Acute pulmonary edema 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Acute respiratory distress syndrome 1 (1.4) 1 (1.4) 1 (1.4) 3 (1.4) 0 (0.0) 3 (1.0) Acute respiratory failure 3 (4.1) 0 (0.0) 2 (2.8) 5 (2.3) 2 (2.7) 7 (2.4) Asthma 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Bronchospasm 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Epistaxis 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Hiccups 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Interstitial lung disease 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Pneumomediastinum 0 (0.0) 1 (1.4) 3 (4.2) 4 (1.8) 1 (1.3) 5 (1.7) Pneumothorax 1 (1.4) 1 (1.4) 0 (0.0) 2 (0.9) 0 (0.0) 2 (0.7) Pneumothorax spontaneous 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Pulmonary congestion 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Pulmonary embolism 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 1 (1.3) 2 (0.7) Pulmonary oedema 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Respiratory acidosis 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Respiratory failure 3 (4.1) 4 (5.5) 3 (4.2) 10 (4.6) 4 (5.3) 14 (4.8) Skin and subcutaneous tissue

disorders 6 (8.2) 1 (1.4) 3 (4.2) 10 (4.6) 5 (6.7) 15 (5.1)

Acne 2 (2.7) 0 (0.0) 0 (0.0) 2 (0.9) 0 (0.0) 2 (0.7) Decubitus ulcer 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Dermatitis 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Dry skin 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 1 (1.3) 2 (0.7) Erythema 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Hyperhidrosis 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Pruritus 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Rash 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 2 (2.7) 4 (1.4) Subcutaneous emphysema 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Urticaria 1 (1.4) 1 (1.4) 0 (0.0) 2 (0.9) 0 (0.0) 2 (0.7) Vascular disorders 2 (2.7) 4 (5.5) 5 (6.9) 11 (5.0) 2 (2.7) 13 (4.4) Deep vein thrombosis 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Flushing 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Hematoma 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 1 (1.3) 2 (0.7) Hypertension 1 (1.4) 2 (2.7) 1 (1.4) 4 (1.8) 0 (0.0) 4 (1.4) Hypotension 1 (1.4) 1 (1.4) 0 (0.0) 2 (0.9) 1 (1.3) 3 (1.0) Orthostatic hypotension 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Shock 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3)

No., number of participants in respective row and column. Every participant is counted a single time for each applicable row and column. Adverse event terms are from MedDRA Version 23.1.


Table S7: Listing of specific adverse events assessed as drug-related by the investigator (safety population) Molnupiravir

200 mg Molnupiravir

400 mg Molnupiravir

800 mg Molnupiravir

combined Placebo Total No. (%) No. (%) No. (%) No. (%) No. (%) No. (%)

Participants in population 73 73 72 218 75 293 with one or more drug-related

adverse events 8 (11.0) 6 (8.2) 10 (13.9) 24 (11.0) 16 (21.3) 40 (13.7)

with no drug-related adverse events 65 (89.0) 67 (91.8) 62 (86.1) 194 (89.0) 59 (78.7) 253 (86.3) Gastrointestinal disorders 0 (0.0) 1 (1.4) 4 (5.6) 5 (2.3) 5 (6.7) 10 (3.4) Abdominal discomfort 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Abdominal pain upper 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 1 (1.3) 2 (0.7) Anal incontinence 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Diarrhea 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 2 (2.7) 3 (1.0) Dyspepsia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 1 (1.3) 2 (0.7) Nausea 0 (0.0) 1 (1.4) 2 (2.8) 3 (1.4) 1 (1.3) 4 (1.4) Vomiting 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) General disorders and

administration site conditions 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3)

Feeling hot 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Hepatobiliary disorders 1 (1.4) 1 (1.4) 1 (1.4) 3 (1.4) 1 (1.3) 4 (1.4) Hepatitis 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Hepatitis acute 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Hepatocellular injury 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Investigations 2 (2.7) 3 (4.1) 3 (4.2) 8 (3.7) 7 (9.3) 15 (5.1) Alanine aminotransferase increased 2 (2.7) 2 (2.7) 1 (1.4) 5 (2.3) 3 (4.0) 8 (2.7) Amylase increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Aspartate aminotransferase

increased 1 (1.4) 2 (2.7) 0 (0.0) 3 (1.4) 2 (2.7) 5 (1.7)

Blood alkaline phosphatase increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7) Blood glucose increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Blood lactate dehydrogenase

increased 0 (0.0) 1 (1.4) 1 (1.4) 2 (0.9) 1 (1.3) 3 (1.0)

Gamma-glutamyltransferase increased

0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 1 (1.3) 2 (0.7)

Glomerular filtration rate decreased 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Hepatic enzyme increased 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Lipase increased 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Platelet count decreased 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3)


Transaminases increased 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Metabolism and nutrition disorders 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Hyperkalemia 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Nervous system disorders 2 (2.7) 0 (0.0) 0 (0.0) 2 (0.9) 1 (1.3) 3 (1.0) Dizziness 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Head discomfort 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Headache 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Psychiatric disorders 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 1 (1.3) 3 (1.0) Abnormal dreams 1 (1.4) 0 (0.0) 1 (1.4) 2 (0.9) 1 (1.3) 3 (1.0) Daydreaming 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Insomnia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Renal and urinary disorders 0 (0.0) 0 (0.0) 2 (2.8) 2 (0.9) 0 (0.0) 2 (0.7) Chromaturia 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Dysuria 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Skin and subcutaneous tissue

disorders 2 (2.7) 1 (1.4) 1 (1.4) 4 (1.8) 2 (2.7) 6 (2.0)

Dry skin 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Erythema 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Hyperhidrosis 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Pruritus 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3) Urticaria 1 (1.4) 1 (1.4) 0 (0.0) 2 (0.9) 0 (0.0) 2 (0.7) Vascular disorders 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3) Flushing 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3)

No., number of participants in respective row and column. Every participant is counted a single time for each applicable row and column. Adverse event terms are from MedDRA Version 23.1.


Table S8: Adverse event rates in (A) participants with prior/concomitant corticosteroids versus (B) participants without corticosteroids (safety population)

(A) Participants with prior/concomitant corticosteroids

Specific adverse event type, No. (%) Molnupiravir

200 mg n=44

Molnupiravir 400 mg

n=50

Molnupiravir 800 mg

n=52


n=146

Placebo n=56

Any adverse event 27 (61.4) 26 (52.0) 30 (57.7) 83 (56.8) 37 (66.1)

Any serious adverse event 8 (18.2) 7 (14.0) 11 (21.2) 26 (17.8) 11 (33.9)

Death 3 (6.8) 3 (6.0) 4 (7.7) 10 (6.8) 2 (3.6)

Any drug-related adverse event 5 (11.4) 4 (8.0) 7 (13.5) 16 (11.0) 13 (23.2)

(B) Participants without prior/concomitant corticosteroids

Specific adverse event type, No. (%) Molnupiravir

200 mg n=29

Molnupiravir 400 mg

n=23

Molnupiravir 800 mg

n=20


n=72

Placebo n=19

Any adverse event 13 (44.8) 10 (43.5) 15 (75.0) 38 (52.8) 9 (47.4)

Any serious adverse event 3 (10.3) 2 (8.7) 2 (10.0) 7 (9.7) 1 (5.3)

Death 3 (10.3) 1 (4.3) 0 (0.0) 4 (5.6) 0 (0.0)

Any drug-related adverse event 3 (10.3) 2 (8.7) 3 (15.0) 8 (11.1) 3 (15.8)

n, number of participants per treatment group. No., number of participants in respective row and column.


Table S9: Adverse events resulting in death (safety population)

(A) Listing of specific adverse events resulting in death

Molnupiravir 200 mg

Molnupiravir 400 mg

Molnupiravir 800 mg

Molnupiravir combined Placebo Total

No. (%) No. (%) No. (%) No. (%) No. (%) No. (%)

Participants in population 73 73 72 218 75 293

with one or more adverse events

resulting in death 6 (8.2) 4 (5.5) 4 (5.6) 14 (6.4) 2 (2.7) 16 (5.5)

with no adverse events resulting in

death 67 (91.8) 69 (94.5) 68 (94.4) 204 (93.6) 73 (97.3) 277 (94.5)

Cardiac disorders 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Cardiac arrest 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3)

Infections and infestations 5 (6.8) 2 (2.7) 3 (4.2) 10 (4.6) 2 (2.7) 12 (4.1) Bacteremia 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3)

Covid-19 4 (5.5) 0 (0.0) 2 (2.8) 6 (2.8) 0 (0.0) 6 (2.0)

Covid-19 pneumonia 0 (0.0) 1 (1.4) 1 (1.4) 2 (0.9) 1 (1.3) 3 (1.0)

Pneumonia bacterial 1 (1.4) 0 (0.0) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3)

Pulmonary sepsis 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.3) 1 (0.3)

Septic shock 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3)

Respiratory, thoracic, and mediastinal disorders 3 (4.1) 0 (0.0) 3 (4.2) 6 (2.8) 0 (0.0) 6 (2.0)

Acute respiratory distress syndrome 0 (0.0) 0 (0.0) 1 (1.4) 1 (0.5) 0 (0.0) 1 (0.3)

Acute respiratory failure 1 (1.4) 0 (0.0) 2 (2.8) 3 (1.4) 0 (0.0) 3 (1.0)

Respiratory failure 2 (2.7) 0 (0.0) 0 (0.0) 2 (0.9) 0 (0.0) 2 (0.7)

Vascular disorders 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3) Shock 0 (0.0) 1 (1.4) 0 (0.0) 1 (0.5) 0 (0.0) 1 (0.3)

No., number of participants in respective row and column. Adverse events were reported during the safety follow up period, i.e., during treatment and 14 days after end of treatment. Every participant is counted a single time for each applicable row and column. Adverse event terms are from MedDRA Version 23.1.


(B) Pairwise comparison of the incidence of adverse events resulting in death

Treatment group

n

(%) Difference in % vs MOV 400 mg

Difference in % vs MOV 800 mg

Difference in % vs Placebo

(95% CI) (95% CI) (95% CI) MOV 200 mg 6 (8.2) 2.7 (-6.2, 12.1) 2.7 (-6.4, 12.1) 5.6 (-2.1, 14.5)

MOV 400 mg 4 (5.5) - -0.1 (-8.7, 8.5) 2.8 (-4.5, 11.0)

MOV 800 mg 4 (5.6) - - 2.9 (-4.4, 11.2)

Placebo 2 (2.7) - - -

95% confidence intervals were based on the Miettinen & Nurminen method.

CI, confidence interval. MOV, molnupiravir. n, number of participants with an adverse event leading to death by treatment group.


Table S10: Rates of sustained recovery through day 29 (A) overall and (B-F) by key participant subgroup (modified intent-to-treat population)

(A) Overall

Treatment No. Number of events (%)

Person- days

Event rate/ 100 person-

days

Median time to recovery (days) a

(95% CI)

Recovery rate at day 29 in %a

(95% CI) MOV 200 mg 73 56 (76.7) 867.0 6.5 9.0 (7.0, 10.0) 81.5 (71.4, 89.7)

MOV 400 mg 73 56 (76.7) 788.0 7.1 9.0 (8.0, 10.0) 85.2 (75.4, 92.6)

MOV 800 mg 72 59 (81.9) 874.0 6.8 9.0 (8.0, 11.0) 84.3 (74.8, 91.6)

Placebo 75 61 (81.3) 896.0 6.8 9.0 (8.0, 11.0) 84.7 (75.5, 91.9)

Pairwise comparisons

Hazard ratio (95% CI)b MOV 200 mg vs. Placebo 0.99 (0.68, 1.45)

MOV 400 mg vs. Placebo 1.13 (0.78, 1.65)

MOV 800 mg vs. Placebo 1.01 (0.69, 1.47)

MOV 400 mg vs. MOV 200 mg 1.12 (0.76, 1.66)

MOV 800 mg vs. MOV 200 mg 1.00 (0.69, 1.47)

MOV 800 mg vs. MOV 400 mg 0.89 (0.61, 1.31)

aFrom product-limit (Kaplan-Meier) method for censored data. bBased on Cox regression model with Efron’s method of tie handling with treatment and randomization stratification factors as covariates. Hazard ratio >1 favors the first group in the pairwise comparison. CI, confidence interval. MOV, molnupiravir. No., number of participants in treatment group and in the respective subgroup category.


(B) Time since sign/symptom onset ≤5 days before randomization


Person- days


days

Median time to recovery (days)a

(95% CI)


(95% CI)

MOV 200 mg 17 12 (70.6) 254.0 4.7 13.0 (7.0, 26.0) 74.9 (52.7, 92.2)

MOV 400 mg 14 9 (64.3) 164.0 5.5 10.0 (5.0, 26.0) 81.5 (55.3, 97.1)

MOV 800 mg 16 15 (93.8) 167.0 9.0 8.5 (6.0, 12.0) 93.8 (75.3, 99.6)

Placebo 19 17 (89.5) 194.0 8.8 9.0 (8.0, 14.0) 100.0 (NA, NA)



MOV 400 mg vs. Placebo 0.65 (0.28, 1.47)

MOV 800 mg vs. Placebo 1.11 (0.55, 2.23)

MOV 400 mg vs. MOV 200 mg 1.23 (0.52, 2.94)

MOV 800 mg vs. MOV 200 mg 1.95 (0.90, 4.26)

MOV 800 mg vs. MOV 400 mg 1.46 (0.63, 3.37)



(C) No prior and/or concomitant remdesivir use for the index episode of Covid-19


Person- days


days

Median time to recovery (days)a

(95% CI)


(95% CI)

MOV 200 mg 57 42 (73.7) 696.0 6.0 9.0 (7.0, 11.0) 78.0 (66.0, 88.0)

MOV 400 mg 56 42 (75.0) 628.0 6.7 10.0 (9.0, 10.0) 83.8 (72.3, 92.4)

MOV 800 mg 53 43 (81.1) 645.0 6.7 9.0 (8.0, 11.0) 84.3 (73.1, 92.7)

Placebo 55 44 (80.0) 691.0 6.4 11.0 (8.0, 12.0) 83.0 (71.8, 91.6)


Hazard ratio (95% CI)b

MOV 200 mg vs. Placebo 1.04 (0.68, 1.59)

MOV 400 mg vs. Placebo 1.16 (0.76, 1.77)

MOV 800 mg vs. Placebo 1.09 (0.72, 1.67)

MOV 400 mg vs. MOV 200 mg 1.04 (0.68, 1.60)

MOV 800 mg vs. MOV 200 mg 1.04 (0.68, 1.60)

MOV 800 mg vs. MOV 400 mg 1.00 (0.65, 1.53)



(D) At least 1 risk factor for severe Covid-19


Person- days


days


(95% CI)


(95% CI) MOV 200 mg 50 35 (70.0) 658.0 5.3 10.0 (8.0, 13.0) 76.7 (63.5, 87.8)

MOV 400 mg 56 43 (76.8) 619.0 6.9 9.0 (8.0, 10.0) 84.9 (73.6, 93.2)

MOV 800 mg 56 47 (83.9) 653.0 7.2 9.0 (7.0, 11.0) 87.0 (76.7, 94.3)

Placebo 54 44 (81.5) 605.0 7.3 9.0 (7.0, 11.0) 86.1 (75.2, 93.9)



MOV 400 mg vs. Placebo 0.97 (0.63, 1.48)

MOV 800 mg vs. Placebo 0.97 (0.64, 1.46)

MOV 400 mg vs. MOV 200 mg 1.32 (0.84, 2.06)

MOV 800 mg vs. MOV 200 mg 1.32 (0.85, 2.05)

MOV 800 mg vs. MOV 400 mg 1.00 (0.66, 1.51)



(E) >60 years old


Person- days


days


(95% CI)


(95% CI) MOV 200 mg 30 17 (56.7) 472.0 3.6 14.0 (9.0, NA) 63.6 (45.7, 81.2)

MOV 400 mg 29 20 (69.0) 369.0 5.4 9.0 (9.0, 14.0) 78.3 (60.7, 91.8)

MOV 800 mg 30 22 (73.3) 409.0 5.4 12.0 (8.0, 16.0) 78.5 (62.1, 91.3)

Placebo 31 23 (74.2) 380.0 6.1 11.0 (7.0, 13.0) 81.9 (65.8, 93.4)


Hazard ratio (95% CI)b

MOV 200 mg vs. Placebo 0.60 (0.32, 1.13)

MOV 400 mg vs. Placebo 0.88 (0.49, 1.61)

MOV 800 mg vs. Placebo 0.86 (0.48, 1.54)

MOV 400 mg vs. MOV 200 mg 1.47 (0.76, 2.81)

MOV 800 mg vs. MOV 200 mg 1.46 (0.77, 2.75)

MOV 800 mg vs. MOV 400 mg 0.97 (0.53, 1.78)



(F) No prior/concomitant glucocorticoid use for the index episode of Covid-19


Person- days


days


(95% CI)


(95% CI) MOV 200 mg 29 19 (65.5) 391.0 4.9 9.0 (7.0, 22.0) 70.1 (52.7, 85.8)

MOV 400 mg 23 16 (69.6) 239.0 6.7 10.0 (7.0, 11.0) 88.3 (69.1, 98.0)

MOV 800 mg 20 16 (80.0) 229.0 7.0 9.0 (7.0, 11.0) 84.2 (65.1, 96.1)

Placebo 19 15 (78.9) 210.0 7.1 10.0 (8.0, 12.0) 88.1 (68.6, 98.0)


Hazard ratiob (95% CI)b MOV 200 mg vs. Placebo 0.87 (0.42, 1.80)

MOV 400 mg vs. Placebo 1.10 (0.49, 2.50)

MOV 800 mg vs. Placebo 1.31 (0.60, 2.84)

MOV 400 mg vs. MOV 200 mg 1.15 (0.53, 2.49)

MOV 800 mg vs. MOV 200 mg 1.06 (0.52, 2.18)

MOV 800 mg vs. MOV 400 mg 1.28 (0.61, 2.71)



Table S11: Changes in the WHO clinical progression scale over time (modified intent-to-treat population) The WHO Clinical Progression Scale is an 11-point ordinal scale (ranging from 0 through 10), measuring the clinical progression of Covid-19.1 The minimally important difference is not known. Scores are assigned as follows:

Score 0: Uninfected, no SARS-CoV-2 viral RNA detected.

Score 1: Asymptomatic, but SARS-CoV-2 viral RNA detected.

Score 2: Symptomatic, but able to function independently.

Score 3: Symptomatic and assistance needed.

Score 4: Hospitalized, without oxygen therapy [Note: Patients hospitalized for observation only were assigned a score of 1, 2, or 3, depending on their symptoms or condition, as per those respective scoring categories.]

Score 5: Hospitalized and administered oxygen by mask or nasal prongs.

Score 6: Hospitalized and administered oxygen by non-invasive ventilation or high flow.

Score 7: Intubated and receiving mechanical ventilation, with a PiO2/FiO2 ≥150 or SpO2/FiO2 ≥200.

Score 8: Receiving mechanical ventilation PiO2/FiO2 <150 (SpO2/FiO2 <200) or vasopressors.

Score 9: Receiving mechanical ventilation PiO2/FiO2 <150 and vasopressors, dialysis, or extracorporeal membrane oxygenation.

Score 10: Dead.

Visit Score category MOV 200 mg MOV 400 mg MOV 800 mg Placebo Total n/m (%) n/m (%) n/m (%) n/m (%) n/m (%)

Baseline 0 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 1 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 2 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 3 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 4 46/73 (63.0) 33/73 (45.2) 34/72 (47.2) 35/75 (46.7) 148/293 (50.5) 5 27/73 (37.0) 37/73 (50.7) 36/72 (50.0) 34/75 (45.3) 134/293 (45.7) 6 0/73 (0.0) 3/73 (4.1) 2/72 (2.8) 6/75 (8.0) 11/293 (3.8) 7 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 8 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 9 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0)


10 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) Missing 0 0 0 0 0

Day 3 0 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 1 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 2 1/73 (1.4) 1/73 (1.4) 0/72 (0.0) 2/75 (2.7) 4/293 (1.4) 3 1/73 (1.4) 0/73 (0.0) 0/72 (0.0) 1/75 (1.3) 2/293 (0.7) 4 27/73 (37.0) 27/73 (37.0) 21/72 (29.2) 24/75 (32.0) 99/293 (33.8) 5 36/73 (49.3) 36/73 (49.3) 42/72 (58.3) 37/75 (49.3) 151/293 (51.5) 6 7/73 (9.6) 9/73 (12.3) 6/72 (8.3) 10/75 (13.3) 32/293 (10.9) 7 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) 8 0/73 (0.0) 0/73 (0.0) 2/72 (2.8) 0/75 (0.0) 2/293 (0.7) 9 1/73 (1.4) 0/73 (0.0) 1/72 (1.4) 1/75 (1.3) 3/293 (1.0)

10 0/73 (0.0) 0/73 (0.0) 0/72 (0.0) 0/75 (0.0) 0/293 (0.0) Missing 0 0 0 0 0

EOT (day 5) 0 2/71 (2.8) 0/68 (0.0) 1/70 (1.4) 0/72 (0.0) 3/281 (1.1) 1 2/71 (2.8) 1/68 (1.5) 1/70 (1.4) 2/72 (2.8) 6/281 (2.1) 2 3/71 (4.2) 5/68 (7.4) 0/70 (0.0) 9/72 (12.5) 17/281 (6.0) 3 0/71 (0.0) 2/68 (2.9) 2/70 (2.9) 1/72 (1.4) 5/281 (1.8) 4 29/71 (40.8) 20/68 (29.4) 27/70 (38.6) 25/72 (34.7) 101/281 (35.9) 5 27/71 (38.0) 31/68 (45.6) 28/70 (40.0) 26/72 (36.1) 112/281 (39.9) 6 7/71 (9.9) 8/68 (11.8) 8/70 (11.4) 8/72 (11.1) 31/281 (11.0) 7 0/71 (0.0) 0/68 (0.0) 0/70 (0.0) 0/72 (0.0) 0/281 (0.0) 8 1/71 (1.4) 1/68 (1.5) 1/70 (1.4) 0/72 (0.0) 3/281 (1.1) 9 0/71 (0.0) 0/68 (0.0) 2/70 (2.9) 1/72 (1.4) 3/281 (1.1)

10 0/71 (0.0) 0/68 (0.0) 0/70 (0.0) 0/72 (0.0) 0/281 (0.0) Missing 2 5 2 3 12

Day 10 0 3/68 (4.4) 4/64 (6.3) 2/67 (3.0) 3/69 (4.3) 12/268 (4.5) 1 10/68 (14.7) 7/64 (10.9) 7/67 (10.4) 7/69 (10.1) 31/268 (11.6) 2 26/68 (38.2) 19/64 (29.7) 22/67 (32.8) 21/69 (30.4) 88/268 (32.8) 3 3/68 (4.4) 4/64 (6.3) 7/67 (10.4) 8/69 (11.6) 22/268 (8.2) 4 8/68 (11.8) 16/64 (25.0) 7/67 (10.4) 13/69 (18.8) 44/268 (16.4) 5 11/68 (16.2) 9/64 (14.1) 14/67 (20.9) 11/69 (15.9) 45/268 (16.8) 6 4/68 (5.9) 2/64 (3.1) 5/67 (7.5) 3/69 (4.3) 14/268 (5.2) 7 0/68 (0.0) 0/64 (0.0) 1/67 (1.5) 0/69 (0.0) 1/268 (0.4) 8 2/68 (2.9) 0/64 (0.0) 0/67 (0.0) 3/69 (4.3) 5/268 (1.9) 9 1/68 (1.5) 0/64 (0.0) 2/67 (3.0) 0/69 (0.0) 3/268 (1.1)

10 0/68 (0.0) 3/64 (4.7) 0/67 (0.0) 0/69 (0.0) 3/268 (1.1) Missing 5 9 5 6 25


Day 15 0 10/67 (14.9) 8/61 (13.1) 10/68 (14.7) 8/70 (11.4) 36/266 (13.5) 1 12/67 (17.9) 12/61 (19.7) 9/68 (13.2) 11/70 (15.7) 44/266 (16.5) 2 25/67 (37.3) 25/61 (41.0) 27/68 (39.7) 27/70 (38.6) 104/266 (39.1) 3 7/67 (10.4) 5/61 (8.2) 4/68 (5.9) 8/70 (11.4) 24/266 (9.0) 4 4/67 (6.0) 3/61 (4.9) 3/68 (4.4) 5/70 (7.1) 15/266 (5.6) 5 4/67 (6.0) 4/61 (6.6) 7/68 (10.3) 4/70 (5.7) 19/266 (7.1) 6 2/67 (3.0) 0/61 (0.0) 0/68 (0.0) 3/70 (4.3) 5/266 (1.9) 7 0/67 (0.0) 0/61 (0.0) 2/68 (2.9) 1/70 (1.4) 3/266 (1.1) 8 3/67 (4.5) 0/61 (0.0) 1/68 (1.5) 0/70 (0.0) 4/266 (1.5) 9 0/67 (0.0) 1/61 (1.6) 4/68 (5.9) 2/70 (2.9) 7/266 (2.6)

10 0/67 (0.0) 3/61 (4.9) 1/68 (1.5) 1/70 (1.4) 5/266 (1.9) Missing 6 12 4 5 27

Day 29 0 25/63 (39.7) 17/59 (28.8) 29/68 (42.6) 22/69 (31.9) 93/259 (35.9) 1 4/63 (6.3) 13/59 (22.0) 7/68 (10.3) 9/69 (13.0) 33/259 (12.7) 2 24/63 (38.1) 21/59 (35.6) 17/68 (25.0) 24/69 (34.8) 86/259 (33.2) 3 3/63 (4.8) 2/59 (3.4) 7/68 (10.3) 7/69 (10.1) 19/259 (7.3) 4 0/63 (0.0) 2/59 (3.4) 0/68 (0.0) 0/69 (0.0) 2/259 (0.8) 5 1/63 (1.6) 0/59 (0.0) 0/68 (0.0) 4/69 (5.8) 5/259 (1.9) 6 0/63 (0.0) 0/59 (0.0) 0/68 (0.0) 0/69 (0.0) 0/259 (0.0) 7 0/63 (0.0) 0/59 (0.0) 2/68 (2.9) 0/69 (0.0) 2/259 (0.8) 8 2/63 (3.2) 0/59 (0.0) 2/68 (2.9) 2/69 (2.9) 6/259 (2.3) 9 0/63 (0.0) 0/59 (0.0) 1/68 (1.5) 0/69 (0.0) 1/259 (0.4)

10 4/63 (6.3) 4/59 (6.8) 3/68 (4.4) 1/69 (1.4) 12/259 (4.6) Missing 10 14 4 6 34

Pairwise comparisons:

Day 3 Pairwise comparison Odds ratio (95% CI)a

MOV 200 mg vs. Placebo 1.20 (0.50, 2.88)

MOV 400 mg vs. Placebo 1.00 (0.42, 2.39)

MOV 800 mg vs. Placebo 0.90 (0.37, 2.20)

MOV 800 mg vs. MOV 200 mg 0.71 (0.27, 1.87)

MOV 800 mg vs. MOV 400 mg 0.89 (0.34, 2.33)

MOV 400 mg vs. MOV 200 mg 0.81 (0.31, 2.08)


EOT (day 5)

Pairwise comparison Odds ratio (95% CI)a MOV 200 mg vs. Placebo 0.77 (0.36, 1.64)

MOV 400 mg vs. Placebo 0.78 (0.37, 1.64)

MOV 800 mg vs. Placebo 0.52 (0.24, 1.13)

MOV 800 mg vs. MOV 200 mg 0.63 (0.28, 1.43)

MOV 800 mg vs. MOV 400 mg 0.66 (0.30, 1.46)

MOV 400 mg vs. MOV 200 mg 1.00 (0.45, 2.18)


MOV 200 mg vs. Placebo 1.18 (0.60, 2.29)

MOV 400 mg vs. Placebo 0.90 (0.46, 1.75)

MOV 800 mg vs. Placebo 0.95 (0.49, 1.84)

MOV 800 mg vs. MOV 200 mg 0.82 (0.42, 1.59)

MOV 800 mg vs. MOV 400 mg 1.05 (0.54, 2.05)

MOV 400 mg vs. MOV 200 mg 0.77 (0.39, 1.51)

Day 15 Pairwise comparison Odds ratio (95% CI)a MOV 200 mg vs. Placebo 1.24 (0.55, 2.82)

MOV 400 mg vs. Placebo 1.37 (0.58, 3.21)

MOV 800 mg vs. Placebo 0.82 (0.38, 1.78)

MOV 800 mg vs. MOV 200 mg 0.66 (0.30, 1.48)

MOV 800 mg vs. MOV 400 mg 0.60 (0.26, 1.40)

MOV 400 mg vs. MOV 200 mg 1.10 (0.45, 2.66)


MOV 400 mg vs. Placebo 0.97 (0.31, 3.06)

MOV 800 mg vs. Placebo 0.79 (0.27, 2.31)

MOV 800 mg vs. MOV 200 mg 0.92 (0.31, 2.70)

MOV 800 mg vs. MOV 400 mg 0.82 (0.27, 2.50)

MOV 400 mg vs. MOV 200 mg 1.13 (0.36, 3.58)


aAnalyses are based on the proportional odds model with WHO-11 score categories as the response variable. Due to sparse data, the final model includes only treatment as covariate. CIs are based on Wald Chi-Squire Test. Odds ratios greater than 1 indicate a more favorable outcome for the first treatment listed.

CI, confidence interval. EOT, end of treatment. m, number of participants with non-missing ordinal scale at the time point assessed. MOV, molnupiravir. n, number of participants in each subcategory.

Day 3 includes post-baseline records up to day 4 relative to randomization. EOT (day 5) includes post-baseline records from day 5 (relative to randomization) up to day 7. End of treatment visits occurring earlier than day 5 (relative to randomization) are included in the day 3 visit. For the proportional odds model, the score categories were collapsed into 3 levels as follows: 0 to 3 (uninfected or ambulatory mild disease) vs. 4,5 (hospitalized: moderate disease) vs. 6 to 10 (hospitalized: severe disease or dead).


Table S12: Changes in the Pulmonary ordinal outcome over time (modified intent-to-treat population)

The Pulmonary Score is a 7-point ordinal scale (ranging from 1 through 7) that focuses on the respiratory sequelae of Covid-19 (based on oxygen requirements), as developed for the NAIDS and NIH Therapeutics for Inpatients with Covid-19 (TICO) protocol.2 The minimally important difference is not known. Scores are assigned as follows:

Score 1: Can independently undertake usual personal activities with minimal or no symptoms.

Score 2: Symptomatic and currently unable to independently undertake usual personal activities.

Score 3: Supplemental oxygen (<4 liters/min or <4 liters/min above premorbid requirements).

Score 4: Supplemental oxygen (≥4 liters/min or ≥4 liters/min above premorbid requirements, but not high-flow oxygen).

Score 5: Non-invasive assisted ventilation or high-flow oxygen.

Score 6: Invasive assisted ventilation, extra-corporeal membrane oxygenation or mechanical circulatory support.

Score 7: Death.


Baseline 1 34/72 (47.2) 19/72 (26.4) 25/72 (34.7) 21/74 (28.4) 99/290 (34.1) 2 11/72 (15.3) 13/72 (18.1) 9/72 (12.5) 13/74 (17.6) 46/290 (15.9) 3 19/72 (26.4) 20/72 (27.8) 15/72 (20.8) 21/74 (28.4) 75/290 (25.9) 4 8/72 (11.1) 17/72 (23.6) 21/72 (29.2) 13/74 (17.6) 59/290 (20.3) 5 0/72 (0.0) 3/72 (4.2) 2/72 (2.8) 6/74 (8.1) 11/290 (3.8) 6 0/72 (0.0) 0/72 (0.0) 0/72 (0.0) 0/74 (0.0) 0/290 (0.0) 7 0/72 (0.0) 0/72 (0.0) 0/72 (0.0) 0/74 (0.0) 0/290 (0.0)

Missing 1 1 0 1 3 Day 3 1 25/72 (34.7) 20/72 (27.8) 21/72 (29.2) 16/73 (21.9) 82/289 (28.4)

2 2/72 (2.8) 7/72 (9.7) 0/72 (0.0) 7/73 (9.6) 16/289 (5.5) 3 21/72 (29.2) 20/72 (27.8) 23/72 (31.9) 25/73 (34.2) 89/289 (30.8) 4 16/72 (22.2) 16/72 (22.2) 19/72 (26.4) 14/73 (19.2) 65/289 (22.5) 5 7/72 (9.7) 9/72 (12.5) 6/72 (8.3) 10/73 (13.7) 32/289 (11.1) 6 1/72 (1.4) 0/72 (0.0) 3/72 (4.2) 1/73 (1.4) 5/289 (1.7) 7 0/72 (0.0) 0/72 (0.0) 0/72 (0.0) 0/73 (0.0) 0/289 (0.0)

Missing 1 1 0 2 4


EOT (day 5)

1 30/71 (42.3) 22/68 (32.4) 26/70 (37.1) 27/70 (38.6) 105/279 (37.6) 2 6/71 (8.5) 5/68 (7.4) 4/70 (5.7) 4/70 (5.7) 19/279 (6.8) 3 17/71 (23.9) 18/68 (26.5) 15/70 (21.4) 16/70 (22.9) 66/279 (23.7) 4 10/71 (14.1) 14/68 (20.6) 14/70 (20.0) 14/70 (20.0) 52/279 (18.6) 5 7/71 (9.9) 8/68 (11.8) 8/70 (11.4) 8/70 (11.4) 31/279 (11.1) 6 1/71 (1.4) 1/68 (1.5) 3/70 (4.3) 1/70 (1.4) 6/279 (2.2) 7 0/71 (0.0) 0/68 (0.0) 0/70 (0.0) 0/70 (0.0) 0/279 (0.0)

Missing 2 5 2 5 14 Day 10 1 44/68 (64.7) 39/64 (60.9) 33/67 (49.3) 38/70 (54.3) 154/269 (57.2)

2 4/68 (5.9) 4/64 (6.3) 4/67 (6.0) 5/70 (7.1) 17/269 (6.3) 3 8/68 (11.8) 8/64 (12.5) 14/67 (20.9) 10/70 (14.3) 40/269 (14.9) 4 5/68 (7.4) 7/64 (10.9) 8/67 (11.9) 10/70 (14.3) 30/269 (11.2) 5 4/68 (5.9) 3/64 (4.7) 5/67 (7.5) 4/70 (5.7) 16/269 (5.9) 6 3/68 (4.4) 0/64 (0.0) 3/67 (4.5) 3/70 (4.3) 9/269 (3.3) 7 0/68 (0.0) 3/64 (4.7) 0/67 (0.0) 0/70 (0.0) 3/269 (1.1)

Missing 5 9 5 5 24 Day 15 1 45/67 (67.2) 44/62 (71.0) 41/68 (60.3) 42/71 (59.2) 172/268 (64.2)

2 7/67 (10.4) 2/62 (3.2) 2/68 (2.9) 5/71 (7.0) 16/268 (6.0) 3 6/67 (9.0) 6/62 (9.7) 14/68 (20.6) 10/71 (14.1) 36/268 (13.4) 4 3/67 (4.5) 5/62 (8.1) 3/68 (4.4) 6/71 (8.5) 17/268 (6.3) 5 2/67 (3.0) 1/62 (1.6) 0/68 (0.0) 4/71 (5.6) 7/268 (2.6) 6 4/67 (6.0) 1/62 (1.6) 7/68 (10.3) 3/71 (4.2) 15/268 (5.6) 7 0/67 (0.0) 3/62 (4.8) 1/68 (1.5) 1/71 (1.4) 5/268 (1.9)

Missing 6 11 4 4 25 Day 29 1 46/63 (73.0) 47/59 (79.7) 47/69 (68.1) 49/69 (71.0) 189/260 (72.7)

2 2/63 (3.2) 2/59 (3.4) 2/69 (2.9) 5/69 (7.2) 11/260 (4.2) 3 4/63 (6.3) 5/59 (8.5) 9/69 (13.0) 7/69 (10.1) 25/260 (9.6) 4 5/63 (7.9) 1/59 (1.7) 3/69 (4.3) 5/69 (7.2) 14/260 (5.4) 5 0/63 (0.0) 0/59 (0.0) 0/69 (0.0) 0/69 (0.0) 0/260 (0.0) 6 2/63 (3.2) 0/59 (0.0) 5/69 (7.2) 2/69 (2.9) 9/260 (3.5) 7 4/63 (6.3) 4/59 (6.8) 3/69 (4.3) 1/69 (1.4) 12/260 (4.6)

Missing 10 14 3 6 33




MOV 400 mg vs. Placebo 1.18 (0.66, 2.12)

MOV 800 mg vs. Placebo 0.97 (0.54, 1.75)

MOV 800 mg vs. MOV 200 mg 0.76 (0.42, 1.37)

MOV 800 mg vs. MOV 400 mg 0.85 (0.47, 1.52)

MOV 400 mg vs. MOV 200 mg 0.89 (0.50, 1.60)

EOT (day 5)


MOV 400 mg vs. Placebo 0.86 (0.47, 1.57)

MOV 800 mg vs. Placebo 0.89 (0.49, 1.62)

MOV 800 mg vs. MOV 200 mg 0.71 (0.39, 1.29)

MOV 800 mg vs. MOV 400 mg 1.03 (0.57, 1.87)

MOV 400 mg vs. MOV 200 mg 0.67 (0.37, 1.22)


MOV 400 mg vs. Placebo 1.27 (0.66, 2.44)

MOV 800 mg vs. Placebo 0.85 (0.45, 1.59)

MOV 800 mg vs. MOV 200 mg 0.57 (0.29, 1.10)

MOV 800 mg vs. MOV 400 mg 0.67 (0.35, 1.29)

MOV 400 mg vs. MOV 200 mg 0.86 (0.43, 1.70)


MOV 400 mg vs. Placebo 1.55 (0.77, 3.14)

MOV 800 mg vs. Placebo 1.01 (0.53, 1.94)

MOV 800 mg vs. MOV 200 mg 0.68 (0.34, 1.36)

MOV 800 mg vs. MOV 400 mg 0.66 (0.33, 1.35)

MOV 400 mg vs. MOV 200 mg 1.08 (0.52, 2.24)



MOV 400 mg vs. Placebo 1.50 (0.67, 3.37)

MOV 800 mg vs. Placebo 0.79 (0.39, 1.61)

MOV 800 mg vs. MOV 200 mg 0.83 (0.40, 1.73)

MOV 800 mg vs. MOV 400 mg 0.55 (0.25, 1.22)

MOV 400 mg vs. MOV 200 mg 1.48 (0.64, 3.42)

aAnalyses are based on the proportional odds model with Pulmonary+ score categories as the response variable. Due to sparse data, the final model includes only treatment as covariate. CIs are based on Wald Chi-Squire Test. Odds ratios greater than 1 indicate a more favorable outcome for the first treatment listed.


Day 3 includes post-baseline records up to day 4 relative to randomization. EOT (day 5) includes post-baseline records from day 5 (relative to randomization) up to day 7. End of treatment visits occurring earlier than day 5 (relative to randomization) are included in the day 3 visit.


Table S13: Changes in the Pulmonary+ ordinal outcome over time (modified intent-to-treat population)

The Pulmonary+ Score is a 7-point ordinal scale (ranging from 1 through 7) that captures the range of disease severity (including coagulation-related complications and respiratory dysfunction) in hospitalized patients with Covid-19, as developed for the NAIDS and NIH Therapeutics for Inpatients with Covid-19 (TICO) protocol.2 The minimally important difference is not known. Scores are assigned as follows:

Score 1: Can independently undertake usual personal activities with minimal or no symptoms.

Score 2: Symptomatic and currently unable to independently undertake usual personal activities.

Score 3: Supplemental oxygen (<4 liters/min or <4 liters/min above premorbid requirements).

Score 4: Supplemental oxygen (≥4 liters/min or ≥4 liters/min above premorbid requirements, but not high-flow oxygen) or any of the following: stroke (NIH Stroke Scale/Score ≤14), meningitis, encephalitis, myelitis, myocardial ischemia, myocarditis, pericarditis, symptomatic congestive heart failure, or arterial or deep venous thrombosis.

Score 5: Non-invasive assisted ventilation or high-flow oxygen, or signs and symptoms of an acute stroke (NIH Stroke Scale/Score >14).

Score 6: Invasive assisted ventilation, extra-corporeal membrane oxygenation or mechanical circulatory support, or vasopressor administration or renal replacement therapy.

Score 7: Death.


Baseline 1 34/72 (47.2) 19/72 (26.4) 25/72 (34.7) 21/74 (28.4) 99/290 (34.1) 2 11/72 (15.3) 13/72 (18.1) 9/72 (12.5) 13/74 (17.6) 46/290 (15.9) 3 18/72 (25.0) 20/72 (27.8) 15/72 (20.8) 21/74 (28.4) 74/290 (25.5) 4 8/72 (11.1) 17/72 (23.6) 21/72 (29.2) 13/74 (17.6) 59/290 (20.3) 5 0/72 (0.0) 3/72 (4.2) 2/72 (2.8) 6/74 (8.1) 11/290 (3.8) 6 1/72 (1.4) 0/72 (0.0) 0/72 (0.0) 0/74 (0.0) 1/290 (0.3) 7 0/72 (0.0) 0/72 (0.0) 0/72 (0.0) 0/74 (0.0) 0/290 (0.0)

Missing 1 1 0 1 3 Day 3 1 25/72 (34.7) 20/72 (27.8) 21/72 (29.2) 16/73 (21.9) 82/289 (28.4)

2 2/72 (2.8) 7/72 (9.7) 0/72 (0.0) 7/73 (9.6) 16/289 (5.5) 3 20/72 (27.8) 20/72 (27.8) 23/72 (31.9) 25/73 (34.2) 88/289 (30.4) 4 16/72 (22.2) 16/72 (22.2) 19/72 (26.4) 14/73 (19.2) 65/289 (22.5) 5 7/72 (9.7) 9/72 (12.5) 6/72 (8.3) 10/73 (13.7) 32/289 (11.1) 6 2/72 (2.8) 0/72 (0.0) 3/72 (4.2) 1/73 (1.4) 6/289 (2.1) 7 0/72 (0.0) 0/72 (0.0) 0/72 (0.0) 0/73 (0.0) 0/289 (0.0)

Missing 1 1 0 2 4


EOT (day 5) 1 30/71 (42.3) 22/68 (32.4) 26/70 (37.1) 27/70 (38.6) 105/279 (37.6) 2 6/71 (8.5) 5/68 (7.4) 4/70 (5.7) 4/70 (5.7) 19/279 (6.8) 3 16/71 (22.5) 18/68 (26.5) 15/70 (21.4) 16/70 (22.9) 65/279 (23.3) 4 10/71 (14.1) 14/68 (20.6) 14/70 (20.0) 14/70 (20.0) 52/279 (18.6) 5 7/71 (9.9) 8/68 (11.8) 8/70 (11.4) 8/70 (11.4) 31/279 (11.1) 6 2/71 (2.8) 1/68 (1.5) 3/70 (4.3) 1/70 (1.4) 7/279 (2.5) 7 0/71 (0.0) 0/68 (0.0) 0/70 (0.0) 0/70 (0.0) 0/279 (0.0)

Missing 2 5 2 5 14 Day 10 1 44/68 (64.7) 39/64 (60.9) 33/67 (49.3) 38/70 (54.3) 154/269 (57.2)

2 4/68 (5.9) 4/64 (6.3) 4/67 (6.0) 5/70 (7.1) 17/269 (6.3) 3 8/68 (11.8) 8/64 (12.5) 14/67 (20.9) 10/70 (14.3) 40/269 (14.9) 4 4/68 (5.9) 7/64 (10.9) 8/67 (11.9) 10/70 (14.3) 29/269 (10.8) 5 4/68 (5.9) 3/64 (4.7) 4/67 (6.0) 4/70 (5.7) 15/269 (5.6) 6 4/68 (5.9) 0/64 (0.0) 4/67 (6.0) 3/70 (4.3) 11/269 (4.1) 7 0/68 (0.0) 3/64 (4.7) 0/67 (0.0) 0/70 (0.0) 3/269 (1.1)

Missing 5 9 5 5 24 Day 15 1 45/67 (67.2) 44/62 (71.0) 41/68 (60.3) 42/71 (59.2) 172/268 (64.2)

2 7/67 (10.4) 2/62 (3.2) 2/68 (2.9) 5/71 (7.0) 16/268 (6.0) 3 6/67 (9.0) 6/62 (9.7) 14/68 (20.6) 10/71 (14.1) 36/268 (13.4) 4 3/67 (4.5) 5/62 (8.1) 3/68 (4.4) 6/71 (8.5) 17/268 (6.3) 5 2/67 (3.0) 1/62 (1.6) 0/68 (0.0) 4/71 (5.6) 7/268 (2.6) 6 4/67 (6.0) 1/62 (1.6) 7/68 (10.3) 3/71 (4.2) 15/268 (5.6) 7 0/67 (0.0) 3/62 (4.8) 1/68 (1.5) 1/71 (1.4) 5/268 (1.9)

Missing 6 11 4 4 25 Day 29 1 46/63 (73.0) 47/59 (79.7) 47/69 (68.1) 49/69 (71.0) 189/260 (72.7)

2 2/63 (3.2) 2/59 (3.4) 2/69 (2.9) 5/69 (7.2) 11/260 (4.2) 3 4/63 (6.3) 5/59 (8.5) 9/69 (13.0) 7/69 (10.1) 25/260 (9.6) 4 5/63 (7.9) 1/59 (1.7) 3/69 (4.3) 5/69 (7.2) 14/260 (5.4) 5 0/63 (0.0) 0/59 (0.0) 0/69 (0.0) 0/69 (0.0) 0/260 (0.0) 6 2/63 (3.2) 0/59 (0.0) 5/69 (7.2) 2/69 (2.9) 9/260 (3.5) 7 4/63 (6.3) 4/59 (6.8) 3/69 (4.3) 1/69 (1.4) 12/260 (4.6)

Missing 10 14 3 6 33




MOV 200 mg vs. Placebo 1.25 (0.70, 2.25)

MOV 400 mg vs. Placebo 1.18 (0.66, 2.12)

MOV 800 mg vs. Placebo 0.97 (0.54, 1.75)

MOV 800 mg vs. MOV 200 mg 0.80 (0.44, 1.44)

MOV 800 mg vs. MOV 400 mg 0.85 (0.47, 1.52)

MOV 400 mg vs. MOV 200 mg 0.93 (0.52, 1.67)

EOT (day 5)


MOV 400 mg vs. Placebo 0.86 (0.47, 1.57)

MOV 800 mg vs. Placebo 0.89 (0.49, 1.62)

MOV 800 mg vs. MOV 200 mg 0.74 (0.41, 1.35)

MOV 800 mg vs. MOV 400 mg 1.03 (0.57, 1.87)

MOV 400 mg vs. MOV 200 mg 0.70 (0.38, 1.28)


MOV 400 mg vs. Placebo 1.27 (0.66, 2.44)

MOV 800 mg vs. Placebo 0.84 (0.45, 1.58)

MOV 800 mg vs. MOV 200 mg 0.57 (0.30, 1.11)

MOV 800 mg vs. MOV 400 mg 0.66 (0.34, 1.28)

MOV 400 mg vs. MOV 200 mg 0.87 (0.44, 1.72)


MOV 400 mg vs. Placebo 1.55 (0.77, 3.14)

MOV 800 mg vs. Placebo 1.01 (0.53, 1.94)

MOV 800 mg vs. MOV 200 mg 0.68 (0.34, 1.36)

MOV 800 mg vs. MOV 400 mg 0.66 (0.33, 1.35)

MOV 400 mg vs. MOV 200 mg 1.08 (0.52, 2.24)



MOV 400 mg vs. Placebo 1.50 (0.67, 3.37)

MOV 800 mg vs. Placebo 0.79 (0.39, 1.61)

MOV 800 mg vs. MOV 200 mg 0.83 (0.40, 1.73)

MOV 800 mg vs. MOV 400 mg 0.55 (0.25, 1.22)

MOV 400 mg vs. MOV 200 mg 1.48 (0.64, 3.42)

aAnalyses are based on the proportional odds model with Pulmonary+ score categories as the response variable. Due to sparse data, the final model includes only treatment as covariate. CIs are based on Wald Chi-Squire Test. Odds ratios greater than 1 indicate a more favorable outcome for the first treatment listed.


Day 3 includes post-baseline records up to day 4 relative to randomization. EOT (day 5) includes post-baseline records from day 5 (relative to randomization) up to day 7. End of treatment visits occurring earlier than day 5 (relative to randomization) are included in the day 3 visit.


Table S14: National Early Warning Score at end-of-treatment (modified intent-to-treat population)

The National Early Warning Score (NEWS) is a 21-point ordinal aggregate score (ranging from 0 through 20) intended to assess the severity of acute illness and early detection of clinical deterioration to allow for initiation of a timely and appropriate clinical response.3 An aggregate score of 5 or 6 (medium) or any single parameter score of 3 indicates the need for urgent clinical review, and an aggregate score of ≥7 (high) indicates the need for emergency clinical review. Aggregate scores of ≤4 are considered low, indicating the need for prompt assessment by a registered nurse. Aggregate scores are calculated as follows:

Physiological parameter Point value Physiological parameter Point value

Respiration rate (breaths per minute) Systolic blood pressure (mmHg) ≤8 3 ≤90 3

9-11 1 91-100 2

12-20 0 101-110 1

21-24 2 111-219 0

≥25 3 ≥220 3

Oxygen saturation (%) Heart rate (beats per minute) ≤91 3 ≤40 3

92-93 2 41-50 1

94-95 1 51-90 0

≥96 0 91-110 1

Any supplemental oxygen 111-130 2

Yes 2 ≥131 3

No 0 Level of consciousness Temperature (°C) Alert 0

≤35 0 3 Voice/pain/unresponsive 3

35.1-36.0 1

36.1-38.0 0

38.1-39.0 1

≥39.1 2



Baseline

Low 54/69 (78.3) 42/68 (61.8) 47/69 (68.1) 51/74 (68.9) 194/280 (69.3)

Medium 8/69 (11.6) 22/68 (32.4) 17/69 (24.6) 18/74 (24.3) 65/280 (23.2)

High 7/69 (10.1) 4/68 (5.9) 5/69 (7.2) 5/74 (6.8) 21/280 (7.5)

Missing 4 5 3 1 13

EOT (day 5)

Low 57/70 (81.4) 45/64 (70.3) 52/69 (75.4) 55/69 (79.7) 209/272 (76.8)

Medium 8/70 (11.4) 8/64 (12.5) 9/69 (13.0) 11/69 (15.9) 36/272 (13.2)

High 5/70 (7.1) 11/64 (17.2) 8/69 (11.6) 3/69 (4.3) 27/272 (9.9)

Missing 3 9 3 6 21


MOV 400 mg vs. Placebo 0.54 (0.25, 1.19)

MOV 800 mg vs. Placebo 0.73 (0.33, 1.61)

MOV 800 mg vs. MOV 200 mg 0.69 (0.31, 1.54)

MOV 800 mg vs. MOV 400 mg 1.34 (0.63, 2.85)

MOV 400 mg vs. MOV 200 mg 0.52 (0.23, 1.15)

aAnalyses are based on the proportional odds model with NEWS categories as the response variable. Due to sparse data, the final model includes only treatment as covariate. CIs are based on Wald Chi-Squire Test. Odds ratios greater than 1 indicate a more favorable outcome for the first treatment listed.


EOT (day 5) includes post-baseline records from day 5 (relative to randomization) up to day 7.


Table S15: SARS-CoV-2 viral RNA error rates (nasopharyngeal sample) as determined by next-generation sequencing (modified intent-to-treat population)

(A) Mean viral RNA error rate compared to baseline

Visit Molnupiravir 200 mg Molnupiravir 400 mg Molnupiravir 800 mg Placebo n Mean change (SD) n Mean change (SD) n Mean change (SD) n Mean change (SD)

Mean SARS-CoV-2 RNA error rate per 10,000 nucleotides with an allele frequency ≥2%

Day 3 19 2.6 (2.32) 25 5.0 (9.87) 18 2.4 (2.58) 22 2.2 (3.44)

EOT (Day 5) 12 4.8 (4.51) 13 3.8 (4.23) 13 5.9 (8.94) 10 2.8 (3.31)

EOT, end of treatment. n, number of participants with baseline and at least one postbaseline test result in the specified analysis window. SD, standard deviation.

The error rate is calculated as the number of nucleotide mutations compared to the baseline sequence per 10,000 nucleotides (with an allele frequency ≥2%) across the entire viral genome (30,000 nucleotides).

Day 3 includes post-baseline records up to day 4 relative to randomization. EOT (day 5) includes post-baseline records from day 5 (relative to randomization) up to day 7. EOT visits occurring earlier than day 5 (relative to randomization) are included in the day 3 visit.


(B) Participants with viral RNA error rates >3, >6, or >9 per 10,000 bases compared to baseline by visit

Visit Molnupiravir 200 mg

Molnupiravir 400 mg

Molnupiravir 800 mg

Placebo

n/m (%) n/m (%) n/m (%) n/m (%)

Number of SARS-CoV-2 RNA errors >3 compared to baseline sample (per 10,000 nucleotides)

Day 3 4/19 (21.1) 12/25 (48.0) 4/18 (22.2) 2/22 (9.1)

EOT (Day 5) 7/12 (58.3) 5/13 (38.5) 5/13 (38.5) 2/10 (20.0)


Day 3 1/19 (5.3) 4/25 (16.0) 2/18 (11.1) 1/22 (4.5)

EOT (Day 5) 5/12 (41.7) 3/13 (23.1) 3/13 (23.1) 1/10 (10.0)


Day 3 1/19 (5.3) 2/25 (8.0) 1/18 (5.6) 1/22 (4.5)

EOT (Day 5) 2/12 (16.7) 1/13 (7.7) 3/13 (23.1) 1/10 (10.0)

EOT, end of treatment. m, number of participants with a baseline and at least one postbaseline test result in the specified analysis window. n, number of participants meeting the specified threshold of mutations. SD, standard deviation.

The error rate is calculated as the number of nucleotide mutations compared to the baseline sequence per 10,000 nucleotides (with an allele frequency ≥2%) across the entire viral genome (30,000 nucleotides).

Day 3 includes post-baseline records up to day 4 relative to randomization. EOT (day 5) includes post-baseline records from day 5 (relative to randomization) up to day 7. EOT visits occurring earlier than day 5 (relative to randomization) are included in the day 3 visit.


Table S16: Participants with undetectable SARS-CoV-2 RNA levels (nasopharyngeal sample) over time (modified intent-to-treat population)

Visit Molnupiravir 200 mg Molnupiravir 400 mg Molnupiravir 800 mg Placebo n/m % (95% CI)a n/m % (95% CI)a n/m % (95% CI)a n/m % (95% CI)a

All participants Baseline 0/69 0.0 (0.0, 5.2) 0/69 0.0 (0.0, 5.2) 0/63 0.0 (0.0, 5.7) 0/65 0.0 (0.0, 5.5) Day 3 7/64 10.9 (4.5, 21.2) 1/62 1.6 (0.0, 8.7) 3/60 5.0 (1.0, 13.9) 4/61 6.6 (1.8, 15.9) EOT (day 5) 12/66 18.2 (9.8, 29.6) 6/59 10.2 (3.8, 20.8) 6/58 10.3 (3.9, 21.2) 10/54 18.5 (9.3, 31.4) Day 10 17/55 30.9 (19.1, 44.8) 19/56 33.9 (21.8, 47.8) 18/57 31.6 (19.9, 45.2) 14/57 24.6 (14.1, 37.8) Day 15 33/60 55.0 (41.6, 67.9) 21/50 42.0 (28.2, 56.8) 26/52 50.0 (35.8, 64.2) 26/60 43.3 (30.6, 56.8)

Day 29 47/55 85.5 (73.3, 93.5) 37/51 72.5 (58.3, 84.1) 44/53 83.0 (70.2, 91.9) 44/54 81.5 (68.6, 90.7)

Participants with baseline RNA titer ≤106 copies/mlb Baseline 0/47 0.0 (0.0, 7.5) 0/42 0.0 (0.0, 8.4) 0/46 0.0 (0.0, 7.7) 0/46 0.0 (0.0, 7.7) Day 3 6/44 13.6 (5.2, 27.4) 1/36 2.8 (0.1, 14.5) 2/43 4.7 (0.6, 15.8) 4/43 9.3 (2.6, 22.1) EOT (day 5) 10/44 22.7 (11.5, 37.8) 5/35 14.3 (4.8, 30.3) 6/41 14.6 (5.6, 29.2) 9/39 23.1 (11.1, 39.3) Day 10 16/37 43.2 (27.1, 60.5) 17/37 45.9 (29.5, 63.1) 15/42 35.7 (21.6, 52.0) 13/41 31.7 (18.1, 48.1) Day 15 25/41 61.0 (44.5, 75.8) 16/31 51.6 (33.1, 69.8) 22/38 57.9 (40.8, 73.7) 21/43 48.8 (33.3, 64.5)

Day 29 35/41 85.4 (70.8, 94.4) 25/33 75.8 (57.7, 88.9) 33/40 82.5 (67.2, 92.7) 33/38 86.8 (71.9, 95.6)

Participants with baseline RNA titer >106 copies/mlb Baseline 0/19 0.0 (0.0, 17.6) 0/26 0.0 (0.0, 13.2) 0/17 0.0 (0.0, 19.5) 0/19 0.0 (0.0, 17.6) Day 3 0/17 0.0 (0.0, 19.5) 0/25 0.0 (0.0, 13.7) 1/17 5.9 (0.1, 28.7) 0/18 0.0 (0.0, 18.5) EOT (day 5) 0/19 0.0 (0.0, 17.6) 1/23 4.3 (0.1, 21.9) 0/17 0.0 (0.0, 19.5) 1/15 6.7 (0.2, 31.9) Day 10 0/17 0.0 (0.0, 19.5) 2/18 11.1 (1.4, 34.7) 3/15 20.0 (4.3, 48.1) 1/16 6.3 (0.2, 30.2) Day 15 5/16 31.3 (11.0, 58.7) 5/18 27.8 (9.7, 53.5) 4/14 28.6 (8.4, 58.1) 5/17 29.4 (10.3, 56.0)

Day 29 10/12 83.3 (51.6, 97.9) 11/17 64.7 (38.3, 85.8) 11/13 84.6 (54.6, 98.1) 11/16 68.8 (41.3, 89.0)

Participants with time from symptom onset prior to randomization ≤5 days Baseline 0/17 0.0 (0.0, 19.5) 0/14 0.0 (0.0, 23.2) 0/11 0.0 (0.0, 28.5) 0/15 0.0 (0.0, 21.8) Day 3 0/15 0.0 (0.0, 21.8) 1/13 7.7 (0.2, 36.0) 0/11 0.0 (0.0, 28.5) 0/13 0.0 (0.0, 24.7) EOT (day 5) 1/17 5.9 (0.1, 28.7) 2/11 18.2 (2.3, 51.8) 1/11 9.1 (0.2, 41.3) 1/12 8.3 (0.2, 38.5) Day 10 2/14 14.3 (1.8, 42.8) 2/10 20.0 (2.5, 55.6) 4/11 36.4 (10.9, 69.2) 0/12 0.0 (0.0, 26.5) Day 15 6/15 40.0 (16.3, 67.7) 3/8 37.5 (8.5, 75.5) 6/10 60.0 (26.2, 87.8) 3/12 25.0 (5.5, 57.2)

Day 29 8/11 72.7 (39.0, 94.0) 6/8 75.0 (34.9, 96.8) 8/11 72.7 (39.0, 94.0) 11/13 84.6 (54.6, 98.1)


Participants with time from symptom onset prior to randomization >5 days Baseline 0/52 0.0 (0.0, 6.8) 0/55 0.0 (0.0, 6.5) 0/52 0.0 (0.0, 6.8) 0/50 0.0 (0.0, 7.1) Day 3 7/49 14.3 (5.9, 27.2) 0/49 0.0 (0.0, 7.3) 3/49 6.1 (1.3, 16.9) 4/48 8.3 (2.3, 20.0) EOT (day 5) 11/49 22.4 (11.8, 36.6) 4/48 8.3 (2.3, 20.0) 5/47 10.6 (3.5, 23.1) 9/42 21.4 (10.3, 36.8) Day 10 15/41 36.6 (22.1, 53.1) 17/46 37.0 (23.2, 52.5) 14/46 30.4 (17.7, 45.8) 14/45 31.1 (18.2, 46.6) Day 15 27/45 60.0 (44.3, 74.3) 18/42 42.9 (27.7, 59.0) 20/42 47.6 (32.0, 63.6) 23/48 47.9 (33.3, 62.8) Day 29 39/44 88.6 (75.4, 96.2) 31/43 72.1 (56.3, 84.7) 36/42 85.7 (71.5, 94.6) 33/41 80.5 (65.1, 91.2)

Prior/concomitant remdesivir use Baseline 0/18 0.0 (0.0, 18.5) 0/17 0.0 (0.0, 19.5) 0/17 0.0 (0.0, 19.5) 0/17 0.0 (0.0, 19.5) Day 3 3/16 18.8 (4.0, 45.6) 0/15 0.0 (0.0, 21.8) 1/17 5.9 (0.1, 28.7) 2/16 12.5 (1.6, 38.3) EOT (day 5) 5/17 29.4 (10.3, 56.0) 4/13 30.8 (9.1, 61.4) 2/16 12.5 (1.6, 38.3) 5/16 31.3 (11.0, 58.7) Day 10 5/15 33.3 (11.8, 61.6) 7/15 46.7 (21.3, 73.4) 5/16 31.3 (11.0, 58.7) 8/15 53.3 (26.6, 78.7) Day 15 7/16 43.8 (19.8, 70.1) 6/13 46.2 (19.2, 74.9) 8/16 50.0 (24.7, 75.3) 12/16 75.0 (47.6, 92.7)

Day 29 12/15 80.0 (51.9, 95.7) 11/15 73.3 (44.9, 92.2) 13/15 86.7 (59.5, 98.3) 12/14 85.7 (57.2, 98.2)

No prior/concomitant remdesivir use Baseline 0/51 0.0 (0.0, 7.0) 0/52 0.0 (0.0, 6.8) 0/46 0.0 (0.0, 7.7) 0/48 0.0 (0.0, 7.4) Day 3 4/48 8.3 (2.3, 20.0) 1/47 2.1 (0.1, 11.3) 2/43 4.7 (0.6, 15.8) 2/45 4.4 (0.5, 15.1) EOT (day 5) 7/49 14.3 (5.9, 27.2) 2/46 4.3 (0.5, 14.8) 4/42 9.5 (2.7, 22.6) 5/38 13.2 (4.4, 28.1) Day 10 12/40 30.0 (16.6, 46.5) 12/41 29.3 (16.1, 45.5) 13/41 31.7 (18.1, 48.1) 6/42 14.3 (5.4, 28.5) Day 15 26/44 59.1 (43.2, 73.7) 15/37 40.5 (24.8, 57.9) 18/36 50.0 (32.9, 67.1) 14/44 31.8 (18.6, 47.6) Day 29 35/40 87.5 (73.2, 95.8) 26/36 72.2 (54.8, 85.8) 31/38 81.6 (65.7, 92.3) 32/40 80.0 (64.4, 90.9)

aThe 95% confidence intervals are based on the Clopper-Pearson method. bThe subgroups are classified based on results from the Q2 SARS-CoV-2 Viral Load Quantitation Assay.

EOT, end of treatment. m, number of participants in each treatment group eligible for this analysis. n, number of participants in each subcategory. Day 3 includes post-baseline records up to day 4 relative to randomization. EOT (day 5) includes post-baseline records from day 5 (relative to randomization) up to day 7. End of treatment visits occurring earlier than day 5 (relative to randomization) are included in the day 3 visit. The qualitative assay used was the Roche Cobas® SARS-CoV-2 real time b-PCR.


Table S17: Mean change in SARS-CoV-2 viral RNA from baseline (nasopharyngeal sample) over time (modified intent-to-treat population with baseline SARS-CoV-2 titer ≥500 copies/mL)

Visit

Molnupiravir 200 mg Molnupiravir 400 mg Molnupiravir 800 mg Placebo n

Baseline mean

Mean changea (SD)

n Baseline

mean Mean changea

(SD) n

Baseline mean

Mean changea (SD)

n Baseline

mean Mean changea

(SD)

SARS-CoV-2 RNA titer (log10 copies/ml) in participants overall Baseline 58 5.34 63 5.55 59 5.04 61 5.15 Day 3 51 5.32 -0.86 (1.277) 58 5.57 -0.86 (1.465) 54 5.13 -0.64 (1.414) 58 5.12 -0.65 (1.470) EOT 55 5.37 -1.28 (1.170) 56 5.52 -1.74 (1.344) 54 5.15 -1.16 (1.380) 50 5.07 -1.24 (1.366) Day 10 49 5.40 -1.43 (1.375) 50 5.38 -1.89 (1.414) 50 5.14 -1.69 (1.433) 52 5.16 -1.68 (1.482) Day 15 51 5.36 -2.28 (1.444) 46 5.44 -2.44 (1.403) 50 4.92 -1.93 (1.450) 54 5.08 -1.89 (1.456)

Day 29 38 5.16 -2.32 (1.420) 39 5.24 -2.32 (1.432) 47 4.93 -2.17 (1.576) 51 5.19 -2.44 (1.487)

SARS-CoV-2 RNA titer (log10 copies/ml) in participants with baseline RNA titer ≤106 copies/ml Baseline 39 4.43 37 4.43 42 4.27 42 4.30 Day 3 34 4.41 -0.51 (0.919) 33 4.37 -0.20 (1.456) 38 4.38 -0.43 (1.291) 40 4.27 -0.51 (1.237) EOT 36 4.40 -0.87 (0.974) 33 4.39 -1.06 (0.876) 37 4.33 -0.72 (1.013) 36 4.31 -0.93 (1.247) Day 10 32 4.41 -1.03 (1.299) 31 4.42 -1.29 (0.986) 35 4.42 -1.23 (1.112) 37 4.40 -1.28 (1.090) Day 15 34 4.43 -1.53 (0.818) 28 4.47 -1.59 (0.882) 37 4.30 -1.40 (1.180) 38 4.29 -1.33 (1.046) Day 29 27 4.44 -1.61 (0.680) 27 4.43 -1.63 (0.957) 34 4.17 -1.41 (1.053) 35 4.39 -1.67 (0.996)

SARS-CoV-2 RNA titer (log10 copies/ml) in participants with baseline RNA titer >106 copies/ml Baseline 19 7.20 26 7.14 17 6.93 19 7.02 Day 3 17 7.14 -1.55 (1.608) 25 7.17 -1.72 (0.957) 16 6.91 -1.14 (1.607) 18 7.00 -0.96 (1.893) EOT 19 7.20 -2.05 (1.148) 23 7.13 -2.71 (1.304) 17 6.93 -2.14 (1.592) 14 7.01 -2.05 (1.363) Day 10 17 7.25 -2.18 (1.220) 19 6.95 -2.87 (1.476) 15 6.81 -2.77 (1.558) 15 7.01 -2.66 (1.869) Day 15 17 7.21 -3.77 (1.267) 18 6.96 -3.76 (0.974) 13 6.70 -3.45 (1.017) 16 6.97 -3.23 (1.450)

Day 29 11 6.93 -4.06 (1.251) 12 7.07 -3.89 (1.025) 13 6.92 -4.17 (0.710) 16 6.92 -4.14 (0.799)

SARS-CoV-2 RNA titer (log10 copies/ml) in participants with time from symptom onset prior to randomization ≤5 days Baseline 17 6.21 13 5.78 11 5.61 15 6.31 Day 3 15 6.13 -1.13 (1.775) 12 5.84 -0.87 (0.832) 11 5.61 -0.83 (1.462) 13 6.37 -0.92 (1.459) EOT 17 6.21 -1.55 (1.148) 10 5.47 -1.78 (1.339) 11 5.61 -1.43 (2.075) 12 6.06 -1.54 (1.794) Day 10 14 6.27 -1.42 (1.682) 9 5.48 -1.64 (1.164) 11 5.61 -2.43 (1.596) 12 6.35 -2.30 (1.742) Day 15 15 6.26 -2.72 (1.758) 8 5.74 -2.86 (1.113) 10 5.44 -2.34 (2.005) 12 6.35 -3.01 (1.446) Day 29 11 5.55 -2.64 (1.734) 6 4.76 -1.83 (0.730) 11 5.61 -2.72 (1.811) 12 6.40 -3.60 (1.672)


SARS-CoV-2 RNA titer (log10 copies/ml) in participants with time from symptom onset prior to randomization >5 days Baseline 41 4.98 50 5.49 48 4.91 46 4.77 Day 3 36 4.98 -0.75 (1.012) 46 5.51 -0.85 (1.597) 43 5.00 -0.59 (1.415) 45 4.76 -0.57 (1.480) EOT 38 4.99 -1.16 (1.176) 46 5.53 -1.73 (1.359) 43 5.03 -1.10 (1.164) 38 4.75 -1.15 (1.216) Day 10 35 5.05 -1.43 (1.260) 41 5.36 -1.94 (1.471) 39 5.00 -1.49 (1.334) 40 4.80 -1.49 (1.364) Day 15 36 4.98 -2.09 (1.275) 38 5.38 -2.35 (1.454) 40 4.79 -1.83 (1.289) 42 4.72 -1.57 (1.308)

Day 29 27 5.00 -2.19 (1.285) 33 5.33 -2.41 (1.516) 36 4.72 -2.00 (1.485) 39 4.81 -2.09 (1.246)

SARS-CoV-2 RNA titer (log10 copies/ml) in participants with prior remdesivir use Baseline 15 4.79 17 5.40 17 4.60 15 4.81 Day 3 12 5.00 -0.46 (1.818) 16 5.33 -0.77 (1.152) 17 4.60 -0.42 (1.535) 14 4.83 -1.02 (1.119) EOT 14 4.83 -0.86 (1.261) 14 5.28 -1.38 (1.208) 17 4.60 -0.62 (1.079) 14 4.86 -1.68 (1.435) Day 10 12 4.90 -1.09 (1.763) 15 5.27 -1.86 (1.421) 13 4.90 -1.59 (1.266) 12 4.93 -1.50 (1.812) Day 15 12 4.97 -1.82 (1.703) 14 5.57 -2.61 (1.655) 15 4.68 -1.63 (1.246) 13 4.81 -1.89 (1.561) Day 29 9 5.06 -2.14 (1.702) 13 5.49 -2.60 (1.389) 13 4.43 -1.62 (1.165) 13 5.02 -2.32 (1.468)

SARS-CoV-2 RNA titer (log10 copies/ml) in participants with no prior remdesivir use Baseline 43 5.53 46 5.60 42 5.21 46 5.26 Day 3 39 5.42 -0.98 (1.060) 42 5.67 -0.89 (1.580) 37 5.37 -0.74 (1.365) 44 5.21 -0.53 (1.557) EOT 41 5.55 -1.42 (1.118) 42 5.59 -1.86 (1.379) 37 5.40 -1.41 (1.443) 36 5.15 -1.07 (1.320) Day 10 37 5.56 -1.54 (1.233) 35 5.43 -1.90 (1.432) 37 5.22 -1.73 (1.502) 40 5.22 -1.73 (1.390) Day 15 39 5.47 -2.42 (1.349) 32 5.39 -2.36 (1.300) 35 5.02 -2.06 (1.528) 41 5.17 -1.89 (1.441) Day 29 29 5.19 -2.38 (1.350) 26 5.12 -2.19 (1.459) 34 5.12 -2.38 (1.675) 38 5.24 -2.49 (1.511)

aMean change from baseline is based on the measurements of participants with values at baseline and at the time point assessed. Baseline measurements are defined as the latest record before first dose for each participant.

EOT, end of treatment. n, number of participants with baseline and at least one postbaseline test result at the time point assessed. SD, standard deviation.

Day 3 includes post-baseline records up to day 4 relative to randomization. EOT (day 5) includes post-baseline records from day 5 (relative to randomization) up to day 7. End of treatment visits occurring earlier than day 5 (relative to randomization) are included in the day 3 visit. The quantitative assay used was the Q2 SARS-CoV-2 Viral Load Quantitation Assay by real time-PCR.


Figure S1: Population pharmacokinetic model-estimated and observed plasma pharmacokinetics of NHC in patients hospitalized for Covid-19 (modified intent-to-treat population of MOVe-IN) compared with healthy volunteers

Mean NHC AUC0-12 ranged from 8260 nmol*h/L (molnupiravir 200 mg) to 31700 nmol*h/L (molnupiravir 800 mg) and mean Cmax from 2540 nmol/L (molnupiravir 200 mg) to 9580 nmol/L (molnupiravir 800 mg).


Figure S2: Disposition of deaths reported in the safety analysis and in the all-cause mortality analysis

MOV, molnupiravir.

Adverse event analyses captured all observed deaths, regardless of timing, resulting from an adverse event. Mortality analyses captured all deaths through day 29 (with imputation as ‘death’ in case of unknown day 29 survival status), regardless of cause.


References 1. WHO Working Group on the Clinical Characterisation and Management of COVID-19 Infection. A

minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis

2020;20:e192-e7.

2. ACTIV-3/TICO LY-CoV555 Study Group, Lundgren JD, Grund B, et al. A Neutralizing Monoclonal

Antibody for Hospitalized Patients with Covid-19. N Engl J Med 2021;384:905-14.

3. Royal College of Physicians. National Early Warning Score (NEWS): standardising the

assessment of acute-illness severity in the NHS. London, UK: Royal College of Physicians; 2012.

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