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Antiviral Nasal Sprays — Human Clinical Trials

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Trials by Ingredient (n = 151)

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Favors treatmentFavors controlMixedNo difference (null)Inconclusive / not assessableResult unknown

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Showing 151 of 151 trials

Nasal spray of an IgM‐like ACE2 fusion protein HH‐120 accelerates SARS‐CoV‐2 clearance: A single‐center propensity score‐matched cohort study
Rui Song et al.. Journal of Medical Virology 95(5) e28805. (2023)
(Extracted from abstract only)
igm-like ace2 fusion protein (hh-120)Nasal spray
Non-Randomized-Comparative
Viral clearance time
Favors treatmentRoB: High
Pharmacokinetic‐based failure of a detergent virucidal for severe acute respiratory syndrome–coronavirus‐2 (SARS‐CoV‐2) nasal infections: A preclinical study and randomized controlled trial
Charles R. Esther et al.. International Forum of Allergy & Rhinology 12(9) 1137-1147. (2022)
baby shampooNasal irrigation
RCTN = 72
SARS-CoV-2 nasal viral load (qRT-PCR Ct value, N1 primer)— Mean difference -5.28 (-9.47–-1.08)
Favors controlRoB: Some Concerns
Tolerance of one‐month intranasal interferon
Scott GM et al.. Journal of Medical Virology 17(2) 99-106. (1985)
leukocyte/lymphoblastoid interferonNasal spray
RCTN = 68
Discontinuation due to upper respiratory symptoms (definite cold or reaction) during treatment
InconclusiveRoB: Some Concerns
Azelastine Nasal Spray for Prevention of SARS-CoV-2 Infections
Thorsten Lehr et al.. JAMA Internal Medicine 185(11) 1309. (2025)
azelastineNasal spray
RCTN = 450
PCR-confirmed SARS-CoV-2 infection (primary endpoint)— Odds ratio 0.31 (0.11–0.87), p=0.02
Favors treatmentRoB: Some Concerns
Otologic Effects of Interferon Beta Serine in Experimental Rhinovirus Colds
Sperber SJ et al.. Archives of Otolaryngology - Head and Neck Surgery 118(9) 933-936. (1992)
interferon beta serineNasal drops
Human-ChallengeN = 40
Laboratory-confirmed RV-39 infection rate
No differenceRoB: Some Concerns
Nasal spray of an IgM-like ACE2 fusion protein HH-120 prevents SARS-CoV-2 infection: Two investigator-initiated postexposure prophylaxis trials
Song et al.. Journal of Medical Virology. (2023)
igm-like ace2 fusion protein (hh-120)Nasal spray
RCT
SARS-CoV-2 infection rate (NS01 trial, continuous close contact)
No differenceRoB: Some Concerns
Phase II Trial of the Impact 0.5% Povidone‐Iodine Nasal Spray (Nasodine®) on Shedding of SARS‐CoV‐2
Peter L. Friedland et al.. The Laryngoscope 134(9) 3947-3952. (2024)
povidone-iodineNasal spray
RCTN = 39
Nasal viral load (log10 TCID50) on Days 2-4 vs baseline (primary endpoint)
Favors treatmentRoB: Some Concerns
Drug resistant rhinoviruses from the nose of experimentally treated volunteers
Dearden C. et al.. Archives of Virology 109(1-2) 71-81. (1989)
r61837Nasal spray
Human-ChallengeN = 46
Virus isolation (positive nasal wash culture)
InconclusiveRoB: High
The Effect of Povidone‐Iodine Nasal Spray on Nasopharyngeal SARS‐CoV‐2 Viral Load: A Randomized Control Trial
Zarabanda D. et al.. The Laryngoscope 132(11) 2089-2095. (2022)
povidone-iodineNasal spray
RCTN = 35
Nasopharyngeal SARS-CoV-2 viral load (cycle threshold by RT-PCR)— Mean difference -0.35 (-1.58–0.89)
No differenceRoB: Some Concerns
Carrageenan nasal spray may double the rate of recovery from coronavirus and influenza virus infections: Re‐analysis of randomized trial data
Harri Hemilä et al.. Pharmacology Research & Perspectives 9(4) e00810. (2021)
iota-carrageenanNasal spray
RCTN = 356
Recovery rate from common cold (all viruses) — Cox regression risk ratio— Rate ratio 1.54 (1.15–2.10), p=0.00
Favors treatmentRoB: Some Concerns
Efficacy of physiological seawater nasal irrigation for the treatment of children with SARS-CoV-2 Omicron BA.2 variant infection: a randomized controlled trial
Lin et al.. World Journal of Pediatrics. (2024)
physiological seawater nasal irrigationNasal spray
Cluster-RandomizedN = 403
Duration of viral shedding from start of trial— Mean difference -0.37, p=0.01
Favors treatmentRoB: High
Clinical evaluation of prophylactic intranasal 1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (CL 88,277) medication against rhinovirus 44 challenge
Yasushi Togo et al.. Medical Microbiology and Immunology 163(1) 37-44. (1977)
1-phenyl-3-(4-phenyl-2-thiazolyl) guanidine (cl 88,277)Nasal spray
Human-ChallengeN = 20
Rhinovirus illness incidence (any illness)
No differenceRoB: Some Concerns
Pharmacokinetics of intranasally applied medication during a cold
Phillpotts RJ et al.. Antiviral Research 4(1-2) 71-74. (1984)
interferon (unspecified)Nasal spray
Human-ChallengeN = 28
Intranasal clearance rate of HuIFN-alpha2 before vs. after rhinovirus challenge
InconclusiveRoB: High
Virucidal Effect of Povidone Iodine on SARS-CoV-2 in Nasopharynx: An Open-label Randomized Clinical Trial
Kamal Arefin M. et al.. Indian Journal of Otolaryngology and Head & Neck Surgery 74(S2) 3283-3292. (2022)
povidone-iodineNasal irrigation
RCTN = 189
Nasopharyngeal clearance of SARS-CoV-2 (RT-PCR negativity) after intervention— Odds ratio 9.27 (2.06–41.8), p=0.01
Favors treatmentRoB: High
Intranasal interferon (rIFN-αA, Ro 22-8181) for contact prophylaxis against common cold: A randomized, double-blind and placebo-controlled field study
Christian Herzog et al.. Antiviral Research 6(3) 171-176. (1986)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 587
Development of common cold in initially symptom-free contact persons (infection rate)
No differenceRoB: Some Concerns
The efficacy of intranasal interferonα-2a in respiratory syncytial virus infection in volunteers
Paul G. Higgins et al.. Antiviral Research 14(1) 3-10. (1990)
interferon alpha-2aNasal spray
Human-Challenge
Incidence of colds (prophylactic trial)
MixedRoB: Some Concerns
Efficacy of a multiple-indication antiviral herbal drug (Saliravira®) for COVID-19 outpatients: A pre-clinical and randomized clinical trial study
Reza Ramazani Khorshiddoust et al.. Biomedicine & Pharmacotherapy 149 112729. (2022)
saliravira (herbal compound)Nasal spray
RCTN = 170
Mean Reduction Rate (MRR) of viral load at Day 4— Mean difference 17.0, p=0.09
No differenceRoB: High
Intranasal tolerance and histopathologic effects of a novel synthetic interferon, rIFN-αCon1
Frederick G. Hayden et al.. Antiviral Research 10(4-5) 225-234. (1988)
interferon alfacon-1 (consensus)Nasal spray
RCTN = 119
Withdrawal from treatment for any reason
InconclusiveRoB: Some Concerns
Failure to demonstrate synergy between interferon-α and a synthetic antiviral, enviroxime, in rhinovirus infections in volunteers
Peter G. Higgins et al.. Antiviral Research 10(1-3) 141-149. (1988)
interferon alpha (unspecified subtype)Nasal spray
Human-ChallengeN = 57
Clinically significant cold (clinical diagnosis)
No differenceRoB: Some Concerns
Evaluation of the safety, tolerability and pharmacokinetics of ALN-RSV01, a novel RNAi antiviral therapeutic directed against respiratory syncytial virus (RSV)
DeVincenzo J. et al.. Antiviral Research 77(3) 225-231. (2008)
aln-rsv01Nasal spray
RCTN = 101
Any respiratory/thoracic/mediastinal adverse event (Study 101 combined)
InconclusiveRoB: Some Concerns
An effective dosage regimen for prophylaxis against rhinovirus infection by intranasal administration of HuIFN-α2
Phillpotts RJ et al.. Antiviral Research 3(2) 121-136. (1983)
interferon alpha (unspecified subtype)Nasal spray
Human-Challenge
Clinically diagnosed colds (mild or worse)
No differenceRoB: Some Concerns
The SHIELD Study: A preliminary analysis of nasal and oral antisepsis to prevent COVID-19
Julie Keating et al.. Antimicrobial Stewardship & Healthcare Epidemiology 2(S1) s75-s75. (2022)
povidone-iodineNasal swab / application
RCTN = 221
SARS-CoV-2 viral load (midturbinate nasal swabs)
InconclusiveRoB: High
Modification of experimental rhinovirus colds by receptor blockade
Frederick G. Hayden et al.. Antiviral Research 9(4) 233-247. (1988)
rhinovirus receptor murine monoclonal antibody (rrma)Nasal drops
Human-Challenge
Infection rate (virus culture-positive or seroconversion) — Study 1
No differenceRoB: Some Concerns
A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults
Edward A. Belongia et al.. The American Journal of Medicine 111(2) 103-108. (2001)
zinc sulfateNasal spray
RCTN = 160
Duration of all symptoms (time to symptom resolution)
No differenceRoB: Some Concerns
A randomized controlled trial of low-dose recombinant human interferons α-2b nasal spray to prevent acute viral respiratory infections in military recruits
LuLu Gao et al.. Vaccine 28(28) 4445-4451. (2010)
interferon alpha-2bNasal spray
RCTN = 1,449
Influenza A virus infection rate (serum IgM seroconversion) - PP analysis— Risk ratio 0.24 (0.15–0.36), p=0.00
Favors treatmentRoB: Some Concerns
SARS-CoV-2 accelerated clearance using a novel nitric oxide nasal spray (NONS) treatment: A randomized trial
Monika Tandon et al.. The Lancet Regional Health - Southeast Asia 3 100036. (2022)
nitric oxide (nons)Nasal spray
RCTN = 306
Mean change from baseline in SARS-CoV-2 RNA (log10 copies/mL) through Day 8 (end of treatment)— Mean difference -0.82 (-1.33–-0.31), p=0.00
Favors treatmentRoB: Some Concerns
A study of intranasally administered interferon A (rIFN-α2A) for the seasonal prophylaxis of natural viral infections of the upper respiratory tract in healthy volunteers
Tannock GA et al.. Epidemiology and Infection 101(3) 611-621. (1988)
interferon alpha-2aNasal spray
RCTN = 412
Laboratory-documented viral infection (virus isolation and/or antibody response)— Risk ratio 1.11 (0.77–1.60)
No differenceRoB: Some Concerns
Astodrimer sodium antiviral nasal spray for reducing respiratory infections is safe and well tolerated in a randomized controlled trial
Alex Castellarnau et al.. Scientific Reports 12(1) 10210. (2022)
astodrimer sodiumNasal spray
RCTN = 41
Any treatment emergent adverse event (TEAE)
InconclusiveRoB: Some Concerns
A randomized, double-blind, placebo-controlled study of an RNAi-based therapy directed against respiratory syncytial virus
John DeVincenzo et al.. Proceedings of the National Academy of Sciences 107(19) 8800-8805. (2010)
aln-rsv01Nasal spray
Human-ChallengeN = 88
Treatment-emergent adverse events
InconclusiveRoB: Some Concerns
Early intervention with azelastine nasal spray may reduce viral load in SARS-CoV-2 infected patients
Jens Peter Klussmann et al.. Scientific Reports 13(1) 6839. (2023)
azelastineNasal spray
RCTN = 90
SARS-CoV-2 viral load kinetics (ORF 1a/b gene) — AUC of viral load decrease over 11 days— Mean difference 5.25, p=0.01
Favors treatmentRoB: Some Concerns
Assessment of safety and intranasal neutralizing antibodies of HPMC-based human anti-SARS-CoV-2 IgG1 nasal spray in healthy volunteers
Thanarath Imsuwansri et al.. Scientific Reports 13(1) 15648. (2023)
hpmc-based human anti-sars-cov-2 igg1 nasal sprayNasal spray
RCTN = 36
Signal inhibition percent (SIP) of SARS-CoV-2 neutralizing antibodies in nasal fluids — ancestral variant
Favors treatmentRoB: Some Concerns
Post-exposure prophylaxis with SA58 (anti-SARS-CoV-2 monoclonal antibody) nasal spray for prevention of symptomatic COVID-19 in healthy adult workers: a randomized single-blind placebo-controlled study
Song et al.. Emerging Microbes & Infections. (2023)
sa58 (anti-sars-cov-2 monoclonal antibody)Nasal spray
RCTN = 1,222
Laboratory-confirmed symptomatic COVID-19— Rate ratio 0.19 (0.08–0.48)
Favors treatmentRoB: Some Concerns
Inhibition of Rhinovirus Replication In Vitro and In Vivo by Acid‐Buffered Saline
James E. Gern et al.. The Journal of Infectious Diseases 195(8) 1137-1143. (2007)
citrate/phosphate bufferNasal spray
Human-ChallengeN = 44
Clinical cold incidence (Jackson criteria: confirmed infection + symptom score ≥6 + rhinorrhea ≥3 days or subject impression of cold)
Favors treatmentRoB: Some Concerns
Efficacy and Safety of the Neuraminidase Inhibitor Zanamivir in the Treatment of Influenzavirus Infections
Frederick G. Hayden et al.. New England Journal of Medicine 337(13) 874-880. (1997)
zanamivirNasal spray
RCTN = 417
Time to alleviation of all major symptoms (confirmed influenza infection)— Mean difference -1.00 (-1.80–-0.10), p=0.02
Favors treatmentRoB: Some Concerns
1524 Design and Implementation Of ICE-COVID, A Double-Blind Randomised Placebo-Controlled Trial on The Efficacy of Iota-Carrageenan Nasal and Throat Spray for Covid-19 Prophylaxis
Jia Yin Lim et al.. British Journal of Surgery 108(Supplement_6). (2021)
iota-carrageenanNasal spray
RCTN = 480
Acquisition of COVID-19 infection
InconclusiveRoB: Some Concerns
The Preventive Effect of Human Interferon-Alpha Preparation on Upper Respiratory Disease
JIRO IMANISHI et al.. Journal of Interferon Research 1(1) 169-178. (1980)
leukocyte/lymphoblastoid interferonNasal drops
RCTN = 86
Number of volunteers who complained of fever due to upper respiratory disease
Favors treatmentRoB: Some Concerns
Interferon-β ser As Prophylaxis Against Experimental Rhinovirus Infection in Volunteers
Higgins PG et al.. Journal of Interferon Research 6(2) 153-159. (1986)
interferon beta serineNasal spray
Human-ChallengeN = 64
Clinically significant colds
No differenceRoB: Some Concerns
Recombinant Human Interferon-γ as Prophylaxis Against Rhinovirus Colds in Volunteers
Paul G. Higgins et al.. Journal of Interferon Research 8(5) 591-596. (1988)
interferon gammaNasal spray
Human-ChallengeN = 43
Significant clinical illness (cold)
Favors controlRoB: Some Concerns
Intranasal Lymphoblastoid Interferon ("Well fer on") Prophylaxis Against Rhinovirus and Influenza Virus in Volunteers
R.J. Phillpotts et al.. Journal of Interferon Research 4(4) 535-541. (1984)
leukocyte/lymphoblastoid interferonNasal spray
Human-ChallengeN = 96
Clinically significant cold (mild or worse) — Trial 1 (rhinovirus)
MixedRoB: Some Concerns
Combined Antiviral-Antimediator Treatment for the Common Cold
Jack M. Gwaltney et al.. The Journal of Infectious Diseases 186(2) 147-154. (2002)
interferon alpha-2bNasal spray
Human-ChallengeN = 150
Total daily symptom severity score (baseline-adjusted means, days 2-5)— Rate ratio 1.51 (1.00–2.26), p=0.05
No differenceRoB: Some Concerns
Interferon-α Nasal Spray Prophylaxis Reduces COVID-19 in Cancer Patients: A Randomized, Double-Blinded, Placebo-Controlled Trial
Michelle K. Yong et al.. Clinical Infectious Diseases 82(2) e208-e216. (2026)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 433
Incidence of COVID-19 infection within 90 days (ITT)— Risk ratio 0.60 (0.33–0.97)
MixedRoB: Low
Effect of a Polynucleotide Interferon Inducer of Fungal Origin on Experimental Rhinovirus Infection in Humans
Aoki FY et al.. Journal of Infectious Diseases 137(1) 82-86. (1978)
brl 5907 (polynucleotide interferon inducer of fungal origin)Nasal drops
Human-ChallengeN = 15
Viral shedding (proportion of subjects shedding rhinovirus)
No differenceRoB: Some Concerns
Effect of a Topical Interferon Inducer on Rhinovirus Infections in Volunteers
Stanley ED et al.. Journal of Infectious Diseases 133(Supplement 2) A121-A127. (1976)
cp-20,961 (avridine)Nasal drops
Human-ChallengeN = 114
Rate of infection (proportion infected after rhinovirus challenge)— Risk difference -0.05
No differenceRoB: High
Efficacy and Tolerance of Intranasally Applied Recombinant Leukocyte A Interferon in Normal Volunteers
Samo TC et al.. Journal of Infectious Diseases 148(3) 535-542. (1983)
leukocyte/lymphoblastoid interferonNasal spray
Human-ChallengeN = 27
Frequency of illness (proportion of treated volunteers ill)
Favors treatmentRoB: Some Concerns
Effect of CP20,961, an Interferon Inducer, on Upper Respiratory Tract Infections Due to Rhinovirus Type 21 in Volunteers
Waldman RH et al.. Journal of Infectious Diseases 138(4) 531-535. (1978)
cp-20,961 (avridine)Nasal spray
Human-ChallengeN = 60
Clinical illness rate
No differenceRoB: Some Concerns
Intranasal Interferon- 2, Treatment of Experimental Rhinoviral Colds
Hayden FG et al.. Journal of Infectious Diseases 150(2) 174-180. (1984)
interferon alpha (unspecified subtype)Nasal spray
Human-ChallengeN = 52
Rhinovirus infection rate (viral isolation and/or seroconversion)
No differenceRoB: Some Concerns
Intranasal Interferon  2 for Prevention of Rhinovirus Infection and Illness
Hayden FG et al.. Journal of Infectious Diseases 148(3) 543-550. (1983)
interferon alpha (unspecified subtype)Nasal drops
Human-ChallengeN = 55
Rhinovirus infection (virus shedding and/or seroconversion)
Favors treatmentRoB: Some Concerns
Prevention of Experimental Coronavirus Colds with Intranasal  -2b Interferon
Turner RB et al.. Journal of Infectious Diseases 154(3) 443-447. (1986)
interferon alpha-2bNasal spray
Human-ChallengeN = 56
Met symptom criteria for a cold
Favors treatmentRoB: Some Concerns
Intranasally Applied Recombinant Leukocyte A Interferon in Normal Volunteers. II. Determination of Minimal Effective and Tolerable Dose
Samo Tc et al.. Journal of Infectious Diseases 150(2) 181-188. (1984)
interferon alpha (unspecified subtype)Nasal spray
Human-ChallengeN = 63
Frequency of illness (proportion of treated volunteers who became ill)
Favors treatmentRoB: Some Concerns
Intranasal Interferon- 2 Prophylaxis of Natural Respiratory Virus Infection
Douglas RM et al.. Journal of Infectious Diseases 151(4) 731-736. (1985)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 413
Number of volunteers experiencing respiratory episodes (medication phase)
No differenceRoB: Some Concerns
Influenza b in households: virus shedding without symptoms or antibody response
HJORDIS M. FOY et al.. American Journal of Epidemiology 126(3) 506-515. (1987)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 53
Influenza B infection (virus isolation or significant antibody titer rise) in households
No differenceRoB: Some Concerns
Ineffectiveness of Recombinant Interferon- serine Nasal Drops for Prophylaxis of Natural Colds
Sperber SJ et al.. Journal of Infectious Diseases 160(4) 700-705. (1989)
interferon beta serineNasal drops
RCT
Rhinovirus-documented cold (1986 study, 4-week treatment period)— Risk ratio 0.48, p=0.30
No differenceRoB: Some Concerns
A first-in-human clinical study of an intranasal spray of a cocktail containing two synergetic antibodies neutralizes Omicron BA.4/5
Zhang et al.. medRxiv (preprint). (2023)
a8g6 antibody cocktailNasal spray
RCTN = 108
Safety and tolerability (adverse events)
InconclusiveRoB: Some Concerns
Tolerance and Efficacy of Intranasal Administration of Recombinant  serine Interferon in Healthy Adults
Sperber SJ et al.. Journal of Infectious Diseases 158(1) 166-175. (1988)
interferon beta serineNasal drops
Human-ChallengeN = 154
Clinical cold (illness) incidence after experimental rhinovirus challenge — efficacy study, all subjects
Favors treatmentRoB: Some Concerns
Intranasal Interferon- 2b for Seasonal Prophylaxis of Respiratory Infection
Monto AS et al.. Journal of Infectious Diseases 154(1) 128-133. (1986)
interferon alpha-2bNasal spray
RCTN = 550
Rhinovirus infection during prophylaxis (twice-daily schedule)— Risk ratio 0.24, p=0.01
Favors treatmentRoB: Some Concerns
Effect of the povidone iodine hypertonic alkaline solution and saline nasal lavage on nasopharyngeal viral load in COVID-19
Batioglu-Karaaltin et al.. Clinical Otolaryngology. (2023)
povidone-iodine / hypertonic alkaline / saline nasal lavageNasal irrigation
RCTN = 120
Nasopharyngeal viral load reduction (quantitative RT-PCR)
No differenceRoB: High
Safety and Effectiveness of SA58 Nasal Spray against SARS-CoV-2 family transmission: an exploratory single-arm trial
Wang et al.. medRxiv (preprint). (2023)
sa58 (anti-sars-cov-2 monoclonal antibody)Nasal spray
Non-Randomized-Comparative
Cumulative incidence of SARS-CoV-2 infection (total effectiveness)
Favors treatmentRoB: High
Intranasal interferon as protection against experimental respiratory coronavirus infection in volunteers
Higgins PG et al.. Antimicrobial Agents and Chemotherapy 24(5) 713-715. (1983)
interferon alpha (unspecified subtype)Nasal spray
Human-ChallengeN = 83
Clinically diagnosed colds (mild or worse)
Favors treatmentRoB: Some Concerns
Intranasal interferon-alpha 2 for prevention of natural rhinovirus colds
Farr BM et al.. Antimicrobial Agents and Chemotherapy 26(1) 31-34. (1984)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 304
Rhinovirus-documented respiratory illness (culture-confirmed rhinovirus infection during treatment)
Favors treatmentRoB: Some Concerns
Antiviral Activity of Intranasally Applied Human Leukocyte Interferon
Stephen B. Greenberg et al.. Antimicrobial Agents and Chemotherapy 14(4) 596-600. (1978)
leukocyte/lymphoblastoid interferonNasal drops
Non-Randomized-Comparative
VSV yield reduction — IF drops 50,000 U vs untreated control— Mean difference -0.17
MixedRoB: High
Lack of Effect of an Interferon Inducer, N,N -Dihexadecyl- m -Xylylenediamine, on Rhinovirus Challenge in Humans
Douglas RG Jr et al.. Antimicrobial Agents and Chemotherapy 15(2) 269-272. (1979)
n,n-dihexadecyl-m-xylylenediamine (cp-28,888-27)Nasal spray
Human-ChallengeN = 62
Virus isolation from nasal washes
No differenceRoB: Some Concerns
Intranasal recombinant alfa-2b interferon treatment of naturally occurring common colds
Hayden FG et al.. Antimicrobial Agents and Chemotherapy 32(2) 224-230. (1988)
interferon alpha-2bNasal spray
RCTN = 228
Median duration of cold (subjective resolution)
No differenceRoB: Some Concerns
Ineffectiveness of postexposure prophylaxis of rhinovirus infection with low-dose intranasal alpha 2b interferon in families
Monto AS et al.. Antimicrobial Agents and Chemotherapy 33(3) 387-390. (1989)
interferon alpha-2bNasal spray
Cluster-RandomizedN = 199
Symptomatic cold episodes (all cycles) — during therapy (5 days)
No differenceRoB: Some Concerns
Development and validation of a product acceptability questionnaire for intranasal Q-Griffithsin COVID-19 prophylaxis (SPRAY PAL)
Elizabeth Cash et al.. BMJ Open 13(9) e073735. (2023)
griffithsin (q-grft)Nasal spray
RCTN = 18
SPRAY PAL product acceptability questionnaire — internal consistency (Cronbach's alpha)
InconclusiveRoB: High
Intranasal pirodavir (R77,975) treatment of rhinovirus colds
Frederick G. Hayden et al.. Antimicrobial Agents and Chemotherapy 39(2) 290-294. (1995)
pirodavirNasal spray
RCTN = 201
Duration of illness (days with cold symptoms)— Mean difference -0.20
No differenceRoB: Some Concerns
Effect of Induced Interferon in Experimental Rhinovirus Infections in Volunteers
Douglas RG Jr et al.. Infection and Immunity 9(3) 506-510. (1974)
cp-20,961 (avridine)Nasal spray
Human-ChallengeN = 29
Clinical illness (number becoming ill)
No differenceRoB: Some Concerns
Safety and efficacy of intranasal pirodavir (R77975) in experimental rhinovirus infection
Frederick G. Hayden et al.. Antimicrobial Agents and Chemotherapy 36(4) 727-732. (1992)
pirodavirNasal spray
Human-ChallengeN = 132
Infection rate (virus shedding or seroconversion) — Prophylaxis Study 1 (6x/day)
Favors treatmentRoB: Some Concerns
Safety tolerability and proof of pharmacology of a dry powder formulation of the antiviral host defense enhancer INNA-051 in healthy adults aged 18-80
Christophe Demaison et al.. Respiratory infections and bronchiectasis PA3911. (2025)
(Extracted from abstract only)
inna-051Other / unspecified delivery
RCTN = 48
Safety and tolerability (drug-related adverse events)
InconclusiveRoB: Some Concerns
Prophylactic intranasal alpha 2 interferon and viral exacerbations of chronic respiratory disease.
Wiselka MJ et al.. Thorax 46(10) 706-711. (1991)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 123
Lower respiratory tract infection
No differenceRoB: Some Concerns
A Clinical Study on the Tolerability of a Liposomal Povidone-Iodine Nasal Spray: Implications for Further Development
Gluck U. et al.. ORL 69(2) 92-99. (2007)
povidone-iodineNasal spray
CrossoverN = 35
Tolerability assessment (subject-rated)
InconclusiveRoB: Some Concerns
Phase II, Randomized, Double-Blind, Placebo-Controlled Studies of Ruprintrivir Nasal Spray 2-Percent Suspension for Prevention and Treatment of Experimentally Induced Rhinovirus Colds in Healthy Volunteers
Frederick G. Hayden et al.. Antimicrobial Agents and Chemotherapy 47(12) 3907-3916. (2003)
ruprintrivirNasal spray
Human-ChallengeN = 202
Proportion of subjects with positive viral culture (prophylaxis 5x/day)
Favors treatmentRoB: Some Concerns
Safety and Efficacy of the Neuraminidase Inhibitor Zanamivir in Treating Influenza Virus Infection in Adults: Results from Japan
Keizo Matsumoto et al.. Antiviral Therapy 4(2) 61-68. (1999)
zanamivirNasal spray
RCTN = 116
Time to alleviation of three major symptoms (fever, headache, myalgia) — all patients (ITT)— Mean difference -1.00 (-1.62–-0.38), p=0.00
Favors treatmentRoB: Some Concerns
Safety and Efficacy of Once Daily Intranasal Zanamivir in Preventing Experimental Human Influenza a Infection
David P. Calfee et al.. Antiviral Therapy 4(3) 143-149. (1999)
zanamivirNasal spray
Human-ChallengeN = 47
Viral shedding (isolation of challenge virus from nasal blow or throat gargle)
MixedRoB: Some Concerns
Evaluation of Intranasal TLR2/6 agonist INNA-051: Safety, Tolerability and Proof of Pharmacology
Francesca A. Mercuri et al.. ERJ Open Research 10(6) 00199-2024. (2024)
inna-051Nasal spray
Human-ChallengeN = 119
Laboratory-confirmed infection incidence (two quantifiable qRT-PCR samples on 2 consecutive days) — ITT population
No differenceRoB: Some Concerns
Efficacy and safety of an antiviral Iota-Carrageenan nasal spray: a randomized, double-blind, placebo-controlled exploratory study in volunteers with early symptoms of the common cold
Ron Eccles et al.. Respiratory Research 11(1) 108. (2010)
iota-carrageenanNasal spray
RCTN = 35
Total Symptom Score (TSS) mean of sum on days 2–4— Mean difference -1.66, p=0.05
Favors treatmentRoB: Some Concerns
Lessons learned from a double-blind randomised placebo-controlled study with a iota-carrageenan nasal spray as medical device in children with acute symptoms of common cold
Tamas Fazekas et al.. BMC Complementary and Alternative Medicine 12(1) 147. (2012)
iota-carrageenanNasal spray
RCTN = 213
Mean total symptom score (TSS) on days 2 to 7— Mean difference -0.20
No differenceRoB: Some Concerns
Efficacy of a Carrageenan nasal spray in patients with common cold: a randomized controlled trial
Martin Ludwig et al.. Respiratory Research 14(1) 124. (2013)
iota-carrageenanNasal spray
RCTN = 211
Duration of disease (time to last day with symptoms followed by all other days without symptoms)— Hazard ratio 1.24 (0.88–1.73), p=0.04
MixedRoB: Some Concerns
Безопасность применения препаратов интерферона в лечении ОРВИ у беременных высокого риска
Ю.В. Давыдова et al.. (2016)
(Extracted from abstract only)
nazoferonNasal drops
Non-Randomized-Comparative
Adverse events / safety and tolerability
InconclusiveRoB: High
Efficacy of povidone-iodine nasal rinse and mouth wash in COVID-19 management: a prospective, randomized pilot clinical trial (povidone-iodine in COVID-19 management)
Saad Alsaleh et al.. BMC Infectious Diseases 24(1) 271. (2024)
povidone-iodineNasal irrigation
RCTN = 25
Viral survival duration (days of RT-PCR detectability)
MixedRoB: High
Carrageenan nasal spray in virus confirmed common cold: individual patient data analysis of two randomized controlled trials
Martin Koenighofer et al.. Multidisciplinary Respiratory Medicine 9(1) 57. (2014)
iota-carrageenanNasal spray
RCTN = 254
Duration of common cold symptoms (all virus-positive patients, ITT)— Mean difference -1.90, p=0.00
Favors treatmentRoB: Some Concerns
Intranasal Chlorpheniramine Maleate for the treatment of COVID-19: Translational and Clinical Evidence
Marcos Sanchez-Gonzalez et al.. Medical Research Archives 10(3). (2022)
chlorpheniramine maleateNasal spray
RCTN = 45
Visual Analogue Scale (VAS) for COVID-19 symptoms
No differenceRoB: High
Efficacy and safety of iota-carrageenan nasal spray versus placebo in early treatment of the common cold in adults: the ICICC trial
Eccles R. et al.. Respiratory Research 16(1) 121. (2015)
iota-carrageenanNasal spray
RCTN = 200
Total Symptom Score Days 2-4 (TSS2-4)— Mean difference -0.61 (-1.32–0.10), p=0.09
No differenceRoB: Some Concerns
Effect of immune drugs to treat acute viral nasopharyngitis
Е. В. Безрукова et al.. Medical Immunology (Russia) 23(5) 1151-1164. (2021)
interferon alpha-2bNasal spray
Non-Randomized-Comparative
General malaise symptom score
Favors treatmentRoB: High
Interferons alpha and gamma, pidotimod, and tilorone in the treatment of acute respiratory infections in patients with allergic rhinitis: a prospective, cohort clinical and immunological study
Kalyuzhin, O.V. et al.. Bulletin of Siberian Medicine 21(2) 48-59. (2022)
interferon alpha-2bNasal drops
Non-Randomized-ComparativeN = 146
Sum score of clinical manifestations of ARI (15 symptoms scored 0-10 each daily)
InconclusiveRoB: High
Chlorpheniramine Intranasal Spray to Accelerate COVID-19 Clinical Recovery in an Outpatient Setting: The ACCROS Trials
Valerio-Pascua et al.. Research Square (preprint). (2022)
chlorpheniramine maleate (intranasal)Nasal spray
RCTN = 101
Percent change in Daily Symptoms Score (DSS) from baseline to Day 7
No differenceRoB: Some Concerns
Efficacy of Nasal Spray Mouth Spray and Mouthwash Containing Limonene Cetylpyridinium Chloride and Monolaurin in COVID-19 Management: A Double-Blind Randomized Placebo-Controlled Trial
Ponphaiboon et al.. Preprints.org. (2025)
cetylpyridinium chloride (+ limonene + monolaurin)Nasal spray
RCTN = 130
Fever and headache symptom severity
No differenceRoB: Some Concerns
Evaluation of the preventive efficacy of recombinant interferon α-2b in ambulance personnel contacting with COVID-19 patients
Vera P. Vavilova et al.. Infekcionnye bolezni 18(4) 33-41. (2020)
interferon alpha-2bOther / unspecified delivery
Non-Randomized-ComparativeN = 150
Number of COVID-19 (SARS-CoV-2) cases during study month
Favors treatmentRoB: High
Pharmacokinetic-based failure of a detergent virucidal for SARS-COV-2 nasal infections
Charles R. Esther et al.. Research square. (2021)
baby shampooNasal irrigation
RCTN = 72
SARS-CoV-2 nasal cavity viral load (qPCR Ct value)
No differenceRoB: Some Concerns
Preventing Upper Respiratory Tract Infections With Prophylactic Nasal Carrageenan: A Feasibility Study
Caroline Halley et al.. Future Microbiology 18(18) 1319-1328. (2023)
(Extracted from abstract only)
iota-carrageenanNasal spray
RCTN = 102
URTI symptoms
No differenceRoB: High
A Pilot Study of 0.4% Povidone-Iodine Nasal Spray to Eradicate SARS-CoV-2 in the Nasopharynx
Rujipas Sirijatuphat et al.. Infection and Drug Resistance Volume 15 7529-7536. (2022)
povidone-iodineNasal spray
Quasi-Experimental
Viable SARS-CoV-2 viral titer (TCID50/mL) in left nasopharynx at baseline vs 3 minutes post-PVP-I
No differenceRoB: High
Efficacy of a Nasal Spray Containing Iota-Carrageenan in the Postexposure Prophylaxis of COVID-19 in Hospital Personnel Dedicated to Patients Care with COVID-19 Disease
Juan Manuel Figueroa et al.. International Journal of General Medicine Volume 14 6277-6286. (2021)
iota-carrageenanNasal spray
RCTN = 400
RT-PCR confirmed symptomatic COVID-19— Odds ratio 0.19 (0.05–0.77), p=0.03
Favors treatmentRoB: Some Concerns
In vitro and clinical studies on the efficacy of α-cyclodextrin and hydroxytyrosol against SARS-CoV-2 infection.
Paolacci S. et al.. European review for medical and pharmacological sciences 25(1 Suppl) 81-89. (2021)
alpha-cyclodextrin and hydroxytyrosolNasal spray
Non-Randomized-Comparative
SARS-CoV-2 infection (RT-qPCR positive)
InconclusiveRoB: High
Study of the Efficacy and Safety of Topical Ivermectin + Iota-Carrageenan in the Prophylaxis against COVID-19 in Health Personnel
Carvallo Héctor et al.. Journal of Biomedical Research and Clinical Investigation 2(1). (2020)
(Extracted from abstract only)
iota-carrageenan + ivermectinNasal spray
RCT
—RoB: High
Decongestant Effect of “Coldamaris Akut”, a Carrageenan- and Sorbitol-Containing Nasal Spray in Seasonal Allergic Rhinitis
Nicole Unger-Manhart et al.. International Journal of General Medicine Volume 17 5105-5121. (2024)
iota-carrageenanNasal spray
CrossoverN = 41
Nasal Congestion Symptom Score (NCSS) change from pre-treatment to mean 2-4h post-treatment— Mean difference 0.02 (-0.19–0.24)
No differenceRoB: Some Concerns
Effectiveness in humans of an antiviral drug based on cholinergic agonists with specific design and route of administration against COVID-19 symptoms in a group of infected patients vs. control group
Orlando Angulo et al.. Qeios. (2021)
nicotinic cholinergic agonist compositionNasal spray
RCTN = 80
Fever— Odds ratio 0.90 (0.36–2.23), p=0.82
No differenceRoB: High
Combined Nasal, Oropharyngeal Povidone Iodine Plus Glycyrrhizic Acid Sprays, Accelerate Clinical and Laboratory Recovery and Reduces Household Transmission of SARS-CoV-2: A Randomized Placebo-Controlled Clinical Trial
Hazem E. Elsersy et al.. Frontiers in Medicine 9 863917. (2022)
povidone-iodine plus glycyrrhizic acidNasal spray
RCTN = 200
PCR-positive rate at day 4 post-treatment
Favors treatmentRoB: Some Concerns
Clinical and interferon-modulating efficacy of a combination of rectal and topical dosage forms of interferon-α2b in acute respiratory infections
O. V. Kalyuzhin et al.. Terapevticheskii arkhiv 90(11) 48-54. (2018)
interferon alpha-2bOther / unspecified delivery
RCTN = 90
Repeat hospitalization for ARI within 3 months
No differenceRoB: High
Egg-Derived Anti-SARS-CoV-2 Immunoglobulin Y (IgY) With Broad Variant Activity as Intranasal Prophylaxis Against COVID-19
Lyn R. Frumkin et al.. Frontiers in Immunology 13 899617. (2022)
anti-sars-cov-2 rbd igyNasal drops
RCTN = 48
Treatment-emergent adverse events (any TEAE) - single ascending dose (Part 1)
InconclusiveRoB: Some Concerns
Povidone-iodine nasal spray (Nasodine®) for the common cold: a randomized, controlled, double-blind, Phase III clinical trial
Thomas M. Polasek et al.. Frontiers in Medicine 12 1565069. (2025)
povidone-iodineNasal spray
RCTN = 260
Nasal Symptom Score (NSS) - primary endpoint - Days 2-6 LSM— Mean difference -0.63 (-1.63–0.37), p=0.22
No differenceRoB: Some Concerns
Efficacy of the Sentinox Spray in Reducing Viral Load in Mild COVID-19 and Its Virucidal Activity against Other Respiratory Viruses: Results of a Randomized Controlled Trial and an In Vitro Study
Panatto et al.. Viruses. (2022)
acidic hypochlorous solution (sentinox)Nasal spray
RCTN = 57
Change in SARS-CoV-2 viral load (log10 copies/mL) from baseline to day 5 (end of treatment) — ITT all subjects— Mean difference 1.02 (-0.35–2.40), p=0.14
No differenceRoB: Some Concerns
Early Negativization of SARS-CoV-2 Infection by Nasal Spray of Seawater plus Additives: The RENAISSANCE Open-Label Controlled Clinical Trial
Luca Cegolon et al.. Pharmaceutics 14(11) 2502. (2022)
hypertonic seawater solution with xylitol, panthenol, and lactic acid (tonimer lab panthexyl 800)Nasal spray
Non-Randomized-Comparative
Viral shedding time (VST) — time to first negative antigenic rapid test for SARS-CoV-2 from first positive RT-PCR— Odds ratio 7.39 (1.83–29.8)
Favors treatmentRoB: High
Safety and efficacy of lentinan nasal drops in patients infected with the variant of COVID-19: a randomized, placebo-controlled trial
Wenhan Fan et al.. Frontiers in Pharmacology 14 1292479. (2023)
lentinanNasal drops
RCTN = 98
Antigen negative conversion rate at day 5 (Phase 2 primary endpoint)
Favors treatmentRoB: Some Concerns
Changes in reverse transcription polymerase chain reaction cycle threshold values of SARS-CoV-2 with topical povidone iodine use: A single-arm open-label interventional study
Shankar S. et al.. Journal of Family Medicine and Primary Care 11(2) 480-486. (2022)
povidone-iodineNasal swab / application
Quasi-Experimental
RT-PCR qualitative result (positive/negative) — nasopharyngeal samples across days
InconclusiveRoB: High
Safety and Effectiveness of SA58 Nasal Spray Against COVID-19 Infection in Medical Personnel: An Open-Label Blank-Controlled Study
Si et al.. China CDC Weekly. (2023)
sa58 (anti-sars-cov-2 monoclonal antibody)Nasal spray
Non-Randomized-Comparative
Cumulative incidence of RT-PCR confirmed COVID-19 cases (person-day rate)
Favors treatmentRoB: High
Efficacy and safety of ribavirin aerosol in children with hand-foot-mouth disease
Zhang HP et al.. Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 16(3) 272-6. (2014)
(Extracted from abstract only)
ribavirinNasal spray
RCTN = 119
Enterovirus negative conversion rate
Favors treatmentRoB: Some Concerns
Astodrimer Sodium Nasal Spray versus Placebo in Non-Hospitalised Patients with COVID-19: A Randomised, Double-Blinded, Placebo-Controlled Trial
Stephen Winchester et al.. Pharmaceutics 16(9) 1173. (2024)
astodrimer sodiumNasal spray
RCTN = 231
SARS-CoV-2 RNA burden (vAUCd1-8) — area under the viral load curve Day 1 through Day 8— Mean difference -1.20 (-3.60–1.20), p=0.34
No differenceRoB: Some Concerns
Intranasal Xylitol for the Treatment of COVID-19 in the Outpatient Setting: A Pilot Study
Evangelina Soler et al.. Cureus 14(7) e27182. (2022)
xylitolNasal spray
RCTN = 50
Time to clinical recovery / COVID-19 symptoms (Visual Analog Scale, VAS)
No differenceRoB: Some Concerns
Epidemiologic effectivness of poludane in preventing influenza and other acute respiratory diseases in troops
Shumilov VI et al.. Voenno-meditsinskii zhurnal 323(1) 45-7, 93. (2002)
(Extracted from abstract only)
poludaneNasal drops
RCTN = 292
Incidence of acute respiratory diseases (ARD)— Rate ratio 0.50, p=0.06
No differenceRoB: High
Abstracts of Presentations at the Association of Clinical Scientists 143(rd) Meeting Louisville, KY May 11-14,2022
Annals of clinical and laboratory science 52(3) 511-525. (2022)
(Extracted from abstract only)
griffithsin (q-grft)Nasal spray
RCTN = 18
Safety (adverse events)
InconclusiveRoB: High
Hydrogen peroxide as an auxiliary treatment for COVID-19 in Brazil: a randomized double-blind clinical trial
Marielle Bazzo Di Domênico et al.. Epidemiology and Health 43 e2021051. (2021)
hydrogen peroxideNasal spray
RCTN = 193
Symptom relief — cough (days 0-2)
No differenceRoB: Some Concerns
Preliminary study on nasal spray of interferon alpha-2b used for prevention of rubella and measles virus infections
Zhao J et al.. Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of ex 19(3) 220-2. (2005)
(Extracted from abstract only)
interferon alpha-2bNasal spray
Quasi-Experimental
Measles virus IgG antibody titer difference between experimental and control groups— Mean difference 1.26
MixedRoB: High
A field trial for evaluating the safety of recombinant human interferon alpha-2b for nasal spray
Chen Q et al.. Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of ex 19(3) 211-5. (2005)
(Extracted from abstract only)
interferon alpha-2bNasal spray
RCT
Headache incidence
InconclusiveRoB: High
A field trial of recombinant human interferon alpha-2b for nasal spray to prevent SARS and other respiratory viral infections
Yu DX et al.. Zhonghua shi yan he lin chuang bing du xue za zhi = Zhonghua shiyan he linchuang bingduxue zazhi = Chinese journal of ex 19(3) 216-9. (2005)
(Extracted from abstract only)
interferon alpha-2bNasal spray
RCTN = 14,391
SARS IgG antibody positive rate
No differenceRoB: Some Concerns
Features of vasomotor rhinitis in patients with a history of COVID-19 infection
Nakudashvili N et al.. Georgian medical news (359) 23-31. (2025)
(Extracted from abstract only)
intranasal antihistamineNasal spray
Non-Randomized-Comparative
Therapeutic efficacy of antihistamine spray (subjective/objective indicators)
InconclusiveRoB: High
The preventive effect of human interferon-alpha on influenza infection; modification of clinical manifestations of influenza in children in a closed community
Isomura S et al.. Biken journal 25(3) 131-7. (1982)
(Extracted from abstract only)
interferon alpha (unspecified subtype)Nasal drops
RCTN = 27
Clinical manifestations of influenza virus infection (severity)
InconclusiveRoB: High
Trial of polyguacyl safety and tolerance
Ershov FI et al.. Voprosy virusologii (4) 418-23. (1981)
(Extracted from abstract only)
polyguacylNasal drops
Non-Randomized-Comparative
Safety and tolerance of polyguacyl in human volunteers
InconclusiveRoB: High
Prevention from naturally acquired viral respiratory infection by interferon nasal spray
Saito H et al.. Rhinology 23(4) 291-5. (1985)
(Extracted from abstract only)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 73
Subjects without elevated antibody titers and without symptoms
No differenceRoB: High
The Limited Effect of Nasal Interferon Induced by Rhinovirus and a Topical Chemical Inducer on the Course of Infection
Gatmaitan BC et al.. Journal of Infectious Diseases 127(4) 401-407. (1973)
cp-20,961 (avridine)Nasal spray
Human-ChallengeN = 38
Clinical illness (common cold)
No differenceRoB: Some Concerns
A Clinical Trial of Hypertonic Saline Nasal Spray in Subjects With the Common Cold or Rhinosinusitis
Adam P. et al.. Archives of Family Medicine 7(1) 39-43. (1998)
hypertonic salineNasal spray
RCTN = 149
Day of well-being (day of symptom resolution)
No differenceRoB: Some Concerns
Purified interferon as protection against rhinovirus infection.
Scott GM et al.. BMJ 284(6332) 1822-1825. (1982)
leukocyte/lymphoblastoid interferonNasal spray
Human-Challenge
Incidence of colds
Favors treatmentRoB: Some Concerns
Clinical efficacy of nitric oxide nasal spray (NONS) for the treatment of mild COVID-19 infection
Stephen Winchester et al.. Journal of Infection 83(2) 237-279. (2021)
nitric oxide (nons)Nasal spray
RCTN = 80
Change from baseline in log10 SARS-CoV-2 RNA concentration— Mean difference -1.21 (-2.07–-0.35), p=0.01
Favors treatmentRoB: Some Concerns
Efficacy and Safety of the Neuraminidase Inhibitor Zanamivirin the Treatment of Influenza A and B Virus Infections
Monto AS et al.. The Journal of Infectious Diseases 180(2) 254-261. (1999)
See also: Commentary: Evidence-Based Medicine
zanamivirNasal spray
RCTN = 1,256
Time to alleviation of clinically significant major symptoms (ITT population)— Mean difference -1.00 (-2.00–0.00), p=0.01
No differenceRoB: Some Concerns
Zanamivir
Susan M. Cheer et al.. Drugs 62(1) 71-106. (2002)
zanamivirNasal spray
RCT
Median time to alleviation of major influenza symptoms (influenza-confirmed adults)— Mean difference -1.00, p=0.05
No differenceRoB: Some Concerns
Safety and Efficacy of the Neuraminidase Inhibitor GG167 in Experimental Human Influenza
Hayden, F. et al.. JAMA 275(4) 295-9. (1996)
zanamivir (gg167)Nasal drops
Human-ChallengeN = 166
Frequency of laboratory-proven infection (viral shedding and/or seroconversion) — prophylaxis
Favors treatmentRoB: Some Concerns
Short-Term Treatment with Zanamivir to Prevent Influenza: Results of a Placebo-Controlled Study
Kaiser L. et al.. Clinical Infectious Diseases 30(3) 587-589. (2000)
(Extracted from abstract only)
zanamivirNasal spray
RCTN = 575
Symptomatic influenza during 5 days of prophylaxis— Odds ratio 0.90 (0.30–2.72), p=0.85
No differenceRoB: Some Concerns
Nasal sprays and behavioural interventions compared with usual care for acute respiratory illness in primary care: a randomised, controlled, open-label, parallel-group trial
Paul Little et al.. The Lancet Respiratory Medicine 12(8) 619-632. (2024)
saline arm
See also: Follow-up: 12-month outcomes (BJGP 2026)
saline nasal sprayNasal spray
RCTN = 6,901
Total number of days of illness due to self-reported respiratory tract illnesses in previous 6 months (all participants)— Rate ratio 0.81 (0.76–0.86), p=0.00
Favors treatmentRoB: Some Concerns
Nasal sprays and behavioural interventions compared with usual care for acute respiratory illness in primary care: a randomised, controlled, open-label, parallel-group trial
Paul Little et al.. The Lancet Respiratory Medicine 12(8) 619-632. (2024)
gel-based arm
See also: Follow-up: 12-month outcomes (BJGP 2026)
gel-based nasal spray (vicks first defence)Nasal spray
RCTN = 6,899
Total number of days of illness due to self-reported respiratory tract illnesses in previous 6 months (all participants)— Rate ratio 0.82 (0.77–0.87), p=0.00
Favors treatmentRoB: Some Concerns
Failure of intranasally administered 4?, 6-dichloroflavan to protect against rhinovirus infection in man
Al-Nakib W. et al.. Archives of Virology 92(3-4) 255-260. (1987)
4',6-dichloroflavanNasal drops
Human-ChallengeN = 59
Clinically diagnosed colds (mild, moderate, or severe)
No differenceRoB: Some Concerns
Daily intranasal palivizumab to prevent respiratory syncytial virus infection in healthy preterm infants: a phase 1/2b randomized placebo-controlled trial
Natalie I. Mazur et al.. eClinicalMedicine 66 102324. (2023)
palivizumabNasal drops
RCTN = 268
Any lab-confirmed RSV infection— Odds ratio 2.20 (0.70–6.50), p=0.14
No differenceRoB: Some Concerns
Prophylactic efficacy and tolerance of low-dose intranasal interferon-alpha2 in natural respiratory viral infections
Frederick G. Hayden et al.. Antiviral Research 5(2) 111-116. (1985)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 287
Respiratory illness episodes
Favors controlRoB: Some Concerns
Human Tolerance and Histopathologic Effects of Long-Term Administration of Intranasal Interferon- 2
Hayden FG et al.. Journal of Infectious Diseases 148(5) 914-921. (1983)
interferon alpha (unspecified subtype)Nasal spray
RCTN = 52
Nasal mucosal irritation signs and/or blood-tinged mucus symptoms
InconclusiveRoB: Some Concerns
Four Compounds Active against Rhinovirus: Comparison in Vitro and in Volunteers
Reed SE et al.. Journal of Infectious Diseases 133(Supplement 2) A128-A135. (1976)
skf 40491, glr9-338, rp l9326, ici 73,602Nasal spray
Human-Challenge
Mean viral titer in nasal wash— Mean difference -0.25
Favors treatmentRoB: Some Concerns
Human monoclonal antibody F61 nasal spray effectively protected high-risk populations from SARS-CoV-2 variants during the COVID-19 pandemic from late 2022 to early 2023 in China
Ying Liu et al.. Emerging Microbes & Infections 13(1) 2284297. (2024)
human monoclonal antibody f61Nasal spray
RCTN = 2,008
Cumulative SARS-CoV-2 infection rate at Day 7 (one-dose cohort)
Favors treatmentRoB: Some Concerns
Intranasal chalcone, Ro 09–0410, as prophylaxis against rhinovirus infection in human volunteers
Al-Nakib W. et al.. Journal of Antimicrobial Chemotherapy 20(6) 887-892. (1987)
chalcone ro 09-0410Nasal spray
Human-ChallengeN = 50
Significant colds (clinical illness)
No differenceRoB: Some Concerns
A pilot randomized controlled trial evaluating a resveratrol/β‐glucan nasal spray for preventing respiratory symptoms in preschool children with recurrent wheezing
Cristiana Indolfi et al.. Pediatric Allergy and Immunology 37(5) e70371. (2026)
(Extracted from abstract only)
resveratrol/carboxymethyl-beta-glucan (linfovir)Nasal spray
RCT
Days with respiratory symptoms— Mean difference -5.40
No differenceRoB: Some Concerns
PROphylaxis for paTiEnts at risk of COVID-19 infecTion (PROTECT-V)
Toby J. L. Humphrey et al.. Trials 24(1) 185. (2023)
(Extracted from abstract only)
niclosamideNasal spray
RCT
Symptomatic SARS-CoV-2 infection
InconclusiveRoB: Some Concerns
Prophylactic activity of intranasal enviroxime against experimentally induced rhinovirus type 39 infection
Hayden FG et al.. Antimicrobial Agents and Chemotherapy 21(6) 892-897. (1982)
enviroximeNasal spray
Human-ChallengeN = 40
Total infection rate (virus isolation or seroconversion)
No differenceRoB: Some Concerns
Therapeutic activity of enviroxime against rhinovirus infection in volunteers
Phillpotts RJ et al.. Antimicrobial Agents and Chemotherapy 23(5) 671-675. (1983)
enviroximeNasal spray
Human-ChallengeN = 55
Clinically diagnosed cold (mild or worse) — all HRV9-challenged volunteers
No differenceRoB: Some Concerns
Suppression of colds in human volunteers challenged with rhinovirus by a new synthetic drug (R61837)
al-Nakib W. et al.. Antimicrobial Agents and Chemotherapy 33(4) 522-525. (1989)
r61837Nasal spray
Human-Challenge
Number of significant colds (Trial 1: First Prophylactic)
No differenceRoB: Some Concerns
Prophylaxis for renal patients at risk of COVID-19 infection: results from the intranasal niclosamide randomised, double blinded, placebo controlled arm of the PROTECT-V platform trial
Toby J. L. Humphrey et al.. BMC Infectious Diseases 25(1) 204. (2025)
niclosamideNasal spray
RCTN = 1,651
Confirmed symptomatic COVID-19 infection during trial treatment— Hazard ratio 1.02 (0.79–1.32)
No differenceRoB: Some Concerns
Topical enviroxime against rhinovirus infection
Levandowski RA et al.. Antimicrobial Agents and Chemotherapy 22(6) 1004-1007. (1982)
enviroximeNasal spray
Human-ChallengeN = 101
RV4-specific cold (clinical cold meeting case definition)
No differenceRoB: Some Concerns
Ineffectiveness of zinc gluconate nasal spray and zinc orotate lozenges in common-cold treatment: a double-blind, placebo-controlled clinical trial.
Eby GA et al.. Alternative Therapies in Health and Medicine 12(1) 34-8. (2006)
(Extracted from abstract only)
zinc gluconateNasal spray
RCTN = 77
Proportion asymptomatic at day 7
No differenceRoB: High
Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19
Zaki F. Aref et al.. International Journal of Nanomedicine Volume 16 4063-4072. (2021)
ivermectinNasal spray
RCTN = 114
PCR negative conversion (2 consecutive negative nasopharyngeal swabs)
Favors treatmentRoB: High
Azelastine Nasal Spray in Non-Hospitalized Subjects with Mild COVID-19 Infection: A Randomized Placebo-Controlled, Parallel-Group, Multicentric, Phase II Clinical Trial
Peter Meiser et al.. Viruses 16(12) 1914. (2024)
azelastineNasal spray
RCTN = 294
Rate of COVID-19-related hospitalization
MixedRoB: Some Concerns
Effects of creating a non-specific, virus-hostile environment in the nasopharynx on symptoms and duration of common cold.
Hull D et al.. Acta Otorhinolaryngologica Italica 27(2) 73-7. (2007)
(Extracted from abstract only)
hydroxypropyl methylcellulose (hpmc)Nasal irrigation
RCTN = 441
Cold symptom severity
Favors treatmentRoB: Some Concerns
Safety and efficacy of the neuraminidase inhibitor GG167 in experimental human influenza.
Hayden FG et al.. JAMA 275(4) 295-9. (1996)
(Extracted from abstract only)
4-guanidino-neu5ac2en (gg167)Nasal spray
Human-ChallengeN = 166
Laboratory-confirmed infection (viral shedding and/or seroconversion) — prophylaxis— Risk difference -0.82, p=0.01
Favors treatmentRoB: Some Concerns
Pharmacodynamic of Recombinant Human Interferon Alpha-2b Nasal Drops and Effective Prophylaxis Against SARS-COV-2 Infection
Hugo Nodarse-Cuni et al.. Journal of Interferon & Cytokine Research 44(6) 271-280. (2024)
(Extracted from abstract only)
interferon alpha-2bNasal drops
Non-Randomized-ComparativeN = 29,082
SARS-CoV-2 infection rate (travelers cohort)
Favors treatmentRoB: Serious
Effects of hypertonic alkaline nasal irrigation on COVID-19
Yilmaz et al.. Laryngoscope Investigative Otolaryngology. (2021)
hypertonic alkaline nasal irrigationNasal spray
Quasi-ExperimentalN = 60
Nasopharyngeal SARS-CoV-2 viral load (copies/µL) at Days 0, 3, and 7
No differenceRoB: Serious
The Real-World Effectiveness of an Intranasal Spray A8G6 Antibody Cocktail in the Post-Exposure Prophylaxis of COVID-19
Li et al.. SSRN (preprint). (2023)
a8g6 antibody cocktailNasal spray
Non-Randomized-ComparativeN = 513
SARS-CoV-2 infection incidence (RT-PCR confirmed COVID-19)— Hazard ratio 0.12 (0.07–0.22), p=0.00
Favors treatmentRoB: Serious
Significance of saline nasal irrigation for COVID-19 infection: observations and reflections from nursing care of nasopharyngeal carcinoma
Yan et al.. Translational Cancer Research. (2024)
saline nasal irrigationNasal irrigation
Retrospective CohortN = 519
COVID-19 infection rate
MixedRoB: Serious
Could preventive intranasal interferon lower the morbidity in children prone to respiratory illness?
Robert M. Douglas et al.. Medical Journal of Australia 152(10) 524-528. (1990)
interferon (unspecified)Nasal spray
Prospective CohortN = 127
Proportion of family episodes classified as 'medicable' (eligible for contact prophylaxis)
InconclusiveRoB: Moderate