Vaccines for the common cold
Appendices
Appendix 1. Glossary
| Term | Definition | Reference |
|---|---|---|
| Common cold | The common cold is a self‐limiting acute upper respiratory tract infection characterised by rhinorrhoea, nasal congestion, sneezing, cough, sore throat, fever, and malaise. | |
| Vaccination | Inoculation with a vaccine, i.e. a preparation of microbial antigen often combined with adjuvants administered to an individual in order to induce protective immunity against microbial infections. The antigen may be in the form of live, avirulent micro‐organisms or purified macromolecular components of micro‐organisms. | |
| Immune system | The collection of cells, tissues, and molecules that mediate resistance to infections | |
| Cell‐mediated immunity | The arm of the adaptative immune response whose role is to combat infections by intracellular microbes. This type of immunity is mediated by T lymphocytes. | |
| Antigenical variability | Microbes have evolved mechanisms to evade immunity. Many bacteria and viruses mutate their antigenic surface molecules and can no longer be recognised by antibodies produced in response to previous infection. | |
| Serotypes | An antigenically distinct subset of a species of an infectious organism that is distinguished from other subsets by serologic (i.e. serum antibody) tests. Humoral immune response to one serotype of microbes, e.g. influenza virus, may not be protective against another serotypes. | |
| Immune responses | Once a foreign organism has been recognised, the immune system enlists the participation of a variety of cells and molecules to mount an appropriate response in order to eliminate or neutralise the organism. | |
| Antigenic molecules | Any molecule capable of being recognised by an antibody or T‐cell receptor. Any substance that elicits an immune response | |
| Allergens | An antigen that elicits an immediate hypersensitivity (allergic) reaction. Allergens are proteins, or chemicals bound to proteins, that induce immunoglobulin E antibody production in atopic individuals. | |
| Immunopotentiation | Non‐specific immunostimulation given by various agents that can stimulate the immune response. It is believed that the mechanism of action is through some modification of local cytokines or growth of innate immune mechanisms. An increase in the functional capacity of the immune response | |
| Opsonisation | The process by which particulate antigens are rendered more susceptible to phagocytosis The process of attaching opsonins, such as immunoglobulin G or complement fragments, to microbial surfaces to target microbes for phagocytosis | |
| Phagocytosis | Macrophages are capable of ingesting and digesting exogenous antigens, such as whole micro‐organisms and insoluble particles, and endogenous matter, such as injured or dead host cells, cellular debris, and activated clotting factors. The process by which certain cells of the innate immune system, including macrophages and neutrophils, engulf large particles (> 0.5‐micrometre diameter), such as intact microbes. The cell surrounds the particle by a cytoskeleton‐dependent process, leading to formation of an intracellular vesicle called a phagosome, which contains the ingested particle. |
Appendix 2. Differences between clinical characteristics of the common cold and influenza
| Feature | Common cold | Influenza | References |
|---|---|---|---|
| Aetiological agent | > 100 viral strains; rhinovirus most common | 3 strains of influenza virus: influenza A, B, C | DDCP 2010; Gwaltney 1967; Gwaltney 2000;
|
| Site of infection | Upper respiratory tract | Entire respiratory system | |
| Symptom onset | Gradual: 1 to 3 days | Sudden: within a few hours | |
| Fever, chills | Occasional, low grade (< 100 ºF) | Fever is usually present with the flu (up to 80% of all flu cases). A temperature of 100 ºF or higher for 3 to 4 days is typically associated with the flu. | |
| Headache | Frequent, usually mild | Characteristic, more severe | |
| General aches, pains | Mild, if any | Characteristic, often severe and affecting the entire body | |
| Cough, chest congestion | Mild to moderate, with hacking cough | Common, may become severe | |
| Sore throat | Common, usually mild | Sometimes present | |
| Runny, stuffy nose | Very common, accompanied by bouts of sneezing | Sometimes present | |
| Fatigue, weakness | Mild, if any | Usual, may be severe and last 2 to 3 weeks | |
| Extreme exhaustion | Never | Frequent, usually in early stages of illness | |
| Season | Year around, peaks in winter months | Most cases between November and February | |
| Antibiotics helpful | No, unless secondary bacterial infection develops | No, unless secondary bacterial infection develops |
Appendix 3. Viral causes of the common cold
| Virus | Estimated annual proportion of cases | References |
|---|---|---|
| Rhinoviruses | 30% to 50%; during autumn 80%. Once considered to be limited to the upper airway, now recognised as an important cause of lower respiratory infections | Arruda 1997; Gwaltney 1985; Heikkinen 2003; Lemanske 2005; Mäkelä 1998; Monto 1993; Regamey 2008 |
| Coronaviruses | 7% to 18% in adults with upper respiratory infections. Responsible for 2.1% of hospital admissions for acute respiratory tract infections in all age groups | |
| Influenza viruses | 5% to 15% | |
| Respiratory syncytial virus (RSV) | In low‐income countries, 15% to 20% In hospital the proportion of children aged between birth and 5 months with RSV acute lower respiratory tract infections ranged between 9% and 87%. Amongst children up to at least 5 years of age reported with RSV, on average 39% (range 20% to 62%) were < 6 months old; on average 24% of cases (range 14% to 38%) were children aged 6 to 11 months, thus an average of 63% of children were under 1 year of age. On average 20% (range 13% to 29%) of children were between 1 and 2 years of age. RSV accounts for approximately 10,000 deaths annually in people over the age of 65 years in the USA. RSV in adults, 5% infection annually | Berman 1991; Falsey 2005; Thompson 2003
|
| Parainfluenza viruses | Acute respiratory infections cause 3% to 18% of all admissions to paediatric hospitals; however, this might vary at different times of the year. Parainfluenza viruses account for 17% of hospitalised illness‐associated virus isolation. In low‐income countries, 7% to 10% Parainfluenza viruses cause 50% to 74.2% of croup cases. | Berman 1991; Denny 1983; Henrickson 2003
|
| Adenoviruses | In low‐income countries, 2% to 4% | |
| Metapneumovirus | 10% short epidemic | |
| Unknown | 20% to 30% |
Appendix 4. CENTRAL search strategy
#1 mh "Common Cold"
#2 "common cold*":ti,ab
#3 "coryza":ti,ab
#4 (acute near/5 ("upper respiratory infection*" or "upper respiratory tract infection*" or urti or uri)):ti,ab
#5 mh "Picornaviridae Infections"
#6 mh Rhinovirus
#7 rhinovir*
#8 "hrv":ti,ab
#9 mh "Paramyxoviridae Infections"
#10 mh "parainfluenza virus 1, human" or mh "parainfluenza virus 3, human"
#11 mh "parainfluenza virus 2, human" or mh "parainfluenza virus 4, human"
#12 "parainfluenza*":ti,ab
#13 mh coronavirus or mh "coronavirus 229e, human" or mh "coronavirus oc43, human"
#14 mh "Coronavirus Infections"
#15 coronavir*
#16 mh adenoviridae or mh "adenoviruses, human"
#17 mh adenoviridae or mh "adenoviruses, human"
#18 adenovir*
#19 mh "respiratory syncytial viruses" or mh "respiratory syncytial virus, human"
#20 mh "Respiratory Syncytial Virus Infections"
#21 ("respiratory syncytial virus*" or rsv):ti,ab
#22 #1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11 or #12 or #13 or #14 or #15 or #16 or #17 or #18 or #19 or #20 or #21
#23 mh Vaccines
#24 mh Vaccination
#25 (vaccin* or inocul* or immuni*):ti,ab
#26 #23 or #24 or #25
#27 #22 and #26 with Cochrane Library publication date Between Sep 2016 and April 2022
Appendix 5. MEDLINE (Ovid) search strategy
1 Common Cold/
2 common cold*.tw.
3 coryza.tw.
4 (acute adj5 (upper respiratory infection* or upper respiratory tract infection* or urti or uri)).tw.
5 Picornaviridae Infections/
6 Rhinovirus/
7 rhinovir*.tw.
8 hrv.tw.
9 Paramyxoviridae Infections/
10 parainfluenza virus 1, human/ or parainfluenza virus 3, human/
11 parainfluenza virus 2, human/ or parainfluenza virus 4, human/
12 parainfluenza*.tw.
13 coronavirus/ or coronavirus 229e, human/ or coronavirus oc43, human/
14 Coronavirus Infections/
15 coronavir*.tw.
16 exp adenoviridae/ or adenoviruses, human/
17 Adenovirus Infections, Human/
18 adenovir*.tw.
19 respiratory syncytial viruses/ or respiratory syncytial virus, human/
20 Respiratory Syncytial Virus Infections/
21 (respiratory syncytial virus* or rsv).tw.
22 or/1‐21
23 exp Vaccines/
24 exp Vaccination/
25 (vaccin* or inocul* or immuni*).tw.
26 or/23‐25 (724637)
27 randomized controlled trial.pt.
28 controlled clinical trial.pt.
29 randomi?ed.ab.
30 placebo.ab.
31 drug therapy.fs.
32 randomly.ab.
33 trial.ab.
34 groups.ab.
35 27 or 28 or 29 or 30 or 31 or 32 or 33 or 34
36 exp animals/ not humans.sh.
37 35 not 36
38 22 and 26 and 37
39 limit 38 to dt=20160901‐20220426
Appendix 6. Embase (Elsevier) search strategy
#28 #27 AND (2016:py OR 2017:py OR 2018:py OR 2019:py OR 2020:py OR 2021:py OR 2022:py)
#27 #23 AND #26
#26 #24 OR #25
#25 random*:ab,ti OR placebo*:ab,ti OR factorial*:ab,ti OR crossover*:ab,ti OR 'cross over':ab,ti OR 'cross‐over':ab,ti OR volunteer*:ab,ti OR assign*:ab,ti OR allocat*:ab,ti OR (((singl* OR doubl*) NEAR/1 blind*):ab,ti)
#24 'randomized controlled trial'/exp OR 'single blind procedure'/exp OR 'double blind procedure'/exp OR 'crossover procedure'/exp
#23 #18 AND #22
#22 #19 OR #20 OR #21
#21 'vaccination'/de
#20 vaccin*:ab,ti OR immuni*:ab,ti OR inocul*:ab,ti
#19 'vaccine'/exp
#18 #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16 OR #17
#17 'respiratory syncytial virus':ab,ti OR 'respiratory syncytial viruses':ab,ti OR rsv:ab,ti
#16 'respiratory syncytial pneumovirus'/de OR 'respiratory syncytial virus infection'/de
#15 adenovir*:ab,ti
#14 'adenovirus'/exp OR 'human adenovirus infection'/de
#13 coronavir*:ab,ti
#12 'coronavirus'/de OR 'coronavirus infection'/de
#11 parainfluenza*:ab,ti
#10 'parainfluenza virus 1'/de OR 'parainfluenza virus 2'/de OR 'parainfluenza virus 3'/de OR 'parainfluenza virus4'/exp
#9 'parainfluenza virus'/exp
#8 'paramyxovirus infection'/de
#7 rhinovir*:ab,ti OR hrv:ab,ti
#6 'rhinovirus infection'/de OR 'human rhinovirus'/de
#5 coryza:ab,ti
#4 'acute upper respiratory infection':ab,ti OR 'acute upper respiratory infections':ab,ti OR 'acute upper respiratory tract infection':ab,ti OR 'acute upper respiratory tract infections':ab,ti OR ((acute NEAR/5 (urti OR uri)):ab,ti)
#3 'viral upper respiratory tract infection'/de OR 'upper respiratory tract infection'/de
#2 'common cold':ab,ti OR 'common colds':ab,ti
#1 'common cold'/de OR 'common cold symptom'/de
Appendix 7. CINAHL (EBSCO) search strategy
S34 S23 AND S33 Limiters ‐ Published Date: 20160101‐20220426
S33 S24 OR S25 OR S26 OR S27 OR S28 OR S29 OR S30 OR S31 OR S32
S32 (MH "Quantitative Studies")
S31 TI placebo* or AB placebo*
S30 (MH "Placebos")
S29 TI random* or AB random*
S28 TI (singl* mask* or doubl* mask* or tripl* mask* or trebl* mask*) or AB (singl* mask* or doubl* mask* or tripl* mask* or trebl* mask*)
S27 TI (singl* blind* or doubl* blind* or trebl* blind* or tripl* blind*) or AB (singl* blind* or doubl* blind* or trebl* blind* or tripl* blind*)
S26 TI clinic* w1 trial* or AB clinic* w1 trial*
S25 PT clinical trial
S24 (MH "Clinical Trials+")
S23 S18 AND S22
S22 S19 OR S20 OR S21
S21 TI (vaccin* or immuni* or inocula*) or AB (vaccin* or immuni* or inocula*)
S20 (MH "Immunization")
S19 (MH "Vaccines+")
S18 S1 OR S2 OR S3 OR S4 OR S5 OR S6 OR S7 OR S8 OR S9 OR S10 OR S11 OR S12 OR S13 OR S14 OR S15 OR S16 OR S17
S17 TI (respiratory syncytial virus* or rsv ) or AB (respiratory syncytial virus* or rsv)
S16 (MH "Respiratory Syncytial Virus Infections")
S15 (MH "Respiratory Syncytial Viruses")
S14 TI adenovir* or AB adenovir*
S13 TI coronavir* or AB coronavir*
S12 (MH "Coronavirus+")
S11 (MH "Coronavirus Infections")
S10 TI parainfluenza* or AB parainfluenza*
S9 (MH "Paramyxovirus Infections")
S8 (MH "Paramyxoviruses")
S7 TI hrv or AB hrv
S6 TI rhinovir* or AB rhinovir*
S5 (MH "Picornavirus Infections")
S4 TI (upper respiratory tract infection* or upper respiratory infection*) or AB (upper respiratory tract infection* or upper respiratory infection*)
S3 TI coryza or AB coryza
S2 TI common cold* or AB common cold*
S1 (MH "Common Cold")
Appendix 8. LILACS (BIREME) search strategy
((mh:"Common Cold" OR "common cold" OR "common colds" OR coryza OR "Resfriado Común" OR "Resfriado Comum" OR "Coriza Aguda" OR "Upper Respiratory Tract Infections" OR "upper respiratory tract infection" OR "Infecciones del Tracto Respiratorio Superior" OR "Infecciones de las Vías Respiratorias Superiores" OR "Infecções do Trato Respiratório Superior" OR "Infecções das Vias Respiratórias Superiores" OR "Infecções das Vias Aéreas Superiores" OR "Infecções do Sistema Respiratório Superior" OR mh:"Picornaviridae Infections" OR "Infecciones por Picornaviridae" OR "Infecções por Picornaviridae" OR "Picornavirus Infections" OR mh:rhinovirus OR rhinovir* OR "Virus de la Coriza" OR "Virus del Resfriado Común" OR "Vírus da Coriza" OR "Vírus do Resfriado Comum" OR hrv OR mh:"Paramyxoviridae Infections" OR parainfluenza* OR mh:"Parainfluenza Virus 1, Human" OR mh:"Parainfluenza Virus 2, Human" OR mh:"Parainfluenza Virus 3, Human" OR mh:"Parainfluenza Virus 4, Human" OR mh:"Coronavirus Infections" OR coronavir* OR mh:coronavirus OR mh:"Coronavirus 229E, Human" OR mh:"Coronavirus OC43, Human" OR mh:"Coronavirus NL63, Human" OR mh:adenoviridae OR mh:"Adenoviruses, Human" OR mh:"Adenovirus Infections, Human" OR adenovir* OR mh:"Respiratory Syncytial Viruses" OR "Virus Sincitiales Respiratorios" OR "Vírus Sinciciais Respiratórios" OR "Virus Sincitial Respiratorio" OR "Vírus Sincicial Respiratório" OR mh:"Respiratory Syncytial Virus, Human" OR "respiratory syncytial virus" OR "Virus Humano Respiratorio Sincitial" OR mh:"Respiratory Syncytial Virus Infections" OR "Infecciones por Virus Sincitial Respiratorio" OR "Infecções por Vírus Respiratório Sincicial" OR rsv) AND (mh:vaccines OR vaccin* OR vacunas OR vacinas OR mh:d20.215.894* OR mh:vaccination OR vacunación OR vacinação OR mh:"Mass Vaccination" OR mh:immunization OR inmunización OR imunização OR mh:e02.095.465.425.400* OR mh:e05.478.550* OR mh:n02.421.726.758.310* OR mh:n06.850.780.200.425* OR mh:n06.850.780.680.310* OR mh:sp2.026.182.113* OR mh:sp8.946.819.838* OR immuni* OR inmuni* OR imuni*) ) AND ( db:("LILACS") AND type_of_study:("clinical_trials")) AND (year_cluster:[2016 TO 2022])
PRISMA flowchart
Screen4Me summary diagram.
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages.
Risk of bias summary: review authors' judgements about each risk of bias item for the included study.
Comparison 1: Adenovirus vaccines versus placebo, Outcome 1: Incidence of the common cold
| Virus vaccines compared to placebo for preventing the common cold in healthy people | ||||||
| Patient or population: young, healthy men in a military facility | ||||||
| Outcomes | Illustrative comparative risks* (95% CI) | Relative effect | No. of participants | Certainty of the evidence | Comments | |
|---|---|---|---|---|---|---|
| Assumed risk | Corresponding risk | |||||
| Placebo | Virus vaccines for preventing the common cold | |||||
| Incidence of the common cold Number of participants with common cold by group | Study population | RR 0.95 | 2307 | ⊕⊝⊝⊝ |
| |
| 12 per 1000 | 11 per 1000 | |||||
| Vaccine safety Follow‐up: mean 9 weeks | The study reported that there were no differences between groups in vaccine‐related adverse events. | 2307 | ⊕⊝⊝⊝ |
| ||
| Mortality: vaccine related and all cause ‐ not reported Follow‐up: mean 9 weeks | See comments | The included study did not report this outcome. | ||||
| *The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; RR: risk ratio | ||||||
| GRADE Working Group grades of evidence | ||||||
| aDowngraded one level due to unclear risk of bias. | ||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Incidence of the common cold Show forest plot | 1 | Risk Ratio (M‐H, Fixed, 95% CI) | Subtotals only | |
