Nasal washings were collected from 27 normal adults during 38 naturally acquired colds. The washings were exhaustively tested using tissue cultures, organ cultures and electron microscopy. Washings yielding no identifiable agent were inoculated into human volunteers, and further specimens obtained from the latter were examined by the same techniques in vitro. Viruses were identified in association with 25 of the original 38 colds (65.7%). Fifteen were rhinoviruses (39.5%), seven coronaviruses (18.4%), two were para-influenza viruses, and one was influenza virus. Use of organ cultures and of volunteers significantly increased the isolation rate. No agent was cultivated from the remaining 13 specimens, although tests in volunteers showed that cold-producing agents were present in five of them (13%). Three specimens gave doubtful results in volunteers, and five others, all collected within a period of six weeks in December and January, apparently contained no infectious agent.

Strains of human coronavirus (HCV) isolated between 1974 and 1976 have been studied in vitro and in volunteers. All strains caused colds in volunteers, and those cultivable in tissue culture (TC) produced significantly more coryza and less sore throat than strains growing only in organ culture (OC). The TC strains were serologically related to 229E, but these isolates produced colds with a frequency and severity that contrasted with the effects of 229E itself. Tests on volunteers' preinfection sera showed that the prevalence of antibody to 229E had increased during the period 1961-1979 and that during 1977-1979 only 11% of subjects had no neutralising antibody against 229E. Susceptibility to the 229E-related isolates PR and TO was associated with low preinfection serum neutralising antibody against the homologous virus, and paired sera frequently showed fourfold or greater antibody rises, most commonly against the homologous strain. Volunteers infected with TO were immune when reinoculated with the same strain approximately 1 year later, but other similar volunteers were at least partly susceptible to infection with a heterologous 229E-related virus after similar time intervals. Although the strains of HCV that were grown in tissue culture were all related to the prototype 229E, they appeared not to be identical with it, and this heterogeneity is probably a significant factor in the epidemiology of HCV infections.

In vitro studies have shown the compound 2-amino-1-(isopropyl sulphonyl)-6-benzimidazole phenyl ketone oxime (enviroxime) to be highly active against rhinoviruses. 48 volunteers were given intranasal and oral enviroxime, or placebo, one day before and for five days after infection with rhinovirus type 9. Symptoms of rhinovirus infection and the virus titre of nasal wash specimens were reduced in the enviroxime group, and there was a significant decrease in rhinorrhoea. Although there were some adverse reactions to oral enviroxime, the results indicate that antiviral activity was due to drug administered in the nasal spray and that enviroxime has potential as an antirhinovirus agent for clinical use.

Antibody rises to various virus subcomponents were measured by enzyme-linked immunosorbent assay in the paired sera of volunteers experimentally infected with human coronavirus 229E group viruses. Most of the antibody made during infection was directed against the virus surface projections, with only small amounts of antibody made against membrane or ribonucleoprotein components.

Paired sera from volunteers inoculated with one of the five recently isolated strains of human coronavirus (HCV), AD, GI, HO, PA, and RO, none of which has been grown in tissue culture, or with strain OC38 were tested against coronavirus antigens by enzyme-linked immunosorbent assay. When HCV strains OC43, 229E, or the 229E-related tissue culture-adapted strains PR and TO were used as antigens, it was shown that all strains fell into one of two antigenic groups. The HCV OC43 group was comprised of strains OC43, GI, HO, and RO, and the HCV 229E group contained strains AD and PA as well as the tissue culture-adapted strains PR, TO, and KI. Enzyme-linked immunosorbent assay of the paired sera with the coronavirus mouse hepatitis virus strain 3 as antigen confirmed the relationship of this virus to the HCV OC43 group but not to the HCV 229E group.

The common cold syndrome and its causes are discussed and the feasibility of prophylaxis considered.

Fifty-two volunteers were given experimental colds by nasal inoculation with rhinoviruses during the course of a 10-day residential stay at the Common Cold Research Unit, Salisbury. Prior to their inoculation with virus, they were assessed on five different measures of recent life stress and they also completed the E.P.I. Clear evidence of a psychosomatic component in colds was obtained. Introverts developed significantly worse symptoms and infections than Extraverts. And life events, when they involved change in the person's general level of activity, were significantly related to magnitude of infection. Infection was assessed daily by measuring the amount of virus present in nasal washings. Some implications of these findings are discussed.

Volunteers were treated with fibroblast interferon or placebo nose drops for four days. On the second day, they received a challenge with rhinovirus type 4. There was no difference in the clinical symptoms or viral shedding between the two groups. The possible reasons for this result are discussed.

An enzyme-linked immunosorbent assay was developed for detecting antibody rises to human coronavirus strain 229E and related strains in paired sera from infected volunteers. There was a close correlation between development of colds infected volunteers. There was a close correlation between development of colds and significant antibody rises detected by the enzyme-linked immunosorbent assay. Furthermore, the assay was more sensitive than a neutralization assay. This enzyme-linked immunosorbent assay is an easy, accurate, and sensitive assay for measuring significant antibody rises to human coronavirus strain 229E group viruses, and it could be useful in the clinical diagnosis of these infections.

The compound 2-amino-1-(isopropyl sulfonyl)-6-benzimidazole phenyl ketone oxime (LY122771-72) at a concentration of 0.2 microgram/ml completely inhibited rhinovirus replication in human embryonic nasal organ cultures, although in the absence of virus the compound did not inhibit ciliary activity when used at a concentration of 25 micrograms/ml. When added 26 hr after infection, the compound stopped rhinovirus production in organ cultures that had already started to release virus. Five rhinovirus types available for infection of volunteers and six recently obtained clinical isolates were shown to be more sensitive to LY122771-72 in tissue culture than the rhinovirus type 31 used in the organ culture experiments. These results suggest that this potential antiviral drgu should be evaluated in humans.

An extract and a filtrate prepared from feces of a child with mild gastroenteritis were shown by electron microscopy to contain numerous astrovirus particles and were given to eight volunteers by mouth. One subject developed diarrheal illness and concurrently shed large amounts of astrovirus in feces, and one other had mild constitutional symptoms with a lower level of virus shedding. Nine other volunteers were given fecal filtrate from the volunteer with diarrhea, and astrovirus shedding subsequently occurred in two of them. The syndrome accompanying virus shedding appeared distinct from that associated with the "W" agent in previous experiments. Thirteen of 16 astrovirus-inoculated subjects subsequently developed a rise in titer of the homologous antibody in serum. It was concluded that astrovirus causes a transmissible infection that is of low pathogenicity for adults. Immunofluorescence of human embryo kidney cells inoculated with astrovirus and shown by electron microscopy to contain 28 nm virus-like particles was used both to detect virus in feces and to assay astrovirus antibody.

The influence of experimentally induced rhinovirus infection on the excretion of ascorbic acid (AA) and two of its possible metabolites, diketogulonic acid (DKG) and oxalic acid was determined in human volunteers receiving a controlled daily intake of AA. There was a significant fall in the excretion of both AA and DKG in the infected subjects but no change in the oxalic acid excretion. A simple absorption test provided no evidence of any impairment of gastrointestinal absorption of AA during infection. Possible mechanisms of this infection-induced change in AA metabolism are discussed.

Sputum, nasal swabs, and throat swabs were obtained from 22 children aged between 5 and 15 years during 72 attacks of wheezy bronchitis. A virus, most commonly a rhinovirus, was isolated in 49% of all episodes and in 64% of 22 severe episodes requiring treatment with corticosteroids; the isolation rate was higher early in the illness than later. Virus was recovered more often from sputum than from the nose or throat, suggesting that viral replication occurs freely in the lower respiratory tract: the cytological findings in sputum were compatible with an inflammatory response to viral infection. Pathogenic bacteria appeared to play a minor role compared with viruses, and routine antibiotic treatment was probably of little value in moost cases. The significance of the results is discussed in relation to the pathogenesis of childhood wheezy bronchitis.

A double-stranded RNA of fungal origin (BRL 5907) was given intranasally to volunteers. Apart from mild local irritancy of the higher dosage, the compound was well tolerated. A double-blind placebo-controlled trial of a three-day course (5 mg per day) of BRL 5907 against challenge with rhinovirus type 4 showed that treatment was associated with a delay in onset of symptoms and a reduction in shedding of virus, but the differences were not statistically significant. Low titers of interferon were found in nasal washings.

Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects.

A study of the effect of cognitive dissonance on symptoms of rhinovirus-induced common colds and their infectivity in 48 volunteers is presented. Subjects, about to be experimentally infected with two common cold viruses (rhinoviruses), were given a choice as to whether or not to receive a “trial anti-viral drug” (in fact a placebo) during the course of their infection. To make this choice difficult, they were also told that if they received the “drug”, their gastric juices would have to be sampled by means of a stomach tube at the end of the experiment. It was predicted from Cognitive Dissonance Theory that all those making this choice, irrespective of the alternative chosen, would justify their decisions by “attenuating” the experienced severity of their colds, and that this effect would be evidenced in their symptoms and possibly in the amount of virus shed as compared to controls who were neither given the placebo nor the choice concerning it.

Ferret trachea organ cultures have been used to measure the therapeutic effect of spiroamantadine against influenza virus A/England/42/72. In untreated cultures virus titres reached their maximum about 5 days after infection, and immunofluorescence studies showed that by the seventh day about 50% of the epithelial cells were infected. Treatment with spiroamantadine (8 μg/ml) starting at times up to 72 h after infection reduced the yield of virus from the cultures. The effect of treatment starting 48 h after infection was compared with that of similar treatment previously reported in infected volunteers. In the latter, virus titres declined more quickly than in the cultures, so that the effects of treatment seemed smaller.

The interaction between short-term sulfur dioxide (SO2) exposure and experimentally induced rhinovirus infection was studied in thirty-two volunteers divided into two groups balanced with respect to age, antibody levels, and nasal mucus flow rates. One group was exposed to SO2 exposure at the threshold limit value (TLV) of 5 ppm during 4 hours; the other group served as controls exposed to pollution-free air under the same conditions. The SO2 exposure caused a 50% decrease in nasal mucus flow rate in the anterior parts of the nose, but there was no difference in the number of colds which developed in the two groups. The group exposed to SO2 had fewer symptoms and a possibly shorter incubation period (P = .06), and virus shedding was at a lower level but more persistent than in the control group. No differences were found in antibody response. The rhinovirus infection in the control group caused a gradual decrease in nasal mucus flow rate starting 2 days after the virus instillation, and after 5 days the rate was less than half its initial value. For future experiments on the interaction between airborne pollutants and rhinovirus infections, a virus challenge by aerosol inhalation is recommended. Our study supports an earlier observation that growth of influenza virus in the nasal cavity of mice was inhibited by exposure to SO2 concentrations of 6 or 20 ppm.

SUMMARYAfter five months of total isolation a wintering party of seventeen British Antarctic Survey (BAS) personnel was inoculated under double blind conditions with placebo, or rhinovirus type 2 which had been propagated in tissue culture. The clinical and virological responses of these subjects were compared with those of volunteers in England who received a similar dose of the same strain. The virus used was apparently partly attenuated for man; at the dosage used its effects in England were similar to a smaller dose of an unattenuated strain, but in the Antarctic it caused relatively severe infections. Both the symptoms and the laboratory evidence of virus infection appeared to be more pronounced in the BAS subjects than in the volunteers in England who received the same challenge. In the former group the infection readily spread to those who were originally given placebo. In the BAS subjects serum antibody titres were well maintained during the isolation period but a significant fall in nasal immunoglobulin concentration was recorded during the 5 months of isolation after the virus challenge. Possible mechanisms for the increased sensitivity to rhinovirus of subjects who have been totally isolated in a small closed community are discussed.