Coronavirus infections of man associated with diseases other than the common cold.

About 14,000 paired sera, from patients with various types of acute infectious diseases with suspected viral origin, were screened by complement fixation against a wide set of viral antigens, including coronavirus OC43. A significant change in OC43 antibodies was recorded in 33 cases and a constant high titre, defined as a titre occurring in the respective age group in less than 1% of all sera examined, was found in 45 cases. On the basis of careful retrospective analysis of hospital case records it was concluded that in 28 cases with an increase of OC43 antibody titres, and in two with titre decrease, a disease could be associated with an acute coronavirus infection. In 16 cases the disease was dominated by respiratory symptoms. Eight of these patients, four children and four adults, had pneumonia. Three of the eight pneumonia patients had, however, another concomitant infection, too. Four patients had neurological symptoms, one had severe perimyocarditis, and in five cases fever was the only symptom recorded. Among the patients with a statistically significant high titre of OC43 antibodies, there were 14 cases where a suggestive association with a disease could be envisaged on the basis of hospital records. Five of these patients had pneumonia. These results suggest that human coronaviruses, so far considered only as one group of causative agents of the common cold, may also be associated with other and more severe diseases in all age groups.

Lack of measurable complement fixing antibodies against viral antigens.

A serological and clinical study was performed to find the common features of 130 patients without antibodies against 11 or more different antigens in the complement fixation (CF) test. These patients (=1.6%) were discovered during hte screening of 8,021 adult patients. Rheumatoid factor(s) (RF) were found in the sera of 113 of the patients. In the remaining 17 patients no common serological or clinical markers were found. Myeloma M-components were found in three cases. The lack of measurable CF antibodies in RF positive cases was apparently due to the inhibitory effect of RF(s) in the CF test. This was indicated by a positive reaction in CF after centrifugal separation of IgM and IgG fractions and also by the detection of antibodies using immunodiffusion method. Possible immune complexes were sought using the platelet aggregation test, which was positive for the sera of 47 (=37%) of the patients. The clinical diagnosis of the 130 CF-nonreactors was rheumatoid arthritis (RA) (ARA criteria) in 23 cases and pulmonary diseases in 65 cases. In a comparison group of equal size there were only 3 RA patients and 15 with pulmonary disease. RA was thus found in 20% of the RF positive CF-nonreacting patients. In the comparison group of 52 RA patients 8 CF-nonreactors were found (=15%). This suggests that the effect of RF(s) from RA patients in CF reaction varies greatly.

Antibodies to human coronavirus OC43 measured by radial haemolysis in gel.

An application of the haemolysis-in-gel (HIG) technique was developed to quantitate antibodies against the human coronavirus OC43. Preinfection and convalescent sera from two patients with verified OC43 infection showed a significant increase in antibody titres measured by HIG as well as by haemagglutination-inhibition (HI). 241 of the other 306 sera tested (80%) caused radial haemolysis in gels containing viral antigen-sensitized erythrocytes and complement. No haemolysis was seen in gels prepared with unifected material. Correlation of the diameter of the haemolysis ring to the respective HI titre was highly significant. However, 62 sera (20%) with HI titres between 8 and 320 were negative in the HIG. Attempts to show that these sera contained nonspecific inhibitors of haemagglutination were unsuccessful. OC43 HI and HIG probably measure different antibody ppulations.