Latest COVID-19 research looks at antibody utility, testing strategies, risk factors

A recent case-control study examined the clinical utility of serum antibodies to SARS-CoV-2. Researchers looked at data from 11,066 patients at Johns Hopkins Hospital in Baltimore who received a nucleic acid amplification test (NAAT) on nasopharyngeal swabs. Of these patients, 115 (1%) were hospitalized adults who were divided into a COVID-19 case group (n=60) or a non-COVID-19 control group (n=55). Laboratory control groups were made up of 513 people who did not receive a NAAT. Enzyme-linked immunosorbent assay was used to detect serum IgG and IgA antibodies against SARS-CoV-2 spike protein. The study results were published July 6 by Annals of Internal Medicine.

For the SARS-CoV-2 IgG assay, sensitivity and specificity were 0.976 (95% CI, 0.928 to 0.995) and 0.988 (95% CI, 0.974 to 0.995), respectively, when the test was performed at least 14 days after symptom onset. For tests done earlier, however, sensitivity was lower. IgG levels remained high during follow-up, up to 58 days. Levels of antibodies to SARS-CoV-2 were related to the risk for acute respiratory distress syndrome, with an increase of 62% (95% CI, 48% to 81%; P<0.001) for every twofold increase in IgG. Among the 11,066 patients who received a NAAT, 457 had repeatedly negative results. In serum samples obtained from 18 of these patients, six who were COVID-19 case-patients and 12 who were non-COVID-19 controls, five of six in the former group and none of 12 in the latter group had antibodies detected (P=0.001). The authors concluded that antibodies to SARS-CoV-2 can indicate infection when measured 14 or more days after symptom onset, are associated with clinical severity, and can provide diagnostic support when patients have negative results on NAAT but COVID-19 is still suspected.

Also on the subject of testing, researchers used a decision analytic model for 1,000 key workers, a category including clinicians and other health care staff, to examine the effects of different testing strategies on absence from work and transmission risks. They compared the baseline strategy of no reverse transcriptase-polymerase chain reaction (RT-PCR) testing with a strategy of testing those with COVID-19-like symptoms in isolation, those without COVID-19-like symptoms in household quarantine, and all staff. Confirmatory retesting scenarios included repeating all initial tests, all initially positive tests, or all initially negative tests, or doing no retests. Infection rates were varied from 0.1% to 20%, the proportion of asymptomatic persons was varied from 10% to 80%, and sensitivity and specificity were varied from 60% to 95% and 90% to 100%, respectively.

The strategy to test all staff changed the risk for workplace transmission by −56.9 to 0.97 workers per 1,000 tests and absence from work by −0.5 to 3.6 days per test. Estimates of tests needed for this strategy ranged from 989.6 to 1,995.9 per 1,000 workers. The strategy of testing those in household quarantine had the most effect on reducing absences (3.0 to 6.9 days per test at 47.0 to 210.4 tests per 1,000 workers) but increased workplace transmission risk by 0.02 to 49.5 infected workers per 1,000 tests, although this could be mitigated by retesting initially negative tests, the researchers noted. They concluded that depending on infection levels and testing capacity, testing staff who are in household quarantine and testing all staff appear to be the best strategies for managing absence duration and transmission risk in COVID-19. The study was published July 8 by Clinical Infectious Diseases.

Two recent studies also looked at risk factors for worse outcomes in COVID-19. The first, a retrospective cohort study published on July 6 by Annals of Internal Medicine, examined the association between obesity and outcomes in 1,687 patients hospitalized with confirmed COVID-19 at two hospitals in New York City. Patients' median body mass index (BMI) was 27 kg/m², and 31.1% were categorized as obese. Over a median follow-up of seven days, the researchers found a J-shaped pattern for in-hospital mortality, where the fully adjusted hazard for death was highest in underweight patients, lowest in overweight patients, and increased progressively with increasing obesity. The fully adjusted hazard ratio for respiratory failure was lowest among normal-weight patients and increased with higher BMI, and patients with respiratory failure also exhibited a J-shaped pattern for in-hospital mortality. The authors concluded that obesity appears to be a risk factor for respiratory failure, partly explaining the extensive use of invasive mechanical ventilation for COVID-19 patients in the United States, but not for in-hospital mortality. They said their results support consideration of obesity prevalence in the community when planning a COVID-19 response.

The second study, published by Emerging Infectious Diseases, followed 178 patients with sickle-cell disease and COVID-19 who were living in the United States from March 20 to May 21. Clinicians caring for patients with sickle-cell disease were asked to report all confirmed cases of COVID-19 to a CDC registry after resolution of acute illness or death. The registry did not include patients with sickle-cell trait or those in whom COVID-19 was suspected but not confirmed. Overall, 69% were hospitalized, 11% were admitted to an ICU, 6% needed a ventilator, 38% needed a transfusion, and 2% needed dialysis. Thirteen patients (7%) died; of these, eight had severe or critical COVID-19 and five had mild or moderate disease. The researchers concluded that patients with sickle-cell disease who develop COVID-19 are at high risk for severe disease and that the case-fatality rate is high. The hospitalization, ICU admission, and mortality rates in their study “are alarming, given that the mean patient age was <40 years,” they wrote. They said that their findings “underscore the need to consider the unique circumstances faced by high-risk subgroups” in COVID-19.

Finally, last week the World Health Organization (WHO) updated its March 29 scientific brief on transmission of SARS-CoV-2, adding information on potential aerosol transmission in non-health care settings. The WHO noted that outbreaks reported in crowded, poorly ventilated indoor settings with close contact, such as choir practices, restaurants, or gym classes, may indicate a potential role for short-range aerosol transmission. The WHO also said, however, that these human-to-human outbreaks could be explained by droplet and fomite transmission and that the close contact involved may have helped to facilitate superspreading events, especially if infection prevention precautions were not taken.