Interpretation
Total number of COVID-19 cases diagnosed by the Italian Regional Reference Laboratories among women of reproductive age was 28.661 in Italy until April 28 with about 51% observed in the age group 40-49 years (10). In our study, 84.6% of cases were registered in the northern regions, in line with the distribution on the total number of COVID-19 cases in Italy, of whom 80% were observed in the North during the study period (10).
Unlike studies regarding Chinese cases (11), which are retrospective and hospital-based, this research, like the UKOSS study (4), is prospective and population-based providing data to hypothesise several factors associated with the development of the disease during pregnancy.
Medical history of the enrolled women shows that multiparas and obese women are more frequent among those with COVID-19 infection compared to the background population of women in reproductive age (12,13). The prevalence of obesity is 17% vs 7% among Italian women of reproductive age (14) and multiparas are 68% vs 49% of the women giving birth in the northern Italian regions (15,16). Pregnant women with non-Italian citizenship have the same prevalence reported in Northern Italy among Italian residents in reproductive age (14,15); however, the proportion presenting with pneumonia is higher compared to Italian women. This difference could be due to a delayed access to care among immigrant women. A higher than expected number of multiparas was affected, probably because living with several children — who are often asymptomatic — may facilitate transmission.
The most common symptoms reported at the time of hospitalisation were fever (63%), cough (71%) and general weakness (48%) like those described by the European Surveillance System (16) among the general population and those reported by pregnant women affected by COVID-19 in other countries (4,5,11).
COVID-19 interstitial pneumonia affected 41.5% of hospitalised women. Previous comorbidities are significantly associated (p= 0.002) to the risk of developing pneumonia. Comorbidities can drastically weaken the immune system and can cause conditions directly related to a greater risk of respiratory infections. Despite the small numbers of this preliminary analysis, the 4 women with autoimmune disease deserve attention.
The clinical picture of patients diagnosed with COVID-19 pneumonia is similar to those described in China and UK (4,5,11), and it seems to be less serious than the effects on the general population (16) although this comparison should consider that the proportion of affected women who access care is greater among pregnant women than the general population. Similarly to the UKOSS study (4), among women affected by COVID-19 pneumonia, 11% had severe complications and were admitted to an ICU whereas among hospitalised patients with SARS-CoV-2, collected by the Italian Integrated surveillance, patients requiring ICU admissions were 22.8% (11). The lower number of women who developed severe symptoms compared to the general population is in line with the hypothesis that changes in the hormonal milieu in pregnancy, which influence immunological responses to viral pathogens, together with the physiological transition to a Type 2 T helper cells environment, which favours the expression of anti-inflammatory cytokines, help to reduce the inflammatory response that, in the very severe COVID-19 infections, is responsible for multi-organ damage (17,18).
Compared to China (19), Italy uses X-rays more often than CT scans in diagnosis, while lung sonograms are used both for pneumonia diagnosis and monitoring. Validation of this diagnostic tool is of primary importance because it is simple, cheap, safe, and easy for OBGYN staff to access (20).
Lymphocyte counts and CRP are confirmed as the best laboratory parameters for testing for the presence of the disease both in women with pneumonia and in those without.
Effectiveness and safety of the drugs used are still uncertain due to the small number of cases and to the limited available knowledge (21). In the present cohort 76.7% of the hospitalised women received at least one pharmacological treatment and 33.8% has been treated with an antiviral (Tab.3). Treatments have been used in percentages considerably higher among women affected by pneumonia, mainly hydroxychloroquine and antivirals combined in approximately half of the cases alongside an empirical antibiotic treatment. Hydroxychloroquine is the most widely used drug, probably due to its ascertained safety profile in pregnant women (21). Information on the use of anticoagulants is lacking and a specific question has been recently added to the data collection form.
There are several open questions on clinical and public health policies aspects that emerge from the data analysis and that merit further research.
With a view to public health policy, it is essential to prepare for an effective vaccination campaign against seasonal flu so that next fall the uptake of flu jabs among pregnant women can be increased from current levels of 7%. A further advantage of this would be to distinguish more easily between seasonal flu and COVID-19. The observation that almost half of the cohort had unaware at-risk contacts in the two weeks before the onset of symptoms highlights the issue of the asymptomatic infections impact and strengthens the recommendations of social distancing and contact tracing measures amongst pregnant women. Given the risk of asymptomatic viral shedding some hospitals started universal screening of patients on labour and delivery. Defining a single, nationwide strategy offering testing for pregnant women is of paramount importance in order to avoid distortions in the estimates of the frequency of the condition resulting from different regional approaches.