EPIDEMIOLOGY OF THE INITIAL PERIOD OF NOVEL CORONAVIRUS (COVID-19) PANDEMIC IN THE REPUBLIC OF MOLDOVA

The health status of with COVID-19 was in 8.0 ± 0.9% of moderate severity – in 34.7±1.5% and satisfactorily severe – in 57.3±1.6% of cases. Conclusions. The identified clinical and epidemiological aspects allowed readjusting the public health policies in order to prevent the spread of COVID-19 infection among


INTRODUCTION
Coronavirus belongs to a large family of viruses that can cause various symptoms such as pneumonia, fever, shortness of breath and lung infection (1). These viruses are common in animals around the world but are known to affect humans in some cases. Although coronaviruses are a large family of viruses, it is considered that only six (229E, NL63, OC43, HKU1, MERS-CoV, and SARS-CoV) could infect humans. Thus, 2019-CoV became the seventh (2,3).
The World Health Organization (WHO) used the term new coronavirus 2019 to refer to a coronavirus that affected the lower respiratory tract of patients with pneumonia in Wuhan, China, on December 29, 2019 (4,5,6). The WHO has announced that the official name of the new type of coronavirus in 2019 is COVID-19 -coronavirus disease (6).
And the current reference name for the virus is Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). This is a single-stranded RNA coronavirus with positive polarity. The virus underwent a genomic sequence, following the nucleic acid testing on specimens from a patient with pneumonia during the 2019-2020 Wuhan coronavirus epidemic. Wuhan beta-coronavirus sequences have similarities to the betacoronaviruses identified in bats. However, the virus is genetically distinct from other coronaviruses, such as SARS-CoV and MERS-CoV (7).
At the end of December 2019, a group of patients was hospitalized with an initial diagnosis of pneumonia with an unknown etiology. These patients have been epidemiologically related to a seafood and wet animals wholesale market in Wuhan, Hubei Province, China (8). Early reports predicted the emergence of a potential Coronavirus outbreak, by estimating the reproduction number of the novel Coronavirus (COVID-19, named by the WHO on 11 February 2020) as being significantly higher than 1 (intervals from 2.24 to 3.58) (9). By April 6, 2020, more than 134,901 people were infected worldwide, by affecting almost every country across the globe. Moreover, at the beinning of April, the mortality rate was calculated in the following countries like Germany, this index being of 1.2%, compared to Italy -11.9%, Spain -8.6%, the Netherlands -8%, the United Kingdom -7.1% and France -9.0% (10,11). Howev-er, the overall mortality rate accounted for 2.2-3.4% (12).
Globally, about 3.4% of reported COVID-19 cases have died. By comparison, seasonal flu generally kills much less than 1% of those infected (13,14). Virus susceptibility appears to be associated with age, gender and other health conditions (15). COVID-19 has now been declared by the WHO as public health emergency of international concern (16).
Due to the rapid spread of the new coronavirus and its effects on human health, the scientific community responded quickly to the new virus and many early research studies have already been published on this epidemic (9)(10)(11)(12)(13)(14). This article is aimed to provide information and evidence on the evolution of the COVID-19 epidemic in the Republic of Moldova at its initial stage. This article can provide meaningful information for future research on this topic and justify the governmental decision-making on management strategies regarding this public health emergency at both community and national level. The combination of epidemiological data can provide an early understanding of the pandemic situation, thus promoting a balanced and welltargeted action from public health perspective.

MATERIAL AND METHODS
The present cross-sectional descriptive study was conducted from March 7 -April 6, 2020. The national surveillance system data of the Republic of Moldova have been reported cases based on standard case definition, namely, COVID-19 suspected, possible or confirmed cases during the initial stage of the epidemic. All cases of COVID-19 were confirmed via molecular biology (Real-Time PCR) techniques. The confirmed case definition was used according to the national legislation in force, namely "A person with laboratory confirmation of COVID-19 infection, regardless of clinical signs and symptoms." The statistical data have been processed via MicrosoftExcel and EpiInfo 7.2.

RESULTS
The first suspected COVID-19 case in the Republic of Moldova was reported on March 7, fol lowed by laboratory confirmation on 08 March in a person who entered the country. In the following week, there was a steady increasing daily tendency, with unique cases being registered. A constant increase in the number of cases were reported over the next 2 weeks, viz. tens of newly-infected people per day, so that over the last week there was a sudden increase in the number of cases, being estimated to around 100 cases per day. On April 6.965 cases were registered, whereas 101 cases had been reported a day before ( fig. 1).  During the initial period of the epidemic, the total number of people infected with the novel coronavirus accounted for 385 patients from rural areas and 539 patients from urban areas. Therefore, the incidence rate made up 41.7±1.6% cases -rural areas and 58.3±1.6%urban areas, respectively. This phenomenon is probably due to the massive internal and exter   1 0 2 2 1 2 4 11 6 1 6 13 17 14 14 15 16 24 28 22      Out the total number of women, 11 women were found pregnant, which made up 1.9% of pregnancy cases. Furthermore, 2 people pregnant were reported as being in the first trimester (25%), 5 pregnant women were in the second trimester of pregnancy (62.5%), and only one woman was in the third trimester of gestation (12.5%).
The study of age-related COVID-19 distribution showed that the most affected were people aged 50-59 years, which included 232 cases, followed by people aged between 40-49 years found in 170 COVID-19 cases. People aged 30-39 years were ranked third among total number, found in 152 confirmed cases, followed by a small difference in-group of people aged 60-69 years, accounting for 147 of infected cases. The least number of infected cases were reported in children (0-9 years) with a total of 37 cases and in those older than 80 years, where only 6 cases were recorded ( fig. 5). Another important epidemiological aspect included within the study refers to people traveling abroad in the last 14 days before the onset of disease. Therefore, the distribution of people who traveled abroad within 14 days before the onset of the disease was 20.2±1.6% (129 cases); those who did not travel abroad 79.8±1.6% (510 cases); those who traveled or admitted to have been in contact with a confirmed case of COVID-19 abroad -22.7±4.0% (25 cases); 43.7±4.7% (48 cases) could not confirm or deny being in contact with infected people; 33.6±4.5% (37 cases) stated that they were not in contact with a confirmed case of COVID-19 abroad ( fig. 6).   . 7). Figure 7. Distribution of cases that were in/no contact with people diagnosed with COVID-19 (in%).
The Republic of Moldova, as well as other countries registered a number of SARS-CoV-2 -infected health care workers. The HCWs were a subject of specific testing strategy, therefore some selection bias could influence the figures regarding the HCWs infection prevalence. The HCWs as general population have been tested in case of COVID-19 suspecting, when they were exposed to the risk in the health care facilities also when they were identified as being in con-tact with a confirmed case. The local initial epidemic stage revealed that out of the total of 965 infected people, 257 were healthcare workers, which made up 26.6±1.4% of cases. Out of these cases, 88 (34.2±3.0%) were nurses, 76 (9.    . 9).

DISCUSSIONS
The epidemiological situation in the Republic of Moldova has evolved following WHO well-known scenarios: "zero", imported cases, clusters and community transmission. The first COVID-19 case, which was confirmed on 8 March 2020, did not surprisingly occur. Furthermore, the infection transmitted among people through close contact, including family members. Clusters and later community transmission were registered.
The present study findings are similar to other studies that found a higher percentage of infected people in urban living environment. Thus, Fan J. et al. (17) found that in China's Gansu Province, the share of urban COVID-19 infected people was 58.3%. The same findings were reported by another study conducted in China in Tianjin Province by Cao C et al. (18) that determined COVID-19 infection in 52.4% of cases from urban areas and in suburban, whereas 47.6% cases were from rural areas. These findings as well as those of the present study can be explained by the fact that SARS-CoV-2 is more easily spread in urban areas due to higher population density, closer contact between subjects and less social distancing compared to rural living environment.
Regarding the age of patients with COVID-19 in the initial period, studies in outbreaks in China found that in Gansu Province, the patients identified in the early period were younger than those identified in the late period, but in general 54 of patients were younger (mean age 38 years) than patients identified in the early stage of the outbreak in Wuhan (mean age 59 years) (4). In this context, the mean age of 45.2 years was recorded in the early period of the COVID-19 epidemic in the Republic of Moldova, which tends to resemble the indices recorded in other (secondary) outbreaks, other than the initial one in the Chinese city of Wuhan. By assumption, COVID-19 have been registered among middle age group, because cases at the beginning of pandemic have been mainly imported, and represent middle-age people who are working abroad with following transmission of the virus among their family members, In the study of Fan J. (17) the distribution of the disease by sex did not differ significantly between the early and late periods, but number of female patients slightly predominated. In contrast, Chen and colleagues reported more men than female patients in the Wuhan outbreak (19). Cao C. and co-workers also re-ported higher prevalence of infection in men in their Tianjin study, accounting for 51.64% and women in 48.06% (18). In the context of these confusing data, it is still premature to interpret the obtained study data where the COVID-19 incidence in women is obviously higher than in men.
As regarding the most affected age group, almost all the studies showed that middle-aged people were the most affected, especially those aged 40-49 years, followed by people aged 50-59 (17,18,19). It could be assumed that this is associated with people migration particularly in Italy and Great Britain, middle-aged females being the most affected ones. The study conducted during the reference period revealed a tendency of increasing COVID-19-associated morbidity in people aged 50-59 years. However, further additional information is required to trace out final conclusions. In Romania, the last official and valid report was made on April 3. By that time, 474 doctors and other medical staff were infected in the neighboring country, out of a total 3,183 cases, the incidence rate being of 14.8%. It should be noted that 318 cases were reported within a hospital in Suceava. On March 30, the incidence rate was 14.5% (25). Compared to these data, our study revealed that the percentage of COVID-19 -confirmed cases among healthcare workers accounted for 26.6±1.4%.
Therefore, there is a great difference in the incidence of infected healthcare workers across the countries worldwide due to economic and sociocultural differences, access to protective equipment, medical staff training and compliance to preventive and control measures etc.
As regarding the clinical aspects of COVID-19 infection worldwide, particularly of patient's condition, 4% of cases were reported as severe, followed by milder or moderate severity level (26). If compared to this index from the Republic of Moldova, our study revealed 8% of patients with severe clinical evolution; therefore, all suspected cases were admitted to the hospital. However, due to the differences among counties regarding hospitals admission criteria as well as assigning of the severity of cases it is difficult to affirm that there were any specific issues regarding the higher diseases' severity. Another indicator evaluated at this stage was the share of closed cases. The global indicator is 32.03% compared to 6.3% of closed cases from the Republic of Moldova. This gap is probably due to the late onset of the pandemic in the Republic of Moldova, considering that the recovery period of patients with COVID-19 lasts up to a month, however, it might vary, depending on the clinical form and manifestations. There are also great concerns regarding the high rate of lethal cases among patients in the Republic of Moldova -34.4% compared to 21.0% worldwide, thus implicitly displaying a lower rate of discharged patients from Moldova -65.6% compared by 79.0% globally (26).