# Epidemiological Patterns of Seasonal Respiratory Viruses during the COVID-19 Pandemic in Madagascar, March 2020-May 2022

Norosoa Harline Razanajatovo, Tsiry Hasina Randriambolamanantsoa, Joelinotahiana Hasina Rabarison, Laurence Randrianasolo, Miamina Fidy Ankasitrahana, Arvé Ratsimbazafy, Antso Hasina Raherinandrasana, Helisoa Razafimanjato, Vololoniaina Raharinosy, Soa Fy Andriamandimby, et al.

► To cite this version:

Norosoa Harline Razanajatovo, Tsiry Hasina Randriambolamanantsoa, Joelinotahiana Hasina Rabarison, Laurence Randrianasolo, Miamina Fidy Ankasitrahana, et al. Epidemiological Patterns of Seasonal Respiratory Viruses during the COVID-19 Pandemic in Madagascar, March 2020-May 2022. Viruses, 2023, 15 (1), pp.12. 10.3390/v15010012. pasteur-04096789

HAL Id: pasteur-04096789

https://riip.hal.science/pasteur-04096789

Submitted on 13 May 2023

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
Article

# Epidemiological Patterns of Seasonal Respiratory Viruses during the COVID-19 Pandemic in Madagascar, March 2020–May 2022

Norosoa Harline Razanajatovo <fnref n="1" />*, Tsiry Hasina Randriambolamanantsoa <fnref n="1" />, Joelinotahiana Hasina Rabarison <fnref n="1" />, Laurence Randrianasolo <fnref n="2" />, Miamina Fidy Ankasitrahana <fnref n="3" />, Arvé Ratsimbazafy <fnref n="1" />, Antso Hasina Raherinandrasana <fnref n="3" />, Helisoa Razafimanjato <fnref n="1" />, Vololoniaina Raharinosy <fnref n="1" />, Soa Fy Andriamandimby <fnref n="1" />, Jean-Michel Heraud <fnref n="4" />,*,† ID, Philippe Dussart <fnref n="1" />,† ID and Vincent Lacoste <fnref n="1" />,†

<figure><img src="image_2.png" /></figure>

check for
updates

**Citation:** Razanajatovo, N.H.; Randriambolamanantsoa, T.H.; Rabarison, J.H.; Randrianasolo, L.; Ankasitrahana, M.F.; Ratsimbazafy, A.; Raherinandrasana, A.H.; Razafimanjato, H.; Raharinosy, V.; Andriamandimby, S.F.; et al.
Epidemiological Patterns of Seasonal Respiratory Viruses during the COVID-19 Pandemic in Madagascar, March 2020–May 2022. *Viruses* 2023, 15, 12. https://doi.org/10.3390/v15010012

Academic Editors: Susana Tereno
Valente, Barbara Baker and Sharon
Lewin

Received: 9 November 2022

Revised: 9 December 2022

Accepted: 16 December 2022

Published: 20 December 2022

<figure><img src="image_3.png" /></figure>

**Copyright:** © 2022 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).

**Abstract:** Three epidemic waves of coronavirus disease-19 (COVID-19) occurred in Madagascar from March 2020 to May 2022, with a positivity rate of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 21% to 33%. Our study aimed to identify the impact of COVID-19 on the epidemiology of seasonal respiratory viruses (RVs) in Madagascar. We used two different specimen sources (SpS). First, 2987 nasopharyngeal (NP) specimens were randomly selected from symptomatic patients between March 2020 and May 2022 who tested negative for SARS-CoV-2 and were tested for 14 RVs by multiplex real-time PCR. Second, 6297 NP specimens were collected between March 2020 and May 2022 from patients visiting our sentinel sites of the influenza sentinel network. The samples were tested for influenza, respiratory syncytial virus (RSV), and SARS-CoV-2. From SpS-1, 19% (569/2987) of samples tested positive for at least one RV. Rhinovirus (6.3%, 187/2987) was the most frequently detected virus during the first two waves, whereas influenza predominated during the third. From SpS-2, influenza, SARS-CoV-2, and RSV accounted for 5.4%, 24.5%, and 39.4% of the detected viruses, respectively. During the study period, we observed three different RV circulation profiles. Certain viruses circulated sporadically, with increased activity in between waves of SARS-CoV-2. Other viruses continued to circulate regardless of the COVID-19 situation. Certain viruses were severely disrupted by the spread of SARS-CoV-2. Our findings underline the importance and necessity of maintaining an integrated disease surveillance system for the surveillance and monitoring of RVs of public health interest.

**Keywords:** viruses; SARS-CoV-2; epidemics; epidemiology; etiology; detection; Madagascar; Africa

## 1. Introduction

Since its emergence in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread throughout the world, infecting billions of people and causing millions of deaths [1]. Madagascar has not been spared by the coronavirus disease-19 (COVID-19) pandemic. The first detection of SARS-CoV-2 cases in Madagascar was reported on March 19, 2020 [2]. Between March and September 2020, the country experienced the first epidemic wave of COVID-19. To limit disease transmission, the authorities implemented mitigation strategies, including non-pharmacological intervention (NPI) measures, such as lockdowns, travel bans, social distancing, the permanent wearing of facial masks, handwashing, and school closures. During this period, the Institut Pasteur de Madagascar (IPM) tested 26,415 nasopharyngeal (NP) swabs from (i) suspected COVID-19 cases,

<footnote n="1">1 National Influenza Center, Virology Unit, Institut Pasteur of Madagascar, Antananarivo 101, Madagascar</footnote>

<footnote n="2">2 Epidemiology and Clinical Research Unit, Institut Pasteur of Madagascar, Antananarivo 101, Madagascar</footnote>

<footnote n="3">3 Direction de la Veille Sanitaire, de la Surveillance Epidémiologique et Ripostes, Ministry of Public Health, Antananarivo 101, Madagascar</footnote>

<footnote n="4">4 Virology Department, Institut Pasteur de Dakar, Dakar 12900, Senegal</footnote>

<footnote>* Correspondence: norosoa@pasteur.mg (N.H.R.); jean-michel.heraud@pasteur.fr (J.-M.H.)</footnote>

<footnote>† These authors contributed equally to this work.</footnote>
(ii) travelers returning from affected areas, and (iii) the contacts of laboratory cases confirmed by real-time RT-PCR. Overall, approximately 21% turned out to be laboratory-confirmed SARS-CoV-2 cases [2]. A second wave occurred from March to May 2021, during which the rate of positivity for SARS-CoV-2 was approximately 29%. Finally, a third wave occurred between December 2021 and February 2022, yielding a detection rate of 33%. Recent studies have shown that the early epidemic periods of SARS-CoV-2 had a significant impact on the circulation pattern of seasonal respiratory viruses (RVs). In addition, the activity of certain viruses with a seasonal profile was delayed [3–7]. Given that the clinical signs and symptoms of COVID-19 are similar to those of RVs, laboratory testing is required for differential diagnosis. In addition, determining trends in RV circulation after the emergence of SARS-CoV-2 is essential for adapting the surveillance system at a national and international level. Our study aimed to (i) identify viral etiologies associated with acute respiratory infection (ARI) in the context of SARS-CoV-2 circulation in Madagascar (from March 2020 to May 2022) and (ii) describe the epidemiology of RVs during the pre-pandemic and pandemic periods.

## 2. Methods

### 2.1. *Study Design*

We used two different specimen sources (SpS) to conduct our study (Supplementary Figure S1). First, we randomly selected 2987 NP swabs (SpS-1) from 20,254 SARS-CoV-2-negative specimens collected from symptomatic cases between March 2020 and February 2022, a period covering the first three epidemic waves of COVID-19 in Madagascar. These specimens originated from various regions of Madagascar. Methodologies for suspected COVID-19 case sampling and SARS-CoV-2 testing were recently published [2]. The randomly selected samples were tested using five multiplex real-time PCR (rtPCR) assays to detect 14 RVs, including influenza (FLU) A and B, respiratory syncytial virus (RSV), human metapneumovirus (HMPV), rhinovirus (HRV), human coronavirus (CoV)-OC43, 229E, NL63, HKU1, parainfluenza viruses (PIV)-1, -2, -3, adenovirus (ADV), and bocavirus (BOV). These five rtPCR assays have already been extensively described [8]. For the second source of specimens (SpS-2), we selected all the NP swabs collected from patients presenting with an influenza-like illness (ILI) or severe acute respiratory infection (SARI) at our healthcare centers or clinics of the Influenza Surveillance Network (ISN). The ISN has been in place for years and monitors the circulation of influenza and other RVs throughout the country through ILI and SARI surveillance sentinel sites [8,9]. Briefly, patients suspected to have the above diseases who visited our sentinel sites were included. Starting in March 2020, outpatients presenting with ILI were tested for FLU and SARS-CoV-2, whereas inpatients presenting with SARI were tested for FLU, SARS-CoV-2, and RSV. We then compared the circulation profile, as well as the demographic and clinical characteristics of the FLU and RSV patients before (January 2018 to February 2020) and during the pandemic period (March 2020 to May 2022).

### 2.2. *Data and Statistical Analyses*

We divided the patients into five age groups: infants and young children (0–4 years), children (5–14 years), adolescents and young adults (15–29 years), adults (30–64 years), and the elderly (≥65 years). For SpS-1, we divided the period according to the three SARS-CoV-2 epidemic waves: wave one (March–September 2020), wave two (March–May 2021), and wave three (December 2021–February 2022). For SpS-2, we considered the pre-pandemic (January 2018–February 2020) and pandemic (March 2020–May 2022) periods. We then compared the proportion of positive cases for each period by taking into account the demographic and clinical variables. Chi-square tests and Fisher exact tests were used to compare the proportion of RV-positive cases during the different periods. We applied the Bonferroni method to adjust the *p*-values if necessary. T-tests and ANOVA were performed to compare the mean ages. *p*-values ≤ 0.05 were considered statistically significant. All the statistical analyses were performed using R (version 4.2.1) software.
## 3. Results

### 3.1. Viral Epidemiology among SARS-CoV-2-Negative Patients during the Epidemic Waves of COVID-19 (SpS-1)

From March 2020 to February 2022, 19% (569/2987) of the tested samples were found to be positive for at least one RV. The proportion of RV-positive samples significantly differed depending on the epidemic wave. The positivity rate was higher in the third wave (25.8%, 258/1001) than in the previous two waves (18.1%, 178/986 and 13.3%, 133/1000 for waves one and two, respectively) (p < 0.001) (Table 1).

<table><caption>**Table 1.** Characteristics of COVID-19-negative patients who tested positive for seasonal respiratory viruses from March 2020 to February 2022.</caption><thead><tr><th rowspan="2">Variable</th><th colspan="2">Global (Wave 1, 2, and 3)</th><th colspan="2">Wave 1 (Mar-Sep 2020)</th><th colspan="2">Wave 2 (Mar-May 2021)</th><th colspan="2">Wave 3 (Dec 2021-Feb 2022)</th><th rowspan="2">p-Value <sup>3</sup></th></tr><tr><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th></tr></thead><tbody><tr><td>Mean age (years)</td><td>32.8</td><td>24.4</td><td>&lt;0.001</td><td>31.4</td><td>24.3</td><td>34.3</td><td>22.2</td><td>32.8</td><td>25.7</td><td>0.408</td></tr><tr><td>Age (years)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>0-4</td><td>428</td><td>165 (38.6)</td><td rowspan="5">&lt;0.001</td><td>139</td><td>59 (42.4)</td><td>134</td><td>44 (32.8)</td><td>155</td><td>62 (40.0)</td><td rowspan="5">0.03 &lt;0.001 &lt;0.001 0.02</td></tr><tr><td>5-14</td><td>234</td><td>56 (23.9)</td><td>79</td><td>12 (15.2)</td><td>77</td><td>18 (23.4)</td><td>78</td><td>26 (33.3)</td></tr><tr><td>15-29</td><td>688</td><td>127 (18.5)</td><td>262</td><td>37 (14.1)</td><td>206</td><td>24 (11.7)</td><td>220</td><td>66 (30.0)</td></tr><tr><td>30-64</td><td>1401</td><td>193 (13.8)</td><td>456</td><td>61 (13.4)</td><td>483</td><td>39 (8.1)</td><td>462</td><td>93 (20.1)</td></tr><tr><td>&ge;65</td><td>207</td><td>21 (10.1)</td><td>48</td><td>8 (16.7)</td><td>83</td><td>3 (3.6)</td><td>76</td><td>10 (13.2)</td></tr><tr><td>ND</td><td>29</td><td>7 (24.1)</td><td>0.002</td><td>2</td><td>1 (50.0)</td><td>17</td><td>5 (29.4)</td><td>10</td><td>1 (10.0)</td><td></td></tr><tr><td>Sex</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>M</td><td>1563</td><td>296 (18.9)</td><td rowspan="3">&lt;0.001</td><td>500</td><td>94 (18.8)</td><td>538</td><td>68 (12.6)</td><td>525</td><td>134 (25.5)</td><td rowspan="3">&lt;0.001</td></tr><tr><td>F</td><td>1420</td><td>272 (19.2)</td><td>484</td><td>84 (17.4)</td><td>462</td><td>65 (14.1)</td><td>474</td><td>123 (25.9)</td></tr><tr><td>ND</td><td>4</td><td>1 (25.0)</td><td>2</td><td>0 (0.0)</td><td>0</td><td>0 (0.0)</td><td>2</td><td>1 (50.0)</td></tr><tr><td>Origin</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Ambulatory</td><td>1812</td><td>401 (22.1)</td><td rowspan="3">&lt;0.001</td><td>843</td><td>159 (18.9)</td><td>477</td><td>91 (19.1)</td><td>492</td><td>151 (30.7)</td><td rowspan="3">&lt;0.001</td></tr><tr><td>Hospital</td><td>885</td><td>126 (14.2)</td><td>134</td><td>19 (14.2)</td><td>334</td><td>25 (7.5)</td><td>417</td><td>82 (19.7)</td></tr><tr><td>ND</td><td>290</td><td>42 (14.5)</td><td>9</td><td>0 (0.0)</td><td>189</td><td>17 (9.0)</td><td>92</td><td>25 (27.2)</td></tr><tr><td>Clinical signs <sup>1</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cough</td><td>1832</td><td>413 (22.5)</td><td rowspan="5">&lt;0.001</td><td>580</td><td>123 (21.2)</td><td>635</td><td>106 (16.7)</td><td>617</td><td>184 (29.8)</td><td rowspan="5">&lt;0.001 &lt;0.001 &lt;0.001 &lt;0.001 0.03 0.03 0.002 &lt;0.001 0.02</td></tr><tr><td>Fever</td><td>1280</td><td>317 (24.8)</td><td>405</td><td>90 (22.2)</td><td>432</td><td>82 (19.0)</td><td>443</td><td>145 (32.7)</td></tr><tr><td>Weakness</td><td>1113</td><td>161 (14.5)</td><td>240</td><td>30 (12.5)</td><td>362</td><td>31 (8.6)</td><td>511</td><td>100 (19.6)</td></tr><tr><td>Runny nose</td><td>921</td><td>242 (26.3)</td><td>292</td><td>58 (19.9)</td><td>296</td><td>62 (20.9)</td><td>333</td><td>122 (36.6)</td></tr><tr><td>Headache</td><td>787</td><td>128 (16.3)</td><td>222</td><td>33 (14.9)</td><td>268</td><td>26 (9.7)</td><td>297</td><td>69 (23.2)</td></tr><tr><td>Sore throat</td><td>520</td><td>95 (18.3)</td><td rowspan="5">&lt;0.001</td><td>139</td><td>19 (13.7)</td><td>174</td><td>21 (12.1)</td><td>207</td><td>55 (26.6)</td><td rowspan="5">&lt;0.001</td></tr><tr><td>Myalgia</td><td>479</td><td>70 (14.6)</td><td>100</td><td>17 (17.0)</td><td>166</td><td>16 (9.6)</td><td>213</td><td>37 (17.4)</td></tr><tr><td>Dyspnea</td><td>421</td><td>56 (13.3)</td><td>109</td><td>17 (15.6)</td><td>173</td><td>14 (8.1)</td><td>139</td><td>25 (18.0)</td></tr><tr><td>Chest pain</td><td>289</td><td>41 (14.2)</td><td>68</td><td>8 (11.8)</td><td>67</td><td>4 (6.0)</td><td>154</td><td>29 (18.8)</td></tr><tr><td>Arthralgia</td><td>252</td><td>33 (13.1)</td><td>130</td><td>13 (10.0)</td><td>66</td><td>5 (7.6)</td><td>56</td><td>15 (26.8)</td></tr><tr><td>Diarrhea</td><td>193</td><td>29 (15.0)</td><td rowspan="3">&lt;0.001</td><td>30</td><td>1 (3.3)</td><td>75</td><td>5 (6.7)</td><td>88</td><td>23 (26.1)</td><td rowspan="3">&lt;0.001</td></tr><tr><td>Vomiting/Nausea</td><td>129</td><td>26 (20.2)</td><td>46</td><td>5 (10.9)</td><td>20</td><td>1 (5.0)</td><td>63</td><td>20 (31.7)</td></tr><tr><td>Abdominal pain</td><td>124</td><td>19 (15.3)</td><td>25</td><td>4 (16.0)</td><td>53</td><td>3 (5.7)</td><td>46</td><td>12 (26.1)</td></tr><tr><td>Intercostal recession</td><td>68</td><td>8 (11.8)</td><td rowspan="2">&lt;0.001</td><td>10</td><td>1 (10.0)</td><td>25</td><td>1 (4.0)</td><td>33</td><td>6 (18.2)</td><td rowspan="2">NA</td></tr><tr><td>Stridor</td><td>51</td><td>6 (11.8)</td><td>19</td><td>1 (5.3)</td><td>11</td><td>1 (9.1)</td><td>21</td><td>4 (19.0)</td></tr><tr><td>Comorbidities <sup>2</sup></td><td>185</td><td>20 (10.8)</td><td>&lt;0.001</td><td>112</td><td>18 (16.1)</td><td>73</td><td>2 (2.7)</td><td>NA</td><td>NA</td><td>0.009</td></tr></tbody></table>

ND: not determined, NA: not applicable. <sup>1</sup> Number of patients that responded "yes" for a given clinical sign.

<sup>2</sup> Comparison between waves 1 and 2 only. <sup>3</sup> Only significant *p*-values are shown (except for the mean age).

Among the positive patients, the sex ratio was 1.1 (296 vs. 272) and the mean age was 24.4 years. There was no statistical difference in the mean age of positive patients between the three epidemic waves. Children < 5 years of age (38.6%; 165/428) were more affected by RVs than those aged > 5 years (15.8%, 404/2559) (p < 0.001). Conversely, patients aged 30-64 years (13.8%, 193/1401) (p < 0.001) and those ≥ 65 (10.1%, 21/207) (p = 0.002) were significantly less affected by RV infection during the study period. A comparison of the proportions of positive samples during the epidemic waves showed no substantial difference for the age group < 5 years, unlike the other age groups, for which we noted a higher infection rate during the third wave (Table 1).
Globally, ambulatory patients (22.1%, 401/1812) had a greater RV-positivity rate than those who were hospitalized (14.2%, 126/885) (*p* < 0.001). This difference was noted in every epidemic wave (Table 1).

Concerning the clinical spectrum, 26.3% (242/921) of tested patients with runny noses were positive for RV (*p* < 0.001). In addition, 24.8% (317/1280) and 22.5% (413/1832) of those presenting with fever and cough, respectively, had an RV infection (*p* < 0.001). Vomiting/nausea, sore throat, and headache were reported in 20.2% (26/129), 18.3% (95/520), and 16.3% (128/787) of RV-positive patients, respectively. A comparison of the occurrences of each symptom showed that all but one (myalgia) investigated symptom showed a statistically significant difference between the different waves (Table 1).

Concerning viral etiologies, HRV (6.3%, 187/2987) was the most frequently detected virus overall. Influenza A was identified in 4.1% (121/2987) of tested cases. The remaining pathogens were found at lower proportions (<2%) (Figures 1a, 2). Analysis of the results according to the epidemic wave showed no influenza cases during the first two waves, whereas the virus predominated during the third wave (12.1%, 121/1001) (Figure 1b–d). A similar proportion of HRV cases was observed during the three waves: 6.6% (65/986), 6.8% (68/1000), and 5.4% (54/1001), respectively. CoV-OC43 (3.7%, 36/986) and RSV (3.1%, 31/1000), identified as the second most prevalent viruses during the first and second waves, respectively, also showed the same rate of detection (Figure 1b,c). Of note, the proportion of RSV and CoV-OC43 cases during the first two waves showed overall inverse trends. Viral co-detection occurred in 1.4% (43/2987) of all cases: 1.5% (15/986), 1.4% (14/1000), and 1.4% (14/1001) during the first, second, and third wave, respectively (Supplementary Table S1).

<figure><img src="image_4.png" /><figcaption>**Figure 1.** Proportion of viral etiologies detected in COVID-19-negative patients during the three waves (a) and during wave 1 (b), wave 2 (c), and wave 3 (d). ADV: adenovirus, BOV: bocavirus, CoV: coronavirus, FLU: influenza, HMPV: human metapneumovirus, HRV: human rhinoviruses, PIV: parainfluenza viruses, RSV: respiratory syncytial viruses.</figcaption></figure>
<figure><img src="image_5.png" /><figcaption>**Figure 2.** Weekly distribution of respiratory viruses detected in samples from COVID-19-negative patients, March 2020 to February 2022, Madagascar. For comparison, the circulation profile of SARS-CoV-2 during the same period is shown.</figcaption></figure>

## 3.2. *Viral Epidemiology among Patients Enrolled through the Influenza Surveillance Network (SpS-2)*

During the pandemic period (March 2020 to May 2022), we collected 6297 NP swabs from our ISN, of which 4882 were outpatients and 1415 were inpatients. Overall, the positivity rates for FLU and SARS-CoV-2 were 5.4% (338/6297) and 24.5% (1543/6297), respectively (Table 2). Among the inpatients, RSV was the most detected virus (39.4%, 557/1415). Of note, only the inpatients were screened for RSV (Table 3). Influenza and SARS-CoV-2 were detected in 5.8% (82/1415) and 5.2% (73/1415) of the inpatients, respectively.
<table><caption>**Table 2.** Characteristics of influenza-positive cases detected among patients enrolled through the Influenza Surveillance Network, Madagascar from January 2018 to May 2022.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Total</th><th colspan="2">Pre-Pandemic Period</th><th colspan="2">Pandemic Period</th><th rowspan="2">p-Value <sup>2</sup></th></tr><tr><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th></tr></thead><tbody><tr><td></td><td>8792</td><td>1076 (12.2%)</td><td>2495</td><td>738 (29.6%)</td><td>6297</td><td>338 (5.4%)</td><td>&lt;0.001</td></tr><tr><td>Mean age (years)</td><td>18.9</td><td>11.4</td><td>7.9</td><td>9.1</td><td>23.3</td><td>14.2</td><td>0.01</td></tr><tr><td>Age (years)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>0-4</td><td>3532</td><td>490 (13.9)</td><td>1573</td><td>365 (23.2)</td><td>1959</td><td>125 (6.4)</td><td rowspan="5">&lt;0.001</td></tr><tr><td>5-14</td><td>1031</td><td>289 (28.0)</td><td>457</td><td>200 (43.8)</td><td>574</td><td>89 (15.5)</td></tr><tr><td>15-29</td><td>1470</td><td>168 (41.9)</td><td>227</td><td>97 (42.7)</td><td>1243</td><td>71 (5.7)</td></tr><tr><td>30-64</td><td>2242</td><td>103 (4.6)</td><td>171</td><td>59 (34.5)</td><td>2071</td><td>44 (2.1)</td></tr><tr><td>&ge;65</td><td>179</td><td>7 (3.9)</td><td>7</td><td>3 (42.9)</td><td>172</td><td>4 (2.3)</td></tr><tr><td>ND</td><td>338</td><td>19 (5.6)</td><td>60</td><td>14 (23.3)</td><td>278</td><td>5 (1.8)</td><td></td></tr><tr><td>Sex</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>M</td><td>4163</td><td>535 (12.9)</td><td>1267</td><td>373 (29.4)</td><td>2896</td><td>162 (5.6)</td><td rowspan="3">&lt;0.001</td></tr><tr><td>F</td><td>4529</td><td>538 (11.9)</td><td>1221</td><td>363 (29.7)</td><td>3308</td><td>175 (5.3)</td></tr><tr><td>ND</td><td>100</td><td>3 (3.0)</td><td>7</td><td>2 (28.6)</td><td>93</td><td>1 (1.1)</td></tr><tr><td>Clinical signs <sup>1</sup></td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Cough</td><td>6679</td><td>1050 (15.7)</td><td>2394</td><td>733 (30.6)</td><td>4285</td><td>317 (7.4)</td><td>&lt;0.001</td></tr><tr><td>Runny nose</td><td>3261</td><td>557 (7.1)</td><td>1258</td><td>398 (31.6)</td><td>2003</td><td>159 (7.9)</td><td>&lt;0.001</td></tr><tr><td>Dyspnea</td><td>1241</td><td>72 (5.8)</td><td>273</td><td>40 (14.7)</td><td>968</td><td>32 (3.3)</td><td>&lt;0.001</td></tr><tr><td>Fever</td><td>5788</td><td>1015 (17.5)</td><td>2354</td><td>728 (30.9)</td><td>3434</td><td>287 (8.4)</td><td>&lt;0.001</td></tr><tr><td>Intercostal recession</td><td>613</td><td>16 (2.6)</td><td>40</td><td>1 (2.5)</td><td>573</td><td>15 (2.6)</td><td></td></tr><tr><td>Weakness</td><td>857</td><td>50</td><td>255</td><td>11 (4.3)</td><td>602</td><td>39 (6.5)</td><td></td></tr><tr><td>Myalgia</td><td>2601</td><td>350 (13.5)</td><td>2324</td><td>295 (12.7)</td><td>277</td><td>55 (20.0%)</td><td>0.05</td></tr><tr><td>Vomiting/Nausea</td><td>360</td><td>39 (10.8)</td><td>95</td><td>22 (23.2)</td><td>265</td><td>17 (6.4)</td><td>&lt;0.001</td></tr><tr><td>Diarrhea</td><td>271</td><td>17 (6.3)</td><td>65</td><td>9 (13.8)</td><td>206</td><td>8 (3.9)</td><td>0.009</td></tr><tr><td>Stridor</td><td>156</td><td>5 (3.2)</td><td>28</td><td>1 (3.6)</td><td>128</td><td>4 (3.1)</td><td></td></tr><tr><td>Headache</td><td>1007</td><td>224 (22.2)</td><td>379</td><td>176 (46.4)</td><td>628</td><td>48 (7.6)</td><td>&lt;0.001</td></tr><tr><td>Sore throat</td><td>1015</td><td>149 (14.7)</td><td>329</td><td>113 (34.3)</td><td>686</td><td>36 (5.2)</td><td>&lt;0.001</td></tr><tr><td>Arthralgia</td><td>139</td><td>4 (2.9)</td><td>1</td><td>0 (0.0)</td><td>138</td><td>4 (2.9)</td><td></td></tr><tr><td>Abdominal pain</td><td>121</td><td>9 (7.4)</td><td>11</td><td>3 (27.3)</td><td>110</td><td>6 (5.5)</td><td>0.04</td></tr><tr><td>Chest pain</td><td>136</td><td>11 (8.1)</td><td>11</td><td>5 (45.5)</td><td>125</td><td>6 (4.8)</td><td>&lt;0.001</td></tr><tr><td>Asthenia</td><td>884</td><td>128 (14.5)</td><td>219</td><td>93 (42.5)</td><td>665</td><td>35 (5.3)</td><td>&lt;0.001</td></tr><tr><td>Aggravation</td><td>61</td><td>0 (0.0)</td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>Comorbidities</td><td>194</td><td>9 (4.6)</td><td>11</td><td>1 (9.1)</td><td>183</td><td>8 (4.4)</td><td>0.4</td></tr></tbody></table>

ND: not determined; ¹ Number of patients that responded “yes” for a given clinical sign; ² Only significant *p*-values are shown (except for the mean age).

<table><caption>**Table 3.** Characteristics of RSV-positive cases detected among patients enrolled through the Influenza Surveillance Network, Madagascar from January 2018 to May 2022.</caption><thead><tr><th rowspan="2"></th><th colspan="2">Total</th><th colspan="2">Pre-Pandemic Period</th><th colspan="2">Pandemic Period</th><th rowspan="2">p-Value <sup>2</sup></th></tr><tr><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th></tr></thead><tbody><tr><td></td><td>1816</td><td>707 (38.9%)</td><td>401</td><td>150 (37.4%)</td><td>1415</td><td>557 (39.4%)</td><td>0.5</td></tr><tr><td>Mean age (years)</td><td>2.9</td><td>1.1</td><td>1.2</td><td>0.7</td><td>3.5</td><td>1.2</td><td>0.1</td></tr><tr><td>Age (years)</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>0-4</td><td>1367</td><td>535 (39.1)</td><td>357</td><td>125 (35.0)</td><td>1010</td><td>410 (40.6)</td><td rowspan="3">0.07</td></tr><tr><td>5-14</td><td>103</td><td>8 (7.8)</td><td>15</td><td>1 (6.7)</td><td>88</td><td>7 (8.0)</td></tr><tr><td>15-29</td><td>13</td><td>3 (23.1)</td><td>1</td><td>1 (100)</td><td>12</td><td>2 (16.7)</td></tr></tbody></table>
<table><caption>**Table 3.** *Cont.*</caption><thead><tr><th rowspan="2"></th><th colspan="2">Total</th><th colspan="2">Pre-Pandemic Period</th><th colspan="2">Pandemic Period</th><th rowspan="2">p-Value <sup>2</sup></th></tr><tr><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th><th>Tested</th><th>Positive</th></tr></thead><tbody><tr><td>30–64</td><td>32</td><td>1 (3.1)</td><td>0</td><td>0 (0.0)</td><td>32</td><td>1 (3.1)</td><td></td></tr><tr><td>≥65</td><td>11</td><td>2 (18.2)</td><td>0</td><td>0 (0.0)</td><td>11</td><td>2 (18.2)</td><td></td></tr><tr><td>ND</td><td>290</td><td>158 (54.5)</td><td>28</td><td>23 (82.1)</td><td>262</td><td>135 (51.5)</td><td></td></tr><tr><td>Sex</td><td></td><td></td><td></td><td></td><td></td><td></td><td></td></tr><tr><td>M</td><td>925</td><td>351 (37.9)</td><td>211</td><td>79 (37.4)</td><td>714</td><td>272 (38.1)</td><td rowspan="3">0.9</td></tr><tr><td>F</td><td>799</td><td>316 (39.5)</td><td>187</td><td>71 (38.0)</td><td>612</td><td>245 (40.0)</td></tr><tr><td>ND</td><td>92</td><td>40 (43.5)</td><td>3</td><td>0 (0.0)</td><td>89</td><td>40 (44.9)</td></tr><tr><td>Clinical signs <sup>1</sup></td><td>N</td><td></td><td>N</td><td></td><td>N</td><td></td><td></td></tr><tr><td>Cough</td><td>1275</td><td>459 (36.0)</td><td>329</td><td>111 (33.7)</td><td>946</td><td>348 (36.8)</td><td></td></tr><tr><td>Runny nose</td><td>1073</td><td>400 (37.3)</td><td>305</td><td>107 (35.1)</td><td>768</td><td>293 (38.2)</td><td></td></tr><tr><td>Dyspnea</td><td>985</td><td>406 (41.2)</td><td>191</td><td>95 (49.7)</td><td>794</td><td>311 (39.2)</td><td></td></tr><tr><td>Fever</td><td>873</td><td>304 (34.8)</td><td>319</td><td>109 (34.2)</td><td>554</td><td>195 (35.2)</td><td></td></tr><tr><td>Intercostal recession</td><td>611</td><td>233 (38.1)</td><td>40</td><td>9 (22.5)</td><td>571</td><td>224 (39.2)</td><td rowspan="3">0.05</td></tr><tr><td>Weakness</td><td>499</td><td>158 (31.7)</td><td>1</td><td>0 (0.0)</td><td>498</td><td>158 (31.7)</td></tr><tr><td>Myalgia</td><td>428</td><td>128 (29.9)</td><td>323</td><td>106 (32.8)</td><td>105</td><td>22 (21.0)</td></tr><tr><td>Vomiting/Nausea</td><td>263</td><td>74 (28.1)</td><td>47</td><td>4 (8.5)</td><td>216</td><td>70 (32.4)</td><td>0.03</td></tr><tr><td>Diarrhea</td><td>187</td><td>49 (26.2)</td><td>47</td><td>5 (10.6)</td><td>140</td><td>44 (31.4)</td><td>0.02</td></tr><tr><td>Stridor</td><td>150</td><td>46 (30.7)</td><td>27</td><td>5 (18.5)</td><td>123</td><td>41 (33.3)</td><td rowspan="3">0.009</td></tr><tr><td>Headache</td><td>116</td><td>18 (15.5)</td><td>10</td><td>1 (10.0)</td><td>106</td><td>17 (16.0)</td></tr><tr><td>Sore throat</td><td>113</td><td>28 (24.8)</td><td>28</td><td>2 (7.1)</td><td>85</td><td>26 (30.6)</td></tr><tr><td>Arthralgia</td><td>97</td><td>26 (26.8)</td><td>0</td><td>0 (0.0)</td><td>97</td><td>26 (26.8)</td><td rowspan="3">0.02</td></tr><tr><td>Abdominal pain</td><td>87</td><td>19 (21.8)</td><td>6</td><td>1 (16.7)</td><td>81</td><td>18 (22.2)</td></tr><tr><td>Chest pain</td><td>83</td><td>10 (12.0)</td><td>73</td><td>2 (2.7)</td><td>10</td><td>8 (80.0)</td></tr><tr><td>Asthenia</td><td>27</td><td>3 (11.1)</td><td>24</td><td>3 (12.5)</td><td>3</td><td>0 (0.0)</td><td></td></tr><tr><td>Aggravation</td><td>61</td><td>9 (14.8)</td><td>8</td><td>2 (25.0%)</td><td>53</td><td>7 (13.2)</td><td>0.03</td></tr><tr><td>Comorbidities</td><td>369</td><td>50 (13.6)</td><td>359</td><td>50 (13.9)</td><td>10</td><td>0 (0.0)</td><td>NA</td></tr></tbody></table>

ND: not determined, NA: not applicable; ¹ Number of patients that responded "yes" for a given clinical sign;

² Only significant p-values are shown (except for the mean age).

The circulation pattern of influenza in Madagascar over the past five years (2018–2022) is shown in Supplementary Figure S2. Between 2018 and March 2020, influenza circulated throughout the year, in general with periods of higher activity during the rainy season (January–March) and the Austral winter season (June–September) [8,9]. After the first detection of SARS-CoV-2 in Madagascar in March 2020, no influenza virus was detected during the first two waves of SARS-CoV-2. Influenza reappeared in late July 2021, after the second wave of SARS-CoV-2. Indeed, influenza B (Victoria lineage) was detected from July to November 2021, causing a major outbreak, and was then replaced by influenza A (A/H3N2 subtype) between February 2022 and April 2022, causing a second seasonal outbreak. The third wave of SARS-CoV-2 took place between December 2021 and February 2022 (Figure 3).

In the meantime, RSV showed a different pattern of circulation than that of the influenza viruses (Supplementary Figure S3). Indeed, from 2018 to 2022, RSV showed clear seasonality, with epidemics occurring during the first quarter of the year and reaching a peak between February and March, with a positivity rate of 50–70% for the tested samples (Figures 3 and S2). During the circulation of SARS-CoV-2, RSV continued to circulate in the country. In 2020 and 2021, the RSV epidemic occurred before the first and second SARS-CoV-2 waves, whereas in 2022, the third SARS-CoV-2 wave occurred before the RSV epidemic (Figure 3).

Analysis of the age susceptibility of RSV showed no substantial difference before (mean age = 0.7 years) or during (mean age = 1.2 years) the COVID-19 pandemic (p = 0.1).
Moreover, there was no statistically significant difference in the proportion of RSV-positive samples by age (p = 0.07) or sex (p = 0.9) between the two periods (Table 3). Influenza showed a different pattern, although the positive patients identified during the COVID-19 pre-pandemic period were much younger (mean age = 9.1 years) than those identified during the epidemic period (mean age = 14.2 years) (p < 0.01) (Table 2). In addition, the proportion of influenza-positive patients by age group was statistically different between the two periods (p < 0.001) (Table 3).

<figure><img src="image_6.png" /><figcaption>**Figure 3.** Weekly distribution of influenza, RSV, and SARS-CoV-2 detected by the Influenza Surveillance Network, January 2020 to May 2022, Madagascar.</figcaption></figure>

Analysis of the age distribution by virus showed three distinct profiles. First, influenza affected all age groups, with a more pronounced infection rate among children (5–14 years), adolescents, and young adults (15–29 years). Second, the RSV infection rate was the highest in children (0–4 years) and declined with age. Finally, the prevalence of SARS-CoV-2 appeared to increase with age, with a higher infection rate observed in adults (30–64 years) (Figure 4).
<figure><img src="image_7.png" /><figcaption>**Figure 4.** Age distribution of patients who tested positive for influenza (FLU), respiratory syncytial viruses (RSV), or SARS-CoV-2 detected from the Influenza Surveillance Network, January 2020 to May 2022, Madagascar.</figcaption></figure>

**4. Discussion**

This study describes the epidemiological profile of RVs before and during the SARS-CoV-2 pandemic in Madagascar. With the exception of RSV, the COVID-19 pandemic influenced the epidemiological trends of all the other investigated respiratory viruses. Indeed, among the 2987 NP specimens negative for SARS-CoV-2 collected from symptomatic patients, only 19% were positive for at least one RV. In earlier studies, we found a higher rate of viral infections (>75%) among patients suffering from either ILI or SARI [8,9]. Although observed at a substantially lower rate than in our previous studies, rhinovirus, the major cause of the common cold, was the most frequently detected virus in this cohort. CoV-OC43 and RSV were the second most frequently detected viruses during the first two epidemic waves of SARS-CoV-2, whereas influenza predominated during the third wave. RSV was not detected in 2020 in this cohort because its inclusion started in March, at the end of the regular circulation period for RSV (first quarter of each year) in Madagascar, as previously described [8,9]. Our results differ from previous observations generated before the COVID-19 pandemic, for which we showed that influenza viruses and RSV were the primary etiologies identified among ILI and SARI patients [8,9]. Nevertheless, they are consistent with those of other studies that reported a significant decline, in particular, of influenza virus, metapneumovirus, parainfluenza virus, and adenovirus during the first waves of COVID-19 [5,6,10–12].

Except for HRV, for which the peak of detection appears to coincide with that of SARS-CoV-2, most of the other targeted viruses were detected between the waves of SARS-CoV-2. Madagascar remained “free of influenza” for almost 18 months following the first identification of confirmed SARS-CoV-2 cases. Similar observations were noted in many parts of the globe [13–15]. Unlike what has been reported elsewhere, in which a change in the timing of or a delay in RSV epidemics occurred [16,17], RSV continued to propagate during the COVID-19 pandemic throughout the country, with similar amplitude and similar epidemiological characteristics. Of note, the national RSV surveillance is focused primarily on children. Similarly, HRV continued to circulate during the study period, although at a lower rate than what we observed previously, indicating that this virus was not strongly affected by the pandemic. Overall, our study highlighted three different patterns of circulation. The first involved viruses that circulated sporadically but demonstrated greater activity when SARS-CoV-2 was not circulating (human CoV, PIV, HMPV, ADV, and BOV). The second concerned viruses that continued to circulate regardless of the COVID-19 situation (HRV, RSV), and the third involved viruses that were
severely disrupted following the spread of SARS-CoV-2 and took longer to reappear (e.g.,
influenza).

Several factors can explain the observed patterns of RV circulation during the pan-
demic. The reduction in the circulation of influenza viruses could be the consequence of the
early introduction of NPI measures for COVID-19 [6,18,19], including a travel ban. Indeed,
a reemergence of influenza viruses occurred at the end of the second SARS-CoV-2 wave
(July 2021), in conjunction with the official relaxation of sanitary measures and the resump-
tion of international flights from June 2021. Whether the late 2021 influenza outbreak was
due to imported cases is yet to be clarified. Furthermore, a decline in host immunity to
new influenza strains cannot be ruled out. Concerning RSV, one of the leading causes of
respiratory infections in infants and children [20,21], the similar dynamics of the circulation
of this virus during the pandemic could be partially explained by the fact that children
under five were not required to wear masks, which allowed RSV to spread within this pop-
ulation. Interestingly, neither the circulation of SARS-CoV-2 nor the implementation of NPI
measures influenced the circulation pattern of HRV. A number of authors have postulated
that NPI measures may affect enveloped viruses but not non-enveloped viruses [22]. As a
non-enveloped virus, HRV is extremely resistant in the environment relative to influenza,
making this virus probably more transmissible than enveloped respiratory viruses and
probably less affected by NPI measures [23–25]. In addition, several studies have suggested
that prior HRV infection leads to the inhibition of SARS-CoV-2 replication [26]. Other
intrinsic factors could also affect the circulation of other RVs during the pandemic, such as
viral interference. Nevertheless, how these mechanisms operate is yet to be determined.

The patients who were positive for RVs were much younger in our current study than the COVID-19-positive patients in our previous study describing the first epidemic wave of SARS-CoV-2 in Madagascar [2] (median age 19.6 vs. 39.3 years, respectively). Host immunity could be a factor in such age susceptibility.

Our study had several limitations. First, during the first months of the pandemic and the different waves, the surveillance capacity was overloaded. As a result, our sentinel sites located throughout the country were unable or found it difficult to ship specimens to the National Influenza Centre, leading to a decrease in the number of specimens collected from suspected ILI and SARI patients at healthcare centers or hospitals. In addition, we observed changes in healthcare-seeking behaviors within communities and at healthcare centers during the first wave of COVID-19, leading to a substantial reduction in the number of medical consultations. Thus, we cannot exclude that we missed a proportion of the sporadic circulation of RVs during these periods, leading to an underestimation of their overall prevalence. Nevertheless, as our study focused on the global circulation of RVs at the community level, we believe that the limitations of our study did not affect the global picture of RV circulation patterns in Madagascar and the observed impact of COVID-19 on them.

**5. Conclusions**

This study confirms the importance of including NPI measures, such as wearing masks, in strategies aimed at reducing the spread of influenza, in addition to vaccination. The impact of NPI measures, in particular, a travel ban during the pandemic, revealed an interesting characteristic of RVs in an insular system such as Madagascar. Indeed, our data suggest that influenza viruses are seeded regularly in the country, leading to seasonal epidemics, but cannot be maintained in the Malagasy population without regular reintroduction. Unlike influenza, RSV and HRV can be maintained within the communities at a local level without requiring annual reintroduction. Therefore, the implementation of RSV vaccination should remain a priority for vulnerable populations.

Our findings underline the importance of an integrated disease surveillance system combined with laboratory surveillance to monitor not only SARS-CoV-2, influenza, and RSV but also other respiratory viruses of interest to public health, with the aim of providing data for decision-making in terms of developing vaccines and therapies [27,28]. Given
that SARS-CoV-2 and RVs share a similar clinical spectrum, the integration of COVID-19
into the panel of clinical diagnoses is crucial for better surveillance and monitoring of
these viruses.

**Supplementary Materials:** The following supporting information can be downloaded at https://www.mdpi.com/article/10.3390/v15010012/s1, Figure S1: Description of the different sources of specimens used in the study and tests performed accordingly; Table S1: List of seasonal respiratory viruses co-detected in patients during the three epidemic waves of SARS-CoV-2 in Madagascar; Figure S2: Weekly distribution of influenza detected from the influenza-like illnesses (ILI) Surveillance Network, Madagascar, January 2018 to May 2022; Figure S3: Weekly distribution of respiratory syncytial viruses (RSV) detected from severe acute respiratory infection (SARI) surveillance, Madagascar, January 2018 to May 2022.

**Author Contributions:** Conceptualization: N.H.R., P.D., V.L., L.R. and J.-M.H.; Methodology: N.H.R., T.H.R., L.R., J.H.R., M.F.A., A.H.R., A.R., H.R., V.R. and S.F.A.; Software: N.H.R. and J.H.R.; Funding Acquisition: N.H.R., P.D., V.L., L.R. and J.-M.H. Project Administration: P.D., V.L. and J.-M.H. Validation: N.H.R. and T.H.R.; Formal Analysis: L.R., J.H.R., M.F.A. and A.H.R.; Investigation: L.R., J.H.R., A.R., M.F.A., A.H.R. and S.F.A.; Data Curation: N.H.R., L.R., J.H.R., M.F.A., A.H.R. and A.R.; Writing—Original Draft Preparation: N.H.R.; Writing—Review and Editing: All authors. All authors have read and agreed to the published version of the manuscript.

**Funding:** For COVID-19 diagnostics and responses, we received (1) technical support from the following organizations: the Pasteur Network, the United Nations Children's Fund (UNICEF), the AFRICA CDC, and the Jack Ma Foundation and (2) financial support from the following funders: the World Health Organization (WHO), the US Centers for Disease Control and Prevention (US CDC: Grant#U5IP000812-05; Grant#U51IP2021000900), the United States Agency for International Development (USAID: Cooperation Agreement 72068719CA00001), and the Office of the Assistant Secretary for Preparedness and Response in the US Department of Health and Human Services (DHHS: grant number IDSEP190051-01-0200). For the ILI and SARI surveillance network, we received technical support from the World Health Organization (WHO) and the US Centers for Disease Control and Prevention (US CDC) and financial support from the United States Agency for International Development (USAID: Cooperation Agreement 72068719CA00001). The positive controls used for SARS-CoV-2 testing were obtained through the European Virus Archive GLOBAL (EVA-GLOBAL) project, which received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No. 871029.

**Institutional Review Board Statement:** The study was conducted in accordance with the Declaration of Helsinki, and approved by the National Ethics Committee of the Madagascar Ministry of Public Health (Authorizations N°096-MSANP/CERBM dated August 27th 2018, and 088-MSANP/CE dated July 13th 2016, respectively, for the ILI and SARI surveillance).

**Informed Consent Statement:** The data used from SpS-1 were obtained from statewide surveillance of a notifiable disease and de-identified and, thus, did not require ethical approval. Although the ILI and SARI surveillance in Madagascar is not considered research, informed consent was given for all ILI and SARI patients included in this study.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** We are deeply indebted to the Ministry of Public Health, the Epidemiology and Research Clinic Unit at the Institut Pasteur de Madagascar, and the sentinel sites involved in the ILI and SARI surveillance network. We are indebted to all the staff from the Institut Pasteur de Madagascar for their dedicated work during the COVID-19 pandemic. We would also like to thank the laboratory technicians at the Virology Unit for their tremendous work.

**Conflicts of Interest:** The authors declare no conflict of interest.

## References

1. Worldometers.info. COVID-19 Coronavirus Pandemic Dover Delaware, USA. 2022. Available online: https://www.worldometers.info/coronavirus/ (accessed on 21 June 2022).
2. Randremanana, R.V.; Andriamandimby, S.-F.; Rakotondramanga, J.M.; Razanajatovo, N.H.; Mangahasimbola, R.T.; Randriambo-lamanantsoa, T.H.; Ranaivoson, H.C.; Rabemananjara, H.A.; Razanajatovo, I.; Razafindratsimandresy, R.; et al. The COVID-19 epidemic in Madagascar: Clinical description and laboratory results of the first wave, March–September 2020. *Influenza Other Respir. Viruses* **2021**, *15*, 457–468. [CrossRef] [PubMed]

3. Gomez, G.B.; Mahé, C.; Chaves, S.S. Uncertain effects of the pandemic on respiratory viruses. *Science* **2021**, *372*, 1043–1044. [CrossRef] [PubMed]

4. Huang, Q.S.; Wood, T.; Jelley, L.; Jennings, T.; Jefferies, S.; Daniells, K.; Nesdale, A.; Dowell, T.; Turner, N.; Campbell-Stokes, P.; et al. Impact of the COVID-19 nonpharmaceutical interventions on influenza and other respiratory viral infections in New Zealand. *Nat. Commun.* **2021**, *12*, 1–7. [CrossRef] [PubMed]

5. Ippolito, G.; La Vecchia, A.; Umbrello, G.; Di Pietro, G.; Bono, P.; Catenacci, S.S.; Pinzani, R.; Tagliabue, C.; Bosis, S.; Agostoni, C.; et al. Disappearance of Seasonal Respiratory Viruses in Children Under Two Years Old During COVID-19 Pandemic: A Monocentric Retrospective Study in Milan, Italy. *Front. Pediatr.* **2021**, *9*, 721005. [CrossRef] [PubMed]

6. Poole, S.; Brendish, N.J.; Clark, T.W. SARS-CoV-2 has displaced other seasonal respiratory viruses: Results from a prospective cohort study. *J. Infect.* **2020**, *81*, 966–972. [CrossRef]

7. Sakamoto, H.; Ishikane, M.; Ueda, P. Seasonal Influenza Activity During the SARS-CoV-2 Outbreak in Japan. *JAMA* **2020**, *323*, 1969–1971. [CrossRef]

8. Razanajatovo, N.H.; Richard, V.; Hoffmann, J.; Reynes, J.-M.; Razafitrimo, G.M.; Randremanana, R.V.; Heraud, J.-M. Viral Etiology of Influenza-Like Illnesses in Antananarivo, Madagascar, July 2008 to June 2009. *PLoS ONE* **2011**, *6*, e17579. [CrossRef]

9. Razanajatovo, N.H.; Guillebaud, J.; Harimanana, A.; Rajatonirina, S.; Ratsima, E.H.; Andrianirina, Z.Z.; Rakotoariniaina, H.; Andriatahina, T.; Orelle, A.; Ratovoson, R.; et al. Epidemiology of severe acute respiratory infections from hospital-based surveillance in Madagascar, November 2010 to July 2013. *PLoS ONE* **2018**, *13*, e0205124. [CrossRef]

10. Maharaj, A.S.; Parker, J.; Hopkins, J.P.; Gournis, E.; I Bogoch, I.; Rader, B.; Astley, C.M.; Ivers, N.; Hawkins, J.B.; VanStone, N.; et al. The effect of seasonal respiratory virus transmission on syndromic surveillance for COVID-19 in Ontario, Canada. *Lancet Infect. Dis.* **2021**, *21*, 593–594. [CrossRef]

11. Redlberger-Fritz, M.; Kundi, M.; Aberle, S.W.; Puchhammer-Stöckl, E. Significant impact of nationwide SARS-CoV-2 lockdown measures on the circulation of other respiratory virus infections in Austria. *J. Clin. Virol.* **2021**, *137*, 104795. [CrossRef]

12. Tang, J.W.; Bialasiewicz, S.; Dwyer, D.E.; Dilcher, M.; Tellier, R.; Taylor, J.; Hua, H.; Jennings, L.; Kok, J.; Levy, A.; et al. Where have all the viruses gone? Disappearance of seasonal respiratory viruses during the COVID-19 pandemic. *J. Med. Virol.* **2021**, *93*, 4099–4101. [CrossRef]

13. Itaya, T.; Furuse, Y.; Jindai, K. Does COVID-19 infection impact on the trend of seasonal influenza infection? 11 countries and regions, from 2014 to 2020. *Int. J. Infect. Dis.* **2020**, *97*, 78–80. [CrossRef]

14. Kim, J.; Gómez, R.E.G.; Hong, K.; Yum, S.; Jang, J.; Chun, B.C. Changing influenza activity in the Southern hemisphere countries during the COVID-19 pandemic. *Int. J. Infect. Dis.* **2021**, *108*, 109–111. [CrossRef]

15. WHO. *FluNet*; WHO: Geneva, Switzerland; Available online: https://www.who.int/tools/flunet (accessed on 6 November 2022).

16. Barrezueta, L.B.; Del Pozo, V.M.; López-Casillas, P.; Raposo, M.B.; Zamorano, M.G.; de la Asunción Pino Vázquez, M. Variation in the seasonality of the respiratory syncytial virus during the COVID-19 pandemic. *Infection* **2022**, *50*, 1001–1005. [CrossRef]

17. Agha, R.; Avner, J.R. Delayed Seasonal RSV Surge Observed During the COVID-19 Pandemic. *Pediatrics* **2021**, *148*, 2021052089. [CrossRef]

18. Davis, W.W.; Mott, J.A.; Olsen, S.J. The role of non-pharmaceutical interventions on influenza circulation during the COVID-19 pandemic in nine tropical Asian countries. *Influenza Other Respir. Viruses* **2022**, *16*, 568–576. [CrossRef]

19. Oh, D.-Y.; Buda, S.; Biere, B.; Reiche, J.; Schlosser, F.; Duwe, S.; Wedde, M.; von Kleist, M.; Mielke, M.; Wolff, T.; et al. Trends in respiratory virus circulation following COVID-19-targeted nonpharmaceutical interventions in Germany, January–September 2020: Analysis of national surveillance data. *Lancet Reg. Health Eur.* **2021**, *6*, 100112. [CrossRef]

20. Meissner, H.C. Viral Bronchiolitis in Children. *N. Engl. J. Med.* **2016**, *374*, 62–72. [CrossRef]

21. Shi, T.; McAllister, D.A.; O'Brien, K.L.; Simoes, E.A.F.; Madhi, S.A.; Gessner, B.D.; Polack, F.P.; Balsells, E.; Acacio, S.; Aguayo, C.; et al. Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: A systematic review and modelling study. *Lancet* **2017**, *390*, 946–958. [CrossRef]

22. Britton, P.N.; Hu, N.; Saravanos, G.; Shrapnel, J.; Davis, J.; Snelling, T.; Dalby-Payne, J.; Kesson, A.M.; Wood, N.; Macartney, K.; et al. COVID-19 public health measures and respiratory syncytial virus. *Lancet Child Adolesc. Health* **2020**, *4*, e42–e43. [CrossRef]

23. Charlton, C.L.; Babady, E.; Ginocchio, C.C.; Hatchette, T.F.; Jerris, R.C.; Li, Y.; Loeffelholz, M.; McCarter, Y.S.; Miller, M.B.; Novak-Weekley, S.; et al. Practical Guidance for Clinical Microbiology Laboratories: Viruses Causing Acute Respiratory Tract Infections. *Clin. Microbiol. Rev.* **2018**, *32*, e00042-18. [CrossRef] [PubMed]

24. Kuitunen, I.; Artama, M.; Mäkelä, L.; Backman, K.; Heiskanen-Kosma, T.; Renko, M. Effect of Social Distancing Due to the COVID-19 Pandemic on the Incidence of Viral Respiratory Tract Infections in Children in Finland During Early 2020. *Pediatr. Infect. Dis. J.* **2020**, *39*, e423–e427. [CrossRef] [PubMed]

25. Leung, N.H.L.; Chu, D.K.W.; Shiu, E.Y.C.; Chan, K.-H.; McDevitt, J.J.; Hau, B.J.P.; Yen, H.-L.; Li, Y.; Ip, D.K.M.; Peiris, J.S.M.; et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. *Nat. Med.* **2020**, *26*, 676–680. [CrossRef] [PubMed]
26. Dee, K.; Goldfarb, D.M.; Haney, J.; Amat, J.A.R.; Herder, V.; Stewart, M.; Szemiel, A.M.; Baguelin, M.; Murcia, P.R. Human rhinovirus infection blocks SARS-CoV-2 replication within the respiratory epithelium: Implications for COVID-19 epidemiology. *J. Infect. Dis.* **2021**, *224*, 31–38. [CrossRef]

27. Chotpitayasunondh, T.; Fischer, T.K.; Heraud, J.-M.; Hurt, A.C.; Monto, A.S.; Osterhaus, A.; Shu, Y.; Tam, J.S. Influenza and COVID-19: What does co-existence mean? *Influenza Other Respir. Viruses* **2021**, *15*, 407–412. [CrossRef]

28. Tang, J.W.; Lam, T.T.; Zaraket, H.; Lipkin, W.L.; Drews, S.J.; Hatchette, T.F.; Heraud, J.M.; Koopmans, M.P.; INSPIRE investigators. Global epidemiology of non-influenza RNA respiratory viruses: Data gaps and a growing need for surveillance. *Lancet Infect. Dis.* **2017**, *17*, e320–e326. [CrossRef]

**Disclaimer/Publisher's Note:** The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.